Revealing cancer subtypes with higher-order correlations applied to imaging and omics data

Figure S9. Screenshot of the interactive Tumor Map visualization, showing HOCUS applied to the TCGA Pancan-12 mutation data. Each point is one tumor sample, which we have color-coded by tissue type. A dotted box highlights the cluster of samples that have both PIK3CA and TP53 mutations, which are usually mutually exclusive. (EPS 751 kb

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas

Cavernous Sinus Involvement by Pituitary Adenomas: Clinical Implications and Outcomes of Endoscopic Endonasal Resection.

Background  Parasellar invasion of pituitary adenomas (PAs) into the cavernous sinus (CS) is common. The management of the CS component of PA remains controversial. Objective  The objective of this study was to analyze CS involvement in PA treated with endoscopic endonasal approaches, including incidence, surgical risks, surgical strategies, long-term outcomes, and our treatment algorithm. Methods  We reviewed a series of 176 surgically treated PA with particular attention to CS involvement and whether the CS tumor was approached medial or lateral to the internal carotid artery. Results  The median duration of follow-up was 36 months. Macroadenomas and nonfunctional adenomas represented 77 and 60% of cases, respectively. CS invasion was documented in 23% of cases. CS involvement was associated with a significantly diminished odds of gross total resection (47 vs. 86%, odds ratio [OR]: 5.2) and increased the need for subsequent intervention (4 vs. 40%, OR: 14.4). Hormonal remission was achieved in 15% of hormonally active tumors. Rates of surgical complication were similar regardless of CS involvement. Conclusion  Our tailored strategy beginning with a medial approach and adding lateral exposure as needed resulted in good outcomes with low morbidity in nonfunctional adenomas. Functional adenomas involving the CS were associated with low rates of hormonal remission necessitating higher rates of additional treatment

Diabetes Insipidus following Endoscopic Transsphenoidal Surgery for Pituitary Adenoma

Objectives  Pituitary adenoma (PA), among the most commonly encountered sellar pathologies, accounts for 10% of primary intracranial tumors. The reported incidence of postoperative diabetes insipidus (DI) is highly variable. In this study, we report our experience with DI following endoscopic transsphenoidal surgery (TSS) for PAs, elucidating the risk factors of postoperative DI, the likelihood of long-term DI, and the impact of DI on the length of stay (LOS). Methods  The study included 178 patients who underwent endoscopic resection of PAs. Early DI was defined as that occurring within the first postoperative week. The mean follow-up was 36 months. Long-term DI was considered as DI apparent in the last follow-up visit. Results  Of the 178 patients included in the study, 77% of the tumors were macroadenomas. Forty-seven patients (26%) developed early DI. Long-term DI was observed in 18 (10.1%) of the full cohort. Age younger than 50 years was significantly associated with a higher incidence of long-term DI ( p  = 0.02). Macroadenoma and gross total resection were significantly associated with higher incidence of early DI ( p  = 0.05 and p  = 0.04, respectively). The mean LOS was 4 days for patients with early postoperative DI and 3 days for those without it. Conclusion  The reported incidence of postoperative DI is significantly variable. We identified age younger than 50 years a risk factor for developing long-term postoperative DI. Gross total surgical resection and tumor size (> 1 cm) were associated with development of early DI. Early DI increased the LOS on average by 1 day

Cavernous Sinus Involvement by Pituitary Adenomas: Clinical Implications and Outcomes of Endoscopic Endonasal Resection

Background  Parasellar invasion of pituitary adenomas (PAs) into the cavernous sinus (CS) is common. The management of the CS component of PA remains controversial. Objective  The objective of this study was to analyze CS involvement in PA treated with endoscopic endonasal approaches, including incidence, surgical risks, surgical strategies, long-term outcomes, and our treatment algorithm. Methods  We reviewed a series of 176 surgically treated PA with particular attention to CS involvement and whether the CS tumor was approached medial or lateral to the internal carotid artery. Results  The median duration of follow-up was 36 months. Macroadenomas and nonfunctional adenomas represented 77 and 60% of cases, respectively. CS invasion was documented in 23% of cases. CS involvement was associated with a significantly diminished odds of gross total resection (47 vs. 86%, odds ratio [OR]: 5.2) and increased the need for subsequent intervention (4 vs. 40%, OR: 14.4). Hormonal remission was achieved in 15% of hormonally active tumors. Rates of surgical complication were similar regardless of CS involvement. Conclusion  Our tailored strategy beginning with a medial approach and adding lateral exposure as needed resulted in good outcomes with low morbidity in nonfunctional adenomas. Functional adenomas involving the CS were associated with low rates of hormonal remission necessitating higher rates of additional treatment

Diabetes Insipidus following Endoscopic Transsphenoidal Surgery for Pituitary Adenoma.

Objectives  Pituitary adenoma (PA), among the most commonly encountered sellar pathologies, accounts for 10% of primary intracranial tumors. The reported incidence of postoperative diabetes insipidus (DI) is highly variable. In this study, we report our experience with DI following endoscopic transsphenoidal surgery (TSS) for PAs, elucidating the risk factors of postoperative DI, the likelihood of long-term DI, and the impact of DI on the length of stay (LOS). Methods  The study included 178 patients who underwent endoscopic resection of PAs. Early DI was defined as that occurring within the first postoperative week. The mean follow-up was 36 months. Long-term DI was considered as DI apparent in the last follow-up visit. Results  Of the 178 patients included in the study, 77% of the tumors were macroadenomas. Forty-seven patients (26%) developed early DI. Long-term DI was observed in 18 (10.1%) of the full cohort. Age younger than 50 years was significantly associated with a higher incidence of long-term DI ( p  = 0.02). Macroadenoma and gross total resection were significantly associated with higher incidence of early DI ( p  = 0.05 and p  = 0.04, respectively). The mean LOS was 4 days for patients with early postoperative DI and 3 days for those without it. Conclusion  The reported incidence of postoperative DI is significantly variable. We identified age younger than 50 years a risk factor for developing long-term postoperative DI. Gross total surgical resection and tumor size (> 1 cm) were associated with development of early DI. Early DI increased the LOS on average by 1 day