The latest medical research on Gynecologic Oncology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about gynecologic oncology gathered by our medical AI research bot.

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Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors.

Breast Cancer

The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells.

MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody.

In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter.

Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer.

Cost-effectiveness of clinical breast examination screening programme among HER2-positive breast cancer patients: a modelling study.

Breast Cancer

For many low- and middle-income countries (LMICs), breast cancer (BC) screening based on mammography is not a viable option. Clinical breast examination (CBE) may represent a pragmatic and cost-effective alternative. This paper examines the cost-effectiveness of CBE screening programme among a patient group for whom its cost-effectiveness is likely to be least evident (HER2-positive patients) and discuss the wider implications for BC screening in LMICs.

A Markov model was used to examine clinical and economic outcomes over a life-time horizon from the patient, public payer, and healthcare sector perspective. HER2-positive patients entered the model at either disease-free survival or metastatic BC state. The downstaging effect of CBE determined the starting probabilities in the no-screening and screening scenarios. The model used a monthly cycle length, with half-cycle correction. Costs and outcomes were discounted at 1.5% annually.

Compared with no-screening, the cost-effectiveness ratio (ICER) per quality-adjusted life-year gained for the CBE screening programme was $1801, $2381, and $4179 from three mentioned perspectives, respectively. The finding of cost-effectiveness remained robust to a range of sensitivity analyses. The parameters to which ICERs are most sensitive are average age of cohorts, reduction in proportion of metastatic patients at diagnosis, cost of CBE, and BC detection rate of the programme.

For HER2-positive patients and compared with no-screening, CBE screening programme in Vietnam is cost-effective from all investigated perspectives. CBE is a 'good value' intervention and should be considered for implementation throughout Vietnam as well as in LMICs where mammography is not feasible.

Risk factors associated with chronic pain after mastectomy: a prospective study with a 5-year follow-up in Japan.

Breast Cancer

Chronic pain is a major complication following breast surgery including breast reconstruction. We previously examined prospective patient-specific and medical/surgical factors that predict chronic pain a year after breast surgery in the Japanese population. Five-year survivorship is essential for breast cancer patients. This report is a 4-year follow-up study following the previous research.

A follow-up observation study was performed 5 years after breast operations. The subjects were patients who underwent breast surgery, including tissue expander/implant (TE/implant), DIEP procedures and mastectomy only. Pain at 5 years was assessed using the Japanese Version of the Short-Form McGill Pain Questionnaire (SF-MPQ-JV). A multiple linear regression model was used to examine the relationships of clinical factors with chronic pain.

Questionnaires were completed by 132 subjects. No factor related to chronic pain was significantly related to the MPQ pain ratings. Among patient characteristics, a psychotic or neurological medical history was related to significantly lower visual analog scale (p = 0.02) and present pain index (p = 0.04) scores. A history of chemotherapy and/or hormone therapy was significantly associated with the frequency of use of pain medication postoperatively (p = 0.05) and effect on the social life of the patients (p = 0.02).

A psychotic or neurological history and a history of chemotherapy and/or hormone therapy were identified as risk factors for chronic pain after breast surgery, but the type of operation was not associated with chronic pain.

Serotonin 5-HT7 receptor is a biomarker poor prognostic factor and induces proliferation of triple-negative breast cancer cells through FOXM1.

Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with poor prognosis and shorter survival due to significant genetic heterogeneity, drug resistance and lack of effective targeted therapeutics. Therefore, novel molecular targets and therapeutic strategies are needed to improve patient survival. Serotonin (5-hydroxytryptamine, 5-HT) has been shown to induce growth stimulatory effects in breast cancer. However, the molecular mechanisms by which 5-HT exerts its oncogenic effects in TNBC still are not well understood.

Normal breast epithelium (MCF10A) and two TNBC cells (MDA-MB-231, BT-546) and MCF-7 cells (ER +) were used to investigate effects of 5-HT7 receptor. Small interfering RNA (siRNA)-based knockdown and metergoline (5-HT7 antagonist) were used to inhibit the activity of 5-HT7. Cell proliferation and colony formation were evaluated using MTS cell viability and colony formation assays, respectively. Western blotting was used to investigate 5-HT7, FOXM1 and its downstream targets protein expressions.

