Object The purpose of this study was to analyze preoperative predictors of endocrinological remission following endonasal endoscopic resection of therapy-resistant prolactin-, growth hormone (GH)–, and adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas and to establish benchmarks for cure by using the most recent consensus criteria. Methods The authors reviewed a prospective database of 86 consecutive functional pituitary adenomas that were resected by a purely endoscopic endonasal transsphenoidal technique. Extent of resection was evaluated on postoperative contrast-enhanced MR imaging. Endocrinological remission was defined according to the most recent consensus criteria. Results The majority of functional adenomas (62.8%) were classified as macroadenomas (> 1 cm in maximum diameter), and 20.9% of lesions had invaded the cavernous sinus (CS) at the time of surgery. A gross-total resection was achieved in 75.6% of all patients. The rate of endocrinological remission differed between various types of functional adenomas. Cure rates were 92.3% (microadenomas) and 57.1% (macroadenomas) for prolactinomas, 75% (microadenomas) and 40% (macroadenomas) for GH-secreting tumors, and 54.5% (microadenomas) and 71.4% (macroadenomas) for ACTH-secreting tumors. Lower rates of cure occurred in GH-secreting macroadenomas due to a high rate of CS invasion, and in ACTH-secreting adenomas due to a high rate of lesions that were not visible on preoperative MR imaging. Whereas univariate analysis showed that macroadenoma, suprasellar, cavernous extension, or extent of resection correlated with cure, on multivariate analysis, only extent of resection and suprasellar extension predicted cure. One patient developed postoperative meningitis that was complicated by hydrocephalus requiring a ventriculoperitoneal shunt. Two patients developed postoperative panhypopituitarism, and 2 patients suffered from CSF leaks, which were treated with lumbar CSF diversion. Conclusions This paper reports benchmarks for endocrinological cure as well as complications in a large series of purely endoscopic pituitary surgeries by using the most recent consensus criteria. The advantages of extended endonasal approaches are most profound in tumors with suprasellar extension and CS invasion.

Object The aim of this study was to determine the preoperative predictors of the extent of resection and endocrinological remission following endonasal endoscopic removal of growth hormone (GH)-secreting pituitary adenomas. Methods The authors analyzed a prospectively collected database of 24 consecutive acromegalic patients who underwent endoscopic endonasal transsphenoidal surgery. The extent of resection was evaluated on postoperative contrast-enhanced MR imaging. Endocrinological remission was defined as normal insulin-like growth factor I (IGFI) serum levels and either a nadir GH level of < 0.4 ng/ml after an oral glucose load or a basal GH serum level < 1 ng/ml. Results The majority of acromegalic patients (83%) had macroadenomas > 1 cm in maximum diameter. Gross-total resection was achieved in 17 (71%) of 24 patients. Notably, endoscopic transsphenoidal surgery allowed complete resection of all lesions without cavernous sinus invasion, regardless of the suprasellar extent. Biochemical remission was achieved in 11 (46%) of 24 patients. A smaller tumor volume and a postoperative reduction in GH serum levels were associated with a higher rate of biochemical cure (p < 0.05). During a 23-month follow-up period 5 patients (21%) underwent Gamma Knife treatment of any residual disease to further reduce excess GH production. Twenty patients (83%) reported significant relief of their symptoms, while 3 (13%) considered their symptoms stable. Two patients (8%) with large macroadenomas experienced postoperative panhypopituitarism, and 2 patients (8%) suffered from CSF leaks, which were treated with lumbar CSF diversion. Conclusions A purely endoscopic endonasal transsphenoidal adenoma resection leads to a high rate of gross-total tumor resection and endocrinological remission in acromegalic patients, even those harboring macroadenomas with wide suprasellar extension. Extended approaches and angled endoscopes are useful tools for increasing the extent of resection.

Endoscopy in combination with extended approaches allow for resection of large pituitary adenomas via a transsphenoidal route. The objective of the current study was to determine a volumetric threshold for lesions with high perioperative morbidity and high rate of subtotal resection following endonasal endoscopic surgery. Thus, we analyzed a prospectively collected database of 71 patients who underwent endoscopic transsphenoidal approaches for macroadenomas (diameter >1 cm). Extend of resection (EOR) was calculated based on volumetric analysis of pre-and post-operative contrast-enhanced MRI. Average EOR was 97.8% and a gross total resection (GTR) was achieved in 76.1% of all patients. GTR was accomplished in 92.0% versus 38.1% of adenomas either without or with CS invasion, respectively. Likewise, GTR was accomplished in 90.2% versus 40.0% of lesions less than or greater then 10 cm(3) respectively. However, even if only subtotal resection was achieved, 90.3% of tumor volume was removed. At 17 months follow-up, visual field defects improved in 80.8% of patients. Complications included permanent diabetes insipidus (5 patients), panhypopituitarism (4 patients), injury to the ophthalmic artery (1 patient) and CSF leak (1 patient). On multivariate logistic regression, two factors negatively predicted GTR: invasion of the CS and volume greater than 10 cm(3). A 10 cm(3) threshold was a stronger predictor of EOR and complication risk than diameter-based measurements. A volume greater than 10 cm(3) and CS invasion may help to identify pituitary lesions associated with a higher likelihood of subtotal resection and post-operative morbidity.

PurposeThe hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Experimental DesignExpression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl2 or 1% O2. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.ResultsIn our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.ConclusionsOur results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy.