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Malignant perivascular epithelioid cell tumor (PEComa) of uterus: A case report with literature review
Joseph J. Noh, Sir-Yeon Hong, Byeong-gie Kim
European Journal of Gynaecological Oncology    2020, 41 (4): 495-499.   DOI: 10.31083/j.ejgo.2020.04.5305
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Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm involving various organs. Approximately 70 cases of gynecologic PEComas have been reported in the literature. Due to the paucity of cases, there is no definite treatment regimen established. We describe disease progression in a case of uterine PEComa with pulmonary metastasis in a 37-year-old woman who had been treated with surgery and various regimens of adjuvant treatment including vincristine, ifosfamide, cisplatin, sirolimus, doxorubicin, olaratumab, pazopanib and dacarbazine. Adequate management and prognosis still seem inconclusive and further case reports with randomized trials are needed to delineate the nature of this neoplasm.
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Development of lymphangiosarcoma after pelvic radiation therapy for uterine cervical cancer: A case report and literature review
Hikari Unno, Seiji Mabuchi, Isao Arai, Tomoko Wakasa, Seiichi Yamamasu
European Journal of Gynaecological Oncology    2020, 41 (3): 326-331.   DOI: 10.31083/j.ejgo.2020.03.5082
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Angiosarcoma accounts for 1-2% of all soft tissue sarcomas. Common sites of occurrence include the skin, breast, soft tissue, and liver. Angiosarcoma of the gastrointestinal (GI) tract is very rare. We herein present a case of a 41-year-old woman with lymphangiosarcoma of the small intestine occurring 7 years after pelvic radiotherapy for uterine cervical cancer.

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Malignant bowel obstruction in recurrent gynecologic cancers: who will benefit from palliative surgical intervention?
Rie Nakamura, Yuko Shimoji, Tadaharu Nakasone, Yusuke Taira, Yoshihisa Arakaki, Tomoko Nakamoto, Keiko Mekaru, Wataru Kudaka, Tatsuya Kinjo, Yoichi Aoki
European Journal of Gynaecological Oncology    2020, 41 (4): 513-516.   DOI: 10.31083/j.ejgo.2020.04.5070
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Purpose of Investigation: To define factors that assist in the selection of patients with gynecologic cancer who have malignant bowel obstruction (MBO) for those who are most likely to benefit from palliative bowel surgery. Materials and Methods: Between 2004 and 2014, 11 women who underwent surgery for bowel obstruction after a discharge for the treatment of gynecologic cancer were included. The diagnosis of MBO was confirmed by symptoms and signs of intestinal obstruction along with abdominal X-ray, or a computed tomography (CT) scan. Results: The median age of women was 58 years and the median time to surgery was six days. Colostomy was performed in seven of eleven patients, ileostomy in three, and bowel resection and anastomosis in two. Postoperative oral intake was achieved in ten of eleven cases, with a median period of 77 (range, 27–224) days. The progression free interval (PFI) of the primary cancer was < 6 months in six patients and ≥ 6 months in five. The median duration of post-operative oral intake in patients with PFI of < 6 and ≥ 6 months was 34.5 (range, 0–65), and 120 (range, 89–224) days, respectively (p = 0.0014). The median survival time after surgery in patients with PFI of < 6 and ≥ 6 months was 43 (range, 11–111), and 156 (range 94–253) days, respectively (p = 0.0206). Conclusion: PFI of primary gynecologic cancer is a good indicator that could help select for those patients who would most likely benefit from palliative bowel surgery. Surgery for MBO should be considered for patients without serious contraindications.
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The impact of pre-existing polycystic ovary syndrome on endometrial cancer recurrence
T. Uehara, A. Mitsuhashi, M. Shozu
European Journal of Gynaecological Oncology    2020, 41 (5): 668-674.   DOI: 10.31083/j.ejgo.2020.05.5038
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Purpose: Polycystic ovary syndrome (PCOS) is a risk factor for the development of endometrial cancer (EC). To the present authors’ knowledge, no study has clarified whether pre-existing PCOS is a prognostic factor for post-surgical EC recurrences. The aim of this study was to determine whether pre-existing PCOS is a risk factor for the recurrence of EC even after the surgical treatment of EC in premenopausal women. Materials and Methods: The authors performed a retrospective cohort study on premenopausal EC patients aged 50 years or younger who underwent surgery at this hospital between 2009 and 2013. The median follow-up period was 65.5 months. Results: Of 46 patients with EC, nine (19.6%) had PCOS. Four of the nine PCOS patients developed recurrence of EC, three of whom died of the disease, whereas only one of 37 patients who did not have PCOS developed EC recurrence (44.4% and 2.7%, respectively; p = 0.003). Univariate analysis showed that the progression-free and overall survival of the patients with pre-existing PCOS was worse than that of patients without pre-existing PCOS (p = 0.008 and p = 0.029, respectively). Multivariate analysis revealed that PCOS was a poor prognostic factor for progression-free survival and a marginal poor prognostic factor for overall survival (p = 0.011 and p = 0.061, respectively). Conclusions: Pre-existing PCOS was a risk factor for recurrence in premenopausal post-operative patients with EC aged 50 years or younger.
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Genomic profiling in gynaecological oncology: the future is now!
Luca Roncati, Maria Vadalà, Pepe Valentina, Veronica Corazzari, Beniamino Palmieri
European Journal of Gynaecological Oncology    2020, 41 (3): 323-325.   DOI: 10.31083/j.ejgo.2020.03.5363
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Nowadays, thanks to next generation sequencing, it is simultaneously possible to search for driver mutations in hundreds of cancer-related genes with high sensibility and specificity, by exploiting formalin-fixed paraffin-embedded tumor material, from biopsy samples and surgical specimens, or circulating tumor DNA in the patient's blood. In addition to indicate the genomic alterations, this modern technology provides information about: the approved therapies in the patient’s cancer type or in other tumor types for a personalized oncology; potential clinical trials; mutational burden and microsatellite instability (MSI). This last datum is particularly relevant because the U.S. Food & Drug Administration (FDA) has approved the use of pembrolizumab for all unresectable or metastatic, MSI-high or mismatch repair deficient, solid malignancies, among which there are 17-32% of sporadic endometrial carcinomas and 10-17% of sporadic ovarian cancers. Similarly, the FDA has approved olaparib for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, characterized by deleterious or suspected deleterious germline or somatic mutations in ‘breast cancer’ (BRCA) genes, who are in complete or partial response to first-line platinum-based chemotherapy. Therefore, we are facing an era of innovation in gynaecological oncology, in which molecular profiling is joining immunomorphological typing for new health goals.