We demonstrated that 5-HT induces cell proliferation of TNBC cells and expression of 5-HT7 receptor and FOXM1 oncogenic transcription factor. We found that expression of 5-HT7 receptor is up-regulated in TNBC cells and higher 5-HT7 receptor expression is associated with poor patient prognosis and shorter patient survival. Genetic and pharmacological inhibition of 5-HT7 receptor by siRNA and metergoline, respectively, suppressed TNBC cell proliferation and FOXM1 and its downstream mediators, including eEF2-Kinase (eEF2K) and cyclin-D1.

Our findings suggest for the first time that the 5-HT7 receptor promotes FOXM1, eEF2K and cyclin D1 signaling to support TNBC cell proliferation; thus, inhibition of 5-HT7 receptor/FOXM1 signaling may be used as a potential therapeutic strategy for targeting TNBC. 5-HT induces cell proliferation of TNBC cells through 5-HT7 receptor signaling. Also, genetic and pharmacological inhibition of 5-HT7 by RNAi (siRNA) and metergoline HTR7 antagonist, respectively inhibits FOXM1 oncogenic transcription factor and suppresses TNBC cell proliferation.

Artificial intelligence computer-aided detection enhances synthesized mammograms: comparison with original digital mammograms alone and in combination with tomosynthesis images in an experimental setting.

Breast Cancer

It remains unclear whether original full-field digital mammograms (DMs) can be replaced with synthesized mammograms in both screening and diagnostic settings. To compare reader performance of artificial intelligence computer-aided detection synthesized mammograms (AI CAD SMs) with that of DM alone or in combination with digital breast tomosynthesis (DBT) images in an experimental setting.

We compared the performance of multireader (n = 4) and reading multicase (n = 388), in 84 cancers, 83 biopsy-proven benign lesions, and 221 normal or benign cases with negative results after 1-year follow-up. Each reading was independently interpreted with four reading modes: DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT. The accuracy of probability of malignancy (POM) and five-category ratings were evaluated using areas under the receiver operating characteristic curve (AUC) in the random-reader analysis.

The mean AUC values based on POM for DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT were 0.871, 0.902, 0.895, and 0.909, respectively. The mean AUC of AI CAD SM was significantly higher (P = 0.002) than that of DM. For calcification lesions, the sensitivity of SM and DM did not differ significantly (P = 0.204). The mean AUC for AI CAD SM + DBT was higher than that of DM + DBT (P = 0.082). ROC curves based on the five-category ratings showed similar proximity of the overall performance levels.

AI CAD SM alone was superior to DM alone. Also, AI CAD SM + DBT was superior to DM + DBT but not statistically significant.

Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients.

Breast Cancer

Although arm lymphedema is a well-known complication following breast cancer surgery, previous studies involving a small population showed inconsistent results regarding the risk. Therefore, we examined the risk factors using a Japanese nationwide database.

Female patients who underwent breast cancer surgery from April, 2016, to March, 2020, were identified from a Japanese nationwide database. Multivariable survival analyses for 19 baseline factors (12 patient characteristics, four tumor characteristics, and three surgical procedures) were conducted to investigate risk factors associated with treatments for postoperative lymphedema (such as lymphatic bypass, compositive drainage therapy, hospitalization, and Kampo use) with a multilevel model to adjust for within-hospital clustering. We also conducted multivariable analysis for five postoperative factors (two local complications and three postoperative therapies) with adjustment for 19 baseline factors.

The study included 84,022 patients; 1547 (1.8%) received treatments for lymphedema during a median follow-up of 119 weeks (interquartile range, 59-187 weeks). Young age, obesity, smoking, collagen diseases, advanced cancer stage, total mastectomy, axillary dissection, postoperative bleeding, chemotherapy, and radiotherapy were identified as risk factors. Postoperative chemotherapy (hazard ratio, 3.78 [95% confidence interval, 3.35-4.26]) and axillary dissection (2.46 [1.95-3.11]) showed the highest odds ratio among the risk factors. The cumulative probabilities in high-risk patients reached approximately 3% at 1 year and 6% at 4 years after surgery.

