Obesity is a significant health issue associated with increased cancer risks, including gynecological malignancies. The worldwide rise in obesity rates is significantly impacting both cancer ...development and treatment outcomes. Adipose tissue plays a crucial role in metabolism, secreting various substances that can influence cancer formation. In obese individuals, dysfunctional adipose tissue can contribute to cancer development through inflammation, insulin resistance, hormonal changes, and abnormal cholesterol metabolism. Studies have shown a strong correlation between obesity and gynecological cancers, particularly endometrial and breast cancers. Obesity not only increases the risk of developing these cancers but is also associated with poorer outcomes. Additionally, obesity affects the perioperative management of gynecological cancers, requiring specialized care due to increased complications and resistance to therapy. Treatment strategies for managing metabolic dysregulation in patients with gynecological cancers include weight management, statin therapy, and insulin-sensitizing medications. Emerging studies suggest that interventions like intermittent fasting and caloric restriction may enhance the effectiveness of cancer treatments. Furthermore, targeting cholesterol metabolism, such as with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shows potential in cancer therapy. In conclusion, addressing metabolic issues, particularly obesity, is crucial in preventing and treating gynecological malignancies. Personalized approaches focusing on weight management and metabolic reprogramming may improve outcomes in these patients.
Obesity is associated with increased incidence of ovarian (OC), cervical (CC) and endometrium cancer (EC). However, the impact of body composition (BC) on overall survival (OS), especially of ...visceral adipose tissue (VAT) is not yet understood.
In 189 women with gynecological malignancies (31 OC, 104 CC, 54 EC, mean age 62.9y; mean BMI 26.8 kg/m
; median follow-up 30.7months) with routine staging CT-scans at baseline (mean interval: 4.3 months), densitometric quantification of total (TAT), visceral, and subcutaneous-fat-area (SAT), inter-muscular-fat-area (IMFA), and skeletal-muscle-index (SMI) was performed to analyze the impact of BC on survival.
With a mean follow-up of 30.7 months 48 patients had died. We observed no significant differences regarding BMI, the adipose- and muscle-distribution between surviving and deceased women. Univariate analyses revealed no significant BC-parameter with impact on OS, which was confirmed by different multivariate models. A subgroup analysis of OC, CC and EC showed only a protective impact of SMI on survival in the subgroup of CC.
Despite the increased incidence of gynecological malignancies in obese, we found no significant impact of BC including VAT on patient survival. Further studies with larger cohorts are needed to quantify BC and its metabolomic impact regarding treatment and prognosis.
The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected ...with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.
In the management of uterine myomas, laparoscopic surgery with morcellation enables a minimal invasive procedure. Cases of unsuspected uterine sarcoma dissemination have been reported and led to ...regulative restrictions. To help to distinguish preoperatively myomas from sarcomas, we assessed the value of six sonographic criteria (Basel Sarcoma Score, BSS) in a prospective outpatient cohort of consecutive patients with uterine masses.
We prospectively evaluated all patients presenting with myoma-like masses planned for surgery with standardized ultrasound examination. BSS including the following criteria was investigated: rapid growth in past three months, high blood flow, atypical growth, irregular lining, central necrosis and oval solitary lesion. For each criterion, a score 0/1 was given. BSS (0–6) equals the sum of all given scores. Histological diagnosis was used as reference.
Among 545 patients, 522 had the final diagnosis of myoma, 16 had peritoneal masses with sarcomatous components (PMSC), and seven had other malignancies. Median BSS for PMSC was 2.5 (range: 0–4) vs 0 for myomas (range: 0–3). The most common sonographic criteria leading to a false positive score in myomas were rapid growth in past three months and high blood flow. For the detection of sarcomatous masses with BSS threshold of >1, sensitivity was 93.8%, specificity 97.9%, and positive predictive value (PPV) and negative predictive value (NPV) were 57.7% and 99.8%, respectively (AUC 0.95).
BSS can help distinguishing between myomas and sarcomatous masses, with high NPV. Caution is required when >1 criterion is present. As a simple tool, it could easily be integrated into routine myoma sonographic examination and help develop standardized assessment of uterine masses for better preoperative triage.
•The Basel-Sarcoma-Score (BSS) is a valuable tool in the preoperative distinction of myoma from uterine sarcoma.•BSS is simple and has high NPV: minimally invasive surgery can be discussed if BSS is negative.•Using a threshold of >1 as cut-off for malignancy showed the best overall test performance.•BSS improves patient counseling and allows for choosing the best surgical procedure.•BSS underscores the value of standardized ultrasound in patients referred for surgery in gynecological oncology.
Evidence suggests potential associations between gynecological malignancies and various immune cell chemicals and systems. However, establishing a causal relationship remains uncertain.
This work ...employed Wald ratio for one single-nucleotide polymorphism (SNP) or the inverse-variance weighted method (IVW) for multiple SNPs to conduct bidirectional two-sample Mendelian randomization (MR) analysis by utilizing genome-wide association study (GWAS) data. We employed supplementary methods, including MR-Egger and weighted median methods, to detect and correct for the influence of horizontal pleiotropy. In addition, we also use colocalization analysis for further validation.
