Search

High-grade serous carcinoma (HGSC) is the most lethal gynecological malignancy in the United States. Late diagnosis and the emergence of chemoresistance have prompted studies into how the tumor microenvironment, and more recently tumor innervation, may be leveraged for HGSC prevention and interception. In addition to stess-induced sources, concentrations of the sympathetic neurotransmitter norepinephrine (NE) in the ovary increase during ovulation and after menopause. Importantly, NE exacerbates advanced HGSC progression. However, little is known about the role of NE in early disease pathogenesis. Here, we investigated the role of NE in instigating anchorage independence and micrometastasis of preneoplastic lesions from the fallopian tube epithelium (FTE) to the ovary, an essential step in HGSC onset. We found that in the presence of NE, FTE cell lines were able to survive in ultra-low-attachment (ULA) culture in a β-adrenergic receptor-dependent (β-AR-dependent) manner. Importantly, spheroid formation and cell viability conferred by treatment with physiological sources of NE were abrogated using the β-AR blocker propranolol. We have also identified that NE-mediated anoikis resistance may be attributable to downregulation of colony-stimulating factor 2. These findings provide mechanistic insight and identify targets that may be regulated by ovary-derived NE in early HGSC.

Aims: STK11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz–Jeghers syndrome. [Correction added on 3 October 2024, after first online publication: 'ST11' in preceding sentence has been corrected to 'STK11' in this version.] It predominantly originates from the para‐adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non‐specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics. Methods and results: IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli–Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra‐ovarian sex cord‐stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo‐ovarian high‐grade serous carcinomas, five ovarian mesonephric‐like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high‐grade serous carcinoma with subclonal loss. Conclusions: STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context. [ABSTRACT FROM AUTHOR]

The American Institute of Ultrasound in Medicine (AIUM) has developed the Practice Parameter for the Performance of Ultrasound of the Female Pelvis, which provides recommendations for high-quality ultrasound examinations in this specialty area. The document outlines indications for pelvic sonography, qualifications and responsibilities of personnel, preparation for the examination, and detailed specifications for evaluating the uterus, adnexae (ovaries and fallopian tubes), and cul-de-sac. It emphasizes the importance of accurate documentation, equipment specifications, quality assurance, safety, infection control, and adherence to the ALARA principle. The parameter was developed in collaboration with various organizations and committees, reflecting a multidisciplinary approach to advancing the safe and effective use of ultrasound in medicine. [Extracted from the article]

The Arabian oryx (Oryx leucoryx) is an antelope that is considered a "vulnerable" species. Lack of knowledge on the structure of its reproductive organs hinders the development of strategies to improve its reproduction. There is only one report on the gross anatomy of the female reproductive organs. With the aim of describing their microanatomy, the ovaries, uterine tubes, uterus, and vagina were collected at necropsy of an adult female oryx. Samples from each organ were analyzed with H&E staining and light microscopy. The squamous to cuboidal germinal epithelium covers the dense tunica albuginea of the ovaries, which encloses the cortex. This merges smoothly with the medulla. The cortex embeds follicles at several stages of development. A rich bed of blood vessels is present in the medulla, especially at the hilum. The uterine tubes are comprised of a serosa, muscularis, and mucosa. The muscularis is constituted of circular smooth muscle covered by a thin layer of longitudinal fibers. The mucosa has longitudinal folds lined by a pseudostratified epithelium with ciliated cells. The uterine horns are constituted of a serosa, muscularis, and mucosa. The muscularis contains an inner circular layer of smooth muscle and an outer longitudinal one. Simple coiled glands are present at the base of the mucosa. From this, highly cellular projections (caruncles) are present, lined by a by a simple columnar epithelium. The cervix contains four dense rings, and its mucosa is lined by longitudinal folds of a simple columnar epithelium, with ciliated cells. Numerous glands are located in the lamina propria and contain simple cuboidal to columnar epithelium. The vaginal wall was made of a serosa, muscularis, and mucosa. The mucosa is made of stratified squamous epithelium non-keratinized. In summary, the histology of the internal reproductive organs of the oryx is like the one of other ruminants. [ABSTRACT FROM AUTHOR]

Adenomatoid tumors are rare benign neoplasms arising from mesothelial cells, commonly found in the female genital system, particularly the uterus and fallopian tubes. The giant cystic variant of adenomatoid tumor is exceptionally rare and can cause massive growth mimicking malignant gynecological conditions. Histology and immunohistochemistry play a crucial role in confirming the diagnosis, with markers such as calretinin, D2‐40, CK7, BAP1, ER, and WT1 proving useful. A 51‐year‐old female with a history of breast cancer presented with pelvic pressure and vague pain. Imaging revealed an enlarged uterus with multiple heterogeneously enhancing masses and a predominantly cystic mass arising from the fundus, all believed to be leiomyomas. Surgical exploration and subsequent pathologic examination identified the cystic tumor as cystic adenomatoid tumor coexisting with leiomyomas, adenomyosis, and abdominal endometriosis. Diagnosing cystic adenomatoid tumor presents challenges, especially in patients with complex gynecologic histories. Cystic adenomatoid tumors typically have a favorable prognosis following surgical intervention. This case demonstrates one of the few reports of a giant cystic adenomatoid tumor (11.5 cm) and highlights diagnostic mimics. As these tumors are typically small and often seen only microscopically, the large size can confuse the pathologist who may be unaware of this feature leading to a misdiagnosis. [ABSTRACT FROM AUTHOR]

In this case, a 66‐year‐old female patient presented with the chief complaint of abdominal distention. Computed tomography and magnetic resonance imaging revealed no enlarged ovaries or obvious primary lesions; however, massive ascites and peritoneal disseminated nodules were observed. Ascites cytology revealed adenocarcinoma and immunohistochemical findings suggested serous carcinoma. The patient then underwent tumor reduction surgery after preoperative chemotherapy for suspected Stage IIIC primary peritoneal carcinoma. Postoperative histopathology revealed carcinoma consisting mainly of high‐grade serous carcinoma (HGSC) and sarcoma. In addition, serous intraepithelial carcinoma (STIC) of the fallopian tube was observed in the fimbriae of the left fallopian tube. Recently, it has been noted in the literature that most cases of peritoneal carcinoma are metastases or dissemination of carcinoma originating from the fimbriae of the fallopian tube. This is a rare case of peritoneal carcinosarcoma with STIC, and its report leads to a better understanding of the disease's features and possible therapeutic approaches. [ABSTRACT FROM AUTHOR]

Our objective is to understand patients’ preexisting values, beliefs, and preferences regarding removal or preservation of the cervix, ovaries, and fallopian tubes at the time of hysterectomy for benign indications. We performed semi-structured interviews from August 2021 to March 2022 with patients referred for hysterectomy. Participants were recruited according to pre-specified diversity axes. The interview guide was informed by literature review, expert stakeholders, and pilot testing. pers. comm. occurred prior to scheduled consultation. Responses were analyzed for themes, with thematic saturation reached. Age of participants (n = 13) ranged from 24 to 60 years. Identified themes included knowledge, decision-making, treatment goals, short- and long-term consequences, fertility, identity, and lack of concern. Many participants expressed lacking necessary knowledge of the risks and benefits of removing the cervix and adnexa. Treatment goals included symptom relief and definitive treatment. Long-term consequences included concerns about menopause and future cancer. Many patients expressed some degree of lack of knowledge, desire to remove most or all pelvic structures, or no attachment to their reproductive organs. Many patients expressed decision-making based on the effects of organ removal on long-term consequences and the relief of current symptoms, rather than immediate surgical risk. This information can help to inform patient-centered surgical counseling. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer, with the highest mortality rate among gynecologic malignancies, often goes undetected until advanced stages due to non‐specific symptoms. Traditional prevention strategies such as bilateral salpingo‐oophorectomy (BSO) are limited to high‐risk women and induce surgical menopause, often leading to significant health concerns. Recent findings suggest that many serous epithelial ovarian cancers originate in the fallopian tubes rather than the ovaries. This has led to the hypothesis that salpingectomy, with preservation of the ovaries, may reduce the risk of ovarian cancer while avoiding the adverse effects of early menopause. Studies show that bilateral salpingectomy (BS) significantly reduces ovarian cancer incidence even in average‐risk women. Bilateral salpingectomy has been demonstrated to be safe with minimal added operative time, no adverse effects on ovarian function and is also cost effective. Opportunistic salpingectomy (OS), at the time of non‐gynecologic surgeries, is a promising strategy for reducing ovarian cancer risk, especially among average‐risk women who have completed childbearing. It offers a safe and cost‐effective alternative to traditional methods. Emerging data supports incorporating OS into standard surgical practices for benign gynecologic conditions and considering it during unrelated abdominal/pelvic surgeries after adequate patient counseling and informed consent. Further training of non‐gynecologic surgeons in OS is recommended to expand its preventive benefits. [ABSTRACT FROM AUTHOR]

Background: Cervical squamous cell carcinoma (SCC) is the most common type of cervical carcinoma. Usually, the cancer metastasizes through lymphatic or hematogenous dissemination. However, it is uncommon for a superficial spreading of cervical cancer to reach the endometrium, fallopian tubes, and the ovaries. Objectives: In the present study, we report 15 cases of superficial spreading SCC and discuss the possible mechanism involved. Methods: We collected 15 samples diagnosed by histopathology after surgery. Immunostaining, which included P16, P63, CD138, CD34, D2-40, and Ki-67, were performed for all samples. Results: All patients were postmenopausal or perimenopausal women. The commonest clinical presentation was vaginal bleeding in 66.67%. All patients were infected with HPV 16. The endometrium was replaced by high-grade squamous intraepithelial lesion (HSIL), which involved the endometrial gland, even squeezing into the myometrium and forming SCC. Bilateral fallopian tubes and ovaries involvement was in 1/15. A total of 10/15 (66.67%) of the women had disease of stage 1B or less. All SCCs were moderately or poorly differentiated. Immunohistochemistry revealed that the tumor cells were positive for P63 and P16, with a high Ki-67 labeling index. There was CD138 positive expression in varying degrees, which was strongly and diffusely expressed in 6/15 (40.00%). Conclusion: Superficial spread of cervical cancer towards the endometrium is a rare but cognizable phenomenon, and a guideline for the management of these cases has not been established. Our present findings suggest that multiple factors may interact with each other simultaneously, contributing to this rare disease. [ABSTRACT FROM AUTHOR]

Background-Adnexal masses are solid or cystic mass originating in the ovaries, fallopian tubes, or surrounding tissues that is often detected incidentally during pelvic imaging. Adnexal mass, which may range from simple cyst to benign or malignant ovarian mass, is one of the most common pathological conditions noted in gynaecologic practice and it can occur in women of all ages1. This study evaluates the adnexal masses for risk of malignancy and diagnostic significance of (Ovarian adnexal reporting and data system) ORADS ultrasound risk scoring system. Methods: This prospective observational study was conducted in the Department of Radio-diagnosis of Mahatma Gandhi Memorial Medical College & M.Y Hospital, Indore, Madhya Pradesh, India after receiving approval by the Institutional Scientific and Ethical Committee. The duration of study was from September 2022 to September 2023.A total of 240 patients who were referred to the Department of Radio-diagnosis for ultrasonography on clinical suspicious of adnexal lesion and were included in the study. Results-Among the 240 cases examined, ORADS 2 was the most prevalent, comprising 96 cases (40%), followed by ORADS 3 with 55 cases (23%). ORADS 1 accounted for 33 cases (15%), ORADS 4 for 35 cases (14%), and ORADS 5 for 21 cases (9%). Out of 240 cases on the basis of histopathological findings/follow up scan all ORADS 1 lesion were benign in contrast ORADS 2 lesions were (1out of 86) 0.8% malignant, ORADS 3 lesion were (4 out of 55) 8% malignant, ORADS 4 lesion were (16 out of 35) 45% malignant and ORADS 5 lesion were (19 out of 21) 89% malignant. Statistically significance correlation was observed with ORADS grading 4 and 5 and risk of malignancy with p values <.0001 and the Area under the curve is 93.2% with a sensitivity of 95.66% and specificity of 75.21% which is statistically significant. Conclusion-ORADS improve the sensitivity and specificity of ultrasound in distinguishing between benign and malignant adnexal masses. [ABSTRACT FROM AUTHOR]

Introduction: While tubal occlusion is a prevalent cause of infertility, accounting for 11–35% of infertility cases among women, there remains a limited understanding of the factors influencing clinical pregnancy following in vitro fertilization (IVF). Methods: In our retrospective, cross-sectional cohort study conducted at a single tertiary center, medical records of women aged 19 to 43 years were analyzed. Logistic regression models were employed to identify the prognostic factors associated with clinical pregnancy after IVF in patients with tubal factor infertility, excluding cases with hydrosalpinx. Results: Data from 219 women diagnosed with tubal occlusion were compared to 1140 cases with non-tubal indication, covering a total of 1359 IVF cycles. A lower maternal age (adjusted odds ratio [AOR]: 0.89, p = 0.001) and a higher embryo quality (AOR: 1.26, p = 0.01) emerged as important factors in clinical pregnancy in the tubal infertility group. Moreover, a lower maternal (AOR:0.91, p < 0.01) and paternal age (p = 0.001), and favorable semen quality (AOR: 1.32, p = 0.03) were critical determinants in the non-tubal infertility group. BMI was generally higher in tubal infertility patients (p = 0.01). Furthermore, FSH level (AOR: 0.93, p = 0.004), AMH level (p < 0.04), number of embryos transferred (AOR: 2.04, p < 0.001), and embryo quality (AOR: 1.26, p < 0.001) came into prominence only in the non-tubal infertility group. The clinical pregnancy rate (34.2%) of women with tubal occlusion did not differ significantly from those in other forms of infertility undergoing IVF (35.4%). Conclusions: Although tubal infertility is typically anticipated to yield the highest clinical pregnancy rates following IVF, it is crucial to acknowledge that both maternal and paternal characteristics can also significantly impact the outcomes. [ABSTRACT FROM AUTHOR]

Purpose: In the milieu of emergency medicine, pelvic and lower abdominal pain present recurrently, with ovarian torsion posing a formidable diagnostic quandary amid multifarious etiologies. Given the burgeoning reliance on CT in acute care settings, it invariably assumes primacy as the principal imaging modality. This study endeavors to elucidate the CT imaging manifestations encountered by surgically confirmed ovarian torsion patients and utilizing CT to differentiate necrosis. Methods: A retrospective analysis (January, 2015- April, 2019) utilizing hospital archives was conducted on patients diagnosed with ovarian torsion, post-surgery. Inclusion criteria encompassed patients who underwent CT examinations within one week of diagnosis. A large array of CT findings encompassing midline orientation, uterine deviation, intraovarian hematoma/mass, and multiple others were systematically documented. Results: 90 patients were diagnosed with ovarian torsion- 53 (59%) had CT within one week of diagnosis, 41(77%) underwent a CT with IV contrast and 12 (23%) without IV contrast. Mean age was 43 years (range 19–77 years), with near equal distribution of involvement of each ovary. Mean maximum ovarian diameter was 11.7 ± 6.3 cm (4.2–34.8 cm). Most common imaging features include the presence of thickened pedicle (43/53, 81%), midline ovary (41/53, 77%), presence of thickened fallopian tube (31/49, 63%), and ipsilateral uterine deviation (33/53, 62%). Based on contemporaneous imaging report, torsion was diagnosed in 25/ 53 studies giving a sensitivity of 47%. Conclusion: Enlarged ovarian dimensions (> 3.0 cm), thickened vascular pedicle or fallopian tube, midline ovarian disposition with ipsilateral uterine deviation, and the presence of a whirlpool sign emerged as predominant CT imaging features in surgically confirmed ovarian torsion cases, serving as pivotal diagnostic aides for radiologists. Concomitant pelvic free fluid and intraovarian hematoma signify necrotic changes, indicative of ischemic severity and disease progression. [ABSTRACT FROM AUTHOR]

Objectives: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. Methods: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. Results: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. Conclusions: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. Clinical relevance statement: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. Key Points: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient. [ABSTRACT FROM AUTHOR]

Prostaglandins have many roles in the equine reproductive tract, including but not limited to luteolysis, luteal support, ovulation, transport through the uterine tube, uterine contraction, embryonic mobility, inflammation, and fibrosis. Altered secretion of inflammatory proteins are likely to disrupt the balance of endometrial function and could impair fertility. Our overall goal was to measure the expression of several prostaglandin- and inflammation-related genes in mares with different degrees of endometrial histological changes. Our hypothesis was that mares with neutrophilic and lymphocytic plasmocytic inflammation, fibrosis, or different biopsy grades would have altered concentrations of prostaglandin E2 (PGE2) and F2α (PGF2α), as well as altered expression of inflammation- and prostaglandin-related genes, compared to mares with minimal to no histological changes on biopsy evaluation. Forty-five endometrial biopsies from estrous mares were assessed by a reproductive pathologist for the degree of neutrophilic inflammation, lymphocytic and plasmocytic inflammation, and fibrosis, and a biopsy grade was assigned based on the Kenney-Doig system. A low-volume uterine lavage was collected from a subset of twenty-six mares prior to biopsy collection and was used to measure PGE2 and PGF2α concentrations via ELISA. Total RNA was extracted from biopsies and mRNA expression was evaluated for twenty-five genes of interest. A restricted maximum likelihood linear model was used to compare differences of mRNA expression, with a statistical significance set at P < 0.05. There was no difference in the abundance of PGE2 or PGF2α between any of the variables tested. Mares with endometrial biopsy grade I had lower expression of NF-kB, PTGS1 and HPGD compared to grade IIA or IIB (P < 0.05). Mares with neutrophilic inflammation had decreased expression of NF-kB, PTGS1, PTGER4, CBR1, mPGES2 and PTGIS compared to mares without inflammation. Mares with mild or minimal endometrial fibrosis had increased expression of mPGES2 and PTGIS , compared to mares with moderate endometrial fibrosis. In conclusion, several genes were identified to be differentially expressed in mares with histological changes compared to mares with no to minimal histological changes. The presence of inflammation and fibrosis may alter the concentration of prostaglandins in endometrial tissue, which could impair many of the uterine reproductive and immune functions during estrus, affecting early embryo survival. • Prostaglandins were differentially expressed based on histological assessment. • Prostaglandin expression was increased in IIA and IIB endometrial biopsies. • mPGES2 and PTGIS relative expression were decreased with moderate fibrosis. • Endometrial biopsies with inflammation had decreased prostaglandin expression. [ABSTRACT FROM AUTHOR]

Background: Turner syndrome (TS) is a female genetic disorder. Most patients with TS have a 45,X haplotype, but a small proportion have low nonholic chimerism. We here report a rare case of chimeric Turner syndrome in an individual with no phenotype aside from difficulties in conception, which may have been due to TS-associated decreased ovarian function. Methods: A 41-year-old female presented with no family history of TS, normal facial build, normal intelligence, and no other common clinical features of TS. The patient experienced spontaneous puberty, regular menstruation of a normal volume, bilateral fallopian tube blockage, and multiple cervical cysts. Results: Karyotype analysis showed 45,X/47,XXX/46,XX cells, whereas fluorescence in situ hybridization also revealed the presence of 48,XXX cells. Conclusions: There is growing evidence that ovarian function declines with age among those with chimeric TS, reducing their chances of conception. Fluorescence in situ hybridization should be recommended among those with difficulties conceiving to detect those with atypical chimeric TS, who may experience ovarian failure at an early age, to enable timely fertility interventions. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic was associated with a profound decline in cancer diagnoses in 2020 in Belgium. Disruption in diagnostic and screening services and patient reluctance to visit health facilities led to fewer new cases and concerns that cancers may be diagnosed at more advanced stages and hence have poorer prognosis. Using data from mandatory cancer registration covering all of Belgium, we predicted cancer incidence, stage distribution and 1‐year relative survival for 2020 using a Poisson count model over the preceding years, extrapolated to 2020 for 11 common cancer types. We compared these expected values to the observed values in 2020 to specifically quantify the impact of the COVID‐19 pandemic, accounting for background trends. A significantly lower incidence was observed for cervical, prostate, head and neck, colorectal, bladder and breast cancer, with limited or no recovery of diagnoses in the second half of 2020 for these cancer types. Changes in stage distribution were observed for cervical, prostate, bladder and ovarian and fallopian tube tumours. Generally, changes in stage distribution mainly represented decline in early‐stage than in late‐stage tumours. One‐year relative survival was lower than predicted for lung cancer and colorectal cancer. Stage shifts are hypothesised to result from alterations in access to diagnosis, potentially due to prioritisation of symptomatic patients, and patient reluctance to contact a physician. Since there were over 5000 fewer cancer diagnoses than expected by the end of 2020, it is critical to monitor incidence, stage distribution and survival for these cancers in the coming years. [ABSTRACT FROM AUTHOR]

Specialized cilia known as ependymal cilia help the cerebrospinal fluid, which is important for nutrient delivery and waste elimination, to circulate in the brain. Many species rely on cilia and flagella for fluid movement and motility. Cilia and flagella, for instance, produce propulsive forces that allow unicellular creatures like Paramecium and Euglena to move through their surroundings. Ciliary transport plays a role in the flow of egg cells, or oocytes, via the fallopian tubes in the female reproductive system. The transfer of the egg towards the uterus is facilitated by the synchronized wave‐like motion produced by the cilia lining the fallopian tubes. Like this, ciliary transport in men aids in the passage of sperm cells via the epididymis. Many scientists and researchers are studying the mechanics of cilia motion and the properties of the viscoelastic fluid layer to develop new treatments and applications in biomedical engineering and for some diseases. Motivated by a wide range of biological applications, the objective of this study is to investigate the heat and mass transfer flow of tri‐layered Newtonian fluids flowing with the help of ciliary beating in a Cartesian coordinate. The fluid is incompressible, and fluid layers are not intermixed. The fluid flow with heat and mass transfer is first modelled in wave and then transmuted into fixed. Solutions for temperature profile, velocity distribution, stresses and concentration distribution are obtained. The influence of incipient parameters is displayed with graphs and plotted with the computational software MATHEMATICA 13.0 in the results section. The key findings obtained from graphs show that the maximum magnitude for temperature and velocity is achieved in the middle layer of fluid whereas in the outer layer concentration profile is maximum. It is predicted that this approach will make an essential contribution to the progress and enhancement of various types of drug delivery systems in the biomedical industry and biomechanics. [ABSTRACT FROM AUTHOR]

The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important to their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the fallopian tube that molecularly, functionally, and architecturally resembles the organ. Global label-free proteomics, innovative assays capturing physiological functions of the fallopian tube (i.e., oocyte transport), and whole-organ single-cell resolution mapping are used to validate these assembloids through a multifaceted platform with direct comparisons to fallopian tube tissue. These techniques converge at a unique combination of assembloid parameters with the highest similarity to the reference fallopian tube. This work establishes (i) an optimized model of the human fallopian tubes for in vitro studies of their pathophysiology and (ii) an iterative platform for customized 3D in vitro models of human organs that are molecularly, functionally, and microanatomically accurate by combining tunable assembloid and tissue mapping methods. [ABSTRACT FROM AUTHOR]

A 33-year-old young woman with a rare female appendage tumor of suspected Wolffian origin was initially diagnosed with a benign lesion after the resection of a tubal lesion due to the benign cytomorphology of the tumor tissue. However, 1 year after surgery, she was diagnosed with stage IV fallopian tube cancer due to a recurrence, which presented with substantial ascites and invasion of multiple organs, including the bilateral ovaries, intestines, pelvic peritoneum, greater omentum, and appendix. After tumor cytoreduction, the patient responded well to treatment, which included a regimen of platinum-based drugs combined with docetaxel, aromatase inhibitors such as letrozole, antihormonal therapy, and targeted therapy with bevacizumab. [ABSTRACT FROM AUTHOR]

Background: Finding an ovary and/or fallopian tube within an indirect inguinal hernia is a rare occurrence that can be detected incidentally during elective surgery or present as a medical emergency requiring immediate intervention. Hence, it poses a difficult clinical picture in a reproductive-age woman with groin mass. Clinical presentation: We describe the case of a 45-year-old Ethiopian woman of Amhara ethnicity who presented with a left inguinal swelling that persisted for 5 years. Physical examination revealed an irreducible, non-tender lump in the left groin and an ultrasonography scan confirmed the presence of an indirect inguinal hernia. The patient was then scheduled for elective hernia repair. During the surgery, both her left ovary and fallopian tube were found within the hernial sac. The contents were released from the sac, high ligation performed, and the inguinal floor repaired with mesh. Discussion: Inguinal hernias in women are rare and often present a diagnostic challenge. Although the exact pathogenesis of inguinal hernias containing female genital organs is unknown, some risk factors have been postulated. Diagnosis should start with a physical exam and imaging, but many of the cases have been intraoperative surprises. Management is primarily surgical, ranging from simple reduction and hernia repair to salpingo-oophorectomy depending on the status of the hernia contents. Conclusion: This report emphasizes the importance of maintaining a high index of suspicion when examining females with inguinal hernias to ensure accurate diagnosis and management of tubo-ovarian hernias. Although rare, inguinal hernias containing female genital organs should be considered in the differential diagnosis of inguinal hernias, as early detection and appropriate surgical management can prevent potential complications. [ABSTRACT FROM AUTHOR]

Low grade serous carcinoma (LGSOC) is a rare epithelial ovarian cancer with unique molecular characteristics compared to the more common tubo-ovarian high-grade serous ovarian carcinoma. Pivotal clinical trials guiding the management of epithelial ovarian cancer lack sufficient cases of LGSOC for meaningful subgroup analysis, hence overall findings cannot be extrapolated to rarer chemo-resistant subtypes such as LGSOC. Furthermore, there is a need for more effective therapies for the treatment of relapsed disease, as treatment options are limited. To address this, we conducted the largest quantitative high-throughput drug screening effort (n = 3436 compounds) in 12 patient-derived LGSOC cell lines and one normal ovary cell line to identify unexplored therapeutic avenues. Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines, our data set identified 60 high and 19 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1 µM). We also revealed a series of known (mTOR/PI3K/AKT) and novel (EGFR and MDM2-p53) drug classes in which LGSOC cell lines showed demonstrable susceptibility to. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) and herpesviruses are detected in patients with epithelial ovarian cancer (EOC). We sought to analyze the prevalence of HPV's 16 and 18, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) DNA in peripheral blood, ovarian, and fallopian tube (FT) tissue samples collected from 97 EOC patients, including 71 cases of high-grade serous ovarian carcinoma (HGSOC), and from 60 women with other tumors or non-neoplastic gynecological diseases. DNA isolates were analyzed by PCR methods, including droplet digital PCR. The results demonstrate that (1) HPV16 DNA has been detected in one-third of the FT and tumor samples from EOCs; (2) the prevalence and quantity of HPV16 DNA were significantly higher in FT samples from HGSOCs, non-HGSOCs, and ovarian metastases than in those from non-neoplastic diseases; (3) CMV and EBV have been detected in approximately one-seventh of EOC samples. The results suggest that HPV16 might be a potential risk factor for EOC development. [ABSTRACT FROM AUTHOR]

In the case of placenta previa‐accreta when the placenta covers the entire anterior uterine wall, it is difficult to avoid transecting the placenta by traditional low‐transverse cesarean section (CS), resulting in catastrophic hemorrhage and fetal anemia. To prevent this critical risk, we developed the CS with transverse uterine fundal incision (TUFI) and this technique has been widely used as a beneficial surgical method in clinical practice owing to its safety advantages for the mother and neonate since our first report. However, the risk of uterine rupture during a subsequent pregnancy remains unclear. Based on our 17 years of experience, patients who require TUFI do not need to avoid this beneficial operative method simply because of their desire to conceive again, as long as certain conditions can be met. To approve a post‐TUFI pregnancy, an appropriate suture method, delay in conception for at least 12 months with evaluation of the TUFI scar, and cautious postoperative management are at a minimum essential. In this article, we showed our recommendation for operative procedure and discuss the current status of the management of post‐TUFI pregnancies based on the evaluation of the TUFI wound scar and experience with postoperative pregnancies. [ABSTRACT FROM AUTHOR]

Heritable mutations in BRCA1 associate with increased risk of high-grade serous tubo-ovarian cancer. Nongenetic risk factors associated with this cancer, which arises from fallopian tube epithelial (FTE) cells, suggests a role for repetitive ovulation wherein FTE cells are exposed to inflammatory signaling molecules within follicular fluid. We previously reported increased NFkB and EGFR signaling in BRCA1- deficient primary FTE cells, with follicular fluid exposure further increasing abundance of interferon-stimulated gene (ISG) transcripts, including the ubiquitin-like protein ISG15 and other ISGylation pathway members. Both NFkB and type I interferon signaling are upregulated by stimulation of cGASSTING or MDA5 and RIGI pattern recognition receptors. Since some pattern recognition receptors and their signal transduction pathway members are ISGylated, we tested the impact of ISG15 and ISGylation on interferon regulatory factor 3 (IRF3) and NFkB signaling through cGAS-STING or RIGI and MDA5 activation. Expression of ISG15 or UBA7, the E1- like ISG15-activating enzyme, in immortalized FTE cells was disrupted by CRISPR gene editing. Activation of IRF3 by RIGI or MDA5 but not cGAS-STING was attenuated by loss of either ISG15 or UBA7 and this was reflected by a similar effect on NFkB activation and downstream targets. Loss of ISGylation decreased levels of both MDA5 and RIGI, with knockdown of RIGI but not MDA5, decreasing IRF3 and NFkB activation in parental cells. These finding indicate that ISGylation enhances the ability of dsRNA to activate cytokine release and proinflammatory signaling. Further work to explore ISGylation as a target for prevention of high-grade serous tubo-ovarian cancer in BRCA1 mutation carriers is warranted. [ABSTRACT FROM AUTHOR]

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer at 61 years old. Among the other three carrier relatives: one has been diagnosed with serous cystadenoma of the ovary and a thyroid nodule with no radiological suspicion of malignancy; the other two present multinodular goiter. Additionally, a sister of three of the carriers suffered from an ovarian teratoma, follicular thyroid carcinoma on multinodular goiter, and high-grade serous ovarian carcinoma. No direct mutation study was performed on her as she had died due to ovarian carcinoma. This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion: Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cardiophrenic metastasis is typically a late stage manifestation of ovarian high grade serous carcinoma. Here we present a case where this was the sole presentation of this disease. This case challenges our current understanding of the natural course of ovarian high grade serous carcinoma. Ovarian cancer is typically described to spread from its primary site within the fallopian tubes or ovaries into the peritoneal cavity and beyond with cardiophrenic lymph node involvement being considered a late stage disease process. Here we present the case of a lady in her 60s where increased metabolic activity of the cardiophrenic lymph node was picked up in the investigation of an adenocarcinoma of the lung. Post‐thoracoscopic resection histopathological analysis of this lymph node showing an epithelial structure with positive immunohistochemical markers PAX8, WT1, ER, and p16 with a p53 wild type‐pattern were the sole presenting features of a high grade serous ovarian carcinoma, that was otherwise undetectable by radiological or hematological screening. Only histopathological analysis after modified radical hysterectomy in gynae‐oncological fashion were able to identify a 4 mm lesion within the left fallopian tube. This case questions our current understanding of the natural history of ovarian carcinomas. [ABSTRACT FROM AUTHOR]

In females, the paramesonephric (syn: Müllerian) duct gives rise to the uterine tubes, uterus, cervix, and part of the vagina. Segmental uterine aplasia resulting from a paramesonephric duct abnormality has been reported in a range of species including bovids, canids, felids, equids, camelids, and lagomorphs. Here we document segmental aplasia of the left paramesonephric duct in a New Zealand white rabbit. The proximal 70 mm of the left uterine tube was present and terminated in adipose tissue. A 10 × 2 × 1-mm tag of cream tissue was present and was composed of sheets of adipose tissue and streams of smooth muscle, but otherwise, there was no evidence of the left uterine horn, supporting a diagnosis of unilateral uterine aplasia (uterus unicornis) analogous to a human class II (unicornuate uterus) lesion of the "no horn" subtype. In addition, our case had a concurrent uterine tube fimbrial cyst, minor cysts in the left kidney, and mammary gland hyperplasia with secretory activity. We suggest the adoption of a uniform classification system specifically for lagomorph uterine anomalies. Large-scale multi-center studies documenting prevalence of such lesions would facilitate identification of trends in laterality and other factors. [ABSTRACT FROM AUTHOR]

Ovarian high‐grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early‐ and late‐stage HGSC and found higher ploidy in late‐stage (median 3.1) than early‐stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole‐genome duplication (WGD) observed in late‐stage disease were determined early in the evolution of HGSC, we analysed archival formalin‐fixed paraffin‐embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser‐capture microdissected and sequenced using shallow whole‐genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next‐generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Increasing evidence is implicating roles for platelets in the development and progression of ovarian cancer, a highly lethal disease that can arise from the fallopian tubes, and has no current method of early detection or prevention. Thrombosis is a major cause of mortality of ovarian cancer patients suggesting that the cancer alters platelet behavior. The objective of this study was to develop a cell culture model of the pathological interactions of human platelets and ovarian cancer cells, using normal FT epithelial cells as a healthy control, and to test effects of the anti-platelet dihomo-gamma-linolenic acid (DGLA) in the model. Both healthy and cancer cells caused platelet aggregation, however platelets only affected spheroid formation by cancer cells and had no effect on healthy cell spheroid formation. When naturally-formed spheroids of epithelial cells were exposed to platelets in transwell inserts that did not allow direct interactions of the two cell types, platelets caused increased size of the spheroids formed by cancer cells, but not healthy cells. When cancer cell spheroids formed using magnetic nanoshuttle technology were put in direct physical contact with platelets, the platelets caused spheroid condensation. In ovarian cancer cells, DGLA promoted epithelial-to-mesenchymal (EMT) transition at doses as low as 100 μM, and inhibited metabolic viability and induced apoptosis at doses ≥150 μM. DGLA doses ≤150 μM used to avoid direct DGLA effects on cancer cells, had no effect on the pathological interactions of platelets and ovarian cancer cells in our models. These results demonstrate that the pathological interactions of platelets with ovarian cancer cells can be modeled in cell culture, and that DGLA has no effect on these interactions, suggesting that targeting platelets is a rational approach for reducing cancer aggressiveness and thrombosis risk in ovarian cancer patients, however DGLA is not an appropriate candidate for this strategy. [ABSTRACT FROM AUTHOR]

Simple Summary: The early crosstalk between the ovulated oocytes and the oviduct occurs in the fimbria, which is sensitive to the sex hormone fluctuation. Morphological and molecular changes were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. A well-differentiated epithelium consisting of ciliated and nonciliated cells was present only during the preovulatory phase when the epithelial surface displayed acidic glycans, complex fucosylated N-glycans, and oligolactosamine residues. Nonciliated cells contained small apical protrusions and thin microvilli, suggesting secretory and absorptive activities. In addition, nonciliated cells expressed HSP60 and HSP90 in the apical blebs as well as nuclear estrogen and progesterone receptors. Interestingly, ciliated cells displayed HSP70, HSP90, and progesterone receptors in the cilia. The findings, in addition to adding to knowledge of the baboon oviduct, may represent a benchmark for translational studies of the primate oviduct, including humans. The oviductal fimbria is the first extraovarian anatomical structure that the cumulus–oocyte complex (COC) encounters, and is sensitive to sex hormone changes. The morphology, glycan pattern, expression of heat shock proteins (HSPs), estradiol receptor (ER), and progesterone receptor (PR) were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. The morphology was investigated by light and scanning electron microscopy; the glycopattern was characterized using conventional and lectin histochemistry; HSPs (60, −70, −90), ER, and PR were localized immunohistochemically. Well-differentiated ciliated and nonciliated cells were present only during the preovulatory phase. The nonciliated cells contained small apical protrusions and thin microvilli. During the preovulatory phase (1) the luminal surface of the fimbria displayed acidic glycans, complex N-glycans containing fucose, and oligolactosamine residues; (2) nonciliated cells expressed HSP60 and HSP90 in the apical blebs, HSP70 in the nucleus and cytoplasm, as well as nuclear ERα and PR; (3) ciliated cells showed HSP70 in the nucleus, cytoplasm, and cilia that also expressed HSP90 and PR. These results are related to the function of the fimbria where the early COC–oviduct crosstalk occurs and may represent a benchmark for translational studies of other primates. [ABSTRACT FROM AUTHOR]

A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side. [ABSTRACT FROM AUTHOR]

The cellular origin of clear cell ovarian carcinoma (CCOC), a major histological subtype of ovarian carcinoma remains elusive. Here, we explored the candidate cellular origin and identify molecular subtypes using integrated genomic/epigenomic analysis. We performed whole exome-sequencing, microarray, and DNA methylation array in 78 CCOC samples according to the original diagnosis. The findings revealed that ARID1A and/or PIK3CA mutations were mutually exclusive with DNA repair related genes, including TP53, BRCA1, and ATM. Clustering of CCOC and other ovarian carcinomas (n = 270) with normal tissues from the fallopian tube, ovarian surface epithelium, endometrial epithelium, and pelvic peritoneum mesothelium (PPM) in a methylation array showed that major CCOC subtypes (with ARID1A and/or PIK3CA mutations) were associated with the PPM-lile cluster (n = 64). This cluster was sub-divided into three clusters: (1) mismatch repair (MMR) deficient with tumor mutational burden-high (n = 2), (2) alteration of ARID1A (n = 51), and (3) ARID1A wild-type (n = 11). The remaining samples (n = 14) were subdivided into (4) ovarian surface epithelium-like (n = 11) and (5) fallopian tube-like (considered as high-grade serous histotype; n = 3). Among these, subtypes (1–3) and others (4 and 5) were found to be associated with immunoreactive signatures and epithelial-mesenchymal transition, respectively. These results contribute to the stratification of CCOC into biological subtypes. [ABSTRACT FROM AUTHOR]

This report presents a rare case of carcinosarcoma of the fallopian tube, a malignancy with a combination of carcinomatous and sarcomatous components. The carcinomatous element predominantly resembles high-grade serous carcinoma (HGSC), and the sarcomatous element exhibits components from Mullerian structures (homologous) or not normally found in the Mullerian structures (heterologous). The case involved a 75-year-old woman with lower abdominal pain diagnosed with a large tumor in the right adnexa through imaging studies. The final diagnosis was tubal carcinosarcoma (carcinomatous components were composed of HGSC (90%), and sarcomatous components were composed of undifferentiated sarcoma and endometrial stromal sarcoma, etc.) without involvement of the ovaries after surgery. The next-generation sequencing (NGS) results identified a TP53 mutation (NM_000546.5; c.578A>G). The patient underwent chemotherapy and showed no recurrence after 36 months. Here, we describe a rare case of carcinosarcoma of the fallopian tube that did not involve both ovaries and analyzed NGS results. [ABSTRACT FROM AUTHOR]

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia, bone mineralization disorders with increased risk of fragility fractures, muscle pain, and progressive weakness. TIO has been associated with increased production of the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) usually by mesenchymal tumors of soft tissue or bone (Phosphaturic Mesenchymal Tumors—PMTs). In rare cases TIO may be observed in association with other malignancies. We report the case of a 66-year-old woman with an occasional diagnosis of both a PMT and an ovarian cancer during the evaluation of TIO. We also systematically review the literature to discover possible correlations between osteomalacia, FGF23 production, and ovarian cancer. Four studies were eligible for the analysis. Two case reports described an association between TIO development and ovarian cancer, whereas the two case-control studies hypothesized a possible correlation between FGF/FGF receptor axis and cancer development. Although it does not provide conclusive evidence regarding the association between TIO and ovarian cancer, this case report highlights the possibility that in the diagnostic workup of suspected TIO, both FGF23-secreting tumors distinct from PMT and tumors unrelated to the clinical presentation of TIO could be identified. This information is important for guiding successful tumor staging and determining the necessity for surgical intervention and/or eventual adjuvant therapy. [ABSTRACT FROM AUTHOR]

Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk. To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA). We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA. We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients – affected genes included GLI1 , PIK3R1 , FOXP1 , FANCD2 , INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses. Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy. • High-grade serous carcinoma (HGSC) carries a high mortality. • Goal: Expand upon methods for early identification of potential candidates for risk-reducing salpingo-oophorectomy (RRSO). • We performed comprehensive NGS on tumor and normal tissues. • We identified rare germline variants in patients with concurrent endometrial and tubo-ovarian cancers. • Comprehensive genetic profiling may aid in early identification of patient relatives who may benefit from RRSO. [ABSTRACT FROM AUTHOR]

The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24–118 months). Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize. • Clonal relationship between temporally distant STICs and HGSCs was established in five of the seven cases. • Similar TP53 mutations were detected by performing next generation targeted sequencing. • Median interval for developing HGSC after risk-reducing salpingo-oophorectomy was 59 months. • These findings support the hypothesis that STIC lesions may metastasize. [ABSTRACT FROM AUTHOR]

The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients. This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug. Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3–50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2–7.4). Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development. • In this trial, 29 platinum-resistant ovarian cancer patients received escalating doses of suvemcitug plus chemotherapy. • No dose-limiting toxicities occurred and no gastrointestinal perforations were reported. • Nine patients showed investigators-confirmed objective response, with a median progression-free survival of 5.4 months. • The recommended dose for phase 2 study is suvemcitug 1.5 mg/kg every two weeks. • The safety and antitumor activities of suvemcitug support its clinical development for platinum-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

The fallopian tubes are essential for human fertility, facilitating the movement of sperm and oocytes to the fertilization site and transporting fertilized oocytes to the uterus. Infertility can result from changes in the fallopian tubes due to tubal endometriosis and women's aging. In this study, we modeled human fallopian tubes with and without endometriosis for different women's age groups to evaluate the chances of normal sperm cells reaching the fertilization site and oocytes arriving at the uterine cavity. For this purpose, we employed a distinctive combination of simulation tools to develop a dynamic three-dimensional (3D) model of normal human sperm cells and oocytes swimming inside normal and endometriosis-affected human fallopian tubes for different women's group ages. We observed that in tubal endometriosis cases, fewer sperm cells reach the fertilization site and more oocytes become trapped in the tube walls compared to normal tubes. Additionally, aging decreases the number of sperm cells and oocytes reaching the fertilization site in normal and endometriosis-affected tubes. Our model evaluates the mechanisms of sperm and oocyte behaviors due to women's aging and fallopian tube issues caused by endometriosis, presenting new avenues for developing diagnostic and treatment tools for tubal endometriosis and age-related infertility issues. [ABSTRACT FROM AUTHOR]

Simple Summary: Poly(adenosine diphosphate–ribose) polymerase inhibitors (PARP-is) play crucial roles in the treatment of ovarian cancer. However, the best therapeutic strategy for recurrence during PARP-i maintenance therapy remains unknown. The aim of this study was to elucidate the efficacy of platinum-based chemotherapy after PARP-i treatment in recurrent ovarian cancer. Eighteen patients were enrolled in the present study. The median progression-free survival (PFS) for all patients was 6.5 months, and the median overall survival (OS) was 17.6 months. The evaluation of the risk factors for PFS revealed that bevacizumab use in subsequent therapies was significantly associated with extended PFS. The median PFS was significantly longer in the chemotherapy with the bevacizumab group than in chemotherapy alone (8.9 months vs. 3.1 months, log-rank p = 0.022). The present study highlighted that platinum-based chemotherapy with bevacizumab in subsequent therapies would provide substantial benefits in the PFS of patients with recurrent ovarian cancer. The clinical outcomes in patients with ovarian cancer have been significantly improved by Poly(adenosine diphosphate–ribose) polymerase inhibitors (PARP-is). However, the best therapeutic strategy for recurrence during PARP-i maintenance therapy remains unknown. Herein, we elucidated the efficacy of platinum-based chemotherapy after PARP-i treatment in recurrent ovarian cancer. Eligible patients had experienced relapses during PARP-i maintenance therapy lasting at least 6 months and had received subsequent platinum-based chemotherapy at our institution between January 2019 and March 2024. Progression-free survival (PFS), overall survival (OS), and risk factors for PFS were evaluated. Sixty-six patients were assessed for eligibility and eighteen were enrolled. The median follow-up period was 14.5 months. The PFS and OS of all patients were 6.5 and 17.6 months, respectively. The evaluation of the risk factors for PFS revealed that age, pathological type, duration of PARP-i maintenance therapy, prior lines of chemotherapy, and PARP-i dose reduction were not significant prognostic markers. However, bevacizumab use in subsequent therapies significantly extended the PFS. The median PFS was 3.1 months in the chemotherapy-alone group and 8.9 months in the chemotherapy with bevacizumab group (log-rank p = 0.022). Platinum-based chemotherapy with bevacizumab in subsequent therapies would provide substantial benefits in the PFS of patients with recurrent ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the in vitro effect of diclofenac on tubal smooth muscle as an alternative to hyoscine‐N‐butyl bromide, which is used for premedication before hysterosalpingography (HSG). Material and Methods: Fallopian tubes were retrieved from seven healthy women after bilateral tubal ligation and in vitro contractility and histological studies were conducted using tissue bath and immunohistochemistry. Results: Diclofenac sodium and hyoscine‐N‐butyl bromide did not significantly change the basal mean tension; however, they decreased the contractions induced by potassium chloride (KCl). The relaxant effect of diclofenac sodium and hyoscine‐N‐butyl bromide was not statistically significantly different. The presence of cyclooxygenase (COX)‐2 enzyme in the fallopian tube was demonstrated by immunohistochemical studies. Conclusions: The in vitro relaxant effect of diclofenac sodium on the fallopian tube is similar to hyoscine‐N‐butyl bromide. Diclofenac may have the potential to be used as an alternative to hyoscine‐N‐butyl bromide in premedication in HSG. [ABSTRACT FROM AUTHOR]

Most extrauterine high-grade serous carcinomas (HGSCs) are thought to develop first in the distal fallopian tube. Most models of HGSC assume origin from relatively stable, noninvasive serous tubal intraepithelial carcinomas. However, widespread tumor involvement in the absence of a serous tubal intraepithelial carcinoma could occur after catastrophic genomic events (CGEs; such as chromothripsis or polyploidy). Twenty-six HGSCs assigned to fallopian tube (n = 9, group 1) and/or ovary (n = 9, group 2), and primary peritoneal (n = 8, group 3) were assessed by microarray (Oncoscan). CGEs were identified in 15/26 (57.7%); chromothripsis-like pattern in 13/26 (50.0%) and polyploidy in 6/26 (23.1%). CGE was seen in 4/9 (44.4%), 9/9 (100%), and 2/8 (25%) cases in groups 1. 2, and 3, respectively. Overall, CGEs were seen in 9/9 (100%) cases with grossly evident ovarian parenchymal involvement versus 6/17 (35.3%) without (P = 0.0024). Ovarian size (measured on the long axis) correlated with CGE positivity (P = 0.016). CGEs are significantly more common in HGSCs with ovarian parenchymal involvement compared with those limited to the fallopian tube and/or extraovarian tissues. These associations suggest geographically different tumor growth patterns and support the subdivision of HGSCs according to not only the stage but also tumor distribution. They have implications for clinical and pathologic presentation, trajectory of tumor evolution, and in the case of primary peritoneal HGSCs, potentially unique precursors to tumor transitions that could inform or influence cancer prevention efforts. [ABSTRACT FROM AUTHOR]

Background and Objectives: Choriocarcinoma is an aggressive oncological disease that manifests as trophoblast tissue proliferation. The vast majority of primary lesions affect the uterus, with primarily extrauterine lesions being a rarity. Choriocarcinoma with an ongoing pregnancy is extremely rare because fetuses usually do not survive the third trimester. Case Report: We present a case of heterotopic tubal choriocarcinoma coexisting with a viable intrauterine pregnancy. A 30-year-old, 39-week pregnant woman (gravida 2, para 2) came to our hospital complaining of acute upper abdominal pain. During routine prenatal screening in the first trimester, no pathological ultrasound findings were detected. Similar abdominal pain episodes had been recorded at 18, 27, and 32 weeks of gestation, when patient was hospitalized for examination and observation, but the cause of symptoms at that time of gestation remained unclear. The patient underwent an emergency caesarean section due to severe abdominal pain and fetal compromise. She delivered a live male infant. During the surgery, around 1000 mL of blood clots were evacuated, and the excision of the right fallopian tube and masses, as well as the control of significant blood loss was performed. Postoperative serum beta-hCG was elevated to 139 482 IU/L, while imaging studies showed no metastasis. The histological examination of the excised tissue samples confirmed a diagnosis of tubal choriocarcinoma. With a FIGO score of 8, the patient received three courses of the EP/EMA regimen. After more than a year, the patient showed no radiographic signs of distant metastasis and is now in complete remission. Conclusions: This case highlights the diagnostic complexity of such extremely rare scenarios. Even though such cases are rare, it demonstrates the necessity for improved diagnostic measures to enhance patient outcomes in similar clinical situations. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow‐up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines.Focus group study.Four online sessions.International panel (n = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists (n = 49).A semi‐structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC.Professionals' opinions and clinical practices regarding isolated STIC management.Regarding pathology, most professionals identified the SEE‐FIM protocol as standard of care for high‐risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work‐up and follow‐up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations.We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. We identified, across different cancer centers, six cases of both BRCA wild-type and BRCA-mutated EOCs spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as per clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for the optimal disease control of this unfortunate patient subset. Albeit not being directly investigated in BM patients, PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited. [ABSTRACT FROM AUTHOR]

Background: Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility. Methods: In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-oneout method. Results: We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility. Conclusion: Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). Methods: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. Results: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3–4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. Conclusions: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone. [ABSTRACT FROM AUTHOR]