Ovariectomy Research Articles

Effectiveness of desertliving cistanche in managing hyperlipidemic osteoporosis in ovariectomized rats through the PI3K/AKT signaling pathway

BackgroundTo aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats.MethodsWe randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed.ResultsCompared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group.ConclusionOur study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.

P-521 Inter-individual variation in gonadotoxicity in female childhood cancer survivors – a genome-wide association study: results from the PanCareLIFE study

Abstract Study question To identify new variants associated with alkylating agent (AA) induced gonadotoxicity among adult female childhood cancer survivors (CCS) using a genome-wide association study approach (GWAS). Summary answer Upon meta-analysis of two independent cohorts, the variant rs78861946 was associated with lower AMH levels in CCS, but not separately in the smaller replication cohort. What is known already Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the inter-individual variability in gonadotoxicity may be explained by genetic polymorphisms. Study design, size, duration A genome-wide association study (GWAS) approach was used to discover new variants associated with AA-induced gonadotoxicity among adult female CCS. The discovery cohort included adult female CCS from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, CNS, total body irradiation, or stem cell transplantation. Results were replicated in the USA-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years) and combined in a meta-analysis. Participants/materials, setting, methods Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in both the discovery and replication cohort. A GWAS was performed using a linear regression model adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study. Main results and the role of chance Three genome-wide significant (<5.0x10E-8 ) and 16 genome-wide suggestive (<5.0x10E-6 ) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. Based on effect allele frequency (EAF) (>0.01 if not genome-wide significant), p-value (<5.0 × 10E−6 ), and biological relevance, 15 SNPs were selected for replication in the independent replication cohort of the St. Jude Lifetime Cohort. None of the SNPs were statistically significantly associated with AMH levels in this smaller cohort. A meta-analysis indicated thatrs78861946 was associated at borderline genome-wide statistical significance (reference/effect allele: C/T;EAF: 0.04, Beta (SE): −0.484 (0.091), p-value= 9.39 × 10E−8). While the sample size of both the discovery and replication cohorts are large for CCS cohorts, they are very small compared to GWASs in the general population. The limited power is likely one of the reasons the identified SNPs were not statistically significant in our replication cohort of SJLIFE. Limitations, reasons for caution While AMH is a valuable surrogate marker for ovarian reserve, it remains a proxy for ovarian reserve and low AMH levels may still coincide with fertility potential and pregnancy. Wider implications of the findings Identification of risk-contributing variants such as rs78861946 may prove useful to better identify patients who are specifically susceptible for alkylating agent-induced gonadal toxicity. Future polygenic risk scores may aid individualized counselling regarding the treatment-related risk of gonadotoxicity and fertility preservation options for female childhood cancer survivors. Trial registration number not applicable

O-061 Ovarian cancer and fertility - current understanding

Abstract Introduction Ovarian cancer is a significant health concern worldwide and is the leading cause of death from gynecologic malignancies. While fertility preservation is essential for many young women diagnosed with cancer, concerns have been raised regarding the potential impact of fertility treatments on the risk of ovarian cancer development. 1. Ovarian Cancer Risk Factors Ovarian cancer is a multifactorial disease with various risk factors contributing to its development. A woman has a risk of 1 in 78 of having ovarian cancer in her life time, risk factors include: • Age: Ovarian cancer risk increases with age, with the highest incidence observed in women over 50 years old. About 12.1% of Ovarian Cancer patients are younger than 44 years old. • Family History: Women with a family history of ovarian or breast cancer, especially first-degree relatives, have an increased risk. • BRCA Mutations: Inherited mutations in BRCA1 and BRCA2 genes significantly elevate the risk of ovarian cancer. • Reproductive Factors: Factors such as nulliparity, early menarche, late menopause, and infertility have been associated with an increased risk of ovarian cancer. 2. Fertility Treatments and Ovarian Cancer Risk Understanding the mechanisms underlying ovarian cancer development is crucial for assessing the potential impact of fertility treatments : • Ovulation Hypothesis: The repeated ovulation theory suggests that each ovulatory cycle increases the risk of DNA damage to ovarian epithelial cells, potentially leading to cancer development. The use of fertility drugs to stimulate ovulation, such as clomiphene citrate and gonadotropins, has been studied , the early studies suggested a potential increased risk, more recent evidence has been conflicting, with some studies reporting no association. • In Vitro Fertilization (IVF): Several large-scale studies have investigated the relationship between IVF and ovarian cancer risk found no significant increase in ovarian cancer risk . • Hormonal Influence: Fertility drugs alter hormonal levels, particularly estrogen and progesterone, which may influence ovarian cancer risk. • Selection Bias: Some studies have suggested that the ovarian cancer risk may be confounded by underlying infertility factors rather than the treatments themselves. 3. Clinical Implications and Recommendations • Individual Risk Assessment: Clinicians should assess each patient's individual risk factors for ovarian cancer, including age, family history, and reproductive history, before initiating fertility treatments. • Informed Consent: Patients should be provided with comprehensive information regarding the potential risks and benefits of fertility treatments • Regular Surveillance: Women undergoing fertility treatments should receive regular gynecologic screenings and follow-up care to monitor for any signs or symptoms of ovarian cancer. • Shared Decision Making: Shared decision making between patients and healthcare providers is essential to ensure that treatment decisions align with patients' preferences and values. 4. Fertility Preservation Options • Most therapeutic options for Ovarian Cancer cause infertility, either by premature ovarian failure caused by cytotoxic agents in chemotherapy or surgical approaches that include unilateral or bilateral oophorectomy • In ovarian cancer patients, Oocyte cryopreservation is still the best option and the only one established along with embryo cryopreservation. Fertility preservation surgery can be suggested depending on histology, stage of disease and pre-existing ovarian reserve. • Ovarian tissue cryopreservation will not be an option as long as the risk of reseeding cancer cells is not fully eliminated. 5. Future Directions Advancements in molecular biology and genetics may shed light on the underlying mechanisms of ovarian cancer development and its potential association with fertility treatments. The artificial ovary and in vitro maturation of oocytes is a very attractive option in these patients, but further milestones have to be achieved

