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Yilin W, Yan C, Xinming Z, Xiaojuan X, Yichen W, Yuying S. MRI characteristics of FIGO stage IA epithelial ovarian cancer (EOC). Eur J Radiol 2025; 188:112157. [PMID: 40367560 DOI: 10.1016/j.ejrad.2025.112157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 04/21/2025] [Accepted: 05/01/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE To investigate the MRI characteristics of FIGO stage IA EOC with different pathologic subtypes in order to improve the radiologists' understanding of these diseases. METHODS In this retrospective study, we recruited patients who underwent surgery due to EOC at our hospital and were staged as FIGO IA from January 2013 to May 2024. The MR imaging and clinical features were evaluated by radiologists specialized in gynecology. Kruskal-Wallis test and Chi-squared test were performed to assess the difference between groups. RESULTS A total of 34 patients with a mean age of 56 years included serous carcinoma 9 cases (26 %), endometrioid carcinoma 9 cases (26 %), clear cell carcinoma 10 cases (29 %), mucinous carcinoma 6 cases (18 %). 2 patients synchronously developed ovarian cancer and uterus endometrial cancer. The median CA125 level was 65.6 U/ml (95 % CI, 21.6 to 92.8) and laterality ratio was 17:18 (left: right). Median diameter of tumor was 10.9 cm (95 % CI, 8.0 to 11.8). There were 6 cases of pure solid tumor, 5 cases of unilocular cystic-solid tumor and 23 multilocular cystic-solid tumor. 17 cases appeared hemorrhage signal and 6 of which had mixed signals in the loculi. As for enhancement pattern, total 10 cases of type I, 11 cases of type II and 13 cases of type III. Solid tissue in 33 (97 %) cases demonstrated restricted diffusion in DWI sequence. 9 cases presented ascites. There were 5 factors showed significant differences among different pathologic subtypes (p < 0.05), including maximum diameter, general morphology, growth pattern of solid tissue, grouped septa and presence of mixed signals in the loculi. CONCLUSION The imaging performance of FIGO stage IA EOC were variable, and there were differences in imaging characteristics among different pathological subtypes, which can improve current understanding of FIGO stage IA EOC and reduce clinical diagnostic omissions.
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Affiliation(s)
- Wang Yilin
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Chen Yan
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
| | - Zhao Xinming
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
| | - Xu Xiaojuan
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Wang Yichen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Sun Yuying
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China
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Liu C, Zhu Y, Dai K, Tan B, Dong H, Lin J, He R, Lu M, Li Y. Accurate prediction of benign and malignant adnexal tumors in surgical resection and conservative treatment: construction and external validation of a diagnostic model based on CEUS, HE4, and O-RADS US v2022 evaluation. J Ovarian Res 2025; 18:123. [PMID: 40481532 PMCID: PMC12143051 DOI: 10.1186/s13048-025-01707-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Accepted: 05/24/2025] [Indexed: 06/11/2025] Open
Abstract
PURPOSE To establish a diagnostic model combining contrast-enhanced ultrasound (CEUS), human epididymis protein 4 (HE4), and Ovarian-Adnexal Reporting and Data Systems (O-RADS) US v2022, verify its diagnostic efficacy, and compare it with subjective evaluation. METHODS From January 2018 to August 2021 (the test group) and from September 2021 to September 2022 (the validation group), the data of patients classified as O-RADS US v2022 categories 2 to 5 who underwent adnexal ultrasound examinations were prospectively and continuously collected. In the test group, univariate and multivariate analyses were used to explore the relationship between age, body mass index (BMI), maximum diameter of the lesion, menopausal status, HE4, cancer antigen 125 (CA125), and the characteristics of CEUS and malignant lesions. Selecting independent influencing factors to construct diagnostic model, which was validated in the external validation group and compared with subjective evaluation. RESULTS The test group included 563 patients (mean age, 48.7 ± 13.2), and the validation group included 246 patients (mean age, 47.6 ± 12.9). Univariate and multivariate analyses showed that enhancement time, enhancement intensity, dynamic changes, and HE4 were independent influencing factors for predicting adnexal malignant tumors. In the validation group, the sensitivities and specificities of O-RADS US v2022, O-RADS US v2022 + CEUS, O-RADS US v2022 + CEUS + HE4, and subjective assessment were 88.89% and 70.69%, 94.44% and 79.31%, 91.67% and 92.53%, and 93.09% and 89.66% respectively. In addition, the combined diagnostic performance of O-RADS US v2022, CEUS and HE4 (AUC = 0.980) was higher than that of O-RADS US v2022 alone (AUC = 0.876, P < 0.001) and the combination of O-RADS US v2022 + CEUS (AUC = 0.908, P < 0.001), and was comparable to the subjective evaluation (AUC = 0.963, P = 0.192). CONCLUSIONS The combined diagnostic model of O-RADS US v2022, CEUS and HE4 can improve the specificity of adnexal ultrasound diagnosis without sacrificing sensitivity, and it has high reliability.
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Affiliation(s)
- Chun Liu
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Yi Zhu
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Keju Dai
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Bo Tan
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Hao Dong
- Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China
| | - Jing Lin
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Rong He
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China
| | - Man Lu
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China.
| | - Yuan Li
- Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, No. 55, Sec. 4, South Renmin Road, Chengdu, 610042, China.
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Almalki YE, Basha MAA, Nada MG, Metwally MI, Libda YI, Ebaid NY, Zaitoun MMA, Mahmoud NEM, Elsheikh AM, Radwan MHSS, Amin MI, Mohamed EM, Tantawy EF, Saber S, Mosallam W, Abdalla HM, Farag MAEAM, Dawoud TM, Khater HM, Eldib DB, Altohamy JI, Abouelkheir RT, El Gendy WM, Alduraibi SK, Alshahrani MS, Ibrahim SA, Radwan AM, Obaya AA, Basha AMA, El-Maghraby AM. Ovarian-Adnexal Imaging-Reporting and Data System (O-RADS) ultrasound version 2019: a prospective validation and comparison to updated version (v2022) in pathologically confirmed adnexal masses. Eur Radiol 2025; 35:3080-3095. [PMID: 39604652 DOI: 10.1007/s00330-024-11235-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 10/11/2024] [Accepted: 10/27/2024] [Indexed: 11/29/2024]
Abstract
OBJECTIVE To evaluate the diagnostic accuracy and reliability of the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound v2019 in classifying adnexal masses (AMs) and compare the old and updated systems (v2022). PATIENTS AND METHODS This prospective study enrolled 977 consecutive women with suspected AMs from three institutions between January 2022 and December 2023. Ultrasound examinations were performed by three experienced radiologists who categorized AMs according to O-RADS ultrasound v2019. The same radiologists retrospectively reviewed the stored ultrasound images and provided the O-RADS ultrasound v2022 classification. Histopathology was used as the reference standard to calculate the diagnostic accuracy of the O-RADS versions in predicting malignant AMs. Inter-observer agreement (IOA) of the O-RADS scoring results was evaluated using the Fleiss kappa (κ) test. RESULTS The final analysis included 803 women with 855 AMs (219 (25.6%) malignant and 636 (74.4%) benign). Both O-RADS versions demonstrated good diagnostic accuracy, with area under the curve (AUC) values ranging from 0.906 to 0.923 (v2019) and 0.919 to 0.936 (v2022). The updated v2022 showed a slightly higher accuracy (82.5-86.7% vs. 80.7-85.3%), sensitivity (93.6-95.0% vs. 92.2-94.1%), and specificity (78.1-84.1% vs. 76.1-82.9%) compared to v2019. The IOA for the overall O-RADS classification was perfect for both versions (κ = 0.96-0.97). CONCLUSIONS The O-RADS ultrasound classification system demonstrated good diagnostic accuracy and reliability in predicting malignant AMs, with the updated v2022 showing modest improvements. KEY POINTS Question Accurate classification of adnexal masses is essential for management. Can updated O-RADS ultrasound v2022 improve diagnostic accuracy and reliability compared to v2019 in predicting malignancies? Findings O-RADS ultrasound v2022 demonstrated slightly higher diagnostic accuracy for identifying malignant adnexal masses compared to v2019, reflecting modest improvements in risk stratification and clinical decision-making. Clinical relevance The updated O-RADS ultrasound v2022 provides improved risk stratification for adnexal masses, enhancing diagnostic confidence, supporting more precise clinical decision-making, and improving patient outcomes through timely intervention or tailored management strategies in ovarian cancer care.
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Affiliation(s)
- Yassir Edrees Almalki
- Division of Radiology, Department of Medicine, Medical College, Najran University, Najran, Kingdom of Saudi Arabia
| | | | - Mohamad Gamal Nada
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Maha Ibrahim Metwally
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Yasmin Ibrahim Libda
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Noha Yahia Ebaid
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed M A Zaitoun
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Nader E M Mahmoud
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Amgad M Elsheikh
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | | | - Mohamed I Amin
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | | | - Engy Fathy Tantawy
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Sameh Saber
- Department of Diagnostic Radiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Walid Mosallam
- Department of Radio-diagnosis, Faculty of Human Medicine, Suez Canal University, Esmaelia, Egypt
| | | | | | - Tamer Mahmoud Dawoud
- Department of Diagnostic Radiology, Faculty of Human Medicine, Tanta University, Tanta, Egypt
| | - Hamada M Khater
- Department of Diagnostic Radiology, Faculty of Human Medicine, Benha University, Benha, Egypt
| | - Diaa Bakry Eldib
- Department of Diagnostic Radiology, Faculty of Human Medicine, Benha University, Benha, Egypt
| | - Jehan Ibrahim Altohamy
- Department of Diagnostic Radiology, National Institute of Urology and Nephrology, Cairo, Egypt
| | - Rasha Taha Abouelkheir
- Department of Diagnostic Radiology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Waseem M El Gendy
- Department of Radiology, Kobry Al Kobba Military Hospital, Cairo, Egypt
| | - Sharifa Khalid Alduraibi
- Department of Radiology, College of Medicine, Qassim University, Buraidah, Kingdom of Saudi Arabia
| | - Majed Saeed Alshahrani
- Department of Obstetrics and Gynecology, Faculty of Medicine, Najran University, Najran, Saudi Arabia
| | - Safaa A Ibrahim
- Department of Obstetrics and Gynecology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed M Radwan
- Department of Obstetrics and Gynecology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed Ali Obaya
- Department of Clinical Oncology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt
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Huang G, Lin W, Jiang T, Cai Y, Lin C, Sun P. Serine/threonine kinase 11 (STK11) associated adnexal tumors: from biology to therapeutic impact. Hum Genomics 2025; 19:28. [PMID: 40102938 PMCID: PMC11921566 DOI: 10.1186/s40246-025-00741-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 03/10/2025] [Indexed: 03/20/2025] Open
Abstract
Female adnexal malignancies, while relatively uncommon, exhibit high mortality rates due to often-late diagnosis. The serine/threonine kinase 11 (STK11) is a tumor suppressor gene, and its inactivation or mutation often leads to an autosomal dominant genetic disorder known as Peutz-Jeghers syndrome (PJS), which is associated with ovarian and cervical cancers. STK11-associated adnexal tumors mostly originate from the ovary, with a low incidence rate but high metastasis rates worldwide. In addition to surgery and chemotherapy, it is necessary to optimize relevant screening policy and targeted therapy. STK11-associated adnexal tumors are difficult to diagnose by histopathology. Although genetic testing involves higher costs, it can serve as a primary preventive measure for high-risk populations with STK11-associated tumors. A more intensive screening program (MISP) is needed for individuals with significant clinical symptoms and a family history of PJS. These tumors may be adequately treated with fertility-sparing surgery in young women with lower malignant potential tumors. Prophylactic adnexectomy, chemotherapy, and immunotherapy may offer potential clinical benefits but also pose significant challenges. Therefore, surgery should be undertaken with careful and comprehensive consideration of the patient's age, reproductive history, risk of malignancy, genetic mutation lineages, post-operative complications, and other conditions. Further research is essential to develop better screening, diagnostic, and treatment strategies.
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Affiliation(s)
- Guanxiang Huang
- Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou, Fujian, 350001, China
- Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children's Hospital), Fuzhou, 350001, Fujian, China
- Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, 350001, Fujian, China
| | - Wenyu Lin
- Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou, Fujian, 350001, China
- Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children's Hospital), Fuzhou, 350001, Fujian, China
- Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, 350001, Fujian, China
| | - Tingting Jiang
- Department of Gynecology and Obstetrics, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China
| | - Yuanjun Cai
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, 350001, Fujian, China
| | - Chengbin Lin
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, 350001, Fujian, China
| | - Pengming Sun
- Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No.18 Daoshan Road, Fuzhou, Fujian, 350001, China.
- Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children's Hospital), Fuzhou, 350001, Fujian, China.
- Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, 350001, Fujian, China.