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New treatment strategy for ovarian cancer with a BRCA gene mutation
Tadahiro Shoji, Kotoka Kikuchi, Hayato Kogita, Nanako Jonai, Hidetoshi Tomabechi, Akiko Kudoh, Eriko Takatori, Takayuki Nagasawa, Masahiro Kagabu, Tsukasa Baba
European Journal of Gynaecological Oncology    2021, 42 (1): 1-9.   DOI: 10.31083/j.ejgo.2021.01.2251
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Mutated BRCA1/2 genes have been identified as causative genes for ovarian cancer, and it has been reported that 10–20% of all epithelial ovarian cancers have a BRCA mutation. As novel treatment drugs utilizing this BRCA gene mutation, significant attention has been paid to adenine dinucleotide poly (ADP-ribose) polymerase inhibitors. Among them, olaparib has been reported to be useful in patients with a BRCA mutation in Study 19 and SOLO-2 trials. It is important to establish a system for genetic counseling and to perform BRCA gene testing in patients with ovarian cancer. For patients with BRCA -mutated advanced cancer, if adequate response to chemotherapy has been achieved, olaparib is recommended as maintenance therapy for both advanced and recurrent cases. For patients without BRCA gene mutation, bevacizumab combined with chemotherapy or as maintenance therapy is also an option.
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The impact of secondary cytoreductive surgery on survival in first recurrence of platinum sensitive epithelial ovarian cancer
Silvia Ortega, José Angel Mínguez, José Manuel Aramendía, Marta Santisteban, Fernando Martinez-Regueira, Pablo Martí-Cruchaga, Juan Luis Alcázar, Matías Jurado
European Journal of Gynaecological Oncology    2020, 41 (4): 523-530.   DOI: 10.31083/j.ejgo.2020.04.8051
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Objective: Analyze the effect on survival of secondary cytoreduction surgery (SCS) in treatment of first recurrence platinum-sensitive epithelial ovarian cancer (REOC). Methods: Retrospective analysis of patients with first REOC who had platinum time-free interval (TFIp) > 6 months and were treated either with SCS followed by chemotherapy or chemotherapy only (CT). Clinical data such as patient's performance status and number of sites with metastases were specifically assessed. The primary endpoint was overall survival (OS). Results: Seventy-one patients were treated either by SCS (n = 37) or CT (n = 34). Complete resection after SCS was achieved in 89% of patients. After a median follow-up of 51.2 months, median OS, and progression-free survival (PFS) were 68.2 and 21.6 months, respectively, for the whole series of the SCS patients had better survival and disease progression survival than the CT only patients (HR: 0.33, 95%CI: 0.17-0.6; p = 0.001) and (HR: 0.28, 95%CI: 0.15-0.5; p = 0.001), respectively. TFIp < 12 months and multiple metastases were most important prognostic factors for risk of death (HR: 7.7 and 6.2, respectively) and recurrence (HR: 5.8 and 3.8, respectively). Probability to undergo successful SCS is related to oligometastatic disease and no residual disease after first surgery (OR: 30.0 and 5.9, respectively). Conclusions: In women with REOC oligometastatic disease and no residual disease at first surgery are associated with successful SCS. In these patients oligometastatic disease and long platinum TFI are associated with improved probability of survival.
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Multicentric assessment of cervical HPV infection co-factors in a large cohort of Greek women
Panteleimon Mnimatidis, Abraham Pouliakis, George Valasoulis, George Michail, Aris Spathis, Christine Cottaridi, Niki Margari, Maria Kyrgiou, Maria Nasioutziki, Alexandros Daponte, Konstantinos Dinas, Evangelos Paraskevaidis, Ioannis Panayiotides, Dimitrios-Dionysios Koutsouris
European Journal of Gynaecological Oncology    2020, 41 (4): 545-555.   DOI: 10.31083/j.ejgo.2020.04.5180
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Purpose of Investigation: Despite the general principle that persistent high risk human papillomavirus (hr-HPV) infection may progressively cause cervical cancer (CxCa), demographic aspects may still identify groups at high risk for HPV infection and consequently for precancerous lesions. The role of demographic parameters on cervical status, the diagnostic accuracy of cytology, HPV genotyping, and their possible combinations, were investigated in this study. Materials and Methods: 11,072 women from diverse locations across Greece participated in the study. Liquid Based Cytologic (LBC) assessment was followed, when necessary, by HPV-genotyping and histologic confirmation. Demographic characteristics were also assessed. Results: Life style parameters such as age, number of sexual partners, condom use, parity and marital status, education level, and combination of smoking/condom use, were significant factors for CIN2+ lesions (p < 0.05). For LSIL+ detection, cytology had maximum sensitivity: 96.90%, HPV-typing: 72.55% and co-testing: 98.97%, for HSIL+ detection: 98.49%, 92.22%, and 99.55% respectively. Conclusions: There are notable relationships between lifestyle, demographic details, and cervical status. Despite the differences in sensitivity and specificity levels, co-testing might offer some marginal improvement in the detection of particular pre-cancerous conditions.
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Malignancy-transformed mature cystic teratoma surgical treatment requires comprehensive staging procedures including pelvic/para-aortic lymphadenectomy
B. Barczyński, K. Frąszczak, M. Bilski, J. Szumiło, I. Wertel, M. Sobstyl, G. Polak, L. Grzybowska-Szatkowska, J. Kotarski
European Journal of Gynaecological Oncology    2020, 41 (3): 484-488.   DOI: 10.31083/j.ejgo.2020.03.5146
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This report presents the case of squamous cell cancer (SCC) originating from a mature cystic teratoma (MCT) diagnosed in pregnant women, in whom retroperitoneal spread to para-aortic lymph nodes was confirmed as the only evidence of extraovarian disease in a relatively short time after primary tumor excision. The 35-year-old multipara was diagnosed in early pregnancy with an ovarian tumor. The patient qualified for elective caesarean section with left ovarian cystectomy. Pathological result proved SCC in MCT and the patient underwent debulking surgery without total pelvic and para-aortic lymphadenectomy. Final staging confirmed ovarian malignancy FIGO IA, and no adjuvant treatment was recommended. Early imaging examination during routine follow-up demonstrated enlarged para-aortic lymph nodes and the patient qualified for total pelvic and para-aortic lymphadenectomy. Postoperative pathology result confirmed metastases in para-aortic lymph nodes and standard adjuvant chemotherapy was administered.

