Biochemical predictors of outcome of pituitary surgery for cushing's disease

Objective: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS forCD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS. Methods: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6-197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse. Results: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol ≥600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol ≥485 nmol/l. Metyrapone test: 11-deoxycortisol ≥345 nmol/l predicted an early failure in 86% of cases (NPV 94%). Conclusion: Predictive factors of surgical failure are morning cortisol ≥200 nmol/l, 11-deoxycortisol ≥345 nmol/l after metyrapone and CRH-stimulated cortisol ≥600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing. Copyrigh

Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia

We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture of DNA methylation information of regions lying outside of traditional CpG islands. Applying this method to primary human bone marrow specimens from patients with Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed DNA methylation patterns. As compared to normal controls, we observed widespread hypermethylation in IDH mutant AMLs, preferentially targeting promoter regions and CpG islands neighboring the transcription start sites of genes. In contrast, AMLs harboring translocations affecting the MLL gene displayed extensive loss of methylation of an almost mutually exclusive set of CpGs, which instead affected introns and distal intergenic CpG islands and shores. When analyzed in conjunction with gene expression profiles, it became apparent that these specific patterns of DNA methylation result in differing roles in gene expression regulation. However, despite this subtype-specific DNA methylation patterning, a much smaller set of CpG sites are consistently affected in both AML subtypes. Most CpG sites in this common core of aberrantly methylated CpGs were hypermethylated in both AML subtypes. Therefore, aberrant DNA methylation patterns in AML do not occur in a stereotypical manner but rather are highly specific and associated with specific driving genetic lesions

CAVERNOUS HEMANGIOMA OF THE MESENCEPHALON: TONSILLOUVEAL TRANSAQUEDUCTAL APPROACH

OBJECTIVE: Recent advances in microsurgical techniques facilitate surgical resection of brainstem lesions that were previously considered inoperable. In this article we present, for the first time, the tonsillouveal transaqueductal approach to access a progressively symptomatic cavernoma within the depth of the tegmentum of the mesencephalon. METHODS: A 52-year-old woman presented with a history of slowly progressive right-sided hemiparesis and ataxia. On magnetic resonance imaging, a relatively large cavernoma involving the tegmentum of the mesencephalon was shown. The sylvian aqueduct was patent and there was no secondary ventriculomegaly. The patient underwent surgery via a suboccipital craniotomy and C1 laminectomy. The right tonsillouveal and medullotonsillar spaces were opened to the level of the choroidal point of the posteroinferior cerebellar artery. The tela choroidea was incised from the foramen of Magendie to the telovelar junction. Looking through the aqueduct and at a point 5 mm superior to its inferior inlet, there was a small cherry-like blister protruding into the aqueductal anterior surface. This was used as an entry point to access the cavernoma. The space around the cavernoma was gently dissected and the cavernoma was circumferentially coagulated to shrink it in a concentric manner toward its center. RESULTS: The total removal of the lesion was achieved and the histopathological findings were consistent with a cavernoma. As a result of noncommunicating hydrocephalus, the patient needed a ventriculoperitoneal shunt. The 1-year postoperative neurological examination was consistent with preoperative findings. CONCLUSION:This report shows, for the first time, direct surgical removal of a cavernous hemangioma in the mesencephalic tegmenturn via the aqueduct. This approach adds to contemporary microneurosurgery, respecting functional anatomy and minimizing neurological deficits