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Zhang Y, Qiu JG, Wang W, Sun FL, Wang X, Liu WJ, Jia XY, Ji H, Wang L, Jiang BH. Suppression of CYLD by HER3 confers ovarian cancer platinum resistance via inhibiting apoptosis and by inducing drug efflux. Exp Hematol Oncol 2025; 14:21. [PMID: 40012003 DOI: 10.1186/s40164-025-00620-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 02/18/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Ovarian cancer (OC) is the most pathogenic gynecological malignant tumor in the world. Due to the difficulty of early diagnosis, most of patients developed chemo-resistance and recurrence during/after chemotherapy. METHODS CCK8 and flow cytometry were utilized to assess drug sensitivity and apoptosis in parental and drug resistant cell lines. CYLD knockdown or overexpressed cells were employed to investigate its regulatory involvement in DDP resistance. Clinical tumor samples have been utilized to investigate the clinical relevance of CYLD. The drug synergistic effects were investigated through drug combination methods and a nude mice model with ABCB1 inhibitor or HER3 inhibitor. RESULTS In this study, we found that CYLD levels were significantly reduced in DDP-resistant cancer tissues and cells compared to the normal tissues and cells. CYLD knockdown in DDP-sensitive cells was sufficient to converse the cells to become DDP resistant by reducing cell apoptosis through increasing Bcl-XL and inhibiting Bax, and by increasing drug efflux via upregulating ABCB1 expression. HER3 expression levels were substantially higher in resistant cancer tissues and cells, and HER3 was the upstream facilitator of suppressing CYLD expression via STAT3 signaling. Furthermore, overexpression of CYLD in resistant cells increased sensitivity to platinum-based chemotherapy both in vitro and in vivo. ABCB1 was a key downstream target of CYLD for regulating tumor growth and therapeutic resistance both in vitro and in vivo, CYLD knockdown promoted the translocation of p65 to nucleus which increased ABCB1 expression through transcriptional activation. High expression levels of HER3 rendered CYLD suppression, consequently, mediated DDP resistance by blocking cell apoptosis pathways and promoting the drug efflux in ovarian cancer. CONCLUSIONS Our findings identify novel HER3/CYLD/ABCB1 axis that regulate tumor growth and DDP resistance, which may be used as potential novel therapeutic target(s) to overcome ovarian cancer DDP resistance.
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Affiliation(s)
- Ye Zhang
- Department of Gynecology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou University, Zhengzhou, 450000, China
| | - Jian-Ge Qiu
- Department of Gynecology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou University, Zhengzhou, 450000, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Wei Wang
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Fan-Li Sun
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Xue Wang
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Wen-Jing Liu
- Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, China
| | - Xiao-Yu Jia
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Hongbin Ji
- Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Lin Wang
- Department of Gynecology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou University, Zhengzhou, 450000, China.
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
| | - Bing-Hua Jiang
- Department of Gynecology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou University, Zhengzhou, 450000, China.
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Jiang M, Yuan C, Lu S, Zhu Y, Chu C, Li W. Diagnostic value of magnetic resonance imaging for malignant ovarian tumors mis-subclassified by the ultrasound-based ADNEX model. Front Oncol 2025; 15:1406735. [PMID: 40071091 PMCID: PMC11893382 DOI: 10.3389/fonc.2025.1406735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 01/29/2025] [Indexed: 03/14/2025] Open
Abstract
Objective Accurately predicting metastatic cancer to the adnexa, stage I and advanced ovarian cancer before surgery is crucial. The ADNEX model, based on ultrasound, is currently the only prediction model that can differentiate between these types. This study aims to analyze MRI features and diagnostic value in malignant ovarian tumors mis-subclassified by the ADNEX model, considering their diverse histopathologic types. Methods From January 2018 to September 2022, 164 patients with pathologically confirmed ovarian malignancies were selected from those who were examined by ultrasound. The clinical and MRI characteristics of 51 patients mis-subclassified by the ADNEX model were compared with histopathological types. Results A total of 30 were confirmed with primary ovarian cancer (5 with HGSOC, 14 with CCC, 2 with EC, 4 with MC, 2 with GCT, 1 with YST, 1 with immature teratoma, and 1 with dysgerminoma). There were 21 patients who had metastatic ovarian tumors (10 with colorectal cancer, 4 with gastric cancer, 2 with uterine cervical cancer, 3 with endometrial cancer, 1 with breast cancer, and 1 with LAMN). The only significant difference between the two groups was in CEA. The mean diameters of the primary and metastatic ovarian tumors were 10.29 cm (range: 3.61 cm-26.02 cm) and 8.58 cm (range: 3.10 cm-20.30 cm), respectively. A total of 42 masses were lobulated (82.35%, 42/51), and 26 masses were solid-cystic (26/51, 50.98%). There was a significant difference between CCC and other tumors, with mean ADC values of 1.01 × 10-3 mm2/s (range: 0.68-1.28×10-3 mm2/s) and 0.74×10-3 mm2/s (range: 0.48-0.99×10-3 mm2/s), respectively (P=0.000). A total of 50 masses presented isointense-T1, hyperintense-T2, and hyperintense-DWI signal on MRI (50/51,98.04%). There were 33 masses that showed intensive enhancement (33/51,64.71%). There were 17 masses who had necrosis (17/51, 33.33%), with the majority being HGSOC and ovarian metastases from colorectal and gastric cancers (12/17, 70.59%). There were 19 masses that presented hemorrhage (19/51,37.25%), with the majority being CCC (10/19, 52.63%). A total of 46 masses were diagnosed correctly by MRI (46/51,90.20%). There were 35 and 15 masses that were rated as O-RADS score 5 and score 4, respectively. One mass was rated as score 3. Conclusions DWI signal, ADC value, degree of enhancement, and characteristic components within the mass on MRI can provide supplementary information for malignant ovarian tumors mis-subclassified by the ADNEX model.
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Affiliation(s)
- Meijiao Jiang
- Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Congcong Yuan
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siwei Lu
- Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunkai Zhu
- Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Caiting Chu
- Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenhua Li
- Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
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Borella F, Carosso M, Chiparo MP, Ferraioli D, Bertero L, Gallio N, Preti M, Cusato J, Valabrega G, Revelli A, Marozio L, Cosma S. Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review. Pathogens 2025; 14:140. [PMID: 40005517 PMCID: PMC11858389 DOI: 10.3390/pathogens14020140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/22/2025] [Accepted: 01/22/2025] [Indexed: 02/27/2025] Open
Abstract
Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC.
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Affiliation(s)
- Fulvio Borella
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
| | - Marco Carosso
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
| | - Maria Pia Chiparo
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
| | - Domenico Ferraioli
- Department of Gynecology, Léon Bérard, Comprehensive Cancer Centre, 69008 Lyon, France;
| | - Luca Bertero
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
| | - Niccolò Gallio
- Gynecology and Obstetrics 2U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (N.G.); (A.R.)
| | - Mario Preti
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
| | - Jessica Cusato
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy;
| | - Giorgio Valabrega
- Department of Oncology, University of Turin, Medical Oncology, Ordine Mauriziano Hospital, 10128 Turin, Italy;
| | - Alberto Revelli
- Gynecology and Obstetrics 2U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (N.G.); (A.R.)
| | - Luca Marozio
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
| | - Stefano Cosma
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, University of Turin, 10126 Turin, Italy; (M.C.); (M.P.C.); (L.M.); (S.C.)
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8
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Zhong D, Gao XQ, Li HX, Wang HB, Liu Y. Analysis of Diagnostic Efficacy of the International Ovarian Tumor Analysis ADNEX Model and the ACR O-RADS US (Ovarian-Adnexal Reporting and Data System) for Benign and Malignant Ovarian Tumors: A Retrospective Study in a Tumor Center in Northeast China. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2025; 38:410-421. [PMID: 38977614 PMCID: PMC11811318 DOI: 10.1007/s10278-024-01170-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 06/12/2024] [Accepted: 06/12/2024] [Indexed: 07/10/2024]
Abstract
This study is to analyze and compare the diagnostic efficacy of the ADNEX model and O-RADS in Northeast China for benign and malignant ovarian-adnexal tumors. From July 2020 to February 2022, ultrasound images of 312 ovarian-adnexal masses included in the study were analyzed retrospectively, and the properties of these masses were identified using the ADNEX model and O-RADS. The diagnostic efficiency of the ADNEX model and O-RADS was analyzed using a ROC curve, and the capacities of the two models in differentiating benign and malignant ovarian masses at the optimum cutoff value were compared, as well as the consistency of their diagnosis results was evaluated. The study included 312 ovarian-adnexal masses, including 145 malignant masses and 167 benign masses from 287 patients with an average age of (46.8 ± 11.3) years. The AUC of the ADNEX model was 0.974, and the optimum cutoff value was the risk value > 24.2%, with the corresponding sensitivity and specificity being 97.93 and 86.83, respectively. The AUC of the O-RADS was 0.956, and the optimum cutoff value was > O-RADS 3, with the corresponding sensitivity and specificity being 97.24 and 85.03, respectively. The AUCs of the two models were 0.924 and 0.911 at the optimum cutoff values, with no statistical differences between them (P = 0.284). Consistency analysis: the kappa values of the two models for the determination and pathological results of masses were 0.840 and 0.815, respectively, and that for the diagnostic outcomes was 0.910. Both the ADNEX model and O-RADS had good diagnostic performance in people from Northeast China. Their diagnostic capabilities were similar, and diagnostic results were highly consistent at the optimum cutoff values.
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Affiliation(s)
- Di Zhong
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Nan Gang District, No.150 of Ha Ping Road, Harbin, 150000, China
| | - Xiao-Qiang Gao
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Nan Gang District, No.150 of Ha Ping Road, Harbin, 150000, China
| | - Hai-Xia Li
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Nan Gang District, No.150 of Ha Ping Road, Harbin, 150000, China
| | - Hong-Bo Wang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Nan Gang District, No.150 of Ha Ping Road, Harbin, 150000, China
| | - Ying Liu
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Nan Gang District, No.150 of Ha Ping Road, Harbin, 150000, China.
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9
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Xu HL, Wei YF, Bao Q, Wang YL, Li XY, Huang DH, Liu FH, Li YZ, Zhao YY, Zhao XX, Xiao Q, Gao S, Chen RJ, Ouyang L, Meng X, Qin X, Gong TT, Wu QJ. Dietary protein intake and PM 2.5 on ovarian cancer survival: A prospective cohort study. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 291:117798. [PMID: 39875252 DOI: 10.1016/j.ecoenv.2025.117798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 12/28/2024] [Accepted: 01/22/2025] [Indexed: 01/30/2025]
Abstract
BACKGROUND Evolving evidence suggests both protein consumption and particulate matter less than 2.5 micrometers (PM2.5) might be related to ovarian cancer (OC) mortality. However, no epidemiological studies have explored their potential interaction. OBJECTIVE The objective of this study was to explore the association of dietary protein, PM2.5, and their interaction with the survival of OC patients. METHODS A prospective cohort study was carried out, which encompassed 658 newly diagnosed OC patients (18-79 years) residing in China. Dietary protein intakes were collected through a food frequency questionnaire examination, including total protein and protein from diverse sources. Average residential PM2.5 concentrations were evaluated using satellite-derived models. We calculated the hazard ratio (HR) and its 95 % confidence interval (CI) by adjusting for multiple variables using Cox proportional risk models. By assessing the relative excess risk due to interaction (RERI) arising from the interplay between PM2.5 exposure and dietary protein intake, we explored the additive interaction between the two. Multiplicative interaction was assessed through a cross-product interaction term. RESULTS During a median follow-up of 37.60 months, 123 deaths were documented. As for all-cause mortality, the multivariate-adjusted HRs (95 % CIs) in the highest vs. the lowest tertile were 0.57 (0.35-0.93), 0.60 (0.36-0.99), and 0.58 (0.37-0.90) for intakes of fish, egg, as well as fruit/vegetable protein, respectively (all P for trend < 0.05). A positive association between PM2.5 exposure and all-cause mortality was observed (HR=1.52; 95 % CI: 1.13-2.05, per interquartile range increment). Notably, dietary fish, egg, and fruit/vegetable protein modified these associations, as patients with lower intakes had significantly higher PM2.5-related mortality in the cohort (all P for interaction < 0.05). CONCLUSIONS This study provides evidence linking the potential interactions between dietary fish, egg, and fruit/vegetable protein intake and PM2.5 exposure on all-cause mortality of OC patients. Our study demonstrates the importance of adherence to a certain protein diet in reducing PM2.5-related mortality risk for OC patients.
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Affiliation(s)
- He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi Bao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ya-Li Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Information Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiao-Ying Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dong-Hui Huang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Zi Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yue-Yang Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Library, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xin-Xin Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Hospice Care, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qian Xiao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ren-Jie Chen
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China
| | - Ling Ouyang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xia Meng
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China
| | - Xue Qin
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China.
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10
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Kougioumtsidou A, Karavida A, Mamopoulos A, Dagklis T, Tsakiridis I, Kopatsaris S, Michos G, Athanasiadis AP, Kalogiannidis I. Performance of International Ovarian Tumor Analysis (IOTA) predictive models in preoperative discrimination between benign and malignant adnexal lesions: preliminary outcomes in a Tertiary Care Hospital in Greece. Arch Gynecol Obstet 2025; 311:113-122. [PMID: 39658706 DOI: 10.1007/s00404-024-07859-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024]
Abstract
OBJECTIVES To apply the International Ovarian Tumor Analysis (IOTA) predictive models, the logistic regression model 2 (LR2) and the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX), in patients with ovarian masses and to compare their performance in preoperative discrimination between benign and malignant adnexal lesions. METHODS This was a retrospective diagnostic accuracy study with prospectively collected data, performed between January 2019 and December 2022, in a single tertiary gynecologic oncology center in Greece. The study included women with an adnexal lesion which underwent surgery within 6 months after of using the LR2 and ADNEX protocol to assess the risk of malignancy. Correlation of the ultrasound findings with the postoperative histopathological analysis was performed. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the models to classify tumors; sensitivity and specificity were determined for each model and their performance was compared. RESULTS Of the136 participants, 117 (86%) had benign ovarian masses and 19 (14%) had malignant tumors. The area under the ROC curve (AUC) of the LR2 model was 0.84 (95% CI 0.74-0.93), which was significantly higher than the AUC for ADNEX model: 0.78 (95% CI 0.67-0.89). At a cut off > 10%, the LR2 model had the highest sensitivity 89.5% (95% CI 66.9-98.7) and specificity 85.1% (95% CI 76.9-91.2) compared to ADNEX model [sensitivity 84.2% (95% CI 60.4-96.6) and specificity 71.8% (95% CI 62.7-79.7)]. CONCLUSIONS IOTA LR2 had the highest accuracy in differentiating between benign and malignant ovarian masses. IOTA LR2 and ADNEX models were both useful tools in discriminating between benign and malignant ovarian masses.
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Affiliation(s)
- Anna Kougioumtsidou
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece.
| | - Aikaterini Karavida
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Apostolos Mamopoulos
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Themistoklis Dagklis
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Ioannis Tsakiridis
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Stergios Kopatsaris
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Georgios Michos
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Apostolos P Athanasiadis
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
| | - Ioannis Kalogiannidis
- 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ippokrateio General Hospital of Thessaloniki, Kostantinoupoleos Street 49, 546 42, Thessaloníki, Greece
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11
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Zeng S, Wang XL, Yang H. Radiomics and radiogenomics: extracting more information from medical images for the diagnosis and prognostic prediction of ovarian cancer. Mil Med Res 2024; 11:77. [PMID: 39673071 PMCID: PMC11645790 DOI: 10.1186/s40779-024-00580-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 11/07/2024] [Indexed: 12/15/2024] Open
Abstract
Ovarian cancer (OC) remains one of the most lethal gynecological malignancies globally. Despite the implementation of various medical imaging approaches for OC screening, achieving accurate differential diagnosis of ovarian tumors continues to pose significant challenges due to variability in image performance, resulting in a lack of objectivity that relies heavily on the expertise of medical professionals. This challenge can be addressed through the emergence and advancement of radiomics, which enables high-throughput extraction of valuable information from conventional medical images. Furthermore, radiomics can integrate with genomics, a novel approach termed radiogenomics, which allows for a more comprehensive, precise, and personalized assessment of tumor biological features. In this review, we present an extensive overview of the application of radiomics and radiogenomics in diagnosing and predicting ovarian tumors. The findings indicate that artificial intelligence methods based on imaging can accurately differentiate between benign and malignant ovarian tumors, as well as classify their subtypes. Moreover, these methods are effective in forecasting survival rates, treatment outcomes, metastasis risk, and recurrence for patients with OC. It is anticipated that these advancements will function as decision-support tools for managing OC while contributing to the advancement of precision medicine.
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Affiliation(s)
- Song Zeng
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Xin-Lu Wang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Hua Yang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
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12
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Wesley T, Escalona RM, Kannourakis G, Ahmed N. Plakin Expression in Serous Epithelial Ovarian Cancer Has the Potential to Impede Metastatic Spread and Epithelial-Mesenchymal Transition: A Comparative Expression Analysis of Immunohistochemical and In Silico Datasets. Cancers (Basel) 2024; 16:4087. [PMID: 39682273 DOI: 10.3390/cancers16234087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
Epithelial ovarian cancer is aggressive and causes high mortality among women worldwide. Members of the plakin family are essential to maintain cytoskeletal integrity and key cellular processes. In this study we characterised the expression of plakins, particularly plectin (PLEC), periplakin (PPL), envoplakin (EVPL), and EMT-related proteins by immunohistochemistry in n = 48 patients' samples to evaluate a potential correlation of plakin expression with EMT as EOC progresses. These tissue plakin and EMT expression analyses were further evaluated by in vitro cell line expression and correlated with the expression of these molecules using publicly available datasets such as Cancer Genome Atlas (TCGA) and Clinical Proteome Tumour Analysis Consortium (CPTAC) datasets. We demonstrate that the expression of PPL and PLEC plakins is decreased in high-grade compared to low-grade EOCs with mixed EMT marker protein expression. This is supported by the correlation of high PPL and PLEC expression with an epithelial rather than mesenchymal phenotype. Our data suggest a partial loss of plakin expression as EOC tumours progress. This may impact the connections of plakins with membrane-bound receptors, which impede the downstream signalling required for the initiation of EMT as the tumours progress.
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Affiliation(s)
- Tamsin Wesley
- Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia
- Health Innovation and Transformation Centre, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3353, Australia
| | - Ruth M Escalona
- Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
| | - George Kannourakis
- Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia
- Health Innovation and Transformation Centre, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3353, Australia
| | - Nuzhat Ahmed
- Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia
- Health Innovation and Transformation Centre, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3353, Australia
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
- Department of Molecular & Translational Science, Monash University, Clayton, VIC 3168, Australia
- Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC 3050, Australia
- Department of Surgery, St Vincent Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia
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13
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MacArthur E, Stone R. Current Science and Practice of Surgical and Nonsurgical Opportunities for Ovarian Cancer Prevention. Clin Obstet Gynecol 2024; 67:676-686. [PMID: 39344701 DOI: 10.1097/grf.0000000000000900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Due to improved understanding of ovarian cancer pathogenesis, we have an unprecedented chance to decrease the burden of disease by maximizing opportunities for prevention. Innovations in surgical options for prevention stem from the discovery that many cases directly or indirectly arise from the fallopian tube. Surgical prevention with salpingectomy alone decreases risk by ≥50%. Effective hormonal and nonhormonal chemopreventive agents are also available. Risk stratification is key to ensuring that options for prevention are appropriately matched to individual risk profile. This evidence-based review provides a critical appraisal of the translational health research endeavors supporting ovarian cancer prevention in clinical practice.
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Affiliation(s)
- Emily MacArthur
- Kelly Gynecologic Oncology Service, Johns Hopkins University, Baltimore, Maryland
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14
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Jin C, Deng M, Bei Y, Zhang C, Wang S, Yang S, Qiu L, Liu X, Chen Q. The predictive value of nomogram for adnexal cystic-solid masses based on O-RADS US, clinical and laboratory indicators. BMC Med Imaging 2024; 24:315. [PMID: 39558247 PMCID: PMC11575063 DOI: 10.1186/s12880-024-01497-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 11/11/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Ovarian cancer remains a leading cause of death among women, largely due to its asymptomatic early stages and high mortality when diagnosed late. Early detection significantly improves survival rates, and the Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) is currently the most commonly used method, but has limitations in specificity and accuracy. While O-RADS US has standardized reporting, its sensitivity can lead to the misdiagnosis of benign masses as malignant, resulting in overtreatment. This study aimed to construct a nomogram model based on the O-RADS US and clinical and laboratory indicators to predict the malignancy risk of adnexal cystic-solid masses. METHODS This retrospective study collected data from patients with adnexal cystic-solid masses who underwent ultrasonography and were pathologically confirmed between January 2021 and December 2023 at the First Affiliated Hospital of Shenzhen University. They were categorized into benign and malignant groups according to pathological findings. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select the most relevant predictors of ovarian cancer. A nomogram model was constructed, and its diagnostic performance was calculated. We bootstrapped the data 500 times to perform internal verification, drew a calibration curve to verify the prediction ability, and performed a decision curve analysis to assess clinical usefulness. RESULTS A total of 399 patients with adnexal cystic-solid masses were included in this study: 327 in the benign group and 72 in the malignant group. Five predictors associated with the risk of malignancy of adnexal cystic-solid masses were selected using LASSO regression: O-RADS, acoustic shadowing, postmenopausal status, CA125, and HE4. The area under the curve, sensitivity, specificity, accuracy, positive and negative predictive values of the nomogram were 0.909, 83.3%, 82.9%, 83.0%, 51.7%, and 95.8%, respectively. The calibration curve of the nomogram showed good consistency between the predicted and actual probabilities, and the decision curve showed good clinical usefulness. CONCLUSION The nomogram model based on O-RADS US and clinical and laboratory indicators can be used to predict the risk of malignancy in adnexal cystic-solid masses, with high predictive performance, good calibration, and clinical usefulness.
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Affiliation(s)
- Chunchun Jin
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Meifang Deng
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Yanling Bei
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Chan Zhang
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Shiya Wang
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Shun Yang
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Lvhuan Qiu
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Xiuyan Liu
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China
| | - Qiuxiang Chen
- Department of Ultrasound, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, No.3002, Sungang West Road, Futian District, Shenzhen, China.
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15
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He X, Bai XH, Chen H, Feng WW. Machine learning models in evaluating the malignancy risk of ovarian tumors: a comparative study. J Ovarian Res 2024; 17:219. [PMID: 39506832 PMCID: PMC11539702 DOI: 10.1186/s13048-024-01544-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 10/23/2024] [Indexed: 11/08/2024] Open
Abstract
OBJECTIVES The study aimed to compare the diagnostic efficacy of the machine learning models with expert subjective assessment (SA) in assessing the malignancy risk of ovarian tumors using transvaginal ultrasound (TVUS). METHODS The retrospective single-center diagnostic study included 1555 consecutive patients from January 2019 to May 2021. Using this dataset, Residual Network(ResNet), Densely Connected Convolutional Network(DenseNet), Vision Transformer(ViT), and Swin Transformer models were established and evaluated separately or combined with Cancer antigen 125 (CA 125). The diagnostic performance was then compared with SA. RESULTS Of the 1555 patients, 76.9% were benign, while 23.1% were malignant (including borderline). When differentiating the malignant from ovarian tumors, the SA had an AUC of 0.97 (95% CI, 0.93-0.99), sensitivity of 87.2%, and specificity of 98.4%. Except for Vision Transformer, other machine learning models had diagnostic performance comparable to that of the expert. The DenseNet model had an AUC of 0.91 (95% CI, 0.86-0.95), sensitivity of 84.6%, and specificity of 95.1%. The ResNet50 model had an AUC of 0.91 (0.85-0.95). The Swin Transformer model had an AUC of 0.92 (0.87-0.96), sensitivity of 87.2%, and specificity of 94.3%. There was a statistically significant difference between the Vision Transformer and SA, and between the Vision Transformer and Swin Transformer models (AUC: 0.87 vs. 0.97, P = 0.01; AUC: 0.87 vs. 0.92, P = 0.04). Adding CA125 did not improve the diagnostic performance of the models in distinguishing benign and malignant ovarian tumors. CONCLUSION The deep learning model of TVUS can be used in ovarian cancer evaluation, and its diagnostic performance is comparable to that of expert assessment.
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Affiliation(s)
- Xin He
- Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China
- Department of Obstetrics and Gynaecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, P.R. China
| | - Xiang-Hui Bai
- Philips Health Technology (China) Co., Ltd. Shanghai Branch, 718 Lingshi Road, Shanghai, 200072, P.R. China
| | - Hui Chen
- Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China.
| | - Wei-Wei Feng
- Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China.
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Chen L, Jin C, Chen B, Debora A, Su W, Zhou Q, Zhou S, Bian J, Yang Y, Lan L. A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels? Br J Radiol 2024; 97:1706-1712. [PMID: 39177575 PMCID: PMC11417353 DOI: 10.1093/bjr/tqae144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 02/19/2024] [Accepted: 08/07/2024] [Indexed: 08/24/2024] Open
Abstract
OBJECTIVE CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients. METHODS We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour's region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram. RESULTS Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort. CONCLUSION Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels. ADVANCES IN KNOWLEDGE This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.
