A multi-centre randomised controlled trial comparing megestrol acetate to levonorgestrel-intrauterine system in fertility sparing treatment of atypical endometrial hyperplasia.

PURPOSE: The objective of the trial was to compare the regression rate of atypical endometrial hyperplasia (AEH) in patients treated with megestrol acetate (MA) vs. levonorgestrel-intrauterine device (LNG-IUS). We also aimed to assess the fertility and pregnancy outcomes in these patients. METHODS: The study was a phase II multi-centre randomised controlled trial on the use of MA compared to LNG-IUS in the treatment of AEH conducted from January 2020 to January 2024 in Singapore. Women who were diagnosed with AEH and between 21 and 40 years old were included. The patients were randomised to receive either MA (160 mg orally daily) or LNG-IUS. The primary outcomes assessed were the regression rates at 3 months, 6 months and 9 months of treatment. The secondary outcomes assessed were the side effects, patient acceptability and fertility outcomes. RESULTS: Thirty-six patients completed the trial. The overall regression rate was 88.9% by 9 months. There was no statistically significant difference in the 9-month complete regression rate between MA vs. LNG-IUS. There was also no significant difference in side effects and weight change between both arms. Nineteen patients were actively pursuing fertility after complete regression. There were 8 pregnancies achieved, with resultant 4 live births and 4 miscarriages. CONCLUSION: Our study confirms a high regression rate of AH with medical treatment. LNG-IUS is a non-inferior treatment compared to megestrol acetate. Successful pregnancy outcomes can be achieved after regression of AEH. Long-term studies of sufficient sample-size are needed to assess for fertility and pregnancy outcomes, risk of recurrence and long-term risk of malignancy. TRIAL REGISTRATION NUMBER: The study was registered with the Health Science Authority (HSA) (License No.: CTA1900087) on September 5, 2019: https://eservice.hsa.gov.sg/prism/ct_r/enquiry.do?action=loadSpecificDetail . The trial was registered retrospectively on ClinicalTrials.gov (ID: NCT05492487) on April 7, 2022: https://clinicaltrials.gov/study/NCT05492487 .

Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case.

Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.

An eight-year analysis of robotic surgery in morbidly obese women with endometrial cancer in a tertiary center in Singapore.

Introduction: Surgical management of endometrial cancer is a total hysterectomy, bilateral salphingo-oophorectomy and pelvic lymph node dissection (THBSO-PLND), which is a challenging surgery in the morbidly obese. Data on morbidly obese women undergoing robotic surgery is limited in Asia. We share our experience in Singapore and aim to demonstrate that robotic surgery is safe and effective in morbidly obese women with endometrial cancer. Materials and Methods: We performed a retrospective analysis of patients with BMI > 40 kg/m2, who underwent robotic surgery from January 2016 to September 2023 at the Singapore General Hospital. We recruited a total of 33 patients who underwent robotic surgery for endometrial malignancy and analysed surgical outcomes, operative complications, and survival rates. Results: The average age of patients was 53 years and mean BMI 45.7. The average operative time was 232 min and average blood loss 184 ml. 3 patients had THBSO while 27 underwent THBSO-PLND. None required conversion to laparotomy. 4 patients required a mini-laparotomy for the retrieval of bulky uterus. 12 required adhesiolysis. 6 patients had additional omentectomy done. The average inpatient stay was 4.8 days. The 1-year mortality rate is 0. However, 1 patient passed away 13 months after surgery due to complications from bowel obstruction and another passed away 39 months later due to disease recurrence. 1 patient readmitted on POD6 due to post-op ileus and another for port-site hematoma. Both were managed conservatively. Conclusion: Robotic surgery is a safe and effective alternative surgical tool for women who are morbidly obese with endometrial cancer.

Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.

Breast metastasis from endometrial clear cell carcinoma: A case report and review of the literature.

Metastasis to the breast from extra-mammary malignancies are rare, accounting for less than 1% of all breast cancers. Endometrial cancer, a common gynecological malignancy, often spreads to the pelvis, abdominal lymph nodes, peritoneum or the lungs. Endometrial metastasis to the breast is extremely rare, and while there have been isolated case reports of endometrial serous carcinoma with breast metastasis, it has not been reported in the case of clear cell carcinoma. We present a rare case of a 70 year old Chinese lady who had a metastatic endometrial clear cell carcinoma with metastasis to the breast, mimicking an inflammatory breast cancer clinically. We reviewed the current literature and describe the challenges in differentiating primary from metastatic breast lesions, as well as clinical, radiological and histopathological features that may help to differentiate the two. Tumour metastasis to the breast via lymphatic or hematogenous route can affect their radiological features: the former mimicking inflammatory breast cancer and the latter with features similar to benign breast lesions. Regardless, histological features with immunohistochemical staining is still the gold standard in diagnosing metastatic breast lesions and determining their tissue of origin. Breast metastases from extra-mammary malignancies are uncommon and it is even rarer for endometrial clear cell carcinoma to spread to the breast. Nonetheless, this case highlights the importance of keeping an open mind and engaging a multidisciplinary team for the care of complex patients.

Identifying ataxia-telangiectasia in cancer patients: Novel insights from an interesting case and review of literature.

Timely genetic testing leading to early diagnosis of A-T is crucial due to its plethora of implications on clinical management, particularly in those who develop malignancies. Thus, clinicians have to be astute in identifying diagnostic clues of A-T.

A machine learning approach to identify predictive molecular markers for cisplatin chemosensitivity following surgical resection in ovarian cancer.