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Mesonephric-like carcinoma of the uterine corpus: A case report and literature review
Hyang Sook Jeong, Yuki Gen, Hui Ryun Joo, Ji Geun Yoo, Seung Geun Yeo, Dong Choon Park
European Journal of Gynaecological Oncology    2020, 41 (5): 664-667.   DOI: 10.31083/j.ejgo.2020.05.5420
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This report describes a woman with uterine mesonephric-like carcinoma and reviews the literature on this rare condition. A 60-year-old woman was referred for abdominal discomfort. Pelvic magnetic resonance imaging showed a tumor, about 7.0 cm in diameter in her left ovary. Surgical exploration, however, showed that both ovaries were grossly free of tumor. Rather, a protruding cancerous mass was found on the left side of her uterus. The tumor was composed of cells with various growth patterns and was diffusely positive for PAX8 and GATA3 on immunohistochemistry. The apical luminal border of the glandular structures was positive for CD10, and the glandular structures were focally positive for EMA. The final diagnosis was mesonephric-like carcinoma, stage pT3N1M. Conclusion: Diagnosing mesonephric-like carcinoma is pathologically challenging because these tumors are rare and present with a wide spectrum of morphologic patterns. Positive staining for PAX8 and GATA3 and a luminal staining pattern of CD10 can support the diagnosis.
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An elderly patient with primary cervical CD5-positive diffuse large B-cell lymphoma: a case report and review of the literature
Gengrong Liu, Zhenglei Shen, Liefen Yin, Zhe Zhang, Lingmei Yin, Ke Wang, Huan Yang, Jin Yao
European Journal of Gynaecological Oncology    2020, 41 (4): 500-503.   DOI: 10.31083/j.ejgo.2020.04.5298
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Objective: To increase our understanding of the clinical features, diagnosis and treatment, and prognosis of primary cervical CD5+ diffuse large B-cell lymphoma (DLBCL) in an elderly patient. Materials and Methods: We analyzed a case of an elderly patient with primary cervical CD5+ DLBCL and reviewed the literature. Results: The clinical features of this patient were not specific and were manifested as fever, significantly elevated LDH, normal blood test results, an unidentified fraction (6.5%) of cells shown by bone marrow puncture, unexpressed T-system and medullary system markers, and a primary lesion of the cervix found upon positron emission tomography-computed tomography (PET-CT). Cervical biopsy plus immunohistochemical staining showed a CD5+DLBCL, and the diagnosis was confirmed and R-CHOP therapy achieved a favorable therapeutic effect. Conclusions: The clinical manifestations of primary cervical CD5+DLBCL are not specific but PET-CT combined with cervical biopsy can clarify the diagnosis with R-CHOPas the preferred therapeutic regimen.
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Demodex folliculorum mite infestation in gynecological cancers: A case control study
Zeyneb Bakacak, Mustafa Kaplanoğlu, Murat Bakacak, Tuncay çelik
European Journal of Gynaecological Oncology    2020, 41 (4): 583-586.   DOI: 10.31083/j.ejgo.2020.04.3687
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Objective: To determine the frequency of Demodex (D.) folliculorum infestation in patients with gynecological cancer. Materials and Methods: This cross-sectional study was conducted between January 2015 and May 2015. Eighty-seven patients with gynecologic cancer and ninety control subjects were included and the patients characterics were recorded. Demodex was detected by standardized skin surface biopsy for skin lesions. Results: No statistically significant difference was found between the groups in terms of age, diabetes mellitus, body mass index (BMI), hypertension, and the use of radiotherapy and chemotherapy. D. folliculorum infestation was increased in the patient group (47.1%) when compared to the control group (8.9%) (p < 0.001). The frequency of D. folliculorum was higher in the cancer groups and particularly in ovarian cancer (58.7%). Conclusions: Patients with gynecological cancers are at risk for D. folliculorum mite infestation and this is explained by the immunosuppressed condition of the patients due to the cancer.
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The role of p16 / Ki-67 dual staining in HPV positive and negative women in the early diagnosis of cervical precancerous lesions: Cytology, colposcopy and conization protocol
Selçuk Kaplan
European Journal of Gynaecological Oncology    2020, 41 (4): 569-576.   DOI: 10.31083/j.ejgo.2020.04.2081
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Aim: The aim of this study was to evaluate the relationship between p16 / Ki-67 dual staining used for the definition of precancerous cervical lesions with histological results and HPV positivity. Materials and Method: This study is a cross-sectional study of 468 patients who were followed up in our center with the diagnosis of cervical intraepithelial neoplasia between 2016 and 2019 using the cytology, colposcopic biopsy and conization results, HPV test and p16 / Ki-67 dual staining results. SPSS 22 program was used in the analysis of the data. In the analysis of qualitative data, chi-square test and binary logistic regression analysis were used. The compatibility of both models with bilateral logistic regression test was good (omnibus test < 0.001). The correct estimate percentage of the model is 71.4% and 80.3%. p <0.05 is considered important. Results: In the binary logistic regression test established between HPV types and p16 / Ki-67 dual staining positivity, other high risk HPV types, HPV 16, 18 and 16-18, increased p16 / Ki-67 positivity ratio in this order. In the binary logistic regression test established between abnormal cytology and p16 / Ki-67 dual staining positivity in the colposcopy results, there was p16 / Ki-67 positivity increasing in proportion with the degree of HGSIL lesions. Conclusion: This study created with cytology / colposcopy and LEEP conization protocol shows that; in effective screening for early diagnosis and treatment in cervical cancer, p16 / Ki-67 biomarkers can be used effectively.
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The outcomes of fertility sparing surgery in epithelial ovarian cancer
Emine Karabuk, Burak Karadag, Ceyda Karadag, M. Faruk Kose, M. Murat Naki, E. Nilufer Guler
European Journal of Gynaecological Oncology    2020, 41 (3): 391-395.   DOI: 10.31083/j.ejgo.2020.03.5147
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Conservative surgery has long been discussed as a treatment option in women with ovarian cancer at reproductive age. However, current guidelines recommend conservative surgery only in selected patients. There is considerable interest on pregnancy and delivery rates after fertility-sparing surgery (FSS), with several ongoing studies on this subject. The aim of the present multi-center study was to evaluate survival and pregnancy outcomes in patients that underwent fertility-sparing surgery. This retrospective study included 19 patients who underwent fertility-sparing surgery due to invasive epithelial ovarian cancer between 2002 and 2014. The median duration of follow-up was 59.5 months (range 10-152 months). A total of 10 full-term pregnancies and 3 spontaneous abortions occurred in 7 patients (36.8%) following FSS. Ten patients (52.6%) underwent prophylactic surgery after a median period of 49 months (16-119 months), while 2 patients (10.5%) developed recurrent disease after prophylactic surgery. Accurate staging in patients with early stage epithelial ovarian cancer and regular follow-up has shown promising reproductive outcomes. In light of the current data, fertility-sparing surgery should be considered in selected patients with stage I epithelial ovarian cancer. There is still no consensus, however, on the selection criteria of eligible patients for fertility-sparing surgery.

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Sustained effects of theory-based physical activity intervention for socioeconomically diverse obese endometrial cancer survivors: A Longitudinal analysis
A. Rossi, C.E. Garber, M. Ortiz, V. Shankar, D.Y. Kuo, N.S. Nevadunsky
European Journal of Gynaecological Oncology    2020, 41 (3): 343-351.   DOI: 10.31083/j.ejgo.2020.03.5163
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Purpose of Investigation: Assess the sustained effects of a 12-week physical activity intervention on physical activity, physical function, waist circumference, and quality of life among urban, socioculturally diverse endometrial cancer survivors. Materials and Methods: Twenty-three obese women with a history of endometrial cancer within the previous five years with no evidence of cancer recurrence volunteered for a 12-week physical activity intervention based on social cognitive theory. Classes were offered 2x/week and included 30 minutes of behavioral counseling and 60 minutes of exercise. Pedometers were distributed, and participants were instructed to walk ≥ 90 min/week at home. A longitudinal analysis of baseline, post-intervention and 12-week follow-up response profile model was fitted using restricted maximum likelihood estimation approach. Results: Mean participant age was 64 ± 8 years, and BMI was 37 ± 6 kg?m-2. Seventy-eight percent of participants were non-white. Improvements in waist circumference (-4.8 cm, p = 0.009), and the six-minute walk test (13 m, p = 0.042) persisted 12 weeks after the completion of the intervention. Among the psychosocial variables, walking self-efficacy (p = 0.022), and outcome expectations (p = 0.040) also retained improvements at follow-up. Quality of life, assessed using the Functional Assessment of Cancer Therapy, improved post-intervention (p < 0.001), but this improvement was not sustained at follow-up (p = 0.14). Conclusion: This physical activity intervention led to meaningful sustained improvements in physical function, waist circumference and physical activity-related psychosocial variables. Replication of these results using controlled design with larger samples sizes should be conducted to confirm these findings and determine the long-term effectiveness of physical activity interventions.