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Affiliation(s)
- Lixuan Chen
- The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Chenyang Jin
- Department of Ultrasound, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
| | - Bo Chen
- The Department of Medical Record, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Asta Debora
- The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Weizeng Su
- The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Qingwen Zhou
- The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Shuai Zhou
- The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Jinyan Bian
- Department of Obstetrics and Gynecology Ultrasound, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
| | - Yunjun Yang
- The Department of Nuclear, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Li Lan
- The Department of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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Borges AL, Brito M, Ambrósio P, Condeço R, Pinto P, Ambrósio B, Mahomed F, Gama JMR, Bernardo MJ, Gouveia AI, Djokovic D. Prospective external validation of IOTA methods for classifying adnexal masses and retrospective assessment of two-step strategy using benign descriptors and ADNEX model: Portuguese multicenter study. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2024; 64:538-549. [PMID: 38477149 DOI: 10.1002/uog.27641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 02/06/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024]
Abstract
OBJECTIVES To externally and prospectively validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SRs), Logistic Regression model 2 (LR2) and Assessment of Different NEoplasias in the adneXa (ADNEX) model in a Portuguese population, comparing these approaches with subjective assessment and the risk-of-malignancy index (RMI), as well as with each other. This study also aimed to retrospectively validate the IOTA two-step strategy, using modified benign simple descriptors (MBDs) followed by the ADNEX model in cases in which MBDs were not applicable. METHODS This was a prospective multicenter diagnostic accuracy study conducted between January 2016 and December 2021 of consecutive patients with an ultrasound diagnosis of at least one adnexal tumor, who underwent surgery at one of three tertiary referral centers in Lisbon, Portugal. All ultrasound assessments were performed by Level-II or -III sonologists with IOTA certification. Patient clinical data and serum CA 125 levels were collected from hospital databases. Each adnexal mass was classified as benign or malignant using subjective assessment, RMI, IOTA SRs, LR2 and the ADNEX model (with and without CA 125). The reference standard was histopathological diagnosis. In the second phase, all adnexal tumors were classified retrospectively using the two-step strategy (MBDs + ADNEX). Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and overall accuracy were determined for all methods. Receiver-operating-characteristics curves were constructed and corresponding areas under the curve (AUC) were determined for RMI, LR2, the ADNEX model and the two-step strategy. The ADNEX model calibration plots were constructed using locally estimated scatterplot smoothing (LOESS). RESULTS Of the 571 patients included in the study, 428 had benign disease and 143 had malignant disease (prevalence of malignancy, 25.0%), of which 42 had borderline ovarian tumor, 93 had primary invasive adnexal cancer and eight had metastatic tumors in the adnexa. Subjective assessment had an overall sensitivity of 97.9% and a specificity of 83.6% for distinguishing between benign and malignant lesions. RMI showed high specificity (95.6%) but very low sensitivity (58.7%), with an AUC of 0.913. The IOTA SRs were applicable in 80.0% of patients, with a sensitivity of 94.8% and specificity of 98.6%. The IOTA LR2 had a sensitivity of 84.6%, specificity of 86.9% and an AUC of 0.939, at a malignancy risk cut-off of 10%. At the same cut-off, the sensitivity, specificity and AUC for the ADNEX model with vs without CA 125 were 95.8% vs 98.6%, 82.5% vs 79.7% and 0.962 vs 0.960, respectively. The ADNEX model gave heterogeneous results for distinguishing between benign masses and different subtypes of malignancy, with the highest AUC (0.991) for discriminating benign masses from primary invasive adnexal cancer Stages II-IV, and the lowest AUC (0.696) for discriminating primary invasive adnexal cancer Stage I from metastatic lesion in the adnexa. The calibration plot suggested underestimation of the risk by the ADNEX model compared with the observed proportion of malignancy. The MBDs were applicable in 26.3% (150/571) of cases, of which none was malignant. The two-step strategy using the ADNEX model in the second step only, with and without CA 125, had AUCs of 0.964 and 0.961, respectively, which was similar to applying the ADNEX model in all patients. CONCLUSIONS The IOTA methods showed good-to-excellent performance in the Portuguese population, outperforming RMI. The ADNEX model was superior to other methods in terms of accuracy, but interpretation of its ability to distinguish between malignant subtypes was limited by sample size and large differences in the prevalence of tumor subtypes. The IOTA MBDs are reliable in identifying benign disease. The two-step strategy comprising application of MBDs followed by the ADNEX model if MBDs are not applicable, is suitable for daily clinical practice, circumventing the need to calculate the risk of malignancy in all patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- A L Borges
- Ginecologia e Obstetrícia, Hospital de São Francisco Xavier, Lisbon, Portugal
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal
| | - M Brito
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
| | - P Ambrósio
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
| | - R Condeço
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
| | - P Pinto
- Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Ginecologia Oncológica, Lisbon, Portugal
- First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - B Ambrósio
- Ginecologia e Obstetrícia, Hospital de Vila Franca de Xira, Vila Franca de Xira, Portugal
| | - F Mahomed
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
| | - J M R Gama
- Faculdade de Ciências da Saúde, Centro de Matemática e Aplicações, Universidade da Beira Interior, Covilhã, Portugal
| | - M J Bernardo
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
| | - A I Gouveia
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal
- Instituto de Biofísica e Engenharia Biomédica, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Ciências Sociais e Humanas, Núcleo de Investigação em Ciências Empresariais, Universidade da Beira Interior, Covilhã, Portugal
| | - D Djokovic
- Maternidade Dr Alfredo da Costa, Ginecologia e Obstetrícia, Lisbon, Portugal
- Faculdade de Ciências Médicas de Lisboa, Ginecologia e Obstetrícia, Universidade Nova de Lisboa, Lisbon, Portugal
- Hospital CUF Descobertas, Ginecologia e Obstetrícia, Lisbon, Portugal
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Lukanović D, Polajžer S, Matjašič M, Kobal B, Černe K. Analysis of ATP7A Expression and Ceruloplasmin Levels as Biomarkers in Patients Undergoing Neoadjuvant Chemotherapy for Advanced High-Grade Serous Ovarian Carcinoma. Int J Mol Sci 2024; 25:10195. [PMID: 39337685 PMCID: PMC11432368 DOI: 10.3390/ijms251810195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/20/2024] [Accepted: 09/21/2024] [Indexed: 09/30/2024] Open
Abstract
Ovarian cancer (OC), particularly high-grade serous carcinoma (HGSC), is a leading cause of gynecological cancer mortality due to late diagnosis and chemoresistance. While studies on OC cell lines have shown that overexpression of the ATP7A membrane transporter correlates with resistance to platinum-based drugs (PtBMs) and cross-resistance to copper (Cu), clinical evidence is lacking. The functionality of ceruloplasmin (CP), the main Cu-transporting protein in the blood, is dependent on, among other things, ATP7A activity. This study investigated ATP7A expression and CP levels as potential biomarkers for predicting responses to PtBMs. We included 28 HGSC patients who underwent neoadjuvant chemotherapy (NACT). ATP7A expression in ovarian and peritoneal tissues before NACT and in peritoneal and omental tissues after NACT was analyzed via qPCR, and CP levels in ascites and plasma were measured via ELISA before and after NACT. In total, 54% of patients exhibited ATP7A expression in pretreatment tissue (ovary and/or peritoneum), while 43% of patients exhibited ATP7A expression in tissue after treatment (peritoneum and/or omentum). A significant association was found between higher ATP7A expression in the peritoneum before NACT and an unfavorable CA-125 elimination rate constant k (KELIM) score. Patients with omental ATP7A expression had significantly higher plasma mean CP levels before NACT. Plasma CP levels decreased significantly after NACT, and higher CP levels after NACT were associated with a shorter platinum-free interval (PFI). These findings suggest that the ATP7A transporter and CP have the potential to serve as predictive markers of chemoresistance, but further research is needed to validate their clinical utility.
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Affiliation(s)
- David Lukanović
- Department of Gynecology, Division of Gynecology and Obstetrics, University Medical Centre Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia; (D.L.); (B.K.)
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Ljubljana, Šlajmerjeva 3, SI-1000 Ljubljana, Slovenia
| | - Sara Polajžer
- Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia;
| | - Miha Matjašič
- Department of Education Studies, Faculty of Education, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
| | - Borut Kobal
- Department of Gynecology, Division of Gynecology and Obstetrics, University Medical Centre Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia; (D.L.); (B.K.)
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Ljubljana, Šlajmerjeva 3, SI-1000 Ljubljana, Slovenia
| | - Katarina Černe
- Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia;
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Abstract
Research reveals that 1% of neoplasms in females under 17 years of age are ovarian neoplasms and though usually benign, malignant tumors may occur in the pediatric age group. This review considers various current concepts of these tumors including the epidemiology, risk factors, clinical presentations, diagnosis, differential diagnosis, and treatment options including the need to provide fertility-sparing surgery as well as their potential impacts on the psychological well-being of children and adolescents. We gathered data from the published articles ranging from studies, meta-analyses, retrospective studies, and reviews. We focused on the articles published in English between January 1, 2000, and August 31, 2023. Only a few articles published prior to 2000 were included for historical perspective.
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Affiliation(s)
- Berrin Ergun-Longmire
- Department of Pediatric and Adolescent Medicine, Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA.
| | - Donald E Greydanus
- Department of Pediatric and Adolescent Medicine, Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
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20
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Mitchell S, Ramajayan T, Sayasneh A. Borderline tumour recurrence: how quickly does the tumour grow? BMJ Case Rep 2024; 17:e259501. [PMID: 38724214 PMCID: PMC11085964 DOI: 10.1136/bcr-2023-259501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
This abstract describes a case of the growth of a serous borderline tumour recurrence and cyst to papillary projection ratio with associated ultrasound images. The aetiology, presentation and management of such cases are explored and compared to the literature.
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Affiliation(s)
- Sian Mitchell
- Department of Women's Health, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Thushanee Ramajayan
- Department of Women's Health, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Ahmad Sayasneh
- Gynaecological Oncology, Guy's and St Thomas's NHS Foundation Trust, London, UK
- School of Life Course Sciences, Faculty of Life Sciences and Medicine, St Thomas Hospital, Westminster Bridge Road, London, UK
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21
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Licaj M, Mhaidly R, Kieffer Y, Croizer H, Bonneau C, Meng A, Djerroudi L, Mujangi-Ebeka K, Hocine HR, Bourachot B, Magagna I, Leclere R, Guyonnet L, Bohec M, Guérin C, Baulande S, Kamal M, Le Tourneau C, Lecuru F, Becette V, Rouzier R, Vincent-Salomon A, Gentric G, Mechta-Grigoriou F. Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway. Nat Commun 2024; 15:1312. [PMID: 38346978 PMCID: PMC10861537 DOI: 10.1038/s41467-024-45595-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 01/29/2024] [Indexed: 02/15/2024] Open
Abstract
Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC.
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Affiliation(s)
- Monika Licaj
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Rana Mhaidly
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Yann Kieffer
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Hugo Croizer
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Claire Bonneau
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
- Department of Surgery, Institut Curie Hospital Group, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Arnaud Meng
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Lounes Djerroudi
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
- Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France
| | - Kevin Mujangi-Ebeka
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Hocine R Hocine
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Brigitte Bourachot
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Ilaria Magagna
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France
| | - Renaud Leclere
- Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France
| | - Lea Guyonnet
- Cytometry platform, PSL University, Institut Curie, 75005, Paris, France
| | - Mylene Bohec
- ICGex Next-Generation Sequencing Platform, PSL University, Institut Curie, 75005, Paris, France
| | - Coralie Guérin
- Cytometry platform, PSL University, Institut Curie, 75005, Paris, France
| | - Sylvain Baulande
- ICGex Next-Generation Sequencing Platform, PSL University, Institut Curie, 75005, Paris, France
| | - Maud Kamal
- Department of Drug Development and Innovation, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France
| | - Christophe Le Tourneau
- Department of Drug Development and Innovation, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France
- INSERM, U900, Paris-Saclay University, Institut Curie, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Fabrice Lecuru
- Breast, gynecology and reconstructive surgery Department, Institut Curie Hospital Group, Paris Cité University, 26, rue d'Ulm, F-75248, Paris, France
| | - Véronique Becette
- Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Roman Rouzier
- Department of Surgery, Institut Curie Hospital Group, 35 rue Dailly, 92210, Saint-Cloud, France
| | - Anne Vincent-Salomon
- Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France
| | - Geraldine Gentric
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.
| | - Fatima Mechta-Grigoriou
- Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
- Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.
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Cai Y, Shu T, Zheng H. Disparities in treatment modalities and survival among older patients with high-grade serous ovarian cancer. BMC Womens Health 2024; 24:100. [PMID: 38326784 PMCID: PMC10851467 DOI: 10.1186/s12905-024-02938-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 01/29/2024] [Indexed: 02/09/2024] Open
Abstract
BACKGROUND Undertreatment of ovarian cancer is common among older women. We aimed to evaluate the treatment modalities offered to older patients and their impact on overall survival (OS). METHODS The study identified 5,055 patients with high-grade serous ovarian cancer and 3584 patients with advanced stage (IIIC + IV) disease from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2017. We performed comparisons of OS and ovarian cancer-specific survival (OCSS) across age groups using a Cox proportional hazards model. RESULTS Very elderly patients (≥ 75 years old) received treatment with significantly less surgical complexity, such as no lymphadenectomy (59.7% vs. 48.6%; p < 0.001) and a lower rate of optimal debulking surgery (44.0% vs. 52.7%; p < 0.001), as well as lower rates of chemotherapy (78.2% vs. 89.4%; P<0.001) and standard treatment (70.6% vs. 85%; p < 0.001). High proportions of both very elderly and elderly patients received neoadjuvant chemotherapy (NACT), with no significant difference (38.7% vs. 36.2%; P = 0.212). Patients aged ≥ 75 years had significantly worse OS and OCSS. CONCLUSION With increasing age, the survival rate of women with ovarian cancer decreases significantly. Noticeably fewer ovarian cancer patients aged over 75 years receive standard treatments, and more very elderly patients are treated with NACT.
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Affiliation(s)
- Yan Cai
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Tong Shu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Hong Zheng
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gynecologic Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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23
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Tavares V, Marques IS, Melo IGD, Assis J, Pereira D, Medeiros R. Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements. Int J Mol Sci 2024; 25:1845. [PMID: 38339123 PMCID: PMC10856127 DOI: 10.3390/ijms25031845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/30/2024] [Accepted: 02/02/2024] [Indexed: 02/12/2024] Open
Abstract
Ovarian cancer (OC) is the female genital malignancy with the highest lethality. Patients present a poor prognosis mainly due to the late clinical presentation allied with the common acquisition of chemoresistance and a high rate of tumour recurrence. Effective screening, accurate diagnosis, and personalised multidisciplinary treatments are crucial for improving patients' survival and quality of life. This comprehensive narrative review aims to describe the current knowledge on the aetiology, prevention, diagnosis, and treatment of OC, highlighting the latest significant advancements and future directions. Traditionally, OC treatment involves the combination of cytoreductive surgery and platinum-based chemotherapy. Although more therapeutical approaches have been developed, the lack of established predictive biomarkers to guide disease management has led to only marginal improvements in progression-free survival (PFS) while patients face an increasing level of toxicity. Fortunately, because of a better overall understanding of ovarian tumourigenesis and advancements in the disease's (epi)genetic and molecular profiling, a paradigm shift has emerged with the identification of new disease biomarkers and the proposal of targeted therapeutic approaches to postpone disease recurrence and decrease side effects, while increasing patients' survival. Despite this progress, several challenges in disease management, including disease heterogeneity and drug resistance, still need to be overcome.
