Update on imaging of ovarian cancer

This review will make familiar with new concepts in ovarian cancer and their impact on radiological practice. Disseminated peritoneal spread and ascites are typical of the most common (70–80 %) cancer type, highgrade serous ovarian cancer. Other cancer subtypes differ in origin, precursors, and imaging features. Expert sonography allows excellent risk assessment in adnexal masses. Owing to its high specificity, complementary MRI improves characterization of indeterminate lesions. Major changes in the new FIGO staging classification include fusion of fallopian tube and primary ovarian cancer and the subcategory stage IIIA1 for retroperitoneal lymph node metastases only. Inguinal lymph nodes, cardiophrenic lymph nodes, and umbilical metastases are classified as distant metastases (stage IVB). In multidisciplinary conferences (MDC), CT has been used to predict the success of cytoreductive surgery. Resectability criteria have to be specified and agreed on in MDC. Limitations in detection of metastases may be overcome using advanced MRI techniques.

Ovarian sertoli-leydig cell tumour with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alphafetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrineinactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

Post-menopausal metrorrhagia - an ovarian thecoma presentation

Os tecomas são tumores raros do ovário, do grupo dos tumores dos cordões sexuais, de natureza sólida e frequentemente unilaterais. Têm maior incidência no período pósmenopausa e normalmente são silenciosos. Quando sintomáticos traduzem-se por dor pélvica e metrorragia (condicionada pela habitual natureza produtora de estrogénios do tumor). Podem ser concomitantes a síndrome de Meigs e/ou de Golin-Goltz e associaremse a transformação benigna ou maligna do endométrio. Embora a ecografia possa ser inespecífica neste contexto, uma avaliação multiparamétrica abrangente em ressonância magnética, incluindo por estudo dinâmico e com ponderação em difusão, permite frequentemente orientar de modo favorável a marcha diagnóstica. Apresentamos um caso raro de tecoma do ovário, com espessamento associado do endométrio, avaliado por ecografia ginecológica por vias supra-púbica e transvaginal bem como tomografia computorizada e ressonância magnética, confirmado cirurgicamente. Tratou-se de uma examinada caucasiana de 61 anos de idade, apresentando-se com metrorragia pósmenopáusica, sem outros sintomas nem contexto familiar relevante. Procedeu-se, a este propósito, a uma revisão da literatura focada no diagnóstico multimodal diferencial, apresentação clínica, tratamento e prognóstico destes tumores.

Papillary carcinoma arising in struma ovarii versus ovarian metastasis from primary thyroid carcinoma: a case report and review of the literature

We present a case of a postmenopausal woman diagnosed with an ovarian mass containing thyroid follicles and foci of papillary thyroid carcinoma during pathological examination. This patient referred having had a metachronous thyroid malignancy 10 years before. The differential diagnosis between a thyroid malignancy arising from a struma ovarii and a metastatic ovarian tumor originating from thyroid-cancer is challenging. Struma ovarii should be considered when thyroid components are the predominant element or when thyroid malignant tissue is identified within an ovarian lesion. Thyroid carcinoma arising from a struma ovarii is reported to occur in a minority of cases. Of these, papillary carcinoma is the most frequent subtype encountered. Regarding primary thyroid carcinomas, papillary carcinomas have a lower metastatic potential when compared to follicular carcinomas, and most of the metastases occur in the cervical lymph nodes. Ovarian metastases are exceedingly rare and generally associated with widespread disease. However, they must be considered in the presence of previous history of malignant thyroid carcinoma. The authors review the main clinical, imaging and therapeutic aspects of both these entities and present the most likely diagnosis.

Severe viral hepatitis in a patient with chronic lymphocytic leukemia (CLL) complicated with autoimmune hemolytic anemia (AIHA), treated with steroids.

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Association of follicle stimulating hormone receptor promoter with ovarian response in IVF-ET patients

Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor (FSHR) gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response. Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response. Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone (FSH) receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses. Results: With a mutation rate of 40%, 63 in 158 cases showed a 29th site G→A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group (60% versus 23.9%; χ2=21.450, p<0.001). Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability (t=0.457, p=0.324) in the basic FSH values between the two groups (normal group, 7.2±2.3 U/L; mutation group, 7.1±2.0 U/L). Conclusion: The activity of FSHR promoter is significantly affected by the 29th site G→A mutation that will weaken promoter activity and result in poor response to FSH.