Rare presentation of recurrent ovarian carcinoma with secondary Budd–Chiari syndrome: a case report

BackgroundBudd–Chiari syndrome (BCS) is a rare condition, usually associated with hematological disorders such as thrombotic diathesis and hypercoagulability. Serum CA-125 level is an established tumor marker of ovarian malignancy; however, cases of primary BCS may also show raised CA-125 levels. BCS in a case of ovarian carcinoma is usually primary in nature due to hypercoagulable state, and raised CA-125 levels with tender hepatomegaly in a treated case of ovarian carcinoma usually imply metastatic recurrence in the liver. However, our case demonstrates an atypical secondary cause of BCS in such a patient caused by extrinsic compression of IVC due to recurrent disease.Case presentationWe report an unusual case of a 69-year-old female who presented with nausea and abdominal pain. She had a 7-year-old history of endometrioid carcinoma of the right ovary for which she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node dissection along with adjuvant chemotherapy. Currently, she had right hypochondrium tenderness, deranged liver function tests (LFT) and raised CA-125 levels, which raised suspicion of hepatic metastasis. However, CECT abdomen revealed peripheral mottled enhancement of liver with multifocal extrahepatic tumor deposits, one of them causing compression of inferior vena cava (IVC) implying a diagnosis of secondary Budd–Chiari syndrome.ConclusionsIn a background of treated ovarian malignancy with raised CA-125 levels and deranged LFT, primary suspicion is of hepatic tumor recurrence. However, in our case, radiological investigation revealed diagnosis of secondary Budd–Chiari syndrome due to perihepatic metastatic recurrence with the absence of frank intrahepatic lesions.

The Outcome of the Laparoscopic Hysterectomy in Al-Yarmouk Teaching Hospital in 2022–2023

Abstract Background: Hysterectomy is a common gynecological procedure used for various benign conditions like abnormal uterine bleeding, uterine prolapse, and fibroids. Different surgical methods, including vaginal, abdominal, laparoscopic, and robotic-assisted approaches, offer unique advantages and disadvantages. Total laparoscopic hysterectomy (TLH), introduced in 1989, offers benefits like smaller incisions, less blood loss, reduced pain, shorter hospital stays, and faster recovery. Objectives: The objective of this study was to evaluate patient outcomes, complications, and satisfaction with laparoscopic hysterectomy surgery. Patients and Methods: This cross-sectional study was conducted in Al-Yarmouk Teaching Hospital in Baghdad, General Surgery Department, from August 2022 to August 2023. Twenty-five patients who underwent laparoscopic hysterectomy for benign conditions were included. Patients were carefully assessed, ruling out malignancies through extensive clinical and radiological examinations, ultimately qualifying for the procedure. Data on patients’ demographics, comorbidities, previous surgical history, uterine size, indication for hysterectomy, type of procedures performed, and postoperative complications were gathered and subjected to analysis. The follow-up duration extended over 3 months, with assessments done on the 3rd day, 10th day, 1st month, and 3rd month postsurgery. Results: The mean age was 51.52 ± 9.47 years. Dysfunctional uterine bleeding was the most common indication (44%), followed by postmenopausal bleeding (32%). Most patients underwent TLH with bilateral salpingo-oophorectomy (BSO) (68%), and the mean operative time was 110 min. Complications were observed in 10 (40%) cases, with common issues being blood transfusion, port-site infection, and bladder injury. Hospitalization lasted 2 days, and postoperative pain reduced gradually over time. Patients who underwent concomitant BSO had significantly higher complications than those with isolated TLH. Postoperative pain levels were comparable between the two groups. Conclusion: Laparoscopic hysterectomy is an effective option for treating benign gynecological conditions, offering benefits like improved postoperative pain control and shorter hospital stays. However, the potential for complications, particularly in cases involving additional procedures, is to be considered.

Mixed Large Cell Neuroendocrine Carcinoma and Endometrioid Adenocarcinoma: A Rare Case Report with Review of Literature

ABSTRACT We report the case of a 60-year-old female who presented with postmenopausal bleeding after she underwent investigations followed by a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. A diagnosis of low-grade endometrioid adenocarcinoma admixed with large cell neuroendocrine carcinoma (NEC) was made based on the histomorphology and immunohistochemical profile. NEC of the endometrium is a rare and highly aggressive neoplasm requiring a multidisciplinary approach for its treatment. As treatment strategies are changing over time, preoperating imaging evaluation and histopathological examination with molecular characterization whenever possible are essential to follow, to offer the appropriate information to surgeons and/or oncologists for optimal management in these patients.

Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

Cutaneous Metastasis of Ovarian Tumor after Hysterectomy and Bilateral Salpingo-oophorectomy: A Case Report

OBJECTIVES Cutaneous metastases are a very rare presentation of ovarian tumors (OV). They occur in about 3.5 percent of cases. The prognosis of cutaneous metastases is not good despite recent treatment modalities. Researchers are looking for much more personalized treatments. The patient had a history of ovarian tumor, for which she had a hysterectomy and bilateral salpingo-oophorectomy. She presented with multiple cutaneous eruptions. The histopathology shows high-grade serous carcinoma of the ovaries. Immunochemistry is positive for cytokeratin 7, WT1, and CAX. She had developed left leg swelling, generalized edema, and complaints of dysuria and difficulty defecating. Many targeted therapies have been developed, such as inhibiting growth factor receptors and immunological treatments that induce cell death, opening the door to precision medicine.

Bilateral ovarian mature cystic teratoma co-existing with granulosa cell tumour: a case report

Background: Mature granulosa cell tumour (GCT) is a rare neoplasm. it accounts for about 1-2% of all ovarian tumours. Even more infrequent is the coexistence of GCT with mature cystic teratoma in the same ovary. Case presentation: A 53-year-old woman with constipation, abdominal swelling, and pain presented to our gynaecology clinic. Physical examination revealed a distended abdomen, ascites, cystocele, stress incontinence, and external haemorrhoids. A cystic teratoma co-existing with a granulosa cell tumour was diagnosed histologically. Adjuvant chemotherapy containing Cisplatin [75mg/m2] and Docetaxel [75mg/m2]) was completed, followed by radiotherapy. She has been clinically stable for two years and is currently on long-term follow-up to forestall recurrence. Conclusion: The coexistence of mature granulosa cell tumour (GCT) with mature cystic teratoma especially in the same ovary is an extremely rare pathology. Although total abdominal hysterectomy and bilateral salpingo-oophorectomy are the treatments of choice in postmenopausal and perimenopausal women, these may not always be feasible owing to the nature of the presentation. Adjuvant chemotherapy and radiotherapy may be beneficial as high cases of recurrence have been reported. Follow-ups are strongly advocated due to the recurrence that can occur even as late as 20 years following the removal of the primary neoplasm.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Transvaginal natural orifice transluminal endoscopic surgery (VNOTES) retroperitoneal sentinel lymph node BIOPSY compared with conventional laparoscopy in patients with endometrial cancer

