Role of Copeptin in Predicting Postoperative Hyponatremia and Hypernatremia in Patients Undergoing Endoscopic Pituitary Adenoma Surgery.

BACKGROUND AND OBJECTIVES: Arginine vasopressin (AVP) is an important hormone responsible for maintaining sodium homeostasis after pituitary surgery. The measurement of AVP levels is difficult because of its short half-life (t1/2). Copeptin is a preprohormone of AVP, and it is a more stable peptide, which can be used as surrogate marker for AVP. This study aims to assess the role of copeptin as a predictor of postoperative hyponatremia and hypernatremia in patients undergoing endoscopic pituitary adenoma surgery. METHODS: This prospective study included 50 patients who underwent endoscopic pituitary adenoma surgery. Serum copeptin levels of these patients were assessed (1) preoperatively (C1), (2) at extubation (C2), and (3) postoperative day 4 (C3). Perioperative data regarding fluid and sodium balance were collected from patients. Statistical analysis was done using the above data. RESULTS: The copeptin values were assessed against the sodium disturbances. 100% of patients who developed transient diabetes insipidus had a relative decrease in C2 from C1 (P - .0002). 88% of patients who developed early hyponatremia had a relative increase in C2 as compared with C1 (P < .01). 75% of patients who developed delayed hyponatremia had a relative increase in C3 as compared with C1 (P = .003). CONCLUSION: A relative increase or decrease in early change in copeptin (C2-C1) can predict development of early hyponatremia or transient central diabetes insipidus, respectively. A relative increase in delayed change in copeptin (C3-C1) can predict development of delayed hyponatremia.

Endoscopic Endonasal Approach for Giant Pituitary Adenoma Occupying the Entire Third Ventricle: Surgical Results and a Review of the Literature.

BACKGROUND: Pituitary macroadenomas occasionally disrupt the sellae diaphragma and extend directly to the third ventricle causing hydrocephalus. We present the results of a single-stage extended endoscopic approach for managing giant pituitary adenomas (GPAs) occupying the entire third ventricle. METHODS: A retrospective study of all GPAs occupying the entire third ventricle operated on via the endoscopic endonasal approach between January 2016 and December 2020 was performed. RESULTS: The study included 8 cases of GPA occupying the entire third ventricle, of which 2 (25%) were functioning adenomas. Of 8 patients, 4 (50%) presented with hydrocephalus, 2 underwent preoperative ventriculoperitoneal shunt, and 2 had an intraoperative external ventricular drain. No patients had postoperative cerebrospinal fluid rhinorrhea. Complete resection of the third ventricular component could be achieved in all cases radiologically; minimal residual tumor was present either in the lateral compartment of the cavernous sinus or over the anterior cerebral artery complex in 5 of 8 (62.5%) patients. Complete resolution of temporal hemianopia was seen in 8 of the 12 eyes (66.67%), and partial resolution was seen in 4 of 12 (33.3%) eyes. At a mean follow-up of 24.62 ± 10.01 months, none of the patients needed another surgical procedure. CONCLUSIONS: The extended endonasal endoscopic approach can be safely and efficiently used for single-stage excision of GPAs that disrupt the diaphragm and occupy the third ventricle. Preoperative cerebrospinal fluid diversion may be used to manage associated acute hydrocephalus in these cases.

High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux.

Recent studies suggest the role of autophagy, an evolutionarily conserved catabolic process, in determining the response of gliomas to treatment either positively or negatively. The study attempts to characterize autophagy in low and high-grade glioma by investigating the autophagic flux and clinical significance of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We evaluated the expression of autophagic markers in resected specimens of low-grade glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and Western blotting. Our results show that expression of autophagy proteins were more prominent in HGG than in LGG. Increased level of autophagic proteins in HGG can be due to an increased rate of autophagy or can be because of blockage in the final degradation step of autophagy (defective autophagy). To distinguish these possibilities, the autophagic flux assay which helps to determine the rate of degradation/synthesis of autophagic proteins (LC3-II and p62) over a period of time by blocking the final degradation step of autophagy using bafilomycin A1 was used . The assessment of autophagic flux in ex vivo culture of primary glioma cells revealed for the first time increased turnover of autophagy in high grade compared to low grade-glioma. Though autophagic markers were reduced in LGG, functionally autophagy was non defective in both grades of glioma. We then investigated whether autophagy in gliomas is regulated by nutrient sensing pathways including mTOR and promote cell survival by providing an alternate energy source in response to metabolic stress. The results depicted that the role of autophagy during stress varies with tissue and has a negative correlation with mTOR substrate phosphorylation. We also evaluated the expression of LC3 and beclin 1 with progression free survival (PFS) using Kaplan-Meier survival analysis and have found that patients with low LC3/beclin 1 expression had better PFS than those with high expression of LC3/beclin 1 in their tumors. Together, we provide evidence that autophagy is non-defective in glioma and also show that high LC3/beclin 1 expression correlates with poor PFS in both LGG and HGG.