This study identified several risk factors for postoperative lymphedema in breast cancer surgery. The treatment initiation increased markedly within the first year and gradually after 1 year post-surgery.

Predictive value of immune genomic signatures from breast cancer cohorts containing data for both response to neoadjuvant chemotherapy and prognosis after surgery.

Breast Cancer

Previous studies of immune genomic signatures (IGSs) in breast cancer have attempted to predict the response to chemotherapy or prognosis and were performed using different patient cohorts. The purpose of this study was to evaluate the predictive functions of various IGSs using the same patient cohort that included data for response to chemotherapy as well as the prognosis after surgery.

We applied five previously described IGS models in a public dataset of 508 breast cancer patients treated with neoadjuvant chemotherapy. The prognostic and predictive values of each model were evaluated, and their correlations were compared.

We observed a high proportion of expression concordance among the IGS models (r: 0.56-1). Higher scores of IGSs were detected in aggressive breast cancer subtypes (basal and HER2-enriched) (P < 0.001). Four of the five IGSs could predict chemotherapy responses and two could predict 5-year relapse-free survival in cases with hormone receptor-positive (HR +) tumors. However, the models showed no significant differences in their predictive abilities for hormone receptor-negative (HR-) tumors.

IGSs are, to some extent, useful for predicting prognosis and chemotherapy response; moreover, they show substantial agreement for specific breast cancer subtypes. However, it is necessary to identify more compelling biomarkers for both prognosis and response to chemotherapy in HR- and HER2 + cases.

Determining a threshold measurement of endometrial thickness for asymptomatic postmenopausal women: A tertiary centre case series.

Australian and New Zealand Journal

An incidental finding of a thickened endometrium on ultrasound in the postmenopausal patient without bleeding is a common presentation to gynaecological services; however there is limited evidence to guide clinical practice as to when hysteroscopic evaluation and endometrial sampling is required.

To determine the endometrial thickness at which endometrial sampling is indicated in asymptomatic postmenopausal women referred with thickened endometrium on ultrasound.

A single-centre retrospective case series of postmenopausal women without bleeding undergoing hysteroscopy was conducted. Logistic regression was used to examine the association between a range of variables and pre-malignant or malignant pathology and endometrial thickness. The optimal endometrial thickness threshold was identified to maximise model sensitivity.

A total of 404 postmenopausal women were included in this study, having undergone a hysteroscopy at the study site between 1 July 2008 and 30 June 2018. The mean (SD) age of patients at presentation was 65 (9.09) years and the mean body mass index was 29.86 kg/m2 (6.52). Of these women, nine (2.2%) were diagnosed with endometrial carcinoma and seven (1.7%) had endometrial hyperplasia with atypia. The most common histopathological finding was of a benign endometrial polyp (153: 37.9%). When including hyperplasia with or without atypia in histopathology of interest, a cut-off of ≥9 mm provides the greatest sensitivity (83.3%) and specificity (63.8%) for a diagnosis of pre-malignant or malignant pathology (classification accuracy of 64.8%; area under the receiver operating characteristic: 0.7358, 95% CI: 0.6439, 0.8278) in this cohort.

Using an endometrial thickness of ≥9 mm can be used as a cut-off for endometrial sampling in postmenopausal women without bleeding.

A novel ADC targeting cell surface fibromodulin in a mouse model of triple-negative breast cancer.

Breast Cancer

Triple-negative breast cancers (TNBCs) are highly aggressive and metastatic. To date, finding efficacious targeted therapy molecules might be the only window of hope to cure cancer. Fibromodulin (FMOD), is ectopically highly expressed on the surface of Chronic Lymphocytic Leukemia (CLL) and bladder carcinoma cells; thus, it could be a promising molecule for targeted therapy of cancer. The objective of this study was to evaluate cell surface expression of FMOD in two TNBC cell lines and develop an antibody-drug conjugate (ADC) to target FMOD positive TNBC in vitro and in vivo.