No relationship between most polymorphisms of steroidogenic acute regulatory (StAR) gene with polycystic ovarian syndrome

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine women’s disorders in reproductive age. Hyperandrogenism has a critical role in the etiology of PCOS and it can cause fault in Steroidogenesis process. During steroidogenesis, steroidogenic acute regulatory protein (StAR) seems to increase the delivery of cholesterol through mitochondrial membrane. Therefore, polymorphisms of StAR might effect on this protein and play a role in the etiology of PCOS. Objective: The aim of this study was to investigate the association between StAR SNPs with PCOS. Thus, seven polymorphisms in this gene: rs104894086, rs104894089, rs104894090, rs137852689, rs10489487, rs104894085 were detected. Materials and Methods: In this case control study, 45 PCOS women, 40 male factor/unexplained infertile women, and 40 fertile women as two control groups were participated from 2008-2012. Polymorphisms were detected using restriction fragment length polymorphism (PCR-RFLP) method. Results: Heterozygote genotyping for rs137852689 SNP (amino acid 218 C > T) was only seen in seven PCOS patients, one in normal ovulatory women, and five in male factor/unexplained infertile women (15.5%, 2.5%, 12.5%, respectively) (p= 0.12). While, it has shown no association between other SNPS with PCOs. Conclusion: The RFLP results for seven chosen SNPs, which located in exon 5 and 7 showed normal status in three groups, it means no heterozygous or homozygous forms of selected SNPs were observed. So, it seems evaluation of the active amino acid sites should be investigated and also the study population should be increased.

Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw) of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH), follicular stimulating hormone (FSH), Luteinal hormone (LH), estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05). Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

Restricted intake and lipid inclusion: effects on ovarian follicular development in Santa Inês ewe lambs.

The reproductive efficiency is directly related to the nutritional management. The diet lipid inclusion, especially with enhanced sources of omega 6 and omega 3 fatty acids, is positively associated to the ovarian follicular development of ruminants. The objective of this study was to evaluate the effects of toasted soybean grain addition on restricted or ad libitum feeding on ovarian follicular development of Santa Inês ewe lambs In conclusion, the diameter of the largest follicle and the number of >5 mm follicles were not influenced by the restricted intake diet nor the lipid inclusion; however, they increased in a direct relationship with the age of the animals.

Female melanoma: the role of ovarian stimulation and antioestrogens cancer therapy A retrospective study with immunohistochemical oestrogen receptors alpha and beta analysis.

Cutaneous melanoma (CM) represents the third most common cancer in Italian women under 49 years old. In the last decades, many molecular studies confirmed that sex hormones have a part in melanogenesis and melanoma genesis. However, many controversies are present regarding the role of exogenous oestrogens intake and endogenous hormonal status in female melanoma. Our study's primary objective is to investigate the features of melanoma in women of fertile age and women in postmenopausal age. The secondary aim is to evaluate the expression of ERα and ERβ by immunohistochemical analysis in women who underwent ovarian stimulation for medically assisted procreation and in women in cancer therapy for breast cancer (BC) comparing to two control groups. The tertiary objective is to correlate ERα and ERβ with the Breslow thickness and other relevant histopathological, clinical and dermoscopic characteristics Results A total of 998 women were included in the study. Women in fertile age are significantly more prone to have CM on the trunk. Conversely, postmenopausal females are more likely to develop CM on acral locations. Breslow thickness and ulceration were statistically significant among postmenopausal women (P-value <0,001). In the group for women with a history of breast cancer (BC), we observed a significantly higher CM percentage with “non-brisk” TILs. Upon immunohistochemical analysis, most cases with inhibitor aromatase therapy displayed a strong cytoplasmatic ERα positivity. Upon the Pearson correlation analysis, no association was shown between nuclear ERβ and Breslow thickness. The meaning of cytoplasmatic ERα in melanoma is still debated. It could suggest a potentially significant role of oestrogen non-genomic pathway in these patients, or it can be a mechanism of ERs modulation in response to aromatase inhibitor therapy. Our work tried to enlighten some of the existing shadows on the role of ERs and hormonal factors in CM.