In IVW analysis, increases in relative count of circulating CD11c
HLA-DR
conventional dendritic cells (cDC) were associated with an elevated risk of breast cancer (OR 95% CI, 1.1295 1.0632-1.2000, P = 8.044 × 10
), while elevated levels of HLA-DR on plasmacytoid dendritic cells (DC) and HLA-DR on DC were protective against breast cancer. In addition, actual count of CD39
resting Treg AC was also shown to be causally associated with the development of ovarian cancer, whereas a high relative count of CD28
CD45RA
CD8
T cells reduced the risk of cervical cancer. Sensitivity analysis revealed almost no evidence of bias in the current study. Multivariable MR (MVMR) analyses further confirmed a direct impact of the CD11c
HLA-DR
cDC immune phenotype on breast cancer. Colocalization analysis showed the lead SNP, rs780094, suggesting HLA-DR GWAS shared a common genetic mechanism with breast cancer.
The MR study identified significant causal relationships between multiple immunophenotypes and breast cancer, aiming to provide clinicians with some reference for cancer prediction and explore further potential associations between immune phenotypes and gynecologic tumors.
To explore the effect of a short-term, hospital-based, multimodal preoperative prehabilitation intervention on perioperative functional ability of patients with gynecological malignant tumors.
...According to the order in which they underwent surgery, 97 patients were divided into the control group (48 cases) and the intervention group (49 cases). The control group was given routine preoperative guidance, whereas the intervention group was given short-term multimodal prehabilitation guidance on the basis of the control group intervention. The 6-min walk test was performed on the day of admission to the hospital, the day before surgery, and the 30th day after surgery.
Compared with the control group, the intervention group had significantly better 6-min walk distance and superior physical and psychological status on the day before surgery and the 30th day after surgery (P < 0.001). For three consecutive days after surgery, the quality of recovery in the intervention group was significantly higher than that in the control group (P < 0.001), and the first ambulation time and exhaust time were achieved earlier in the intervention group than in the control group (P < 0.05).
The preoperative intervention group showed improved preoperative exercise ability and reduced anxiety in patients with gynecological cancer. Furthermore, this intervention improved the overall health of patients and accelerated their postoperative recovery.
•This study designed a prehabilitation strategy for gynecological tumor patients.•This strategy is a short-term multimodal prehabilitation intervention program.•The strategy improves the overall health of patients and promotes their recovery.•The strategy offers new ideas to improve the health of gynecologic tumor patients.
The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. ...Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.
•Introducing tissue expression of HOXA11 as a diagnostic marker for endometriosis•CD10 and HOXA11 co-expression identify endometriotic tissue with high sensitivity.•Co-expression differentiates endometriotic lesions from other pathological lesions.
•Inhibiting cell cycle regulator WEE1 induces mitotic catastrophe & cancer cell death.•Gynecological cancers are a plausible target for WEE1 inhibition.•Multiple clinical trials reported promising ...results for WEE1 inhibitors.
The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.
Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i. The primary objective was to summarize the efficacy of WEE1i in gynecological malignancies regarding objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression-free survival (PFS). Secondary objectives included toxicity profile, Maximum Tolerated Dose (MTD), pharmacokinetics, drug-drug interactions and exploratory objectives such as biomarkers for response.
26 records were included for data extraction. Almost all trials used the first-in-class WEE1i adavosertib; one conference abstract reported about Zn-c3. The majority of the trials included diverse solid tumors (n = 16). Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in combination with chemotherapy ranged between 23% and 43% in these trials. Median PFS ranged from 3.0 to 9.9 months. The most common adverse events were bone marrow suppression, gastrointestinal toxicities and fatigue. Mainly alterations in cell cycle regulator genes TP53 and CCNE1 were potential predictors of response.
This report summarizes encouraging clinical development of WEE1i in gynecological cancers and considers its application in future studies. Biomarker-driven patient selection might be essential to increase the response rates.
To date, surgery, chemotherapy and radiotherapy are mainly used to treat or remove gynecological malignancies. However, these approaches have their limitations when facing complicated female diseases ...such as advanced cervical and endometrial cancer (EC), chemotherapy-resistant gestational trophoblastic neoplasia and platinum-resistant ovarian cancer. Instead, immunotherapy, as an alternative, could significantly improve prognosis of those patients receiving traditional treatments, with better antitumor activities and possibly less cellular toxicities. Its’ development is still not fast enough to meet the current clinical needs. More preclinical studies and larger-scale clinical trials are required. This review aims to introduce the landscape and up-to-date status of immunotherapy against gynecological malignancies, with a discussion of the challenges and future direction.
●Gynecological malignancies bring a huge burden on women's health.●Immunotherapy is a promising treatment for gynecological malignancies.●Diverse immune strategies provide different outcomes for patients.●New and combined immune strategies remain to be found.
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