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Bevacizumab in combination with metronomic oral cyclophosphamide: an effective and well-tolerated treatment for patients with recurrent ovarian cancer
C.J. Heesterbeek, A.M. Thijs, R.H.M. Hermans, D. Boll, G.-J. Creemers
European Journal of Gynaecological Oncology    2020, 41 (3): 364-367.   DOI: 10.31083/j.ejgo.2020.03.5267
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Purpose of Investigation: In this study the authors describe their clinical experience with metronomic oral cyclophosphamide and bevacizumab in terms of efficacy and tolerability in patients with recurrent ovarian cancer beyond first-line treatment. Materials and Methods: This retrospective, descriptive study included 59 patients with recurrent ovarian cancer. They were treated with intravenous bevacizumab (10 mg/kg, once every three weeks) in combination with oral cyclophosphamide (100 mg once daily). Patients had received at least one line of platinum-based chemotherapy prior to combined bevacizumab and cyclophosphamide treatment. Both platinum sensitive patients and platinum resistant patients were included. Results: Treatment with combined bevacizumab and cyclophosphamide was administered as a third line therapy in 42.4% of patients. The median number of cycles of bevacizumab administered with oral cyclophosphamide was 7 (range 1-40). A response was demonstrated in 37 (62.7%) patients, with a median progression free survival of 6 months (range 0-44). No toxicity was recorded in the medical report of 39% of patients, with only mild toxicities reported in the others. Conclusion: Bevacizumab combined with metronomic cyclophosphamide appears to be a well-tolerated and effective therapy with sustainable remissions in this selective group heavily pretreated ovarian cancer patients. This regimen should be considered in patients who are not suitable or have no need for more toxic systemic treatment.

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The prognostic significance and immuno-expression of survivin, mutant p53 and bcl-2 in 92 cases of epithelial ovarian cancer
Chados Nikolaos, Gregoriou Odysseas, Salakos Nicolaos, Kondis Agatha, Deligeoroglou Efthymios
European Journal of Gynaecological Oncology    2020, 41 (4): 517-522.   DOI: 10.31083/j.ejgo.2020.04.5335
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Background: Survivin is a member of the inhibitors of apoptosis protein family, commonly detected in human cancers and fetal tissue, with the ability to regulate programmed cell death and cell division. Aim of this study is to investigate the immuno-expression of survivin and its correlation with other anti-apoptotic markers (mutant p53 and bcl-2) in human ovarian cancer and assess the prognostic significance and possible therapeutic role of this protein in the future. Materials and Methods: Ninety-two cases of primary epithelial ovarian cancer over a 10-year period were included in the study. Sixty-six cases were diagnosed with serous ovarian cancer and twenty-six with endometrioid. All cases were fixed in formalin and paraffin-embedded standard techniques and processed by an immunostain method, in order to assess the survivin-positive cases and their prevalence in nucleus or cytoplasm. Results: Survivin cytoplasmic immuno-expression is associated with more advanced stage and grade of the ovarian disease. Nuclear survivin was more pronounced in tumors with better prognosis. Mutant p53 and bcl-2 were also positively co-expressed and associated with poor survival rate in all cases of serous ovarian carcinoma. Neither survivin nor bcl-2 were expressed in any case of endometrioid ovarian cancer. Conclusion: Survivin can play a key role as a potential future tumor marker to determine prognosis and predict response to various therapies.
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Ten-year survival in patients with endometrial adenoacanthoma and endometrial adenocarcinoma with malignant squamous cell differentiation
U. Indraccolo, R. Martinello, G. Scutiero, G. Bernardi, C. Borghi, O. Brasile, P. Greco
European Journal of Gynaecological Oncology    2020, 41 (3): 361-363.   DOI: 10.31083/j.ejgo.2020.03.5376
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Objectives: It is acknowledged that squamous differentiation in the endometrial adenocarcinoma does not affect the outcome of type I cancer. However, it has been recently reported that the so-called shadow cell differentiation is likely present in endometrial adenoacanthomas. As the shadow cells differentiation suggests a caspase-independent cell death, based on the previous reports it can be hypothesized that the endometrial adenoacanthoma would have a better prognosis than the endometrial adenocarcinoma with squamous differentiation. Methods: From a database of 829 endometrial cancer, 34 endometrial adenoacanthomas and 18 endometrial adenocarcinomas with malignant squamous differentiation were assessed. The Kaplan-Meier curves were generated and compared for endometrial adenoacanthomas and endometrial adenocarcinomas with malignant squamous differentiation. Results: the 10-year survival in patients with adenocarcinoma with malignant squamous differentiation is significantly lower than the survival in patients with adenoacanthoma. Advanced stage (2009 FIGO II or over) was more likely found in adenocarcinoma with malignant squamous differentiation at the surgery time. Matching groups for the FIGO stage, there were no difference in overall survival. Conclusion: patients with endometrial adenoacanthoma have a better prognosis than patients with endometrial adenocarcinoma with malignant squamous differentiation probably because of the earlier stage diagnosis.

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Relationship between usefulness of irinotecan and pegylated liposomal doxorubicin therapy and the UGT1A1 genotype in patients with recurrent ovarian cancer (TGCU 104 study)
T. Shoji, E. Takatori, M. Kagabu, M. Futagami, Y. Yokoyama, H. Tokunaga, N. Yaegashi, T. Ohta, T. Watanabe, T Sugiyama
European Journal of Gynaecological Oncology    2020, 41 (3): 380-385.   DOI: 10.31083/j.ejgo.2020.03.5156
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Objective: The authors investigated the relationship between the usefulness of CPT-11 + PLD combination therapy and the UGT1A1 genotype. Materials and Methods: Forty-one patients who provided informed consent were divided into the following two groups according to UGT1A1 genotypes: wild type and non-wild type. Adverse events, antitumor effect, and outcomes were compared between these two groups. Results: Twenty-three patients were wild type and 18 were non-wild type for UGT1A1. A total of 94 and 73 treatment cycles were prescribed to the wild-type and non-wild-type groups, respectively. No significant differences in the incidence of any grade 3 or higher adverse events were observed between the two groups. However, the next treatment cycle was postponed in 9.6% of the wildtype group and 12.3% of the non-wild-type group (p = 0.891). The antitumor effects as assessed by response rate were 26.1% in the wildtype group and 55.6% in the non-wild-type group (p = 0.054). The median observation period was 13 months. The median progression-free survival was three months in the wild-type group vs. five months in non-wild-type group (p = 0.913), while the median overall survival was 24 vs. 22 months (p = 0.535). Conclusions: This study did not demonstrate a statistically significant difference in the usefulness of CPT-11 + PLD combination therapy for recurrent ovarian cancer between the two groups of UGT1A1 genotypes. This study was considered to have significance as the first study conducted in Japan to prospectively evaluate the relationship between the usefulness of CPT-11-based chemotherapy and the UGT1A1 genotype for recurrent ovarian cancer.

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Decreased expression of estrogen receptors alpha and beta in peripheral blood lymphocytes from the endometrial cancer patients and women with endometriosis
Marcin Jedryka, Agnieszka Chrobak, Anna Chelmonska-Soyta, Daria Fijalkowska, Rafal Matkowski
European Journal of Gynaecological Oncology    2020, 41 (3): 375-379.   DOI: 10.31083/j.ejgo.2020.03.5054
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Aim: Endometriosis and endometrial cancer are described as typical estrogen-dependent gynaecological diseases. The question arises if estrogens, working through their receptors, could influence the immunological activity of lymphocytes in these disorders. Here, we evaluated transcriptional expression of the estrogen receptors alpha and beta (ERα and ERβ) in T lymphocytes isolated from the peripheral blood in endometrial cancer and endometriosis patients. Methods: Peripheral blood was collected from ten patients with endometrial cancer, nine with endometriosis, and ten disease-free controls. After isolation of the T lymphocytes, purity was confirmed by flow cytometry and the relative level of ERα and ERβ mRNA was determined using RT-qPCR analysis. Results: Both ERα and ERβ were significantly decreased in T lymphocytes isolated from patients with either endometrial cancer or endometriosis when compared to the healthy controls. We measured no difference in the mRNA levels of ERα between endometrial cancer patients and endometriosis group, but ERβ expression in endometrial cancer women was twice as high than in the endometriosis group. Conclusion: Decreased transcription of nuclear estrogen receptor isoforms characterizes T lymphocytes from women with endometrial cancer and endometriosis.

