Impact of growth hormone-secreting pituitary adenoma on limbic system and its correlation with cognitive impairment.

Purpose: To assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function. Method: 91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University -48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform. Results: Compared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90. Conclusion: Patients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment.

Using 2-dimensional hand photographs to predict postoperative biochemical remission in acromegaly patients: a transfer learning approach.

Background: The primary treatment goals in acromegaly patients are complete surgical removal of underlying pituitary tumors and biochemical remission. One of the challenges in developing countries is the difficulty in monitoring postoperative biochemical levels in acromegaly patients, particularly those who live in remote areas or regions with limited medical resources. Methods: In an attempt to overcome the abovementioned challenges, we conducted a retrospective study and established a mobile and low-cost method to predict biochemical remission in acromegaly patients after surgery, the efficacy of which was assessed retrospectively using the China Acromegaly Patient Association (CAPA) database. A total of 368 surgical patients from the CAPA database were successfully followed up to obtain their hand photographs. Demographics, baseline clinical characteristics, pituitary tumor features, and treatment details were collated. Postoperative outcome, defined as biochemical remission at the last follow-up timepoint, was assessed. Transfer learning with a new mobile tailored neurocomputing architecture, MobileNetv2, was used to explore the identical features that could be used as predictors of long-term biochemical remission after surgery. Results: As expected, the MobileNetv2-based transfer learning algorithm was shown to predict biochemical remission with statistical accuracies of 0.96 and 0.76 in the training cohort (n=803) and validation cohort (n=200), respectively, and the loss function value was 0.82. Conclusions: Our findings demonstrate the potential of the MobileNetv2-based transfer learning algorithm in predicting biochemical remission for postoperative patients who are at home or live far away from a pituitary or neuroendocrinological treatment center.

Clinicopathological characteristics and features of molecular subtypes of breast cancer at high altitudes.

Background: Breast cancer is one of the major malignancies threatening women's health worldwide. The incidence of breast cancer at high altitudes increased over the years. But few studies focused on the characteristics of clinicopathology and molecular subtypes among breast cancer at high altitudes, which are still unknown. Tibet, with an average altitude over 4000 meters, is a representative city at high altitudes, lying in the Qinghai-Tibetan Plateau in southwestern China. This study aimed to identify the clinicopathological characteristics and features of molecular subtypes among Tibetan women with breast cancer, and provide evidence for cancer prevention and personalized therapeutics in high-altitude regions. Methods: Between May 2013 and March 2022, 104 Tibetan women from high-altitude regions (Tibetan-group) and 34 Han Chinese women from low-altitude regions (Han-group), consecutively diagnosed with breast cancer in the Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, were included in the study. We retrospectively reviewed the clinical character, altitudes of residence, tumor size, lymph nodes metastasis, distant metastasis, pathological type, immunohistochemical index, and molecular subtype. Results: In the study, we calculated the patient delay, equal to the period from symptoms onset to hospital visits. The patient delay of Tibetan-group was 7.47 ± 11.53 months, which was significantly longer than that of Han-group, 7.22 ± 22.96 months (p<0.05). Body Mass Index (BMI) was significantly different (p<0.05). Tumors in Tibetan-group were significantly larger than those in Han-group, 4.13 ± 2.98cm and 2.51 ± 0.82cm in diameter, respectively (p<0.05). According to ordinal logistic regression analysis, exposure to high altitudes might result in more advanced T stage (OR=2.45 95%CI 1.10-5.44). 41.3% (43/104) of cases in Tibetan-group had lymph node positive disease, whereas the percentage was found in 38.26% (13/34) in Han-group(p<0.05). The distribution of molecular subtypes was quite significantly different between two groups (p<0.05), according to the comparison of constituent ratios. Conclusion: Our study verified that breast cancer at high altitudes possessed its own unique clinicopathological characteristics and distinct features of molecular subtypes. It broadened the understanding of this heterogenous disease and also provided valuable evidence for cancer prevention and personalized therapeutics of breast cancer at high altitudes.

Prediction of the Recurrence of Non-Functioning Pituitary Adenomas Using Preoperative Supra-Intra Sellar Volume and Tumor-Carotid Distance.

Background: Currently, it is difficult to estimate the possibility of recurrence of nonfunctioning pituitary adenomas (NFPAs). Markers such as Ki-67 or transcription factors rely on postoperative pathology, while few indices can be used for preoperative prediction. Therefore, we aimed to investigate the predictive effectiveness of supra-intrasellar volume and tumor-carotid distance based on measurements derived from preoperative magnetic resonance imaging (MRI) data. Method: Ninety-eight cases of NFPAs were evaluated, along with their clinical characteristics and MRI features. Four radiologic indices were analyzed, including intrasellar tumor volume, suprasellar tumor volume, maximum horizontal tumor diameter, and intercarotid distance. The ratio of supra-intrasellar volume and ratio of tumor-carotid distance were measured using 3D Slicer software, and the sum of two ratios was defined as the V-D value. The correlation between recurrence and multiple factors was analyzed using univariate and multivariate logistic regression and Kaplan-Meier analysis, and ROC curves were used to estimate the prognostic performance of radiologic measurements in NFPAs. Result: The supra-intrasellar volume ratio, tumor-carotid distance ratio and V-D value were significantly correlated with the recurrence of NFPAs. The predictive importance of the V-D value reached 84.5%, with a sensitivity of 83.7% and specificity of 67.3%. The cutoff limit of the V-D value was 1.53, and patients with V-D values higher than 1.53 tended to relapse much earlier. Conclusion: The V-D value has predictive importance for the recurrence of NFPAs preoperatively. Patients with higher V-D values will undergo recurrence earlier and should be given greater consideration in terms of surgery and follow-up time.

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis.

Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable. Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment. Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007). Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy.

MEG3/MIR-376B-3P/HMGA2 axis is involved in pituitary tumor invasiveness.

OBJECTIVE: To date, long noncoding RNAs (lncRNAs) have proven to function as key regulators in tumorigenesis. Among these lncRNAs, MEG3 displays low levels in various neoplasms and tumor cell lines. However, the regulatory mechanism of MEG3 and MIR-376B-3P, one of the microRNAs from downstream gene clusters of the DLK1-MEG3 locus, remains insufficiently defined. METHODS: The authors used quantitative real-time polymerase chain reaction analysis to analyze whether decreased MEG3 and MIR-376B-3P expression levels were associated with the invasiveness of clinical nonfunctioning pituitary adenomas (CNFPAs) in 30 patients. Furthermore, functional experiments unveiled the pathophysiological role of MEG3, MIR-376B-3P, and HMGA2 in pituitary-derived folliculostellate (PDFS) cell lines. Moreover, dual-luciferase reporter assay, Western blot analysis, and immunofluorescence were applied to reveal the correlations among MEG3, MIR-376B-3P, and HMGA2. RESULTS: MEG3 and MIR-376B-3P were decreased in patients with CNFPA, and their transcriptional levels were highly associated with invasive CNFPAs. Moreover, excessive expression of MEG3 and MIR-376B-3P inhibited tumorigenesis and promoted apoptosis in PDFS cells. Importantly, the authors found that MEG3 acted as an enhancer of MIR-376B-3P expression. Furthermore, as a target gene of MIR-376B-3P, HMGA2 served as an oncogene in pituitary adenoma and could be negatively regulated by MEG3 via enriching MIR-376B-3P. CONCLUSIONS: This study offers a novel mechanism of an MEG3/MIR-376B-3P/HMGA2 regulatory network in CNFPAs, which may become a breakthrough for anticancer treatments.