Yan Hu

Plasma Proteomics and Metabolomics of Aromatase Inhibitors-Related Musculoskeletal Syndrome in Early Breast Cancer Patients

Background: Aromatase inhibitors-related musculoskeletal syndrome (AIMSS) is a common side effect experienced by early breast cancer patients undergoing endocrine therapy. This condition can result in medication discontinuation and a diminished quality of life. The objective of this study was to characterize AIMSS, investigate its pathogenesis, and identify potential biomarkers at both the protein and metabolic levels. Methods: We collected peripheral blood samples from 60 women diagnosed with breast cancer undergoing aromatase inhibitor therapy, of whom 30 had AIMSS and 30 did not. The samples were analyzed using four-dimensional data-independent acquisition (DIA)-based proteomics and untargeted metabolomics, employing liquid chromatography–mass spectrometry (LC–MS) on the latest platform. Results: The mean age of participants was 49.2 (11.3) years in the AIMSS group and 50.1 (11.5) years in the non-AIMSS group. There were no statistically significant differences between the two groups in terms of age, BMI, education level, clinical stage, and treatment. In total, we identified 3473 proteins and 1247 metabolites in the samples. The chemokine signaling pathway (p = 0.015), cytokine–cytokine receptor interaction (p = 0.015), complement and coagulation cascades (p = 0.004), neuroactive ligand–receptor interaction (p = 0.004), and the estrogen signaling pathway (p = 0.004) were significant enriched in differentially expressed proteins (DEPs). GnRH secretion (p < 0.001), sphingolipid signaling pathways (p < 0.001), endocrine resistance (p < 0.001), the estrogen signaling pathway (p = 0.001), endocrine and other factor-regulated calcium reabsorption (p = 0.001), dopaminergic synapse (p = 0.003), regulation of lipolysis in adipocytes (p = 0.004), biosynthesis of cofactors (p = 0.004), thyroid hormone synthesis (p = 0.008), aldosterone synthesis and secretion (p = 0.001), taurine and hypotaurine metabolism (p = 0.011), ovarian steroidogenesis (p = 0.011), and the cAMP signaling pathway (p = 0.011) were significantly enriched in differentially expressed metabolites (DEMs). Complement C3 (p = 0.004), platelet factor 4 (p = 0.015), KRT10 (p = 0.004), KRT14 (p = 0.004), beta-estradiol (p = 0.019), testosterone (p = 0.023), sphingosine (p < 0.001), and 1-stearoyl-2-arachidonoyl-sn-glycerol (p = 0.039) could be the monitoring and therapeutic targets for AIMSS. Conclusions: This study offered new insights into the mechanisms underlying musculoskeletal symptoms associated with aromatase inhibitors. It also highlighted potential biomarkers for predicting and addressing these symptoms in breast cancer patients, paving the way for improved intervention strategies.

Supragastric lesser sac: an insidious site for surgical exploration during the debulking surgery in advanced ovarian cancer

Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery. We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022. Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9). Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.

Risk factors associated with HPV persistence after conization in high-grade squamous intraepithelial lesion

Persistence of HPV infection in patients with high-grade squamous intraepithelial lesion (HSIL) undergoing cervical excision is considered strongly associated with the recurrence and progression of cervical dysplasia. This study aims to review potential risk factors for persistence of HPV infection in patients with HSIL, thus optimizing the postoperative monitoring program and clinical treatment. Through literature review, published data about estimated prognostic risk factors for persistence of HPV infection in patients with HSIL after conization within two decades were searched and analyzed, and their references were manually reviewed as well. Women with persistence of HPV infection after cervical excision were at an extremely high risk of disease recurrence and progression to cervical cancer. Some clinicopathological and even physiological elements involving viral, organic human body and treatment factors, such as human papillomavirus (HPV) 16, high viral load, age older than 50 years and positive surgical margin were of prognostic significance in persistent HPV infection in patients with HSIL, yet some of which still remained controversial. Monitoring prognostic factors in women with persistence of HPV infection who have underwent cervical excision for HSIL are of great significance, especially the follow-up within 2 years postoperatively, which significantly improves the clinical outcome.

Risk factors associated with the persistence of human papillomavirus after cervical excision in patients with high-grade squamous intra-epithelial neoplasia

To evaluate risk factors associated with the persistence of human papillomavirus (HPV) after cervical excision in patients with high-grade squamous intra-epithelial neoplasia (HSIL). A retrospective cohort study enrolled 550 patients who underwent cervical excision for HSIL between January 2015 and January 2018. The effects of various factors were assessed using univariate and multi-variate analyses. The mean age of patients was 42.6 [standard deviation (SD) 8.7, range 22-64] years, and the mean duration of follow-up was 29.0 (SD 4.8, range 24-36) months. Persistent HPV infection after cone excision was detected in 78 (14.2%) patients. Univariate logistic regression analysis revealed that advanced age (>35 years), menopausal status, HPV type (HPV16/18), abnormal vaginal micro-ecological morphology, type of excision (loop electrosurgical excision procedure) and positive margin were closely associated with the persistence of HPV. Multi-variate analysis indicated that menopausal status [odds ratio (OR) 4.708, 95% confidence interval (CI) 2.770-8.001; p < 0.001], abnormal vaginal micro-ecological morphology (OR 2.320, 95% CI 1.372-3.922; p = 0.002) and positive margin (OR 3.346, 95% CI 1.261-8.876; p = 0.015) were significant risk factors for the persistence of HPV after treatment. Furthermore, infection with HPV16/18 increased the risk of persistent infection, and a higher rate of HPV persistence was found in patients who were infected with HPV18 (OR 1.020, 95% CI 0.415-2.505) or co-infected with HPV16/18 (OR 2.064, 95% CI 0.272-2.041) compared with HPV16. Persistent HPV infection after surgical treatment for HSIL is considered to be strictly related to the recurrence and progression of disease. Patients who are at increased risk of HPV persistence should receive intensive follow-up after surgery, especially in the first year.