Biomarker-Based Models for Preoperative Assessment of Adnexal Mass: A Multicenter Validation Study

Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50

Internal Iliac Artery Ligation in Obstetrics and Gynecology: Surgical Anatomy and Surgical Considerations

The internal iliac artery (IIA) is the main arterial vessel of the pelvis. It supplies the pelvic viscera, pelvic walls, perineum, and gluteal region. In cases of severe obstetrical or gynecologic hemorrhage, IIA ligation can be a lifesaving procedure. Regrettably, IIA ligation has not gained widespread popularity, primarily due to limited surgical training and concerns regarding possible complications, including buttock claudication, impotence, and urinary bladder and rectum necroses. Nowadays, selective arterial embolization or temporary balloon occlusion are increasingly utilized alternatives, which can be applied preoperatively or intraoperatively for threatening severe genital or pelvic bleeding. However, IIA ligation retains its relevance, as the previously described procedures are not always available and have limitations. This article provides a step-by-step guide to the IIA ligation procedure and its possible complications. It also includes a detailed description of the anatomy of the IIA and pelvic arterial anastomoses. This review highlights the importance of a thorough understanding of pelvic anatomy as a prerequisite for safe IIA ligation and posits that training in this procedure should be an integral part of obstetrics and gynecology curricula

Long-term quality of life assessment after excisional treatment for cervical dysplasia

We evaluated factors influencing long-term health-related quality of life (HRQoL) after excisional treatments of low- and high grade squamous intraepithelial cervical lesions (SIL) in three groups of women (n = 160): nulliparas interested in reproduction (A), parous women interested in reproduction (B) and women without pregnancy desire (C). The HRQoL was assessed using the disease-specific FACIT-CD and the generic SF36v2 questionnaires. Anxiety and depression were evaluated by Beck’s inventories. After median follow-up of 5 (2–18) years, FACIT-CD total score and the score for Emotional Well-Being (EWB) were significantly lower in group A. The total, EWB and REL (Relationships) scores of FACIT-CD were the highest in group B. Women operated for HSIL demonstrated lower REL quality in comparison to those with LSIL. Neither SF36v2 nor FACIT-CD total scores differed in relation to SIL grade or type of excision. ‘SF36v2 Mental Component Summary Score’ and ‘being parous and interested in fertility’ were independent predictors of disease-specific FACIT-CD score.Impact Statement What is already known on this subject? Long-term consequences of excisional treatments for cervical dysplasia on health-related quality of life (HRQoL) are not well reported. What do the results of this study add? Our study provides data on HRQoL in women treated with large loop excision of the transformation zone (LLETZ) or cold knife conization (CKC) obtained during the longest (median 5 years) follow-up as reported to date. We were able to show that having children and planning further pregnancies positively influenced HRQoL in these patients. In addition, we identified nulliparas with pregnancy desire as psychologically the most vulnerable group within the studied cohort. What are the implications of these findings for clinical practice and/or further research? Even several years after LLETZ or CKC, women may suffer from impaired Emotional Well-Being and reduced HRQoL. Awareness and assessment of these long-term consequences should be part of surveillance after excisional treatments for cervical dysplasia

Association of Macronutrients Composition, Physical Activity and Serum Androgen Concentration in Young Women with Polycystic Ovary Syndrome

The roles of dietary macronutrients and physical activity (PA) in patients with PCOS have not been sufficiently reported, especially in adolescent girls. To address this knowledge gap, we evaluated the associations between serum concentrations of total testosterone (tT), free testosterone (fT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and dietary macronutrients intake as well as different types and levels of PA. The study population consisted of 96 girls of Caucasian ancestry, aged 14–18 years: 61 participants with polycystic ovary syndrome (PCOS) and 35 healthy controls. Serum tT, fT, A, DHEA-S, and SHBG were determined in fasting blood. Macronutrient intake and PA levels were assessed by using the three-day food record method and the Beliefs and Eating Habits Questionnaire (KomPAN), respectively. We found several positive correlations between dietary macronutrients such as total fat, saturated fatty acids (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and hormonal parameters across the entire cohort and in healthy girls. A positive correlation between SHBG and total protein consumption as well as an inverse correlation between SHBG and carbohydrate intake could be determined. No correlation between androgens and macronutrients was found in the PCOS group. In contrast, we observed an inverse correlation between androgen concentrations (except of DHEA-S) and “work/school” and/or “leisure time” PA only in PCOS patients. Moreover, the hormone levels differed according to PA intensity. In conclusion, the impact of diet and PA was strikingly different in adolescents with and without PCOS. These findings indicate that disturbed hormonal homeostasis in PCOS, at least in the youngest patients, likely “overtrump” dietary influences, and otherwise, PA offers a therapeutic potential that requires further evaluation of the long-term effects in randomized studies. (ClinicalTrial.gov Identifier: NCT04738409.

Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes

Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis

Paraaortic Lymphadenectomy in Gynecologic Oncology—Significance of Vessels Variations

Lymphadenectomy has been an essential part of the surgical treatment in surgical oncology, as the lymphatic channels and nodes are the main dissemination pathway for most of the gynecological cancers. Pelvic and paraaortic lymphadenectomy are frequent surgical procedures in gynecologic oncology. Paraaortic lymph node dissection facilitates staging, prognosis, surgical and postoperative management of patients. It is one of the most challenging retroperitoneal surgeries. A comprehensive knowledge of the paraaortic region is mandatory. Intraoperative bleeding is the most common complication during lymphadenectomy due to direct vascular injury, poor tissue handling, exuberant retraction and possible anatomical variations of the vessels in the paraaortic region. Approximately, one-third of women will have at least one anatomic variation in the paraaortic region. It must be stressed that anomalous vessels may be encountered in every woman who will undergo surgery. Consequently, detailed knowledge of anatomical vessels variations is required in order to prevent iatrogenic vessel injury. The importance of these variations is well described in urology, vascular and general surgery. Conversely, in oncogynecological surgery, there are few articles, which described some of the vessels variations in the paraaortic region. The present article aims to propose a surgical classification and to describe the majority of vessels variation, which could be encountered during paraaortic lymphadenectomy in gynecologic oncology. Moreover, surgical considerations in order to prevent anomalous vessels injury are well described

New Aspects of Sarcomas of Uterine Corpus—A Brief Narrative Review

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma

New Aspects of Sarcomas of Uterine Corpus—A Brief Narrative Review

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma