The occurrence of hemorrhage from pituitary adenoma (so-called "pituitary apoplexy") was investigated in a consecutive series of 560 cases operated on during the past 30 years. There were 93 cases (16.6%) in which hemorrhage from pituitary adenomas was confirmed either clinically or surgically. These patients were analyzed in terms of age, sex, symptoms and signs, size of tumor, hormonal function, and histological types of adenomas, and computerized tomography findings. In 90 cases (16.6%), hematoma or old bloody fluid was verified within the tumor tissue at surgery. Three other patients presented with subarachnoid hemorrhage, but there was no detectable intratumor hematoma in any of them. Among these 93 patients, 42 (7.5%) showed no evidence of clinical symptoms related to hemorrhage (asymptomatic hemorrhage). Fifty-one patients (9.1%) had definite histories of an acute episode that suggested sudden bleeding (symptomatic hemorrhage: pituitary apoplexy). Thirty-eight patients (6.8%) had a major attack manifested by disturbances of consciousness, hemiparesis, loss of vision, or ocular palsy. In two acromegalic patients, pituitary apoplexy developed during bromocriptine treatment. There was one case of sudden death due to massive hemorrhage from the tumor 14 months after the completion of postoperative radiation therapy. The other 13 symptomatic patients (2.3%) developed a minor attack which included headache, nausea, vomiting, and vertigo. Bleeding from pituitary adenomas was not statistically correlated with any of the following factors: sex, hormonal function of adenomas, and histological types, but it was correlated with age. The number of asymptomatic cases in the third decade was significantly greater than that of the whole group of pituitary adenoma patients in the same decade. The present investigation revealed that the incidence of pituitary apoplexy was unexpectedly high: a major attack in 6.8% of pituitary adenoma patients, a minor attack in 2.3%, and asymptomatic hemorrhage in 7.5% of the cases. This risk of pituitary apoplexy should be kept in mind in treating pituitary adenomas.

SummaryBackgroundIntracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.MethodsIn a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.FindingsOf 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).InterpretationIn this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects i...

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A lthough malignant tumors metastasizing into the pituitary fossa are not infrequent events in autopsy series, 6,10,17,18 pituitary metastasis (PM) is rarely diagnosed ante mortem. 3,14,18 According to the Brain Tumor Registry of Japan, only 0.4% of intracranial metastatic tumors are located in the pituitary gland. 5 These tumors account for only 1% of surgically treated pituitary tumors. 8,16,31 Recently, as the number of patients diagnosed with cancer has increased and their survival time has been extended, PMs have been diagnosed more frequently than before. 16,20,24 Many authors have reported their own experiences or their institutional series on PMs. 3,11,13,14,20,26,31 There are also reviews involving large numbers of reported cas- results Between 1995 and 2010, 201 patients with PMs were treated by the participating physicians. The diagnosis of PM was histologically verified in 69 patients (34.3%). In the other 132 patients (65.7%), the PM was diagnosed by their physicians based on neuroimaging findings and clinical courses. The most frequent primary tumor was lung (36.8%), followed by breast (22.9%) and kidney (7.0%) cancer. The average interval between diagnosis of primary cancer and detection of PM was 2.8 ± 3.9 (SD) years. Major symptoms at diagnosis were visual disturbance in 30.3%, diabetes insipidus in 27.4%, fatigue in 25.4%, headache in 20.4%, and double vision in 17.4%. Major neuroimaging features were mass lesion in the pituitary stalk (63.3%), constriction of tumor at the diaphragmatic hiatus (44.7%), hypothalamic mass lesion (17.4%), and hyperintensity in the optic tract (11.4%). Surgical treatment was performed in 26.9% of patients, and 74.6% had radiation therapy; 80.0% of patients who underwent radiotherapy had stereotactic radiotherapy. The median survival time was 12.9 months in total. Contributing factors for good prognosis calculated by Cox proportional hazard analysis were younger age, late metastasis to the pituitary gland, smaller PM size, and radiation therapy. The Kaplan-Meier survival was significantly better in patients with breast cancer and renal cell cancer than in those with lung cancer. coNclusioNs At the time of this writing, approximately 60% (120/201) of PMs had been treated by stereotactic radiation therapy in Japan. The median survival time was much longer than that reported in past series. To confirm the changes of clinical features and medical practice, a prospective and population-based survey is mandatory.

Organic-inorganic hybrid materials, composed of phases that interact on a nanoscale and a microstructure that mimics the extracellular matrix, can potentially provide attractive scaffolds for bone regeneration. In the present study, hybrid scaffolds of gelatin and bioactive glass (BG) with a fibrous microstructure were prepared by a combined sol-gel and electrospinning technique and evaluated in vitro. Structural and chemical analyses showed that the fibers consisted of gelatin and BG that were covalently linked by 3-glycidoxypropyltrimethoxysilane to form a homogeneous phase. Immersion of the gelatin-BG hybrid scaffolds in a simulated body fluid (SBF) at 37 C resulted in the formation of a hydroxyapatite (HA)-like material on the surface of the fibers within 12 h, showing the bioactivity of the scaffolds. After 5 days in SBF, the surface of the hybrid scaffolds was completely covered with an HA-like layer. The gelatin-BG hybrid scaffolds had a tensile strength of 4.3 6 1.2 MPa and an elongation to failure of 168 6 14%, compared to values of 0.5 6 0.2 MPa and 63 6 2% for gelatin scaffolds with a similar microstructure. The hybrid scaffolds supported the proliferation of osteoblastic MC3T3-E1 cells, alkaline phosphatase activity, and mineralization during in vitro culture, showing their biocompatibility. The results indicate that these gelatin-BG hybrid scaffolds prepared by a combination of sol-gel processing and electrospinning have potential for application in bone regeneration.