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Cesarean scar perforation in laparoscopic hysterectomy for endometrial cancer: a case report
Azusa Kimura, Kenro Chikazawa, Ken Imai, Ito Takaki, Tomoyuki Kuwata, Ryo Konno
European Journal of Gynaecological Oncology    2021, 42 (1): 179-182.   DOI: 10.31083/j.ejgo.2021.01.2256
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Perioperative complications tend to increase when performing hysterectomy in patients with a history of caesarean section. Therefore, the laparoscopic hysterectomy procedure requires careful consideration. Herein, we report the case of a patient with a history of caesarean section who underwent total laparoscopic hysterectomy for endometrial cancer. A 59-year-old woman was diagnosed with stage IA endometrial cancer preoperatively, and she underwent laparoscopic hysterectomy, bilateral adnexectomy, and pelvic lymphadenectomy. During these procedures, the bladder was observed to tightly adhere to the scar of a previous caesarean section, and the uterine was perforated due to detachment near the uterus to avoid damage to the bladder. After 2 years, there were no symptoms of recurrence. Our findings further demonstrated that bladder adhesions should be considered in laparoscopic surgery for patients with endometrial cancer who have a history of caesarean section.
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Endometrial stromal nodule: report of 8 cases and literature review
J. An, G. Ruan, X.Y. Xie, Y.Q. Shi, X.D. Mao, B.H. Dong, P.M. Sun
European Journal of Gynaecological Oncology    2020, 41 (3): 332-338.   DOI: 10.31083/j.ejgo.2020.03.5039
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Endometrial stromal nodule (ESN) is a rare and benign tumor of endometrial stromal origin that accounts for less than 10% of uterine mesenchymal neoplasms. It is difficult and yet essential to preoperatively differentiate endometrial stromal nodule from other types of mesenchymal malignancies, considering that the therapeutic options and clinical outcomes are totally different. To better guide clinical practice, the authors herein report eight cases diagnosed with endometrial stromal nodule and analyze the clinical and pathological characteristics, and also perform a literature review of endometrial stromal nodule. Authors of the present study conclude that conservative surgery with fertility-sparing is feasible for a suspected diagnosis of endometrial stromal nodule when ultrasonography suggests hypoechoic masses with cystic degeneration or liquefaction and magnetic resonance imaging showed a well circumscribed mass exhibiting isointensity on T1-weighted images, hyperintensity on T2-weighted images, and hyperintensity on diffusion-weighted images.

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Uterine Cancer Normogram to Predict Lymph Node Metastasis: Comparison to the Mayo Algorithm and an External Validation of a Model in a North American Population
Michelle F. Benoit, Kristy K. Ward
European Journal of Gynaecological Oncology    2020, 41 (5): 681-684.   DOI: 10.31083/j.ejgo.2020.05.5401
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Objective: We sought to compare two intraoperative uterine cancer normograms for prediction of lymph node (LN) metastasis. We used the widely known Mayo criteria, comparing it to an algorithm provided by Koskas et al. to predict likelihood of LN metastasis. Design: 490 uterine cancer patients from a single practice provider were included in the review. Data was abstracted to include age, race, stage, tumor size, grade, histologic subtype, depth of invasion, cervical involvement, lymphovascular space involvement (LVSI), and microsatellite instability (MSI). Patient comorbidities were analyzed to include body mass index (BMI), diabetes, and hypertension. Laboratories for these comorbidities were included. Those patients staged 1, 2, and 3 were included in final analysis. Results: The receiver operator curve (ROC) for the Koskas normogram was 0.78 when 4% was used as the cutoff for LN metastasis, with a sensitivity of 78% and specificity of 60%. When a 5% cutoff was used, the ROC was 0.71. For every percentage point that the French score rose, the chance of being LN positive increased by 0.8% (p < 0.001). The three point Mayo criteria odds ratio (OR) was 7.4 and the ROC was 0.57. Lymph node metastasis also correlated with MSI as seen on immunohistochemistry (IHC) testing. Conclusions: The Koskas normogram provided a better predictive algorithm for risk assessment of LN metastasis. Our results are comparable with those previously published by Koskas et al. providing an external validation of this normogram previously used in an European population. These intraoperative variables can be incorporated into real time risk assessment for LN metastasis and operative decision making. Mayo criteria, not using tumor size, could spare an additional 40% of patients an unnecessary LND compared to standard 3 point Mayo criteria--with better predictive value.
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Likelihood of incidental finding of gynecological cancer in women undergoing hysterectomy for benign indications
Mustafa Ayhan Ekici, Ali Can Onal, Caglar Cetin
European Journal of Gynaecological Oncology    2020, 41 (3): 402-407.   DOI: 10.31083/j.ejgo.2020.03.5435
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Objective: The aim of this study was to determine the incidence of unexpected gynecological malignancy (UGM) after hysterectomy performed for benign indications. Methods: We analysed patient sample data extracted from a medical database between 1 January 2007 and 10 August 2019 for 2740 women who underwent a hysterectomy for benign indications. The Kolmogorov-Smirnov test, Kruskal-Wallis test and Chi-square test were performed. Statistical significance was reached if p < 0.05. Results: The most common primary indications for hysterectomy were leiomyomata (1403, 51%), abnormal uterine bleeding (784, 28.61%), and pelvic organ prolapse (504, 18.39%). A laparotomic, laparoscopic or vaginal hysterectomy was performed in 1452 (53%), 836 (30.5%) and 452 (16.5%) women, respectively. unexpected gynecological malignancy after hysterectomy was diagnosed in 22 (0.80%) women. The incidence of unexpected uterine malignancies (UUM), unexpected endometrial cancer, and unexpected uterine malignancies without endometrial cancer was 0.54%, 0.40% and 0.14% respectively. Mean ages were not significantly different for abdominal, laparoscopic and vaginal hysterectomy groups (51.75 ± 9.83, 51.32 ± 9.51, 51.39 ± 10.04 years respectively, p = 0.299). No signi?cant difference in the incidence of unexpected gynecological malignancy was noted between the groups [laparotomy 0.47%, laparoscopy 0.22%, vaginal 0.11%, p = 0.066]. The incidence of unexpected leiomyosarcoma [laparatomic 0.11%, laparascopic 0.03%, vaginal 0.0%] and unexpected endometrial carcinoma [laparatomic 0.26%, laparascopic 0.11%, vaginal 0.03%] was significantly higher in abdominal and laparascopic hysterectomy groups than the vaginal hysterectomy group and no significant difference was observed between the abdominal and laparoscopic hysterectomy groups (p = 0.037, p = 0.028, p = 0.108, respectively). Conclusion: The incidence of unexpected gynecological malignancy diagnosed after hysterectomy performed for benign conditions was very low, if the correct indications were selected.