Two TNBC-derived cell lines 4T1 and MDA-MB-231 were used in this study. The specific binding of anti-FMOD monoclonal antibody (mAb) was evaluated by flow cytometry and its internalization was verified using phAb amine reactive dye. A microtubulin inhibitor Mertansine (DM1) was used for conjugation to anti-FMOD mAb. The binding efficacy of FMOD-ADC was assessed by immunocytochemistry technique. The anti-FMOD mAb and FMOD-ADC apoptosis induction were measured using Annexin V-FITC and flow cytometry. Tumor growth inhibition of anti-FMOD mAb and FMOD-ADC was evaluated using BALB/c mice injected with 4T1 cells.

Our results indicate that both anti-FMOD mAb and FMOD-ADC recognize cell surface FMOD molecules. FMOD-ADC could induce apoptosis in 4T1 and MDA-MB-231 cells in vitro. In vivo tumor growth inhibition was observed using FMOD-ADC in 4T1 inoculated BALB/c mice.

Our results suggests high cell surface FMOD expression could be a novel bio-marker TNBCs. Furthermore, FMOD-ADC could be a promising candidate for targeting TNBCs.

Ethical implementation of mitochondrial donation in Australia.

Australian and New Zealand Journal

Australia has recently legalised mitochondrial donation. However, key ethical and legal issues still need to be addressed. This paper maps the rele...

Post-repair laxative management in obstetric anal sphincter injury guidelines: A narrative review.

Australian and New Zealand Journal

Childbirth is a common factor which increases the risk of obstetric anal sphincter injuries (OASIS). Damage to the anal sphincters increases the risk of anal incontinence, which has a debilitating impact on the quality of life. Post-repair laxatives are prescribed in this group of women. However, there is no consensus regarding the type or frequency with which they are used, and available guidelines lack consistency and evidence to support the recommendations.

The aim was to review and compare the international, national and local Australian management guidelines for recommendations regarding laxative use in women after OASIS.

An online literature search of medical and nursing databases such as PubMed, Embase, MEDLINE, CINAHL, Web of Science, Scopus and Cochrane was performed between January 2000 and October 2020. Full-text articles with MeSH headings and Text Words [TW] identified guidelines in the prevention, management and care of OASIS. The search terms included 'obstetric anal sphincter injury', 'OASIS', 'perineal tear', 'postpartum continence', 'bowel injury', 'aperient', 'laxative use' and 'bulking agents'.

Thirteen guidelines were included. Laxatives were recommended in most guidelines; however, there was a lack of consistency regarding the type of laxative used, frequency, dose and duration of use. Guidelines were based on historical evidence, with paucity of recently acquired data identified.

There is no consensus regarding an optimal laxative regime for women who sustain an anal sphincter injury after childbirth. Further research is required to develop evidence-based robust clinical guidelines regarding laxative use in women who sustain OASIS.

Gestational diabetes screening from the perspective of consumers: Insights from early in the COVID-19 pandemic and opportunities to optimise experiences.

Australian and New Zealand Journal

Consumer perspectives are a cornerstone of value-based healthcare. Screening and diagnosis of gestational diabetes mellitus (GDM) were among many of the rapid changes to health care recommended during the COVID-19 pandemic. The changes provided a unique opportunity to add information about women's perspectives on the debate on GDM screening.

The aim of this qualitative study was to explore women's perspectives and understanding of GDM screening and diagnosis comparing the modified COVID-19 recommendations to standard GDM screening and diagnostic practices.

Women who had experienced both the standard and modified GDM screening and diagnostic processes were recruited for telephone interviews. Data analysis used inductive reflexive thematic analysis. Online surveys were disseminated to any registrant not included in interviews to provide an opportunity for all interested participants to provide their perspective.

Twenty-nine telephone interviews were conducted and 19 survey responses were received. Seven themes were determined: (1) information provision from clinicians; (2) acceptability of GDM screening; (3) individualisation of GDM screening methods; (4) safety nets to avoid a missed diagnosis; (5) informed decision making; (6) women want information and evidence; and (7) preferred GDM screening methods for the future.

Overall, women preferred the modified GDM screening recommendations put in place due to the COVID-19 pandemic. However, their preference was influenced by their prior screening experience and perception of personal risk profile. Women expressed a strong need for clear communication from health professionals and the opportunity to be active participants in decision making.