IntroductionTo explore the possibility of treatment with VNOTES sentinel lymph node dissection concept in patients with endometrial cancer. MethodsPatients who underwent VNOTES sentinel lymph node biopsy with the Comba modification were compared to patients who underwent conventional laparoscopic sentinel lymph node biopsy performed by the same surgical team. A total of 38 patients who underwent sentinel lymph node biopsy + total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (BSO) were compared with 19 patients who underwent VNOTES retroperitoneal sentinel lymph node biopsy + hysterectomy and BSO. Surgical steps were described. ResultsThe average operation time, perioperative blood loss, the number of sentinel lymph nodes, presence of complications, and preoperative-postoperative hemoglobin-hematocrit differences, tumor stages, grades, largest tumor diameter, depths of invasion, and histological subtypes were similar in both the VNOTES and conventional laparoscopy groups. The postoperative pain scores were lower and the hospital stay was shorter in the VNOTES group than in the conventional laparoscopy group. No disease recurrence had been detected in either group at the time of writing. ConclusionCompared to conventional laparoscopy, sentinel lymph node biopsy with the VNOTES technique provides similar surgical results and is more advantageous in terms of postoperative pain and hospital length of stay.

Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers.

To estimate the incidence of primary peritoneal cancer after preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation. A total of 6310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy. The 20-year cumulative incidence of peritoneal cancer post-oophorectomy was estimated using the Kaplan-Meier method. A left-truncated Cox proportional hazards analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the age at oophorectomy, year of oophorectomy, and family history of ovarian cancer as well as hormonal and reproductive risk factors. Fifty-five women developed primary peritoneal cancer (n = 45 in BRCA1, 8 in BRCA2, and 2 in women with a mutation in both genes). Their mean age at oophorectomy was 48.9 years. The annual risk of peritoneal cancer was 0.14% for women with a BRCA1 mutation and 0.06% for women with a BRCA2 mutation. The 20-year cumulative risk of peritoneal cancer from the date of oophorectomy was 2.7% for BRCA1 carriers and 0.9% for BRCA2 mutation carriers. There were no peritoneal cancers in BRCA1 carriers who had the operation before age 35 or in BRCA2 carriers who had the operation before age 45. For BRCA1 mutation carriers, the annual risk of peritoneal cancer for 20 years post-oophorectomy is 0.14% per year. The risk is lower for BRCA2 carriers (0.06% per year).

Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization.

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RT&Aacute;qPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT full&Aacute;length transcriptome sequencing. EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to full&Aacute;length transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report

BackgroundMature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.Case presentationWe report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.ConclusionOvarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.

Estrogen alleviates liver fibrosis and restores metabolic homeostasis in ovariectomy-induced liver injury and carbon tetrachloride (CCl4) exposure

AimGiven estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations. MethodsFemale mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl4) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes. ResultsOvary removal exacerbated CCl4-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl4 treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl4. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment. ConclusionEstrogen supplementation alleviates liver injury induced by OVX and CCl4, highlighting its protective effects against fibrosis and associated metabolic alterations.

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life.

Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity. Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO<40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO<50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype. Females with PBO<40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity. Females who underwent PBO<40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions. Females with premenopausal bilateral oophorectomy (PBO)<40 years had lower FA versus referents. Females with PBO<40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens.

Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T. To assess the gonadal contribution to the circulating pool of 11-oxyandrogens. We used liquid chromatography-tandem mass spectrometry to measure 13 steroids, including traditional and 11-oxyandrogens in: (I) paired gonadal and peripheral vein blood samples obtained during gonadal venograms from 11 patients (7 women), median age 37 (range 31-51 years); and (II) 17 women, median age 57 (range 41-81 years) before and after bilateral salpingo-oophorectomy (BSO). We also compared CYP11B1, 17α-hydroxylase/17,20-lyase (CYP17A1), and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) mRNA expression in adrenal, ovarian, and testicular tissue. A4, T, estradiol, estrone, progesterone, 17α- and 16α-hydroxyprogesterone were all higher in gonadal veins vs. periphery (p < 0.05 for all), while four 11-oxyandrogens were similar between matched gonadal and peripheral vein samples. Equally, in women who underwent BSO, A4 (median [interquartile range]: 59.7 [47.7-67.6] ng/dL vs. 32.7 [27.4-47.8] ng/dL, p < 0.001) and T (24.1 [16.4-32.3] vs.15.5 [13.7-19.0] ng/dL, p < 0.001) declined, while 11-oxyandrogens remained stable. Gonadal tissue displayed negligible CYP11B1 mRNA. Despite producing substantial amounts of A4 and T, human gonads are not relevant sources of 11-oxyandrogens.