Ovarian cancer is associated with poor prognosis. Platinum resistance contributes significantly to the high rate of tumour recurrence. We aimed to identify a set of molecular markers for predicting platinum sensitivity. A signature predicting cisplatin sensitivity was generated using the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas databases. Four potential biomarkers (CYTH3, GALNT3, S100A14, and ERI1) were identified and optimized for immunohistochemistry (IHC). Validation was performed on a cohort of patients (n = 50) treated with surgical resection followed by adjuvant carboplatin. Predictive models were established to predict chemosensitivity. The four biomarkers were also assessed for their ability to prognosticate overall survival in three ovarian cancer microarray expression datasets from The Gene Expression Omnibus. The extreme gradient boosting (XGBoost) algorithm was selected for the final model to validate the accuracy in an independent validation dataset (n = 10). CYTH3 and S100A14, followed by nodal stage, were the features with the greatest importance. The four gene signature had comparable prognostication as clinical information for two-year survival. Assessment of tumour biology by means of gene expression can serve as an adjunct for prediction of chemosensitivity and prognostication. Potentially, the assessment of molecular markers alongside clinical information offers a chance to further optimise therapeutic decision making.

Relevance of enlarged cardiophrenic lymph nodes in determining prognosis of patients with advanced ovarian cancer.

Ovarian cancer often presents at an advanced stage with widespread peritoneal and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of treatment for disease confined to peritoneum. But in patients with distant metastases, the role and rationale is less obvious. One of the the most common sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this paper, we described the management of a patient with International Federation of Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent complete cytoreduction including excision of enlarged CPLN, following neoadjuvant chemotherapy. We examined the literature to determine the prognostic value of enlarged CPLN and their relevance in managing patients with advanced ovarian cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision of CPLN is feasible without major complications. But as its correlation with overall or progression-free survival is not yet evident, large-scale prospective studies are warranted.

Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques.

INTRODUCTION: Assisted reproductive techniques (ARTs) result in a deficient luteal phase, requiring the administration of intramuscular, intravaginal or oral exogenous progesterone. Dydrogesterone, an oral retroprogesterone with good bioavailability, has been used in assisted reproductive cycles with outcomes that are comparable to those of vaginal or intramuscular progesterone. However, there are limited reviews on its use for luteal phase support in ARTs, in terms of pregnancy outcomes and associated fetal anomalies. This study aimed to review the live birth rates and associated fetal anomalies of women who were given dydrogesterone for luteal phase support in assisted reproductive cycles at a tertiary hospital in Singapore. METHODS: This retrospective descriptive study included 1,050 women who underwent in vitro fertilisation/intracytoplasmic sperm injection at the Centre for Assisted Reproduction of Singapore General Hospital between 2000 and 2011. The women were given dydrogesterone for luteal phase support. The main outcome measures were rates of pregnancy, live birth, miscarriage and fetal anomalies. RESULTS: The pregnancy and live birth rates were 34.7% and 27.7%, respectively. Among those who achieved pregnancy, 17.0% miscarried, 0.8% had ectopic pregnancies and 0.3% had molar pregnancies. Fetal anomalies were detected in 1.9% of pregnancies, all of which were terminated by choice. CONCLUSION: Since the outcomes of dydrogesterone are comparable to those of intramuscular and vaginal progesterone, it is a reasonable option to provide luteal phase support for women who are uncomfortable with injections or vaginal insertions. Randomised controlled studies are needed to determine the optimal dosage of dydrogesterone for luteal phase support in ARTs.

Novel management of a giant cervical myoma in a premenopausal patient.

Cervical myomas are rare and account for <1% of uterine leiomyomas. Clinical complications include bulk-related symptoms of pelvic pain, abnormal bleeding and infertility. While hysterectomies may be readily performed for postmenopausal women; the management of women with cervical myomas of childbearing age remains a challenge.Traditionally described fertility-preserving procedures such as myomectomy, endometrial ablation or myolysis may only be applied to leiomyomas within the uterine corpus. Little is known about the surgical management of its cervical counterpart.Radical abdominal trachelectomy has been described as a potential fertility-preserving procedure in the management of women with early cervical cancer. As such, we present a case of a giant cervical myoma that was treated with an abdominal trachelectomy in an attempt to preserve fertility.

A randomised controlled trial of expectant management versus surgical evacuation of early pregnancy loss.

OBJECTIVE: To show whether a clinically significant difference in success rates exists between expectant and surgical management of early pregnancy loss. STUDY DESIGN: Randomised controlled trial comparing expectant versus surgical management of early pregnancy loss over a 1-year period from 1st January to 31st December 2009 at Sultanah Aminah Hospital, Johor Bahru. Pregnant women with missed or incomplete miscarriages at gestations up to 14 weeks were recruited in this study. The success rate in the surgical group was measured as curettage performed without any complications during or after the procedure, while the success rate in the expectant group was defined as complete spontaneous expulsion of products of conception within 6 weeks without any complication. RESULTS: A total of 360 women were recruited and randomised to expectant or surgical management, with 180 women in each group. There was no statistically significant difference in the success rate between the groups and between the different types of miscarriage. With expectant management, 131 (74%) patients had a complete spontaneous expulsion of products of conception, of whom 106 (83%) women miscarried within 7 days. However, the rates of unplanned admissions (18.1%) and unplanned surgical evacuations (17.5%) in the expectant group were significantly higher than the rates (7.4% and 8% respectively) in the surgical group. The complications in both groups were similar.