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The effect of six scheduled cycles of neoadjuvant chemotherapy on prognosis in advanced ovarian cancer
H. Ishibashi, M. Miyamoto, T. Aoyama, H. Soyama, H. Matsuura, H. Iwahashi, M. Takano, K. Furuya
European Journal of Gynaecological Oncology    2020, 41 (3): 386-390.   DOI: 10.31083/j.ejgo.2020.03.5102
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urpose: This study evaluated the appropriate number of cycles of neoadjuvant chemotherapy (NAC) before interval debulking surgery (IDS) in advanced ovarian cancer. Materials and Methods: Cases with advanced ovarian cancer who received a combination of taxane and platinum as NAC and IDS at this institution between 2001 to 2016 were identified. The cases were divided into two groups; patients who received six or four scheduled cycles of NAC (groups A and B, respectively). Results: Thirty-six cases were in group A and 35 cases in group B. Progression-free survival (PFS) and overall survival (OS) in group A were better than those in group B (p = 0.01, < 0.01). In multivariate analysis, six scheduled cycles of NAC was an independent better prognostic factor for PFS (hazard ratio (HR), 0.56, p = 0.04) and OS (HR, 0.39; p = 0.01). Conclusion: In advanced ovarian cancer, six scheduled cycles of NAC demonstrated a better prognosis.

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Epidemiologic profile of benign versus oncologic gynecology populations: similar procedures, different patients
Lindsey Buckingham, Lori Cory, Colleen Brensinger, Xiaochen Zhang, Robert A. Burger, Fiona Simpkins, Emily M. Ko
European Journal of Gynaecological Oncology    2020, 41 (3): 396-401.   DOI: 10.31083/j.ejgo.2020.03.5283
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Objective: We sought to compare preoperative comorbidities in patients undergoing benign versus oncologic gynecologic surgeries. Methods: All cases of benign and malignant gynecologic surgeries in the National Surgery Quality Improvement Program (NSQIP) database between 2006-2012 were identified. Gynecologic cancers were grouped by site: uterus, ovary, cervix, and “other” including labia, vulva, vagina, pelvis, and retroperitoneum. Preoperative comorbidities were captured. Descriptive analyses were performed. 94,935 patients underwent gynecologic surgeries: 87.8% benign and 12.2% oncologic. The prevalence of cardiovascular disease, pulmonary disease, and neurologic disease differed between benign and oncologic groups (p < 0.001). In uterine, ovarian and other cancers, greater than 40% of patients had one or more comorbidities and > 5% had 2 or more, (p < 0.001). Gynecologic oncology patients were significantly older, had higher BMI, greater proportion black, and had more comorbidities than patients undergoing benign gynecologic surgery. Comorbidity profiles also differed significantly by type of gynecologic cancer. Preoperative and postoperative optimization, risk assessments, and appropriate reimbursement coverage should account for these baseline differences.

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The effect of age on prediction of concurrent endometrial cancer in patients with atypical endometrial hyperplasia
Yusuf Cakmak, Tufan Oge
European Journal of Gynaecological Oncology    2020, 41 (4): 531-535.   DOI: 10.31083/j.ejgo.2020.04.5351
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Purpose: To evaluate the effect of age on prediction of concurrent endometrial cancer (EC) in patients with atypical endometrial hyperplasia (AEH). Materials and Methods: Medical data of 176 patients who were diagnosed with atypical endometrial hyperplasia and underwent surgical treatment enrolled the study group. Clinicopathological features, preoperative and postoperative information were collected. The age distrubition for patients with atypical endometrial hyperplasia and endometrial cancer were examined and stratified according to five-year age increments. Results: Concurrent endometrial cancer was detected in 35(19.8%) patients. atypical endometrial hyperplasia and lower grade hyperplasia (simple or complex) was found in 82(46.5%) and 27(15.3%) patients, respectively. Endometrial cancer was most frequently seen in 51-60 age group. Endometrial cancer in final pathology significantly increased (p = 0,0005) after the age of 53 with sensitivity of 65.52% and 76.67%. Conclusion: Endometrial cancer increases significantly after the age of 53 in patients with atypical endometrial hyperplasia. Based on this study it is recommended that clinicians shoud be aware of this knowledge while informing patients and planning treatment.
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A systematic review and meta-analysis on the effects of metformin on survival outcomes and risk in women with cervical cancer
Yi-fan Luo, Li-xiang Ren, Ming-yan Jiang, Yang Chu
European Journal of Gynaecological Oncology    2020, 41 (4): 504-507.   DOI: 10.31083/j.ejgo.2020.04.5192
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Objective: A systematic review and meta-analysis was conducted to quantitatively assess the effects of metformin on both the treatment and risk of cervical cancer in women. Materials and Methods: A search was conducted in a number of databases including CNKI, VIP, Wanfang Digital Journal Full-text Database, PubMed, Cochrane, and Web of Science. In accordance with inclusion and exclusion criteria screening in the literature, Newcastle-Ottawa scale and RevMan 5.3 software were employed to perform the meta-analysis. Results: A total of five studies taken from four articles involving 149,742 participants were finally included in meta-analysis, two random clinical trials (RCTs) and three retrospective cohort studies. Evaluation of metformin usage in two of the studies did not show significant association with five-year overall survival (OS) of patients receiving adjuvant whole-pelvic radiation therapy (WPRT) as a primary therapy compared to those . not using metformin (RR = 1.08, 95% CI 1.00-1.18, p = 0.06). In the three other studies metformin use was associated with a significant reduction in cervical cancer risk in diabetes mellitus patients (RR = 0.60, 95% CI 0.44-0.82, p = 0.001). Conclusion: Merformin use is associated with a reduction in cervical cancer risk in patients with diabetes mellitus, but is not associated with five-year OS of patients receiving WPRT. Further studies are required to confirm survival outcomes for use of metformin in cervical cancer.
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Case series of uterine smooth muscle tumors of uncertain malignant potential (STUMP)
J. H. Sang, J. I. Choi, S.-H. Chung
European Journal of Gynaecological Oncology    2020, 41 (3): 492-494.   DOI: 10.31083/j.ejgo.2020.03.5306
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Uterine smooth-muscle tumors of uncertain malignant potential(STUMP) cannot be categorized as benign or malignant. In this paper, the authors describe several cases presenting with STUMP. The authors reported five cases of STUMP treated in Soonchunhyang University Bucheon Hospital from 2013 to 2016. Four patients remain recurrence free (26-60 months) and one patient was lost to follow-up one month after STUMP diagnosis, revisited three years later, and was diagnosed with high-grade (Stage IIa) ovarian serous carcinoma after a staging operation. The authors suggested that regular follow-up after surgery was important in STUMP, and more aggressive surgical management, including salpingo-oophorectomy, should be considered.

