Predictive value of cyst/tumor volume ratio of pituitary adenoma for tumor cell proliferation.

BACKGROUND: MRI has been widely used to predict the preoperative proliferative potential of pituitary adenoma (PA). However, the relationship between the cyst/tumor volume ratio (C/T ratio) and the proliferative potential of PA has not been reported. Herein, we determined the predictive value of the C/T ratio of PA for tumor cell proliferation. METHODS: The clinical data of 72 patients with PA and cystic change on MRI were retrospectively analyzed. PA volume, cyst volume, and C/T ratio were calculated. The corresponding intraoperative specimens were collected. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the Ki67 index and nuclear atypia. Patients were categorized according to the Ki67 index (< 3% and ≥ 3%) and nuclear atypia (absence and presence). Univariate and multivariate analyses were used to identify the significant predictors of the Ki67 index and nuclear atypia. The receiver operating characteristic curve assessed the prediction ability of the significant predictors. RESULTS: Larger tumor volumes, smaller cyst volumes, and lower C/T ratios were found in patients with higher Ki67 indexes and those with nuclear atypia (P < 0.05). C/T ratio was an independent predictor of the Ki67 index (odds ratio = 0.010, 95% confidence interval = 0.000-0.462) and nuclear atypia (odds ratio = 0.010, 95% confidence interval = 0.000-0.250). The predictive value of the C/T ratio did not differ significantly from that of tumor volume (P > 0.05) but was better than that of cyst volume (P < 0.05). The area under the curve of the C/T ratio for predicting the Ki67 index and nuclear atypia was larger than that for predicting cyst volume and tumor volume. CONCLUSIONS: C/T ratios can be used to predict PA tumor proliferation preoperatively. Our findings may facilitate the selection of surgery timing and the efficacy evaluation of surgery.

MRI features of pituitary adenoma apoplexy and their relationship with hypoxia, proliferation, and pathology.

OBJECTIVE: We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology. METHODS: Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining. RESULTS: The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67. CONCLUSION: When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger.

Analysis of operative efficacy for giant pituitary adenoma.

BACKGROUND: Surgical treatment of giant pituitary adenomas is difficult due to complicated dissection of the sellar area. The extent of tumor resection affects the efficacy of surgical treatment. This study is to investigate the efficacy of microsurgical treatment for giant pituitary adenoma and to analyze the relationship between treatment efficacy and tumor resection extent. METHODS: A retrospective analysis was performed in 36 patients who received microsurgery to remove giant pituitary adenomas. The sizes of tumors before and after surgery were calculated with a novel method called the "platform-like volume calculation formula". The relationships between extent of resection and the visual impairment recovery, and improvement of serum hormone level before and after operation were analyzed. RESULTS: Two deaths were observed after surgery. And the gross and near-total resection was achieved in 8 cases, subtotal resection in 8 cases, mostly partial resection in 15 cases, and partial resection in 5 cases. The average resection rate was 72.8%. The resection rate of tumor with cavernous sinus invasion was significantly lower than those of patients without cavernous sinus invasion (P < 0.05). The improvement rate of hormone level in functional adenoma was 80.0%. Follow-up observations were carried out for 3 ~ 28 months in 25 cases. Visual improvement was observed in 64.0% of the cases. CONCLUSIONS: Microsurgical treatment can improve the visual impairment of the majority of cases and significantly decrease the serum hormone levels of functional adenoma. The extent of resection was significantly associated with cavernous sinus invasion.

α-LA attenuates microcystin-LR-induced hepatocellular oxidative stress in mice through Nrf2-mediated antioxidant and detoxifying enzymes.

Microcystins constitute a class of toxins synthesized by cyanobacteria and are known to inflict significant damage on the antioxidant defense system of living organisms, primarily targeting the liver. α-Lipoic acid (α-LA) is universally recognized as a potent antioxidant in biological systems. It exerts its beneficial effects through multiple mechanisms-directly neutralizing reactive oxygen species (ROS) and free radicals, and indirectly enhancing antioxidant defenses by facilitating the regeneration of glutathione (GSH). However, the precise modus operandi of α-LA's protective effect against Microcystin-LR-induced hepatotoxicity remains incompletely elucidated. The present study, therefore, employed α-LA to explore its protective role against Microcystin-LR exposure in mice. A model of Microcystin-LR-induced hepatic injury was established by administering Microcystin-LR into the peritoneal cavity of BALB/c mice daily over a two-week period. Thereafter, BALB/c mice were pre-treated with varying concentrations of α-LA via oral gavage for a duration of 7 days, followed by a 7-day exposure to Microcystin-LR. Our findings reveal that α-LA pre-treatment significantly mitigated hepatic pathologies in Microcystin-LR-exposed mice. Furthermore, α-LA administration led to a notable elevation in the activities and expression levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione-indicative of its antioxidative capacity. Concurrently, a significant decrease was observed in the activities and expression levels of malondialdehyde and cytochrome P450 2E1. Consequently, α-LA emerges as a promising therapeutic candidate for the amelioration of liver oxidative damage subsequent to Microcystin-LR exposure.

In Silico Analysis Identifies Upregulated lncRNA DLGAP1-AS1 Which Is Correlated to Poor Prognosis and Promotes Cell Proliferation in Glioblastoma.

Long noncoding RNAs have been reported to regulate the tumorigenesis, growth, and metastasis of glioblastomas. In this study, we identified 1623 differently expressed mRNAs and 38 lncRNAs utilizing the CGGA and TCGA databases. Among these mRNAs and lncRNAs, we focused on DLGAP1-AS1 in this study. The results demonstrated that DLGAP1-AS1 was higher in WHO IV glioma than in WHO II and WHO III gliomas, higher in WHO III glioma than in WHO II glioma samples, higher in IDH1 wildtype glioma than in IDH1-mutant glioma samples, and higher in 1p/19q noncodeletion glioma than in 1p/19q codeletion glioma samples. Moreover, we observed that higher expression levels of DLGAP1-AS1 were correlated to shorter OS time in both low-grade and high-grade gliomas. Next, we evaluated the function of DLGAP1-AS1 in GBM using in vivo experiments. The data revealed that DLGAP1-AS1 knockdown greatly hindered U87 cell and U251 cell proliferation. Using coexpression network analysis, we identified that ATG4A was a potential downstream target of DLGAP1-AS1. The further analysis showed that ATG4B was significantly upregulated and correlated to shorter OS time in gliomas using both the CGGA and TCGA databases. Finally, we showed that ablated ATG4B greatly hindered GBM cell proliferation. Our conclusion suggested that DLGAP1-AS1 may be a potential prognosis biomarker and facilitated the occurrence and development of glioma via ATG4A in GBM.

Risk factors for delayed postoperative hyponatremia in patients with non-functioning pituitary adenomas undergoing transsphenoidal surgery: A single-institution study.

Purpose: We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery (TSS) in patients with a non-functional pituitary adenoma (NFPA). Methods: We retrospectively collected the clinical data of patients who underwent TSS for NFPA between January 2016 and January 2021. The pituitary region was preoperatively scanned with 3.0 T magnetic resonance imaging. The risk factors for delayed postoperative hyponatremia for NFPA were identified by univariate and multivariable logistic regression analysis. Results: We selected 166 patients with NFPA who fulfilled the inclusion criteria. Delayed postoperative hyponatremia occurred in 28 patients and did not in 138. Multivariable logistic regression analyses demonstrated that higher odds of developing delayed postoperative hyponatremia were independently associated with larger craniocaudal dimension (OR = 1.128, P = 0.034), as well as preoperative hyperprolactinemia (OR = 2.618, P = 0.045) and larger preoperative pituitary stalk deviation angle (OR = 3.033, P = 0.022). Conclusion: We identified the independent risk factors for delayed hyponatremia after TSS for NFPA; these included preoperative hyperprolactinemia, craniocaudal diameter, and preoperative pituitary stalk deviation angle.

Establishment and Validation of an Integrated Model to Predict Postoperative Recurrence in Patients With Atypical Meningioma.

BACKGROUND: This study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM). MATERIALS AND METHODS: A retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model. RESULTS: After multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05-5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III-IV (HR, 2.73; 95% CI, 1.01-7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52-19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16-6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759-0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716-0.918) and good match between the predicted and observed probability of recurrence-free survival. CONCLUSION: Our study established an integrated model to predict the postoperative recurrence of AM.

Role of prolactin/adenoma maximum diameter and prolactin/adenoma volume in the differential diagnosis of prolactinomas and other types of pituitary adenomas.

The present study aimed to investigate the function of the prolactin/adenoma maximum diameter (PRL/MD) and the prolactin/adenoma volume (PRL/V) in the differential diagnosis of prolactinomas and other types of pituitary adenomas. A total of 118 patients with pituitary adenoma, hyperprolactinemia and a plasma PRL <250 µg/l were enrolled. Clinical data from these patients were retrospectively analyzed. A receiver operating characteristic curve was plotted. The function of PRL, PRL/MD and PRL/V in the differential diagnosis of prolactinomas and other types of pituitary adenomas was compared. The results revealed that a PRL of 55.65 µg/l was the most accurate [sensitivity (SE), 0.800; specificity (SP), 0.716; positive predictive value (PPV), 0.857; negative predictive value (NPV), 0.933; and Youden index (YI), 0.516]. The PRL/MD with the highest diagnostic value was 4.03 µg/(l × mm) (SE, 0.800; SP, 0.898; PPV, 0.727; NVP, 0.929; and YI, 0.698). The PRL/V with the highest diagnostic value was 54.00 µg/(l × cm3) (SE, 0.900; SP, 0.966; PPV, 0.900; NVP, 0.966; and YI, 0.866). The PRL/MD tended to be of higher diagnostic accuracy than PRL, but this difference was not statistically significant (P=0.097). The differentiation ability of PRL/V was significantly stronger than that of PRL (P=0.028). Thus, serum PRL, PRL/MD and PRL/V levels may be able to differentiate prolactinomas from other types of hyperprolactinemia-causing pituitary adenomas prior to treatment. PRL/V may be better than the PRL level in achieving a differential diagnosis, and the optimal PRL/V ratio for differentiating prolactinomas from other types of hyperprolactinemia-causing pituitary adenomas was 54.00 µg/(l × cm3).

Assessment and Treatment of Peritumoral Cortical Veins in Parasagittal Meningiomas with Application of 3-Dimensional Imaging Fusion Model.

BACKGROUND: Operation of cortical veins is the keystone of parasagittal meningioma (PSM) resection. Little is known about pathologic changes of the veins and proper treatment. We built 3-dimensional (3D) image fusion models by neuronavigation to analyze the features of peritumoral cortical veins for PSMs and explore intraoperative treatment options. METHODS: We performed a prospective study of 42 consecutive surgically treated PSM patients who underwent preoperative evaluation of peritumoral cortical veins using a 3D venous-tumor fusion model established by a neuronavigation system. We categorized cortical veins into 3 types: single-end anastomosis (type a), tumor-to-end anastomosis (type b), and end-to-end anastomosis (type c). We present surgical strategies to operate these veins. RESULTS: Preoperative evaluation demonstrated 39 patients with peritumoral cortical veins. The 3D models show 100% of the veins (95 in total), which were confirmed intraoperation. The postoperative complication rates after vein injury were 60% (type a), 16.7% (type c), and 0% (type b). Ten patients (23.8%) had residual tumor because of venous protection (equal to Simpson grade III). After correlation analysis, type b and c cortical veins were positively correlated with tumor volume. CONCLUSIONS: The anastomoses of cortical veins may provide compensation for venous transaction. There may be a time-evolution relationship between different cortical veins (type a to c to b). Treatment of cortical veins should follow the following principles: single-end veins must be protected, tumor-to-end veins should be transacted directly, and end-to-end veins could be cut selectivity based on the degree of occlusion of the superior sagittal sinus. Detailed preoperative assessment of peritumoral cortical veins is critical for proper treatment.

Fluid-fluid level on magnetic resonance images may predict the occurrence of pituitary adenomas in cystic sellar-suprasellar masses.

The aim of the present study was to evaluate the value of identifying fluid-fluid level via preoperative magnetic resonance (MR) images in differentiating pituitary adenomas from craniopharyngioma, Rathke's cleft cyst (RCC), and other cystic sellar-suprasellar lesions. The data of 293 consecutive patients who underwent surgery for sellar-suprasellar lesions between July 2010 and December 2012 was retrospectively reviewed, and a total of 133 cystic cases were included in the present study. MR images and pathological features of all subjects were examined. Among the 133 cystic sellar-suprasellar masses, there were 78 cases of pituitary adenomas, 31 cases of craniopharyngioma, 21 cases of RCC, one case of epidermoid cyst and two cases of abscess. Fluid-fluid levels were identified n 43 cases (55.13%) of cystic pituitary adenomas, with a single fluid level in 23 cases, two fluid levels in 8 cases, and three levels or more in 12 cases. Two cases (6.45%) of craniopharyngioma, and one case (4.76%) of RCC presented single fluid level. No instances of fluid-fluid levels were observed in epidermoid cyst or abscess. Fluid-fluid levels were typically exhibited on axial T2-weighted images. The identification of fluid-fluid level in cysts provides useful diagnostic value in distinguishing pituitary adenoma from other sellar-suprasellar lesions. The findings of the present study suggest that a sellar-suprasellar mass with a fluid-fluid level inside the tumor is most likely a pituitary adenoma, particularly if multiple fluid levels are observed in the same tumor. The fluid-fluid level is typically clearly depicted on axial or sagittal MR images, suggesting subacute or chronic hemorrhage in pituitary adenomas.

Uneven Distribution of Regional Blood Supply Prompts the Cystic Change of Pituitary Adenoma.

BACKGROUND: Previous studies have suggested that the cystic change of pituitary adenoma might be related to the blood supply and metabolism of the tumor; however, the exact pathologic mechanism underlying the cystic change remains unknown. OBJECTIVES: We aimed to assess the features of regional blood supply of pituitary adenoma and examine its relationship with the cystic change of pituitary adenoma. METHODS: Patients (N = 79) with pituitary adenoma admitted to our hospital were divided into the parenchyma group (n = 40) or the cystic change group (n = 39). Dynamic contrast-enhanced magnetic resonance imaging of the pituitary adenoma was conducted for the parenchyma group and the steepest slopes (SSmax, reflecting regional blood supply) at different areas were calculated. The location of cystic change of the pituitary adenoma was recorded and analyzed for the cystic change group. RESULTS: The parenchyma group showed an upper SSmax of 2.52 ± 1.18, a lower SSmax of 2.89 ± 1.46, a left SSmax of 2.71 ± 1.31, and a right SSmax of 2.66 ± 1.29. The difference between the upper and lower SSmax was statistically significant (P < 0.001), with no difference between the left and right regions (P = 0.668). The location of cystic change of the pituitary adenoma was mainly in the upper region, accounting for 48.7% of cases. CONCLUSIONS: Regional blood supply is unevenly distributed in the parenchymal pituitary adenoma, with reduced blood supply in the upper than the lower region. Cystic change mainly occurs in the upper region of pituitary adenoma.

The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas.

