Qian Wang

Efficacy of sentinel lymph node mapping in endometrial cancer with low‐ or high‐intermediate risk

AbstractBackground and ObjectivesThis study was aimed to evaluate the efficacy of sentinel lymph node (SLN) mapping using indocyanine green (ICG) in Chinese women with endometrial cancer (EC).MethodsConsecutive EC patients undergoing SLN mapping at Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. Overall and bilateral SLN detection rates and SLN locations were presented. Sensitivity, negative predictive value (NPV), and agreement rate were calculated and were compared between patients with low‐intermediate (LIR) or high‐intermediate risk (HIR).ResultsThere were 454 patients screened, with SLN mapping with ICG performed in 428 patients and systematic lymphadenectomy performed in 159 patients. Overall and bilateral SLN detection rates were 96.50% and 82.71%, respectively. The sensitivity of SLN mapping was 80.00%, and the NPV was 97.76%. SLNs were most commonly located in obturator and external iliac regions. Efficacy of SLN mapping was higher in LIR patients than in HIR patients, with sensitivities of 100.00% and 75.00% (p > 0.05), NPVs of 100.00% and 90.00% (p = 0.002), and agreement rates of 100.00% and 92.31% (p = 0.007), respectively.ConclusionSLN mapping with ICG had acceptable diagnostic efficacy in Chinese women with EC, but may cause more missed diagnoses in patients with HIR due to relatively low NPV and agreement rate.

The efficiency of a combined injection technique for sentinel lymph node mapping in intermediate‐high‐risk endometrial cancer

AbstractBackground and ObjectivesSentinel lymph node (SLN) mapping was considered for treating endometrial cancer (EC) which was apparent confined to the uterus. Nevertheless, intermediate‐high‐risk EC patients have super high risk to undergo isolated para‐aortic lymph node metastases comparing with low‐risk patients. Therefore, this investigation aimed to compare the efficacy of two SLN methods in detecting para‐aortic lymph node metastases.MethodsAccording to SLN mapping injection methods, intermediate‐high‐risk EC patients who received both SLN mapping and systematic lymphadenectomy were divided into the combined group (fundal and cervical injections) and the cervical group (cervical injection only).ResultsThe para‐aortic SLN detection rate in the combined group (40.4%) was higher than that in the cervical group (4.4%) with p < 0.001. While the differences concerning the sensitivity, false‐negative rate, and negative predictive value between the two groups were not significant. The survival outcomes of patients were comparable between the two groups.ConclusionOur data showcased that the combined (fundal and cervical) injection had a higher detection rate of para‐aortic SLNs than cervical injection only. The efficiency of SLN mapping and the survival outcomes were not significantly different between the two groups. Further investigations are warranted to assess the value of combined injection regarding SLN technique.

Fertility-preserving treatment outcome in endometrial cancer or atypical hyperplasia patients with polycystic ovary syndrome

This study aimed to investigate the impact of polycystic ovary syndrome (PCOS) on fertility-sparing treatment in young patients with atypical endometrial hyperplasia (AEH) or endometrioid endometrial cancer (EEC). A total of 285 patients with EEC (n=76, FIGO stage IA, without myometrium invasion) or AEH (n=209) who received progestin-based fertility-sparing treatment were evaluated retrospectively. Among the 285 patients, 103 (36.1%), including 70 AEH cases and 33 EEC cases, were diagnosed with PCOS. General characteristics, cumulative 16- and 32-week complete response (CR) rate, pregnancy outcome and recurrence were compared between patients with or without PCOS. The cumulative 16-week CR rate was lower in the PCOS group than in the non-PCOS group (18.4% vs. 33.8%, p=0.006). Patients with PCOS took longer treatment duration to achieve CR (7.0 months vs. 5.4 months, p=0.006) and shorter time to relapse after CR (9.6 months vs. 17.6 months, p=0.040) compared with non-PCOS group. After adjusting for patient age, body mass index, PCOS, homeostasis model assessment-insulin resistance index, and serum testosterone levels, we found that body mass index ≥25 kg/m² (HR=0.583; 95% CI=0.365-0.932; p=0.024) and PCOS (HR=0.545; 95% CI=0.324-0.917; p=0.022) were significantly correlated with lower 16-week CR rate. PCOS was associated with lower 16-week CR rate, longer treatment duration and shorter recurrence interval in patients with AEH or EEC receiving fertility-preserving treatment.

UniCAS: A foundation model for cervical cytology screening

Cervical abnormality screening is pivotal for prevention and treatment. However, the substantial size of whole slide images (WSIs) makes examination labor-intensive and time-consuming. Current deep learning-based approaches struggle with the morphological diversity of cervical cytology and require specialized models for distinct diagnostic tasks, leading to fragmented workflows. Here, we present UniCAS, a cytology foundation model pre-trained on 48,532 cervical WSIs encompassing diverse patient demographics and pathological conditions. UniCAS enables various clinical analysis tasks, achieving state-of-the-art performance in slide-level diagnosis, region-level analysis, and pixel-level image enhancement. In particular, by integrating a multi-task aggregator for slide-level diagnosis, UniCAS achieves area under the curve (AUC) values of 92.60%, 92.58%, and 98.39% for cancer screening, candidiasis testing, and clue cell diagnosis, respectively, while reducing diagnostic time by 70% compared with conventional approaches. This work establishes a paradigm for efficient multi-scale analysis in automated cervical cytology, bridging the gap between computational pathology and clinical diagnostic workflows.

Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis

AbstractChronic stress has been shown to facilitate progression of epithelial ovarian cancer (EOC), however, the neuro-endocranial mechanism participating in this process still remains unclear. Here, we reported that chronic restraint stress (CRS) promoted the abdominal implantation metastasis of EOC cells and the expression of epithelial–mesenchymal transition-related markers in tumor-bearing mouse model, including TWIST, SLUG, SNAIL, and β-catenin. We observed that β-catenin co-expressed with SLUG and norepinephrine (NE) in tumor tissues obtained from nude mice. Further ex vivo experiments revealed that NE promoted migration and invasion of ovarian cancer cells and SLUG expression through upregulating expression and improving transcriptional function of β-catenin in vitro. A human phosphor-kinase array suggested that NE activated various kinases in ovarian cancer cells, and we further confirmed that AKT inhibitor reduced NE-mediated pro-metastatic impacts and activation of the β-catenin/SLUG axis. Furthermore, the expression levels of NE and β-catenin were examined in ovarian tumor tissues by using tumor tissue arrays. Results showed that the expression levels of both NE and β-catenin were associated with poor clinical stage of serous EOC. Moreover, we found that melatonin (MLT) effectively reduced the abdominal tumor burden of ovarian cancer induced by CRS, which was partially related to the inhibition of the NE/AKT/β-catenin/SLUG axis. Collectively, these findings suggest a novel mechanism for CRS-mediated ovarian cancer metastasis and MLT has a potential therapeutic efficacy against ovarian cancer.

Dietary phytoestrogen intake and lung cancer risk: an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial

Abstract Phytoestrogens (PEs) have estrogen-like activity and were found to lower incidences of several hormone-dependent cancers. Emerging evidence suggests that estrogen may play a role in lung cancer carcinogenesis. We aim to evaluate dietary PE intake and lung cancer risk using data from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. A total of 1706 lung cancer cases were identified. The association between lung cancer risk and PE intake (in quartiles) was calculated using the Cox proportional hazard models adjusting for potential confounders. Stratified analyses by smoking status, sex and histology were also performed. The highest quartile of total PE intake was associated with a reduced risk of lung cancer compared with the lowest quartile [hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.73–0.99 for >1030 μg/day versus <290 μg/day] (P trend = 0.56). Similar patterns were observed among ever smokers (HR = 0.84, 95% CI: 0.71–0.98), non-small cell histology (HR = 0.84, 95% CI: 0.72–0.99), male (HR = 0.84, 95% CI: 0.69–1.03) and female (HR = 0.80, 95% CI: 0.64–0.99 for 510–1030 μg/day, HR = 0.84, 95% CI: 0.67–1.06 for >1030 μg/day versus <290 μg/day) subjects with no significant linear trend observed. Despite a lower consumption compared with the Asian population, increased PE intake still appears to decrease lung cancer risk in a Caucasian-dominant population. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of PEs on lung carcinogenesis and the interaction between PEs, smoking and endogenous estrogens.

Sodium molybdate inhibits the growth of ovarian cancer cells via inducing both ferroptosis and apoptosis

Ovarian cancer has the most mortality of all gynecologic malignancies. High-grade serous ovarian carcinoma (HGSOC) is the most common and deadly type of ovarian cancer. Tumor recurrence occurs due to the emergence of chemotherapy resistance. Thus, searching for new therapeutic strategies is essential for the management of ovarian cancer. Deregulation of iron metabolism can be used by ovarian cancer cells to survive, proliferate and metastasize. Here we report that sodium molybdate, a soluble molybdenum (Mo) compound, induces the elevation of the labile iron pool (LIP) in ovarian cancer cells, correlated with the down-regulation of genes involved in extracellular matrix organization. Sodium molybdate also induces depletion of glutathione (GSH) through mediating the production of nitric oxide (NO). Elevation of LIP and depletion of GSH promote the ferroptosis of ovarian cancer cells. Meanwhile, nitric oxide induces mitochondrial damage through inhibiting mitochondrial aconitase activity, ATP production, and mitochondrial membrane potential, leading to apoptosis of ovarian cancer cells. In vivo study shows that sodium molybdate reduces tumor burden in nude mice. Xenografts treated with sodium molybdate are characterized by obvious iron accumulation, increased expression of the iron storage protein ferritin, and lipid peroxide product 4-hydroxynonenal. In addition, an elevated percentage of apoptotic cells is observed in xenografts treated with sodium molybdate. Taken together, these results demonstrate that sodium molybdate can induce both ferroptosis and apoptosis of ovarian cancer cells, making it a potential therapeutic candidate for ovarian cancer.

Dyadic coping in young and middle-aged women with gynecological cancer: a latent class analysis

Cancer is a shared stress that can cause psychosocial and emotional burdens for both patients and their partners. This study aimed to identify patterns of dyadic coping (DC) among young and middle-aged women with gynecological cancer and to assess between-group differences. Between June 2021 and November 2021, patients with gynecological cancer who received therapy in a tertiary-grade hospital in Shandong, China, completed questionnaires including a demographic questionnaire, the Dyadic Coping Inventory, the PROMIS-Anxiety Short Form, the PROMIS-Depression Short Form, and the revised Conflict Tactics Scale and were classified into subtypes by latent class analysis. The sample consisted of 339 patients. Approximately one-third of the patients, especially cervical cancer patients, were exposed to varying degrees of DC issues. Three patterns were identified: class 1, middle-DC group (33.6%); class 2, low-DC group (32.2%); and class 3, high-DC group (34.2%). Postmenopausal patients were more likely to be included in class 1, while patients with cervical cancer were more likely to be included in class 2 (p < 0.05). Additionally, patients in class 2 were more likely to report insufficient emotional support (p < 0.05). A positive correlation was found for social relationship domains, and a negative correlation was found for anxiety and depression (p < 0.05). The findings indicated a high prevalence of DC in young and middle-aged women with gynecological cancer. Overall, participants scored in the low-to-middle range in terms of DC levels, and patients with cervical cancer and those with insufficient emotional support were more likely to report DC issues and require additional attention.