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Unicentric castleman disease in the differential diagnosis of a paravesical mass: A case report
Luyanne Azevedo Cabral Ferreira, Rafaela de Lacerda Trajano Pinel, Rodrigo Neves Ferreira, Antônio Chambô Filho
European Journal of Gynaecological Oncology    2020, 41 (4): 644-647.   DOI: 10.31083/j.ejgo.2020.04.5268
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Castleman disease is a rare condition with variable forms of clinical presentation. Diagnosis is therefore difficult and the ideal management of the disease has yet to be defined. Prognosis varies as a function of histologic type. Treatment can range from curative surgery for the unicentric form of the disease to a combination of treatments for the multicentric form. This paper describes an unusual case of unicentric Castleman disease in which the differential diagnosis included several gynaecological malignancies. The lesion was resected, with histopathology and immunohistochemistry confirming the diagnosis. The surgical procedure was completed without complications and follow-up of the patient over one year has shown no signs of recurrence. A literature review was performed, and the possible conditions to be included within the differential diagnoses are discussed.
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Survival-associated transcriptome analysis in ovarian cancer
Xiaofeng Xu, Xuan Zhou, Yijin Wang, Tao Liu, Jian Fu, Qian Yang, Jun Wu, Huaijun Zhou
European Journal of Gynaecological Oncology    2020, 41 (3): 455-461.   DOI: 10.31083/j.ejgo.2020.03.5153
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Purpose of investigation: Ovarian Cancer (OC) is one of the most lethal gynecologic cancers worldwide. Despite the standard treatment, including radical resection, systemic chemotherapy, and targeted drugs for patients, survival rates remain low. This study provides new ideas for the diagnosis and treatment of Ovarian Cancer. Material and Methods: We performed Kaplan-Meier analysis on the transcriptome of Ovarian Cancer based on RNA-Seq data from The Cancer Genome Atlas (TCGA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment were used for pathway and functional enrichment. Protein-protein interaction (PPI) network was constructed and visualized by SRING and Cytoscape. Results: A total of 1693 genes associated with survival were identified. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analysis revealed that these selected genes were differently enriched in numerous functional pathways. The top ten hub genes (RIPK4, HSPA8, FOS, STAT1, CD40LG, FGF2, RAC1, CXCR4, PRPF19, and CXCL10) were identified in our PPI network. Three highly connected cluster modules were differently enriched in several functional pathways. Conclusion: These key biomarkers in Ovarian Cancer may have diagnostic and therapeutic value in the future.

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Is the Risk of Malignancy Index a predictive tool for preoperative differentiation between borderline ovarian tumor and ovarian cancer?
S.R Oh, J.-W. Park
European Journal of Gynaecological Oncology    2020, 41 (3): 368-374.   DOI: 10.31083/j.ejgo.2020.03.5197
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Purpose: To determine an appropriate Risk of Malignancy Index (RMI) cutoff value by comparative analysisof the four malignancy risk indices for distinguishing between borderline ovarian tumor (BOT) and ovarian cancer (OC). Materials and Methods: Retrospective analysis of the medical records of 339 patients (115 BOTsand 224 OCs). Results: There were no significant differences in the area under the ROC curve (AUC) for RMI 1, RMI 2, RMI 3, and RMI 4 (0.792, 0.791, 0.785, and 0.785, respectively). However, the diagnostic capability of the RMI was significantly greater than that of other factors. Conclusion: This study is the first to investigate the performance of the four Risk of Malignancy Indices for distinguishing between BOT and invasive OC. Although there were no significant differences between RMI scores, the RMIs were very effective at predicting an accurate preoperative diagnosis in patients with all BOT and OC histotypes.

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Neoadjuvant chemotherapy followed by radical surgery for Stage IB2 cervical cancer in pregnancy
X.F. Xu, Q. Li, A.Y. Dai, H.J. Zhou, J.X. Ling
European Journal of Gynaecological Oncology    2020, 41 (3): 489-491.   DOI: 10.31083/j.ejgo.2020.03.5288
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Background: Pregnancy with cervical cancer (CC) represents an important challenge. Case Report: The authors report a case of a 34-year old diagnosed with Stage IB2 squamous cell cervical cancer at 24+-week gestation who was then treated with neoadjuvant chemotherapy followed by cesarean section and radical hysterectomy with good outcome of both the mother and the baby. Conclusion: The results of this case study, combined with previous reports and the authors’ clincal experience, support the combination of paclitaxel and cisplatin for neoadjuvant chemotherapy when treating FIGO Stage IB2 cervical cancer in pregnancy.

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Utility of colposcopy in the management of ASCUS and LSIL in women younger than 25-year-old: A retrospective multicenter study
Behiye Pinar Goksedef, Burak Giray, Canan Kabaca, Murat Ekmez, Sinan Gulec, Esra Keles, Isa Aykut Ozdemir, Suleyman Salman, Derya Sivri Aydin
European Journal of Gynaecological Oncology    2020, 41 (5): 685-688.   DOI: 10.31083/j.ejgo.2020.05.5405
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Objective: We aimed to analyze the colposcopy-guided biopsy results in women aged 21-24 years with clinical suspicion for cervical lesion and/or cytological abnormality. Methods: This was a retrospective cohort study conducted on 461 patients undergoing colposcopic examination and biopsy between the ages of 21-24. The colposcopy-guided biopsy results of women with atypical squamous cells of undetermined significance (atypical squamous cells of undetermined significance) cytology were cervical intraepithelial neoplasia (cervical intraepithelial neoplasia) 2 in 9 patients and cervical intraepithelial neoplasia 3 in 5 patients. Results: The colposcopy-guided biopsy results of women with low-grade squamous intraepithelial lesion (low-grade squamous intraepithelial lesion) cytology were cervical intraepithelial neoplasia 2 in 17 patients, cervical intraepithelial neoplasia 3 in 10 patients, and invasive cancer in 1 patient. One of the high-grade squamous intraepithelial lesion (high-grade squamous intraepithelial lesion) patients had invasive cervical cancer. The cytology results of women with cervical intraepithelial neoplasia 1 after 6 months from colposcopy-guided biopsy were atypical squamous cells of undetermined significance (n = 11), and low-grade squamous intraepithelial lesion (n = 6). The cytology results of women with cervical intraepithelial neoplasia 1 after 12 months were atypical squamous cells of undetermined significance in 2 women, and low-grade squamous intraepithelial lesion in 2 women. The cytology results after 12 months from colposcopy-guided biopsy were high-grade squamous intraepithelial lesion in 16 of 433 women who underwent follow-up (3.7%). There were no significant statistically differences between cervical intraepithelial neoplasia 2 patients with and without treatment in terms of cytology results at 6 months (p = 1.00). However, there were significant statistically differences between cervical intraepithelial neoplasia 2 patients with and without treatment in terms of cytology results at 12 months (p = 0.042). Conclusions: Colposcopic examination should perform in women aged 21-24 years with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion due to the possibility of high-grade squamous intraepithelial lesion and invasive cancer.
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Morphological analysis of peritoneal dissemination of ovarian cancer based on levels of carbonyl reductase 1 expression
F. Oyama, Y. Asano, H. Shimoda, K. Horie, J. Watanabe, Y. Yokoayama
European Journal of Gynaecological Oncology    2020, 41 (3): 352-360.   DOI: 10.31083/j.ejgo.2020.03.5094
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Purpose of Investigation: When carbonyl reductase 1 (CR1) is highly expressed in human ovarian cancer cells in vivo, tumor growth is reported to be inhibited. Conversely, when expression of CR1 decreases, tumor growth, invasion, and metastasis are reported to increase. Thus, the aim of the current study was to examine dynamic changes in ovarian cancer cells under different CR1 expression levels in artificial human peritoneal tissue (AHPT). Materials and Methods: Serous ovarian cancer cells with different levels of CR1 expression were produced by transfection of HRA human ovarian carcinoma cells with CR1 DNA or CR1 siRNA. The transfected cells were seeded in AHPT and observed over time until peritoneal development of carcinomatosis. Apoptotic cells in the AHPT were compared using TUNEL staining and fluorescence-based flow cytometry. Results: Cells transfected with CR1 DNA or CR1 siRNA did not differ from control cells in terms of their adherence to the mesothelium. After 24 hours, when cells had invaded the tissue below the mesothelium, proliferation of CR1-overexpressing cells was inhibited while proliferation of CR1-suppressing cells increased. At 72 hours, CR1-suppressing cells had invaded the stroma. CR1-overexpressing cells had a markedly higher rate of apoptosis than control or CR1-suppressing cells. Moreover, electron microscopy revealed apoptotic bodies in cells overexpressing CR1. Differences in tumor growth depending on the extent of CR1 expression have been noted in vivo, and similar results were obtained in the present in vitro model of AHPT. High and low levels of CR1 expression did not affect cell adherence to the mesothelium, but low levels did result in cells invading and proliferating below the mesothelium. Conclusion: The present results have also demonstrated that tumor inhibition by CR1 involves an increase in apoptosis.