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Affiliation(s)
- Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP), Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-072 Porto, Portugal
- ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal
| | - Inês Soares Marques
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP), Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal
- Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
| | - Inês Guerra de Melo
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP), Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-072 Porto, Portugal
| | - Joana Assis
- Clinical Research Unit, Research Center of IPO Porto (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072 Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP), Pathology and Laboratory Medicine Department, Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (Porto.CCC), 4200-072 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-072 Porto, Portugal
- ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal
- Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
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24
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Richau CS, Scherer NDM, Matta BP, de Armas EM, de Barros Moreira FC, Bergmann A, Pereira Chaves CB, Boroni M, dos Santos ACE, Moreira MAM. BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer. Cancer Med 2024; 13:e6729. [PMID: 38308422 PMCID: PMC10905552 DOI: 10.1002/cam4.6729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 10/20/2023] [Accepted: 11/07/2023] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival. METHODS The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2. RESULTS A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival. CONCLUSION Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2.
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Affiliation(s)
| | | | - Bruna Palma Matta
- Tumoral Genetics and Virology ProgramInstituto Nacional de CâncerRio de JaneiroBrazil
- Present address:
Hospital BP ‐ A Beneficência Portuguesa de São PauloSão PauloBrazil
| | | | | | - Anke Bergmann
- Clinical EpidemiologyInstituto Nacional de CâncerRio de JaneiroBrazil
| | | | - Mariana Boroni
- Bioinformatics and Computational Biology LaboratoryInstituto Nacional de CâncerRio de JaneiroBrazil
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25
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Zhu K, Ma J, Tian Y, Liu Q, Zhang J. An immune-related exosome signature predicts the prognosis and immunotherapy response in ovarian cancer. BMC Womens Health 2024; 24:49. [PMID: 38238671 PMCID: PMC10795461 DOI: 10.1186/s12905-024-02881-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 01/03/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Cancer-derived exosomes contribute significantly in intracellular communication, particularly during tumorigenesis. Here, we aimed to identify two immune-related ovarian cancer-derived exosomes (IOCEs) subgroups in ovarian cancer (OC) and establish a prognostic model for OC patients based on immune-related IOCEs. METHODS The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq data, as well as clinical and prognostic information. Consensus clustering analysis was performed to identify two IOCEs-associated subgroups. Kaplan-Meier analysis was used to compare the overall survival (OS) between IOCEs-high and IOCEs-low subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to investigate the mechanisms and biological effects of differentially expressed genes (DEGs) between the two subtypes. Besides, an IOCE-related prognostic model of OC was constructed by Lasso regression analysis, and the signature was validated using GSE140082 as the validation set. RESULTS In total, we obtained 21 differentially expressed IOCEs in OC, and identified two IOCE-associated subgroups by consensus clustering. IOCE-low subgroup showed a favorable prognosis while IOCE-high subgroup had a higher level of immune cell infiltration and immune response. GSEA showed that pathways in cancer and immune response were mainly enriched in IOCE-high subgroup. Thus, IOCE-high subgroup may benefit more in immunotherapy treatment. In addition, we constructed a risk model based on nine IOCE-associated genes (CLDN4, AKT2, CSPG5, ALDOC, LTA4H, PSMA2, PSMA5, TCIRG1, ANO6). CONCLUSION We developed a novel stratification system for OV based on IOCE signature, which could be used to estimate the prognosis as well as immunotherapy for OC patient.
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Affiliation(s)
- Kaibo Zhu
- Department of Pathology, Women's Hospital School of Medicine Zhejiang University, No.3, East Qingchun Road, Shangcheng District, Hangzhou, China
| | - Jiao Ma
- Department of Pathology, Zhejiang Hospital, Hangzhou, China
| | - Yiping Tian
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Qin Liu
- Department of Pathology, Women's Hospital School of Medicine Zhejiang University, No.3, East Qingchun Road, Shangcheng District, Hangzhou, China.
| | - Jun Zhang
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital Zhejiang University School of Medicine, No.1, Xueshi Road, Shangcheng District, Hangzhou, China.
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Deshmukh R, Singh R, Sharma S, Mishra AK, Harwansh RK. A Snapshot of Selenium-enclosed Nanoparticles for the Management of Cancer. Curr Pharm Des 2024; 30:841-858. [PMID: 38462835 DOI: 10.2174/0113816128297329240305071103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/12/2024] [Accepted: 02/22/2024] [Indexed: 03/12/2024]
Abstract
Among the primary causes of mortality in today's world is cancer. Many drugs are employed to give lengthy and severe chemotherapy and radiation therapy, like nitrosoureas (Cisplatin, Oxaliplatin), Antimetabolites (5-fluorouracil, Methotrexate), Topoisomerase inhibitors (Etoposide), Mitotic inhibitors (Doxorubicin); such treatment is associated with significant adverse effects. Antitumor antibiotics have side effects similar to chemotherapy and radiotherapy. Selenium (Se) is an essential trace element for humans and animals, and additional Se supplementation is required, particularly for individuals deficient in Se. Due to its unique features and high bioactivities, selenium nanoparticles (SeNPs), which act as a supplement to counter Se deficiency, have recently gained worldwide attention. This study presented a safer and more economical way of preparing stable SeNPs. The researcher has assessed the antiproliferative efficiency of SeNPs-based paclitaxel delivery systems against tumor cells in vitro with relevant mechanistic visualization. SeNPs stabilized by Pluronic F-127 were synthesized and studied. The significant properties and biological activities of PTX-loaded SeNPs on cancer cells from the lungs, breasts, cervical, and colons. In one study, SeNPs were formulated using chitosan (CTS) polymer and then incorporated into CTS/citrate gel, resulting in a SeNPs-loaded chitosan/citrate complex; in another study, CTS was used in the synthesis of SeNPs and then situated into CTS/citrate gel, resulting in Se loaded nanoparticles. These formulations were found to be more successful in cancer treatment.
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Affiliation(s)
- Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Rajesh Singh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Sandeep Sharma
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Ashwini Kumar Mishra
- Delhi Institute of Pharmaceutical Sciences and Research University, Delhi 110017, India
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27
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Koh YC, Huang WZ, Nagabhushanam K, Ho CT, Pan MH. 3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma. Mol Nutr Food Res 2024; 68:e2300108. [PMID: 37876143 DOI: 10.1002/mnfr.202300108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/07/2023] [Indexed: 10/26/2023]
Abstract
SCOPE Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.
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Affiliation(s)
- Yen-Chun Koh
- Institute of Food Sciences and Technology, National Taiwan University, Taipei, 10617, Taiwan
| | - Wei-Zhe Huang
- Institute of Food Sciences and Technology, National Taiwan University, Taipei, 10617, Taiwan
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ, 08901, USA
| | - Min-Hsiung Pan
- Institute of Food Sciences and Technology, National Taiwan University, Taipei, 10617, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City, 404, Taiwan
- Department of Health and Nutrition Biotechnology, Asia University, Taichung City, 41354, Taiwan
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28
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Zhang C, Qin M. Extracellular vesicles targeting tumor microenvironment in ovarian cancer. Int J Biol Macromol 2023; 252:126300. [PMID: 37573911 DOI: 10.1016/j.ijbiomac.2023.126300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/17/2023] [Accepted: 08/10/2023] [Indexed: 08/15/2023]
Abstract
Ovarian cancer (OC) is a prevalent neoplastic condition affecting women. Extracellular vesicles (EVs), nano-sized membrane vesicles, are secreted by various cells in both physiological and pathological states. The profound interplay between EVs and the tumor microenvironment (TME) in ovarian cancer is crucial. In this review, we explores the pivotal role of EVs in facilitating intercellular communication between cancer cells and the TME, emphasizing the potential of EVs as promising diagnostic markers and innovative therapeutic targets for ovarian cancer. The comprehensive analysis outlines the specific mechanisms by which EVs engage in communication with the constituents of the TME, including the modulation of tumor growth through EVs carrying matrix metalloproteinases (MMPs) and EV-mediated inhibition of angiogenesis, among other factors. Additionally, the we discuss the potential clinical applications of EVs that target the TME in ovarian cancer, encompassing the establishment of novel treatment strategies and the identification of novel biomarkers for early detection and prognosis. Finally, this review identifies novel strategies for therapeutic interventions, such as utilizing EVs as carriers for drug delivery and targeting specific EV-mediated signaling pathways. In summary, this manuscript offers valuable insights into the role of EVs in ovarian cancer and highlights the significance of comprehending intercellular communication in the realm of cancer biology.
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Affiliation(s)
- Chunmei Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, China
| | - Meiying Qin
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, China.
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29
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Miao K, Zhao N, Lv Q, He X, Xu M, Dong X, Li D, Shao X. Prediction of benign and malignant ovarian tumors using Resnet34 on ultrasound images. J Obstet Gynaecol Res 2023; 49:2910-2917. [PMID: 37696522 DOI: 10.1111/jog.15788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/24/2023] [Indexed: 09/13/2023]
Abstract
OBJECTIVE To develop deep learning (DL) prediction models using transvaginal ultrasound (TVS), transabdominal ultrasound (TAS), and color Doppler flow imaging (CDFI) of TVS (CDFI_TVS) to automatically predict benign or malignant ovarian tumors. METHODS This retrospective study included women with ovarian tumors who underwent ultrasound between August 2018 and October 2022. Histopathological analysis was used as a reference standard. The dataset was preprocessed by clipping, flipping, and rotating images to generate a larger, more complicated, and diverse dataset to improve accuracy and generalizability. The dataset was then divided into training (80%) and test (20%) sets. The weights of the models, modified from the residual network (ResNet) with the TVS, TAS, and CDFI_TVS images (hereafter, referred to as DLTVS , DLTAS , and DLCDFI_TVS , respectively) were developed. The area under the receiver operating characteristic curve (AUC) analysis in the test set was used to compare the predictive value of DL for malignancy. RESULTS A total of 2340 images from 1350 women with adnexal masses were included. DLTVS had an AUC of 0.95 (95% CI: 0.93-0.97) for classifying malignant and benign ovarian tumors, comparable with that of DLTAS (AUC, 0.95; 95% CI: 0.91-0.98; p = 0.96) and DLCDFI_TVS (AUC, 0.88; 95% CI: 0.84-0.93; p = 0.02). Decision curve analysis indicated that DLTVS performed better than DLTAS and DLCDFI_TVS . CONCLUSION We developed DL models based on TVS, TAS, and CDFI_TVS on ultrasound images to predict benign and malignant ovarian tumors with high diagnostic performance. The DLTVS model had the best prediction compared with the DLTAS and DLCDFI_TVS models.
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Affiliation(s)
- Kuo Miao
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ning Zhao
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qian Lv
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xin He
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mingda Xu
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiaoqiu Dong
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dandan Li
- Department of Control Science and Engineering, Harbin Institute of Technology, Harbin, China
| | - Xiaohui Shao
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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30
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Tran TH, Egilman D. Response to Micha et al. (2022) talc powder and ovarian cancer: what is the evidence? Arch Gynecol Obstet 2023; 308:1907-1908. [PMID: 36574007 DOI: 10.1007/s00404-022-06883-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 12/11/2022] [Indexed: 12/28/2022]
Affiliation(s)
| | - David Egilman
- Department of Family Medicine, Brown University, Providence, USA
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31
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Yang Y, Wang H, Liu Z, Su N, Gao L, Tao X, Zhang R, Gu Y, Ma L, Wang R, Xu W, Xie Y, Zhang W, Zhang H, Xue G, Ru T, Dai Q, Li J, Jiang Y. Effect of differences in O-RADS lexicon interpretation between senior and junior sonologists on O-RADS classification and diagnostic performance. J Cancer Res Clin Oncol 2023; 149:12275-12283. [PMID: 37430161 PMCID: PMC10465637 DOI: 10.1007/s00432-023-05108-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/12/2023]
Abstract
PURPOSE To assess the consistency of Ovarian-Adnexal Reporting and Data System (O-RADS) lexicon interpretation between senior and junior sonologists and to investigate its impact on O-RADS classification and diagnostic performance. METHODS We prospectively studied 620 patients with adnexal lesions, all of whom underwent transvaginal or transrectal ultrasound performed by a senior sonologist (R1) who selected the O-RADS lexicon description and O-RADS category for the lesion after the examination. Meanwhile, the junior sonologist (R2) analyzed the images retained by R1 and divided the lesion in the same way. Pathological findings were used as a reference standard. kappa (к) statistics were used to assess the interobserver agreement. RESULTS Of the 620 adnexal lesions, 532 were benign and 88 were malignant. When using the O-RADS lexicon, R1 and R2 had almost perfect agreement regarding lesion category, external contour of solid lesions, presence of papillary inside cystic lesions, and fluid echogenicity (к: 0.81-1.00). Substantial agreement in solid components, acoustic shadow, vascularity and O-RADS categories (к: 0.61-0.80). Consistency in classifying classic benign lesions in the O-RADS category was only moderate (к = 0.535). No significant difference in diagnostic performance between them using O-RADS (P = 0.1211). CONCLUSION There was good agreement between senior and junior sonologists in the interpretation of the O-RADS lexicon and in the classification of O-RADS, except for a moderate agreement in the interpretation and classification of classic benign lesions. Differences in O-RADS category delineation between sonologists had no significant effect on the diagnostic performance of O-RADS.
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Affiliation(s)
- Ya Yang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Hongyan Wang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Zhenzhen Liu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Na Su
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Luying Gao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Xixi Tao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Rui Zhang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Yang Gu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Li Ma
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Ruojiao Wang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Wen Xu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Yuhuan Xie
- Department of Ultrasound, Dongguan People’s Hospital Affiliated to Southern Medical University, Dongguan, China
| | - Wenjun Zhang
- Department of Ultrasound, Taihe Hospital, the Affiliated to Hubei University of Medicine, Shiyan, China
| | - Heng Zhang
- Department of Ultrasound, Zhuhai People’s Hospital, Zhuhai, China
| | - Gaiqin Xue
- Department of Ultrasound, Shanxi Provincial Cancer Hospital, Shanxi, China
| | - Tong Ru
- Prenatal Diagnosis Center, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Qing Dai
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Jianchu Li
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730 China
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Lazurko C, Linder R, Pulman K, Lennox G, Feigenberg T, Fazelzad R, May T, Zigras T. Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review. Curr Oncol 2023; 30:8159-8171. [PMID: 37754507 PMCID: PMC10528002 DOI: 10.3390/curroncol30090592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/29/2023] [Accepted: 08/31/2023] [Indexed: 09/28/2023] Open
Abstract
Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.