OBJECTIVE: The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas (NFPMAs) is not well known, and hyperprolactinemia caused by a NFPMA is currently associated with diagnostic uncertainty. Thus, the aim of this study was to evaluate the prevalence of hyperprolactinemia in NFPMAs. METHODS: A meta-analysis of all existing articles in PubMed was conducted. The search string was designed as "(non-functioning pituitary tumor OR non-functioning pituitary tumor OR non-functioning pituitary macroadenomas OR non-functioning pituitary macroadenomas OR non-functioning pituitary adenomas OR non-functioning pituitary adenomas) and hyperprolactinemia". References of the articles found were also reviewed. Study selection and data extraction were performed independently by two reviewers. Data were analyzed with STATA 11.0 software (StataCorp LP, USA). The fixed effects model was used to evaluate these studies. RESULTS: The search identified 57 published studies, seven of which were accepted for the final meta-analysis. The authors found an overall estimated 40.2% prevalence of (95% CI, 36.6%-43.7%) hyperprolactinemia in NFPMAs. CONCLUSIONS: Given the high frequency of hyperprolactinemia in NFPMAs, a diagnosis of NFPMA or prolactinoma should be made more carefully.

Clinical analysis of infarction in pituitary adenoma.

OBJECTIVES: This study is to summarize the clinical manifestations, imaging findings, treatment and prognosis of pituitary apoplexy caused by ischemic infarction. METHODS: From January 2010 to March 2014, 412 patients with pituitary adenoma were admitted in the Department of Neurosurgery at Fuzhou General Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging examinations were performed, including computed tomography and magnetic resonance imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar, parasellar, anterior and posterior classification. Hematoxylin and eosin staining and immunohistochemical staining were used for identifying pituitary adenoma. RESULTS: Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients had typical clinical stroke symptoms. Preoperatively, high blood growth hormone concentration was presented in 6 cases, full hypopituitarism in 2 cases, dysfunction of corticosteroids and gonads in 4 cases, and single gonadal dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed computed tomography or magnetic resonance images, and sellar settlement in 7 cases. Eight patients were conducted with transsphenoidal resection, and secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5 cases, and few dark blood clots in 2 cases. CONCLUSIONS: Pituitary ischemic infarction stroke is clinically rare, but can be correctly diagnosed before surgery by imaging examinations. The pathological characteristics of the tumor are necrosis and fibrosis, which are easy for resection. Therefore, pituitary adenoma usually has good prognosis.

Guidance value of MRI for transsphenoidal surgery of pituitary adenomas with cystic degeneration.

OBJECTIVE: This study is to evaluate the surgical outcomes of transsphenoidal surgery in pituitary adenoma (PA) patients with cystic degeneration by using MRI. METHODS: Eighty-three patients with surgically and pathologically confirmed PA were enrolled. They were divided into three groups according to preoperative MR images: substantive adenoma group (n = 40), cystic degeneration without fluid-fluid level group (n = 19), cystic degeneration with fluid-fluid level group (n = 24). The PA was removed by transsphenoidal surgery and the surgical outcomes were retrospectively compared. RESULTS: The number of cases with abundant blood supply was 17 cases (42.5%) in substantive adenoma group, 13 cases (68.4%) in cystic degeneration without fluid-fluid level group and 16 cases (66.7%) in cystic degeneration with fluid-fluid level group. Blood supply in cystic degeneration with fluid-fluid level group was significantly richer than that in substantive adenoma group (P < 0.05). Peritumoral adhesion was significantly greater in cystic degeneration with fluid-fluid level group than in substantive adenoma group. And, PA with fluid-fluid level has significantly lower tumor total resection rate and MVD as well as higher recurrence rate (P < 0.05). Differences in cerebrospinal fluid leakage and postoperative diabetes insipidus were both not significant among the three groups (P > 0.05). CONCLUSIONS: Compared with other types of PA, cystic degeneration with fluid-fluid level were often richer in blood supply, greater in adhesion with peritumoral structures and easier to be found with tumor residual. Thus, more patience should be needed during the surgeries and more dynamic reviews are required postoperatively.