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PTEN and CD146 expression in endometrioid adenocarcinoma
Q. Huang, Y. He, X. Cao, C. Yi
European Journal of Gynaecological Oncology    2020, 41 (3): 439-443.   DOI: 10.31083/j.ejgo.2020.03.5051
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Objective: Endometrioid adenocarcinoma is the most common pathological type of endometrial carcinoma. This study aimed to examine the expression of PTEN and CD146 in endometrioid adenocarcinoma, and to investigate their relationship with clinical characteristics of endometrioid adenocarcinoma. Materials and Methods: The expression of PTEN and CD146 in 126 specimens of endometrioid adenocarcinoma was detected by immunohistochemical technique, and the correlation of their expression with clinical parameters of the patients was analyzed. Results: PTEN expression in endometrioid adenocarcinoma group was lower than that in endometrial hyperplasia group and endometrial polyp group, while CD146 expression in endometrioid adenocarcinoma group was higher than that in endometrial hyperplasia group and endometrial polyp group (p < 0.05). High expression of CD146 was associated with his tological grade and depth of invasion of endometrioid adenocarcinoma, but there was no correlation between PTEN expression and clinical parameters. Conclusions: CD146 and PTEN may be promising biomarkers and targets for the diagnosis and treatment of endometrioid adenocarcinoma.

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Preserving fertility in patients with granulosa cell tumors of the ovary
L. Nejković, J. Stulić, I. Rudić Biljić Erski, A. Ristić, R. Aničić, M. Vasiljević
European Journal of Gynaecological Oncology    2020, 41 (3): 462-464.   DOI: 10.31083/j.ejgo.2020.03.5048
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Granulosa cell tumors of the ovary are rare ovarian neoplasms developing from ovarian stromal cells. They are characterized by insidious growth, low malignancy potential, and late recurrence. Due to the production of estrogen by these tumors, the frequent symptoms that occur in these patients develop as a result of hyperestrogenism. Standard treatment involves surgery in all patients. Fertility-sparing surgery is considered safe in young patients only in case of early-stage IA and IC tumors, where it is necessary to perform a unilateral salpingo-oophorectomy and complete staging. Surgical staging includes peritoneal washing, multiple peritoneal biopsies, omental biopsy, and biopsy of any suspicious area.

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Introduction of minimally invasive surgery for the treatment of endometrial cancer in Japan: a review
Yuichiro Miyamoto, Michihiro Tanikawa, Kenbun Sone, Mayuyo Mori-Uchino,Tetsushi Tsuruga, Yutaka Osuga
European Journal of Gynaecological Oncology    2021, 42 (1): 10-17.   DOI: 10.31083/j.ejgo.2021.01.2264
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Minimally invasive surgery is now becoming the standard surgical method for early stage endometrial cancer. In this review, we describe the path minimally invasive surgery has travelled from being an exceptional treatment to be the current standard in Japan. At the beginning of the 21th century, laparoscopic surgery has been employed for the treatment of gynecologic malignancies including cervical cancer and endometrial cancer. Robotic-assisted surgical system, which appeared a little later than laparoscope, has begun to be actively applied to surgical treatments for gynecologic malignancies that require particularly elaborate technologies. Both laparoscopic and robotic surgery have attracted the attention of surgeons because they enable safe, precise and less invasive surgery. Since the safety of minimally invasive surgery depends largely on the skill and experience of the surgeon, there is an urgent need to establish an educational system for implementing minimally invasive surgery. Here we describe various issues regarding minimally invasive surgery that Japan is currently facing, such as the medical economy, regulations by the Japanese health insurance system, a shortage of surgeons, the roles of academic organizations to educate surgeons and guide the appropriate implementation of minimally invasive surgery.
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Juvenile ovarian mature teratoma with malignant transformation diagnosed after laparoscopic surgery: A case report
Nozomu Yanaihara, Chihiro Sato, Masami Iwamoto, Kazu Ueda, Aikou Okamoto
European Journal of Gynaecological Oncology    2020, 41 (3): 465-467.   DOI: 10.31083/j.ejgo.2020.03.5056
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Malignant transformation of an ovarian mature teratoma is rare, and it might be diagnosed following laparoscopic surgery in women of reproductive age. Here we report a rare juvenile case of squamous cell carcinoma arising in an ovarian mature teratoma. A 29-year-old woman with a preoperative diagnosis of ovarian mature teratoma underwent single-incision laparoscopic surgery, in which tumor resection was performed extracorporeally following fine-needle aspiration of the cystic contents. Histopathological examination revealed squamous cell carcinoma arising in a mature teratoma of the right ovary. Subsequent right salpingo-oophorectomy and partial omentectomy showed no evidence of a residual malignant component. Because the rate of tumor rupture is significantly higher with the laparoscopic approach than with the laparotomy approach, maximum efforts should be made to avoid intraoperative tumor spillage in cases of an ovarian mature teratoma considering the possibility of unexpected malignancy.

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Clear-cell carcinoma of the endometrium:type I or type II endometrial carcinoma?
Jingyuan Wang, Xiaoping Li, Danhua Shen, Xiao Wang, Zhiqi Wang, Jianliu Wang
European Journal of Gynaecological Oncology    2020, 41 (3): 449-454.   DOI: 10.31083/j.ejgo.2020.03.5245
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Purpose of Investigation: To determine if clear cell carcinoma (CCC) should be classified as a type I or type II carcinoma and provide guidance for clinical treatment. Material and Methods: This study included three groups of endometrial carcinomas: 92 cases of CCC were collected from 22 hospitals in China from January 2003 to November 2014, 272 cases of EMA were collected from Peking University People’s Hospital from February 2003 and July 2016, and 192 cases of USC were collected from 22 hospitals in China from February 2001 to December 2014. The 2009 FIGO staging system was used and information concerning clinicopathological features was collected. Results: The mean age in the CCC and USC groups was higher than that of the EMA group (p < 0.001). There was no significant difference in the FIGO Stage between the CCC and EMA groups (p = 0.158). There was no significant difference in the extent of myometrial invasion between the three groups (p = 0.064), but there was a significant difference in cervical involvement, adnexal metastasis, and lymph node metastasis (p = 0.017, p < 0.001, and p < 0.001). The patients in the CCC, EMA, and USC groups were followed up for an average of 105.6 ± 7.5 months, 135.0 ± 2.2 months, and 92.1 ± 4.4 months, respectively. Fourteen cases with CCC recurred, and 13 ended in death. There was no significant difference between the CCC and the EMA groups in recurrence and death rates (p = 0.035 > 0.0167, p = 0.018 > 0.0167, 0.0167 = 0.05/3), but the prognosis in the USC group was worse. Conclusions: CCC may follow an overlapping or a third pathway of carcinogenesis, rather than belong to the type II carcinogenesis. Therefore, if CCC should be classified as a type I or type II carcinoma is yet to be determined. Additional studies of the clinicopathological features underlying CCC will facilitate more elective management and avoid unnecessary or non-elective treatments.
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Current Issue

  • Volume 42, Issue 2