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Affiliation(s)
- Caitlin Lazurko
- Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Revital Linder
- Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Kate Pulman
- Division of Gynecologic Oncology, Trillium Health Partners, Credit Valley Hospital, Mississauga, ON L5M 2N1, Canada
| | - Genevieve Lennox
- Division of Gynecologic Oncology, Trillium Health Partners, Credit Valley Hospital, Mississauga, ON L5M 2N1, Canada
| | - Tomer Feigenberg
- Division of Gynecologic Oncology, Trillium Health Partners, Credit Valley Hospital, Mississauga, ON L5M 2N1, Canada
| | - Rouhi Fazelzad
- Department of Library and Information Services, University Health Network Library and Information Services, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada
| | - Taymaa May
- Division of Gynecologic Oncology, Department of Surgical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2M9, Canada
| | - Tiffany Zigras
- Division of Gynecologic Oncology, Trillium Health Partners, Credit Valley Hospital, Mississauga, ON L5M 2N1, Canada
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Rubina H, Ratnagiri R, Uppin MS, Ayesha S, Lakshmi K M, Chowdary SB, Uppin SG. A Clinical and Immunopathological Analysis of Carcinoma of the Ovary with an Emphasis on Post-chemotherapy Histopathologic Changes. Indian J Surg Oncol 2023; 14:545-552. [PMID: 37900629 PMCID: PMC10611652 DOI: 10.1007/s13193-023-01756-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 04/25/2023] [Indexed: 10/31/2023] Open
Abstract
Ovarian cancers are a heterogeneous group of malignant tumors that differ with respect to pathogenesis, morphology, molecular features, and behavior. Pathologists and clinicians need to be aware of the advances in diagnosis and the changes which occur after chemotherapy to offer the optimal treatment to each patient. The present work aims to study the morphologic and immunohistochemical (IHC) profile of primary ovarian cancers with an assessment of post-chemotherapy changes. A total of 51 cases were included in the study from June 2017 to June 2019 (prospective and retrospective). The demographic and clinical details of the patients were collected. The gross and microscopic features of the tumors were studied, and the post-chemotherapy changes were evaluated. A chi-square test was used to determine the association of tumor morphology, the chemotherapy response score (CRS), and stage of the tumor with survival (PFS and OS). The mean patient age was 47.5 years, and high-grade serous carcinoma (66.6%) (HGSC) was the most common subtype followed by mucinous carcinoma and endometrioid carcinoma. Immunohistochemical analysis with WT1 and p53 helped in the diagnosis of HGSC. The CRS was 1 and 2 in most of the cases. The follow-up for patients of HGSC was available for a period of 1-27 months with a mean survival for primary resection of 24 months and for post-NACT resection was 17 months. This difference was not statistically significant (p = 0.38). High-grade serous carcinoma was the most common ovarian cancer in our series, and immunohistochemistry played an important role in the diagnosis. We could not demonstrate any survival benefit of preoperative chemotherapy in our series.
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Affiliation(s)
- Hassan Rubina
- Department of Pathology, Nizam’s Institute of Medical Sciences, Hyderabad Punjagutta, India
| | - Ranganath Ratnagiri
- Department of Pathology, Nizam’s Institute of Medical Sciences, Hyderabad Punjagutta, India
- Department of Surgical Oncology, Nizam’s Institute of Medical Sciences, Hyderbad, India
| | - Megha S. Uppin
- Department of Pathology, Nizam’s Institute of Medical Sciences, Hyderabad Punjagutta, India
| | - Sobiya Ayesha
- Department of Pathology, Nizam’s Institute of Medical Sciences, Hyderabad Punjagutta, India
| | - Meher Lakshmi K
- Department of Medical Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India
| | - Stalin Bala Chowdary
- Department of Medical Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India
| | - Shantveer G. Uppin
- Department of Pathology, Nizam’s Institute of Medical Sciences, Hyderabad Punjagutta, India
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Shang J, Lei T, Wu L, Lin M, Xie H. Comparison of performance between O-RADS, IOTA simple rules risk assessment and ADNEX model in the discrimination of ovarian Brenner tumors. Arch Gynecol Obstet 2023; 308:961-970. [PMID: 37186266 DOI: 10.1007/s00404-022-06903-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/20/2022] [Indexed: 05/17/2023]
Abstract
PURPOSE To describe the clinical and sonographic features of ovarian benign Brenner tumor (BBT) and malignant Brenner tumor (MBT), and to compare performance of four diagnostic models in differentiating them. METHODS Fifteen patients with BBTs and nine patients with MBTs were retrospectively identified in our institution from January 2003 and December 2021. One ultrasound examiner categorized each mass according to ovarian-adnexal reporting and data system (O-RADS), international ovarian tumor analysis (IOTA) Simple Rules Risk (SR-Risk) assessment and assessment of different neoplasias in the adnexa (ADNEX) models with/without CA125. Receiver operating characteristic curves were generated to compare diagnostic performance. RESULTS Patients with MBT had higher CA125 serum level (62.5% vs. 6.7%, P = 0.009) and larger maximum diameter of lesion (89 mm vs. 43 mm, P = 0.009) than did those with BBT. BBT tended to have higher prevalence of calcifications (100% vs. 55.6%, P = 0.012) and acoustic shadowing (93.3% vs. 33.3%, P = 0.004), and lower color scores manifesting none or minimal flow (100.0% vs. 22.2%, P < 0.001). Areas under curves of O-RADS, IOTA SR-Risk and ADNEX models with/without CA125 were 0.896, 0.913, 0.892 and 0.896, respectively. There were no significant differences between them. CONCLUSION BBTs are often small solid tumors with sparse color Doppler signals, which contain calcifications with posterior acoustic shadowing. The most common pattern of MBT is a large multilocular-solid or solid mass with irregular tumor borders, and most were moderately or richly vascularized at color Doppler. These four models have excellent performance in distinguishing them.
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Affiliation(s)
- JianHong Shang
- Department of Ultrasonic Medicine, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Road 58#, Guangzhou, 510080, Guangdong, China
| | - Ting Lei
- Department of Ultrasonic Medicine, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Road 58#, Guangzhou, 510080, Guangdong, China
| | - LiHong Wu
- Department of Ultrasonic Medicine, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Road 58#, Guangzhou, 510080, Guangdong, China
| | - MeiFang Lin
- Department of Ultrasonic Medicine, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Road 58#, Guangzhou, 510080, Guangdong, China
| | - HongNing Xie
- Department of Ultrasonic Medicine, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Road 58#, Guangzhou, 510080, Guangdong, China.
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Pelayo M, Sancho-Sauco J, Sánchez-Zurdo J, Perez-Mies B, Abarca-Martínez L, Cancelo-Hidalgo MJ, Sainz-Bueno JA, Alcázar JL, Pelayo-Delgado I. Application of Ultrasound Scores (Subjective Assessment, Simple Rules Risk Assessment, ADNEX Model, O-RADS) to Adnexal Masses of Difficult Classification. Diagnostics (Basel) 2023; 13:2785. [PMID: 37685323 PMCID: PMC10486436 DOI: 10.3390/diagnostics13172785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/11/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Ultrasound features help to differentiate benign from malignant masses, and some of them are included in the ultrasound (US) scores. The main aim of this work is to describe the ultrasound features of certain adnexal masses of difficult classification and to analyse them according to the most frequently used US scores. METHODS Retrospective studies of adnexal lesions are difficult to classify by US scores in women undergoing surgery. Ultrasound characteristics were analysed, and masses were classified according to the Subjective Assessment of the ultrasonographer (SA) and other US scores (IOTA Simple Rules Risk Assessment-SRRA, ADNEX model with and without CA125 and O-RADS). RESULTS A total of 133 adnexal masses were studied (benign: 66.2%, n:88; malignant: 33.8%, n:45) in a sample of women with mean age 56.5 ± 7.8 years. Malignant lesions were identified by SA in all cases. Borderline ovarian tumors (n:13) were not always detected by some US scores (SRRA: 76.9%, ADNEX model without and with CA125: 76.9% and 84.6%) nor were serous carcinoma (n:19) (SRRA: 89.5%), clear cell carcinoma (n:9) (SRRA: 66.7%) or endometrioid carcinoma (n:4) (ADNEX model without CA125: 75.0%). While most teratomas and serous cystadenomas have been correctly differentiated, other benign lesions were misclassified because of the presence of solid areas or papillae. Fibromas (n:13) were better identified by SA (23.1% malignancy), but worse with the other US scores (SRRA: 69.2%, ADNEX model without and with CA125: 84.6% and 69.2%, O-RADS: 53.8%). Cystoadenofibromas (n:10) were difficult to distinguish from malignant masses via all scores except SRRA (SA: 70.0%, SRRA: 20.0%, ADNEX model without and with CA125: 60.0% and 50.0%, O-RADS: 90.0%). Mucinous cystadenomas (n:12) were misdiagnosed as malignant in more than 15% of the cases in all US scores (SA: 33.3%, SRRA: 16.7%, ADNEX model without and with CA125: 16.7% and 16.7%, O-RADS:41.7%). Brenner tumors are also difficult to classify using all scores. CONCLUSION Some malignant masses (borderline ovarian tumors, serous carcinoma, clear cell carcinoma, endometrioid carcinomas) are not always detected by US scores. Fibromas, cystoadenofibromas, some mucinous cystadenomas and Brenner tumors may present solid components/papillae that may induce confusion with malignant lesions. Most teratomas and serous cystadenomas are usually correctly classified.
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Affiliation(s)
- Mar Pelayo
- Universitary Hospital HM Puerta del Sur, HM Rivas, 3428521 Madrid, Spain;
| | - Javier Sancho-Sauco
- Department of Obstetrics and Gynecology, Universitary Hospital Ramón y Cajal, Alcalá de Henares University, 3428034 Madrid, Spain; (J.S.-S.); (L.A.-M.)
| | | | - Belén Perez-Mies
- Department of Pathology, Universitary Hospital Ramón y Cajal, Alcalá de Henares University, 3428034 Madrid, Spain;
| | - Leopoldo Abarca-Martínez
- Department of Obstetrics and Gynecology, Universitary Hospital Ramón y Cajal, Alcalá de Henares University, 3428034 Madrid, Spain; (J.S.-S.); (L.A.-M.)
| | - Mª Jesús Cancelo-Hidalgo
- Department of Obstetrics and Gynecology, Universitary Hospital of Guadalajara, Alcalá de Henares University, 3428034 Madrid, Spain;
| | | | - Juan Luis Alcázar
- Department of Obstetrics and Gynecology, Clínica Universidad de Navarra, 3431008 Pamplona, Spain;
| | - Irene Pelayo-Delgado
- Department of Obstetrics and Gynecology, Universitary Hospital Ramón y Cajal, Alcalá de Henares University, 3428034 Madrid, Spain; (J.S.-S.); (L.A.-M.)
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Zuckerman AL, Pourvaziri A, Ebb DH, Boyraz B. Case 26-2023: A 15-Year-Old Girl with Abdominal Pain and an Ovarian Mass. N Engl J Med 2023; 389:750-758. [PMID: 37611126 DOI: 10.1056/nejmcpc2211422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]
Affiliation(s)
- Andrea L Zuckerman
- From the Department of Obstetrics and Gynecology, Tufts Medical Center (A.L.Z.), the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Massachusetts General Hospital, and the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Harvard Medical School - all in Boston
| | - Ali Pourvaziri
- From the Department of Obstetrics and Gynecology, Tufts Medical Center (A.L.Z.), the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Massachusetts General Hospital, and the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Harvard Medical School - all in Boston
| | - David H Ebb
- From the Department of Obstetrics and Gynecology, Tufts Medical Center (A.L.Z.), the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Massachusetts General Hospital, and the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Harvard Medical School - all in Boston
| | - Baris Boyraz
- From the Department of Obstetrics and Gynecology, Tufts Medical Center (A.L.Z.), the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Massachusetts General Hospital, and the Departments of Radiology (A.P.), Pediatrics (D.H.E.), and Pathology (B.B.), Harvard Medical School - all in Boston
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Reuter S, Schmalfeldt B, Haas SA, Zapf A, Cevirme S, Prieske K, Wölber L, Müller V, Zöllner C, Jaeger A. Impact of Introducing a PACU24 Concept on the Perioperative Outcome of Patients with Advanced Ovarian Cancer Treated with Cytoreductive Surgery. Geburtshilfe Frauenheilkd 2023; 83:1022-1030. [PMID: 37588253 PMCID: PMC10427201 DOI: 10.1055/a-2055-9349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 03/15/2023] [Indexed: 08/18/2023] Open
Abstract
Introduction Patients with ovarian cancer who undergo multivisceral surgery usually require intensive care monitoring postoperatively. In view of the ever-fewer numbers of high-care/intensive care beds and the introduction of fast-track treatment concepts, it is increasingly being suggested that these patients should be cared for postoperatively in 24-h Post Anesthesia Care Units (PACU24). No analyses have been carried out to date to investigate whether such a postoperative care concept might be associated with a potential increase in postoperative complications in this patient cohort. Methods A PACU24 unit was set up in our institution in 2015 and it has become the primary postoperative care pathway for patients with ovarian cancer who have undergone cytoreductive (debulking) surgery. A structured, retrospective analysis of data from patients treated before (control group) and after (PACU group) the introduction of this care concept was carried out, with a particular focus on postoperative complications and secondary admission to an intensive care unit where necessary. Results The data of 42 patients were analyzed for the PACU group and 45 patients for the control group. According to the analysis, the preoperative and surgical data of both groups were comparable (age, ASA, BMI, FIGO stage, duration of surgery, blood loss). The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM score) as a measure for the risk of postoperative complications was higher in the PACU group (11.1% vs. 9.7%, p = 0.001). Patients in the PACU group underwent bowel resection with anastomosis significantly more often (76.3% vs. 33.3%, p < 0.001), although the extent of surgery was otherwise comparable. The total number, type and severity of postoperative complications and the duration of the overall stay in hospital did not differ between the two groups. None of the patients required secondary transfer from the PACU or normal ward to an intensive care unit (ICU). Summary Our data support the assumption that the care concept of transferring patients to a PACU24 represents a safe and cost-saving care pathway for the postoperative care of patients even after complex gynecological-oncological procedures.
