Pseudocapsule-Based Resection for Pituitary Adenomas via the Endoscopic Endonasal Approach

IntroductionThe endoscopic endonasal approach (EEA) is a safe and effective treatment for pituitary adenomas (PAs). Since extracapsular resection (ER) of PAs improves tumor resection and endocrine remission rates, the interface between the pseudocapsule and gland draws increasing attention. However, it is difficult to precisely dissect the tumor along the exact boundary, and complete removal of the tumor increases the risks of normal tissue damage and cerebrospinal fluid (CSF) leakage. In this study, we investigated the extracapsular resection as well as the pseudocapsule histology to evaluate the effectiveness and safety of pseudocapsule-related surgical interventions.MethodsFrom December 2017 to December 2019, 189 patients of PAs via EEA in our single center were analyzed retrospectively. The images, operative details, and clinical follow-up of patients were collected. Sixty-four patients underwent pseudocapsule-based ER, and 125 patients also underwent traditional intracapsular resection (IR) with or without intensive excision for FPAs. The clinical characteristics, tumor resection, endocrinological outcomes, and postoperative morbidities of the two groups were compared. Informed consent for publication of our article was obtained from each patient. Histological examination of pseudocapsule was performed using hematoxylin and eosin and reticulin staining.ResultsThe gross total recession was 62 (96.9%) in the ER group and 107 (85.6%) cases in the IR group, whereas the endocrine remission rate was 29/31 (93.5%) and 40/53 (75.5%) cases, respectively. Anterior pituitary functions were not aggravated postoperatively in any patient, but transient diabetes insipidus (DI) occurred more in the IR group (64.0%) than in ER (48.4%). Pseudocapsule specimens were obtained in 93 patients, and clusters of small cell aggregation were detected in 11 pseudocapsule specimens (11.8%) whereas other patients showed no remarkable developed pseudocapsule. Intraoperative CSF leak occurred more in the ER group (28.1%) than in the IR group (13.6%), but no difference was seen between two groups postoperatively. No case of intracranial hematoma or pituitary crisis occurred in both groups. After a mean follow-up of 22.8 months, tumor recurrence was observed in 4 (2.1%) cases.ConclusionPseudocapsule-based extracapsular resection of PAs via EEA is an effective and safe procedure to achieve complete resection with high and sustained endocrine remission and without deteriorating pituitary function.

The Involvement of miRNAs in Pituitary Adenomas Pathogenesis and the Clinical Implications

Pituitary adenomas (PAs) account for the top three primary intracranial tumors in terms of total incidence rate. PAs can cause severe endocrine disorders and even malignant features, such as invasion, metastasis, and recurrence. Therefore, the early diagnosis and accurate prognosis would be greatly beneficial for clinical treatment of PAs. MicroRNAs (miRNAs) are small, protein-noncoding RNAs that regulate gene expression posttranscriptionally. They regulate essential physiological processes, including proliferation, growth, and apoptosis, and also they involve in the invasion and metastasis of malignant tumors. At the tissue level, differential miRNA expression in endocrine malignancies including PAs has been reported. When miRNAs have been successfully detected in various biofluids and cell-free environments, their important roles as potential screening or prognostic biomarkers have been extensively investigated. The current work reviews recent studies on the emerging roles of miRNAs in PAs and the clinical significance.

Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas

Background Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. Methods The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient’s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. Results Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient’s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. Conclusions According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.

Targeting Aggressive Pituitary Adenomas at the Molecular Level—A Review

Pituitary adenomas (PAs) are mostly benign endocrine tumors that can be treated by resection or medication. However, up to 10% of PAs show an aggressive behavior with invasion of adjacent tissue, rapid proliferation, or recurrence. Here, we provide an overview of target structures in aggressive PAs and summarize current clinical trials including, but not limited to, PAs. Mainly, drug targets in PAs are based on general features of tumor cells such as immune checkpoints, so that programmed cell death 1 (ligand 1) (PD-1/PD-L1) targeting may bear potential to cure aggressive PAs. In addition, epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and their downstream pathways are triggered in PAs, thereby modulating tumor cell proliferation, migration and/or tumor angiogenesis. Temozolomide (TMZ) can be an effective treatment of aggressive PAs. Combination of TMZ with 5-Fluorouracil (5-FU) or with radiotherapy could strengthen the therapeutic effects as compared to TMZ alone. Dopamine agonists (DAs) are the first line treatment for prolactinomas. Dopamine receptors are also expressed in other subtypes of PAs which renders Das potentially suitable to treat other subtypes of PAs. Furthermore, targeting the invasive behavior of PAs could improve therapy. In this regard, human matrix metalloproteinase (MMP) family members and estrogens receptors (ERs) are highly expressed in aggressive PAs, and numerous studies demonstrated the role of these proteins to modulate invasiveness of PAs. This leaves a number of treatment options for aggressive PAs as reviewed here.