Chemo-physical and biological mechanisms behind the anticancer activity of plasma activated Ringer's Lactate solution for the treatment of peritoneal carcinosis from primitive epithelial ovarian/tubular tumor

Cancer research and development of targeting agents in this field is based on robust studies using preclinical models. The failure rate of standardized treatment approaches for several solid tumors has led to the urgent need to fine-tune more sophisticated and faithful preclinical models able to recapitulate the features of in vivo human tumors, with the final aim to shed light on new potential therapeutic targets. Epithelial Ovarian Cancer (EOC) serous histotype (HGSOC) is one of the most lethal diseases in women due to its high aggressiveness (75% of patients diagnosed at FIGO III-IV state) and poor prognosis (less of 50% in 5 years), whose therapy often fails as chemoresistance sets in. This thesis aimed at using the novel perfusion-based bioreactor U-CUP that provides direct perfusion throughout the tumor tissue seeking to obtain an EOC 3D ex vivo model able to recapitulate the features of the original tumor including the tumor microenvironment and maintaining its cellular heterogeneity. Moreover, we optimized this approach so that it can be successfully applied to slow-frozen tumoral tissues, further extending the usefulness of this tool. We also investigated the effectiveness of Plasma Activated Ringer’s Lactate solution (PA-RL) against Epithelial Ovarian Cancer (EOC) serous histotype in both 2D and 3D cultures using ex-vivo specimens from HGSOC patients. We propose PA-RL as a novel therapy with local intraperitoneal administration, which could act on primary or metastatic ovarian tumors inducing a specific cancer cell death with reduced damage on the surrounding healthy tissues.

Plasma-activated liquids as promising tools for non-invasive selective treatment of epithelial ovarian cancer

Plasma medicine is a branch of plasma-promising biomedical applications that uses cold atmospheric plasma (CAP) as a therapeutic agent in treating a wide range of medical conditions including cancer. Epithelial ovarian cancer (EOC) is a highly malignant and aggressive form of ovarian cancer, and most patients are diagnosed at advanced stages which significantly reduces the chances of successful treatment. Treatment resistance is also common, highlighting the need for novel therapies to be developed to treat EOC. Research in Plasma Medicine has revealed that plasma has unique properties suitable for biomedical applications and medical therapies, including responses to hormetic stimuli. However, the exact mechanisms by which CAP works at the molecular level are not yet fully understood. In this regard, the main goal of this thesis is to identify a possible adjuvant therapy for cancer, which could exert a cytotoxic effect, without damaging the surrounding healthy cells. An examination of different plasma-activated liquids (PALs) revealed their potential as effective tools for significantly inhibiting the growth of EOC. The dose-response profile between PALs and their targeted cytotoxic effects on EOC cells without affecting healthy cells was established. Additionally, it was validated that PALs exert distinct effects on different subtypes of EOC, possibly linked to the cells' metabolism. This suggests the potential for developing new, personalized anticancer strategies. Furthermore, it was observed that CAP treatment can alter the chemistry of a biomolecule present in PAL, impacting its cytotoxic activity. The effectiveness of the treatment was also preliminarily evaluated in 3D cultures, opening the door for further investigation of a possible correlation between the tumor microenvironment and PALs' resistance. These findings shed light on the intricate interplay between CAP and the liquid substrate and cell behaviour, providing valuable insights for the development of a novel and promising CAP-based cancer treatment for clinical application.

Clinical impact of next-generation sequencing multi-gene panel highlighting the landscape of germline alterations in ovarian cancer patients

BRCA1 and BRCA2 are the most frequently mutated genes in ovarian cancer (OC), crucial both for the identification of cancer predisposition and therapeutic choices. However, germline variants in other genes could be involved in OC susceptibility. We characterized OC patients to detect mutations in genes other than BRCA1/2 that could be associated with a high risk to develop OC, and that could permit patients to enter the most appropriate treatment and surveillance program. Next-Generation Sequencing analysis with a 94-gene panel was performed on germline DNA of 219 OC patients. We identified 34 pathogenic/likely-pathogenic variants in BRCA1/2 and 38 in other 21 genes. Patients with pathogenic/likely-pathogenic variants in non-BRCA1/2 genes developed mainly OC alone compared to the other groups that developed also breast cancer or other tumors (p=0.001). Clinical correlation analysis showed that low-risk patients were significantly associated with platinum sensitivity (p<0.001). Regarding PARP inhibitors (PARPi) response, patients with pathogenic mutations in non-BRCA1/2 genes had significantly worse PFS and OS. Moreover, a statistically significant worse PFS was found for every increase of one thousand platelets before PARPi treatment. To conclude, knowledge about molecular alterations in genes beyond BRCA1/2 in OC could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for OC patients.