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Affiliation(s)
- Susanne Reuter
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Barbara Schmalfeldt
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Sebastian A. Haas
- Klinik und Poliklinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsmedizin Rostock, Rostock, Germany
| | - Antonia Zapf
- Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Sinan Cevirme
- Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Prieske
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Linn Wölber
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Volkmar Müller
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Zöllner
- Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Anna Jaeger
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
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Borella F, Fucina S, Mangherini L, Cosma S, Carosso AR, Cusato J, Cassoni P, Bertero L, Katsaros D, Benedetto C. Hormone Receptors and Epithelial Ovarian Cancer: Recent Advances in Biology and Treatment Options. Biomedicines 2023; 11:2157. [PMID: 37626654 PMCID: PMC10452581 DOI: 10.3390/biomedicines11082157] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/03/2023] [Accepted: 07/22/2023] [Indexed: 08/27/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is a significant cause of cancer-related mortality in women. Despite advances in diagnosis and treatment, EOC remains a challenging disease to manage, and the 5-year survival rate is still poor. The role of hormone receptors (HRs) in EOC carcinogenesis and prognosis has been actively explored; however, the role of hormone therapy (HT) in the treatment of these tumors is not well established. Most available data on HT mainly come from retrospective series and small early clinical trials. Several of these studies suggest that HT may have a role in adjuvant, maintenance therapy, or in the case of recurrent disease, especially for some subtypes of EOC (e.g., low-grade serous EOC). Furthermore, HT has recently been combined with targeted therapies, but most studies evaluating these combinations are still ongoing. The main aim of this review is to provide an overview of the progress made in the last decade to characterize the biological and prognostic role of HRs for EOC and the developments in their therapeutic targeting through HT.
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Affiliation(s)
- Fulvio Borella
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
| | - Stefano Fucina
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
| | - Luca Mangherini
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (L.M.); (P.C.); (L.B.)
| | - Stefano Cosma
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
| | - Andrea Roberto Carosso
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
| | - Jessica Cusato
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy;
| | - Paola Cassoni
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (L.M.); (P.C.); (L.B.)
| | - Luca Bertero
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (L.M.); (P.C.); (L.B.)
| | - Dionyssios Katsaros
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
| | - Chiara Benedetto
- Gynecology and Obstetrics 1U, Departments of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy; (S.F.); (S.C.); (A.R.C.); (D.K.); (C.B.)
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Dey G, Bharti R, Braley C, Alluri R, Esakov E, Crean-Tate K, McCrae K, Joehlin-Price A, Rose PG, Lathia J, Gong Z, Reizes O. LCK facilitates DNA damage repair by stabilizing RAD51 and BRCA1 in the nucleus of chemoresistant ovarian cancer. J Ovarian Res 2023; 16:122. [PMID: 37370140 PMCID: PMC10294509 DOI: 10.1186/s13048-023-01194-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
Poly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success of this therapy in the treatment of HR repair deficient cancers has not translated to HR-proficient cancers. Our studies identify the novel role of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in the regulation of HR repair in endometrioid epithelial ovarian cancer (eEOC) model. We show that DNA damage leads to direct interaction of LCK with the HR repair proteins RAD51 and BRCA1 in a kinase dependent manner RAD51 and BRCA1 stabilization. LCK expression is induced and activated in the nucleus in response to DNA damage insult. Disruption of LCK expression attenuates RAD51, BRCA1, and BRCA2 protein expression by hampering there stability and results in inhibition of HR-mediated DNA repair including suppression of RAD51 foci formation, and augmentation of γH2AX foci formation. In contrast LCK overexpression leads to increased RAD51 and BRCA1 expression with a concomitant increase in HR DNA damage repair. Importantly, attenuation of LCK sensitizes HR-proficient eEOC cells to PARP inhibitor in cells and pre-clinical mouse studies. Collectively, our findings identify a novel therapeutic strategy to expand the utility of PARP targeted therapy in HR proficient ovarian cancer.
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Affiliation(s)
- Goutam Dey
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Rashmi Bharti
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Chad Braley
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Ravi Alluri
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Emily Esakov
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Katie Crean-Tate
- Division of Gynecologic Cancer, Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Keith McCrae
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Case Comprehensive Cancer Center, Cleveland, OH, USA
| | | | - Peter G Rose
- Division of Gynecologic Cancer, Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Justin Lathia
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Zihua Gong
- Case Comprehensive Cancer Center, Cleveland, OH, USA
- Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ofer Reizes
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
- Case Comprehensive Cancer Center, Cleveland, OH, USA.
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Ronsini C, Pasanisi F, Molitierno R, Iavarone I, Vastarella MG, De Franciscis P, Conte C. Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:3831. [PMID: 37298026 PMCID: PMC10253482 DOI: 10.3390/jcm12113831] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/16/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023] Open
Abstract
Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.
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Affiliation(s)
- Carlo Ronsini
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Francesca Pasanisi
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Rossella Molitierno
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Irene Iavarone
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Maria Giovanna Vastarella
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Pasquale De Franciscis
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie n.1, 80122 Naples, Italy; (C.R.); (R.M.); (I.I.); (M.G.V.); (P.D.F.)
| | - Carmine Conte
- Dipartimento Salute della Donna e del Bambino, Fondazione Universitaria Policlinico A. Gemelli, Largo Agostino Gemelli, 8, 00168 Rome, Italy;
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Di Nisio V, Antonouli S, Colafarina S, Zarivi O, Rossi G, Cecconi S, Poma AMG. Repeated Rounds of Gonadotropin Stimulation Induce Imbalance in the Antioxidant Machinery and Activation of Pro-Survival Proteins in Mouse Oviducts. Int J Mol Sci 2023; 24:ijms24119294. [PMID: 37298244 DOI: 10.3390/ijms24119294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/14/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Controlled ovarian stimulation (COS) through gonadotropin administration has become a common procedure in assisted reproductive technologies. COS's drawback is the formation of an unbalanced hormonal and molecular environment that could alter several cellular mechanisms. On this basis, we detected the presence of mitochondrial DNA (mtDNA) fragmentation, antioxidant enzymes (catalase; superoxide dismutases 1 and 2, SOD-1 and -2; glutathione peroxidase 1, GPx1) and apoptotic (Bcl-2-associated X protein, Bax; cleaved caspases 3 and 7; phosphorylated (p)-heat shock protein 27, p-HSP27) and cell-cycle-related proteins (p-p38 mitogen-activated protein kinase, p-p38 MAPK; p-MAPK activated protein kinase 2, p-MAPKAPK2; p-stress-activated protein kinase/Jun amino-terminal kinase, p-SAPK/JNK; p-c-Jun) in the oviducts of unstimulated (Ctr) and repeatedly hyperstimulated (eight rounds, 8R) mice. While all the antioxidant enzymes were overexpressed after 8R of stimulation, mtDNA fragmentation decreased in the 8R group, denoting a present yet controlled imbalance in the antioxidant machinery. Apoptotic proteins were not overexpressed, except for a sharp increase in the inflammatory-related cleaved caspase 7, accompanied by a significant decrease in p-HSP27 content. On the other hand, the number of proteins involved in pro-survival mechanisms, such as p-p38 MAPK, p-SAPK/JNK and p-c-Jun, increased almost 50% in the 8R group. Altogether, the present results demonstrate that repeated stimulations cause the activation of the antioxidant machinery in mouse oviducts; however, this is not sufficient to induce apoptosis, and is efficiently counterbalanced by activation of pro-survival proteins.
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Affiliation(s)
- Valentina Di Nisio
- Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, SE-14186 Stockholm, Sweden
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-14186 Stockholm, Sweden
| | - Sevastiani Antonouli
- Department of Clinical Chemistry, Faculty of Medicine, University of Ioannina, PC-45110 Ioannina, Greece
| | - Sabrina Colafarina
- Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy
| | - Osvaldo Zarivi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy
| | - Gianna Rossi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy
| | - Sandra Cecconi
- Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy
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Song K, Artibani M. The role of DNA methylation in ovarian cancer chemoresistance: A narrative review. Health Sci Rep 2023; 6:e1235. [PMID: 37123549 PMCID: PMC10140645 DOI: 10.1002/hsr2.1235] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 05/02/2023] Open
Abstract
Background and Aims Ovarian cancer (OC) is the most lethal gynecological cancer. In 2018, it was responsible for over 180,000 deaths worldwide. The high mortality rate is the culmination of a lack of early diagnosis and high rates of chemotherapy resistance, which is synonymous with disease recurrence. Over the last two decades, an increasingly significant role of epigenetic mechanisms, in particular DNA methylation, has emerged. This review will discuss several of the most significant genes whose hypo/hypermethylation profiles are associated with chemoresistance. Aside from functionally elucidating and evaluating these epimutations, this review will discuss recent trials of DNA methyltransferase inhibitors (DNMTi). Finally, we will propose future directions that could enhance the feasibility of utilizing these candidate epimutations as clinical biomarkers. Methods To perform this review, a comprehensive literature search based on our keywords was conducted across the online databases PubMed and Google Scholar for identifying relevant studies published up until August 2022. Results Epimutations affecting MLH1, MSH2, and Ras-association domain family 1 isoform A (DNA damage repair and apoptosis); ATP-binding cassette subfamily B member 1 and methylation-controlled J (drug export); secreted frizzled-related proteins (Wnt/β-catenin signaling), neurocalcin delta (calcium and G protein-coupled receptor signaling), and zinc finger protein 671 all have potential as biomarkers for chemoresistance. However, specific uncertainties relating to these epimutations include histotype-specific differences, intrinsic versus acquired chemoresistance, and the interplay with complete surgical debulking. DNMTi for chemoresistant OC patients has shown some promise; however, issues surrounding their efficacy and dose-limiting toxicities remain; a personalized approach is required to maximize their effectiveness. Conclusion Establishing a panel of aberrantly methylated chemoresistance-related genes to predict chemoresponsiveness and patients' suitability to DNMTi could significantly reduce OC recurrence, while improving DNMTi therapy viability. To achieve this, a large-scale prospective genome-wide DNA methylation profile study that spans different histotypes, includes paired samples (before and after chemotherapy), and integrates transcriptomic and methylomic analysis, is warranted.
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Affiliation(s)
- Kaiyang Song
- Green Templeton CollegeUniversity of OxfordOxfordUK
| | - Mara Artibani
- Ovarian Cancer Cell Laboratory, Medical Research Council (MRC) Weatherall Institute of Molecular MedicineUniversity of OxfordOxfordUK
- Nuffield Department of Women's & Reproductive HealthUniversity of OxfordOxfordUK
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Pelayo M, Pelayo-Delgado I, Sancho-Sauco J, Sanchez-Zurdo J, Abarca-Martinez L, Corraliza-Galán V, Martin-Gromaz C, Pablos-Antona MJ, Zurita-Calvo J, Alcázar JL. Comparison of Ultrasound Scores in Differentiating between Benign and Malignant Adnexal Masses. Diagnostics (Basel) 2023; 13:diagnostics13071307. [PMID: 37046525 PMCID: PMC10093240 DOI: 10.3390/diagnostics13071307] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/26/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Subjective ultrasound assessment by an expert examiner is meant to be the best option for the differentiation between benign and malignant adnexal masses. Different ultrasound scores can help in the classification, but whether one of them is significantly better than others is still a matter of debate. The main aim of this work is to compare the diagnostic performance of some of these scores in the evaluation of adnexal masses in the same set of patients. This is a retrospective study of a consecutive series of women diagnosed as having a persistent adnexal mass and managed surgically. Ultrasound characteristics were analyzed according to IOTA criteria. Masses were classified according to the subjective impression of the sonographer and other ultrasound scores (IOTA simple rules -SR-, IOTA simple rules risk assessment -SRRA-, O-RADS classification, and ADNEX model -with and without CA125 value-). A total of 122 women were included. Sixty-two women were postmenopausal (50.8%). Eighty-one women had a benign mass (66.4%), and 41 (33.6%) had a malignant tumor. The sensitivity of subjective assessment, IOTA SR, IOTA SRRA, and ADNEX model with or without CA125 and O-RADS was 87.8%, 66.7%, 78.1%, 95.1%, 87.8%, and 90.2%, respectively. The specificity for these approaches was 69.1%, 89.2%, 72.8%, 74.1%, 67.9%, and 60.5%, respectively. All methods with similar AUC (0.81, 0.78, 0.80, 0.88, 0.84, and 0.75, respectively). We concluded that IOTA SR, IOTA SRRA, and ADNEX models with or without CA125 and O-RADS can help in the differentiation of benign and malignant masses, and their performance is similar to the subjective assessment of an experienced sonographer.
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Affiliation(s)
- Mar Pelayo
- Department of Radiology, Hospital HM Puerta del Sur, 28938 Móstoles, Spain;
- Department of Radiology, Hospital HM Rivas, 28521 Madrid, Spain
| | - Irene Pelayo-Delgado
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
- Correspondence: (I.P.-D.); (J.L.A.)
| | - Javier Sancho-Sauco
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | | | - Leopoldo Abarca-Martinez
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | - Virginia Corraliza-Galán
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | - Carmen Martin-Gromaz
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | - María Jesús Pablos-Antona
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | - Julia Zurita-Calvo
- Department of Obstetrics and Gynecology, Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.S.-S.); (L.A.-M.); (V.C.-G.); (C.M.-G.); (M.J.P.-A.); (J.Z.-C.)
| | - Juan Luis Alcázar
- Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, 31008 Pamplona, Spain
- Correspondence: (I.P.-D.); (J.L.A.)
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Luo HJ, Hu ZD, Cui M, Zhang XF, Tian WY, Ma CQ, Ren YN, Dong ZL. Diagnostic performance of CA125, HE4, ROMA, and CPH-I in identifying primary ovarian cancer. J Obstet Gynaecol Res 2023; 49:998-1006. [PMID: 36609691 DOI: 10.1111/jog.15540] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 12/25/2022] [Indexed: 01/09/2023]
Abstract
AIMS To evaluate the ability of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), and Copenhagen Index (CPH-I) to identify primary ovarian cancer (OC) from borderline and benign ovarian tumors (OTs) and explore ideal cutoff points. METHODS A total of 684 OTs containing 276 OC patients, 116 ovarian borderline OTs and 292 benign OTs patients who underwent surgery in our hospital were included. We retrospectively searched the results of CA125 and HE4 before patients' surgery from the hospital's electronic medical records system. ROMA and CPH-I were calculated according to their menopausal status and age, respectively. Diagnostic performance of these four were assessed by drawing receiver operating characteristic (ROC) curves. RESULTS CA125, HE4, ROMA, and CPH-I were all significantly higher in OC women compared with borderline OTs (p < 0.001), followed by benign OTs (p < 0.001). Area under the curves (AUCs) for distinguishing OC were 0.850 (0.818-0.882), 0.891 (0.865-0.916), 0.910 (0.888-0.933) and 0.906 (0.882-0.930), respectively, and the corresponding ideal cutoff values for CA125, HE4, ROMA, and CPH-I were 132.5, 68.6, 23.8, and 6.4, respectively. The difference between ROMA and CPH-I was not significant (p = 0.97), but both were higher than CA125 and HE4 (p < 0.05). HE4 showed a significantly higher AUC than CA125 (p < 0.05). For postmenopausal women, CA125 performed equivalently to ROMA (p = 0.73) and CPH-I (p = 0.91). CONCLUSIONS In identifying patients with OC, ROMA and CPH-I outperformed single tumor marker. The diagnostic performance of HE4 was significantly higher than that of CA125. CA125 was more suitable for postmenopausal women.
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Affiliation(s)
- Hui-Jing Luo
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhi-Dong Hu
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Cui
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Xiao-Fang Zhang
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Wen-Yan Tian
- Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao-Qun Ma
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Ya-Nv Ren
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Zuo-Liang Dong
- Department of Clinical Laboratory Center, Tianjin Medical University General Hospital, Tianjin, China
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Sharma T, Nisar S, Masoodi T, Macha MA, Uddin S, Akil AAS, Pandita TK, Singh M, Bhat AA. Current and emerging biomarkers in ovarian cancer diagnosis; CA125 and beyond. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 133:85-114. [PMID: 36707207 DOI: 10.1016/bs.apcsb.2022.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Ovarian cancer (OC) is one of the most common causes of cancer-related death in women worldwide. Its five-year survival rates are worse than the two most common gynecological cancers, cervical and endometrial. This is because it is asymptomatic in the early stages and usually detected in the advanced metastasized stage. Thus, survival is increasingly dependent on timely diagnosis. The delay in detection is contributed partly by the occurrence of non-specific clinical symptoms in the early stages and the lack of effective biomarkers and detection approaches. This underlines the need for biomarker identification and clinical validation, enabling earlier diagnosis, effective prognosis, and response to therapy. Apart from the traditional diagnostic biomarkers for OC, several new biomarkers have been delineated using advanced high-throughput molecular approaches in recent years. They are currently being clinically evaluated for their true diagnostic potential. In this chapter, we document the commonly utilized traditional screening markers and recently identified emerging biomarkers in OC diagnosis, focusing on secretory and protein biomarkers. We also briefly reviewed the recent advances and prospects in OC diagnosis.
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Affiliation(s)
- Tarang Sharma
- Department of Medical Oncology, Dr. B.R Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Sabah Nisar
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Tariq Masoodi
- Laboratory of Cancer immunology and genetics, Sidra Medicine, Doha, Qatar
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Jammu and Kashmir, India
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar; Laboratory Animal Research Center, Qatar University, Doha, Qatar
| | - Ammira Al-Shabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Tej K Pandita
- Center for Genomics and Precision Medicine, Texas A&M College of Medicine, Houston, TX, United States
| | - Mayank Singh
- Department of Medical Oncology, Dr. B.R Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
| | - Ajaz A Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
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Mirzaoglu M, Yavuzkir S, Mirzaoglu C, Yurt N, Dagli AF, Ozcan Yildirim S, Sahin İ, Aydin S. Use of asprosin and subfatin for differential diagnosis of serous ovarian tumors. Biotech Histochem 2023; 98:140-146. [PMID: 36281766 DOI: 10.1080/10520295.2022.2135763] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Asprosin (ASP) and subfatin are hormones that regulate glucose metabolism. The role of ASP and subfatin in serous ovarian tumors has not been investigated. We investigated the expression of subfatin and asprosin in 30 serous benign, 30 serous borderline, 30 malignant and 30 control ovarian tissues. We investigated ASP and subfatin immunoreactivity and quantification was achieved using an ELISA method. ASP and subfatin were localized in the epithelial parts of normal ovarian tissues; however, in cancer tissues, immunoreactivity was detected in the parenchymal areas. Biochemical analysis of ovarian tissues revealed significantly decreased ASP and subfatin compared to the control. We propose that ASP and subfatin are promising candidates for biomarkers to distinguish serous benign, serous borderline and malignant ovarian cancers.
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Affiliation(s)
- Miyase Mirzaoglu
- Department of Obstetrics and Gynecology, Medical School, Firat University, Elazig, Turkey
| | - Seyda Yavuzkir
- Department of Obstetrics and Gynecology, Medical School, Firat University, Elazig, Turkey
| | - Cetin Mirzaoglu
- Department of Cardiology, Elazig Fethi Sekin City Hospital, Health Science University, Elazig, Turkey
| | - Nurdan Yurt
- Department of Obstetrics and Gynecology, Medical School, Firat University, Elazig, Turkey
| | | | - Sena Ozcan Yildirim
- Department of Histology and Embryology, Medical School, Firat University, Elazig, Turkey
| | - İbrahim Sahin
- Department of Medical Biology, Medical School, Erzincan Binali Yildirim University, Erzincan, Turkey.,Department of Medical Biochemistry and Clinical Biochemistry, Firat Hormones Research Group, Medical School, Firat University, Elazig, Turkey
| | - Suleyman Aydin
- Department of Medical Biochemistry and Clinical Biochemistry, Firat Hormones Research Group, Medical School, Firat University, Elazig, Turkey
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Xu L, Lee SI, Kilcoyne A. MR Imaging of Epithelial Ovarian Neoplasms Part II. Magn Reson Imaging Clin N Am 2023; 31:53-64. [DOI: 10.1016/j.mric.2022.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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48
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Hu Y, Chen B, Dong H, Sheng B, Xiao Z, Li J, Tian W, Lv F. Comparison of ultrasound-based ADNEX model with magnetic resonance imaging for discriminating adnexal masses: a multi-center study. Front Oncol 2023; 13:1101297. [PMID: 37168367 PMCID: PMC10165107 DOI: 10.3389/fonc.2023.1101297] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 04/03/2023] [Indexed: 05/13/2023] Open
Abstract
Objectives The ADNEX model offered a good diagnostic performance for discriminating adnexal tumors, but research comparing the abilities of the ADNEX model and MRI for characterizing adnexal tumors has not been reported to our knowledge. The aim of this study was to evaluate the diagnostic accuracy of the ultrasound-based ADNEX (Assessment of Different NEoplasias in the adneXa) model in comparison with that of magnetic resonance imaging (MRI) for differentiating benign, borderline and malignant adnexal masses. Methods This prospective study included 529 women with adnexal masses who underwent assessment via the ADNEX model and subjective MRI analysis before surgical treatment between October 2019 and April 2022 at two hospitals. Postoperative histological diagnosis was considered the gold standard. Results Among the 529 women, 92 (17.4%) masses were diagnosed histologically as malignant tumors, 67 (12.7%) as borderline tumors, and 370 (69.9%) as benign tumors. For the diagnosis of malignancy, including borderline tumors, overall agreement between the ADNEX model and MRI pre-operation was 84.9%. The sensitivity of the ADNEX model of 0.91 (95% confidence interval [CI]: 0.85-0.95) was similar to that of MRI (0.89, 95% CI: 0.84-0.94; P=0.717). However, the ADNEX model had a higher specificity (0.90, 95% CI: 0.87-0.93) than MRI (0.81, 95% CI: 0.77-0.85; P=0.001). The greatest sensitivity (0.96, 95% CI: 0.92-0.99) and specificity (0.94, 95% CI: 0.91-0.96) were achieved by combining the ADNEX model and subjective MRI assessment. While the total diagnostic accuracy did not differ significantly between the two methods (P=0.059), the ADNEX model showed greater diagnostic accuracy for borderline tumors (P<0.001). Conclusion The ultrasound-based ADNEX model demonstrated excellent diagnostic performance for adnexal tumors, especially borderline tumors, compared with MRI. Accordingly, we recommend that the ADNEX model, alone or with subjective MRI assessment, should be used for pre-operative assessment of adnexal masses.
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Affiliation(s)
- Yanli Hu
- Department of Ultrasonography, Chongqing Health Center for Women and Children, Chongqing, China
- Department of Ultrasonography, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bo Chen
- Department of Ultrasonography, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongmei Dong
- Department of Ultrasonography, Chongqing Health Center for Women and Children, Chongqing, China
- Department of Ultrasonography, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Furong Lv, ; Hongmei Dong,
| | - Bo Sheng
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhibo Xiao
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia Li
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Tian
- Department of Radiology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- Department of Radiology, Chongqing Health Center for Women and Children, Chongqing, China
| | - Furong Lv
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Furong Lv, ; Hongmei Dong,
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Israelsson P, Björk E, Nagaev I, Nagaeva O, Lundin E, Mincheva-Nilsson L, Ottander U. NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer. Am J Reprod Immunol 2023; 89:e13647. [PMID: 36335434 PMCID: PMC10077899 DOI: 10.1111/aji.13647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/28/2022] [Accepted: 10/26/2022] [Indexed: 11/07/2022] Open
Abstract
PROBLEM Tumors compromise the patients' immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome-induced impairment of NKG2D cytotoxicity in HGSC. METHOD OF STUDY Paired pre- and post-operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D-mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture-derived exosomes, previously studied by us, were used for comparison. RESULTS HGSC exosomes from patients' sera downregulated NKG2D-mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D-mediated cytotoxic response of the HGSC patients' own NK cells in postoperative compared to preoperative samples was noted. CONCLUSIONS Surgical removal of the primary tumor has a beneficial effect, relieving the exosome-mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.
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Affiliation(s)
- Pernilla Israelsson
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.,Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden.,Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Emma Björk
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.,Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden
| | - Ivan Nagaev
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden
| | - Olga Nagaeva
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden
| | - Eva Lundin
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Lucia Mincheva-Nilsson
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden
| | - Ulrika Ottander
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden
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Rizzuto I, Slade L, Yanling Y, Oehler MK. Synchronous Urinary Bladder Urothelial Carcinoma and Transitional Cell Carcinoma of the Ovary: A Case Report. Case Rep Oncol 2023; 16:912-918. [PMID: 37900783 PMCID: PMC10601757 DOI: 10.1159/000533269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 07/13/2023] [Indexed: 10/31/2023] Open
Abstract
Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian tumours defined as a tumour composed of epithelial elements, histologically resembling urothelium and its neoplasms. Ovarian metastases from primary urinary tract carcinomas are rare. The differential diagnosis of primary TCC of the ovary versus metastatic bladder TCC is challenging because of histological similarity. We present the case of a 49-year-old premenopausal woman who was initially diagnosed with non-invasive papillary urothelial carcinoma of bladder (NIPUC) and after 2 years with a synchronous TCC of the ovary while being investigated for suspected relapse. She underwent a radical cystectomy, total hysterectomy, bilateral salpingo-oopharectomy, and pelvic lymph node dissection. The final diagnosis of synchronous NIPUC of the bladder and TCC of the ovary was made by histopathology and immunohistochemical studies.
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Affiliation(s)
- Ivana Rizzuto
- Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Laura Slade
- Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Yang Yanling
- Department of Anatomical Pathology, SA Pathology, Flinders Medical Centre, Bedford Park Adelaide, Bedford Park, SA, Australia
| | - Martin Klaus Oehler
- Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia
- Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
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