Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.

Results after treatment of craniopharyngiomas: further experiences with 73 patients since 1997.

OBJECT: The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature. METHODS: A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months. RESULTS: Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors' former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%-66.7% vs 2.6%-50.0%) but were less frequent after transsphenoidal approaches (5.2%-19.2% vs 2.9%-45.7%). CONCLUSIONS: Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients' condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.

Benefit of 1.5-T intraoperative MR imaging in the surgical treatment of craniopharyngiomas.

BACKGROUND: As low-field magnetic resonance imaging (MRI) has very limited significance for intraoperative control of total tumor removal (TTR), we examined the influence of 1.5-T MRI, incorporating higher resolution into the intraoperative strategy of craniopharyngioma surgery. METHODS: Surgery with intraoperative imaging was performed in 25 selected patients in whom tumor resection was anticipated to be difficult according to pre-operative findings. RESULTS: Intraoperative MRI confirmed the intended extent of tumor removal in 15 patients (14 TTRs, one intended incomplete removal, while a second procedure was scheduled due to complex shape). Misinterpretation was false positive or negative in one patient each. The extent of removal was not achieved as expected in eight patients (expectation: seven TTRs, one incomplete removal). In three patients, the expected TTR was achieved by resuming surgery. In another case, that goal was accomplished by performing an unscheduled second procedure. In total, by using intraoperative imaging, the rate of TTR was increased by 16% (four patients), leading to 80% in the entire series. Compared with the literature, the rate of new ophthalmologic and endocrine deficits is acceptable; the rate of other surgical complication is slightly higher but not directly caused by intraoperative imaging. CONCLUSION: Intraoperative 1.5-T MRI provides benefits because of good early prediction of TTR (sensitivity, positive predictive value: 93.8%; specificity, negative predictive value: 88.9%) and a low rate of false-positive results. Moreover, extended resection of remnants visualized is enabled and helps to increase the rate of TTR but does not exclude recurrence.

Hormone receptor expression in craniopharyngiomas: a clinicopathological correlation.

BACKGROUND: Extensive neurosurgical resection of craniopharyngiomas often requires lifetime hormonal substitution. OBJECTIVE: We investigated the effect of the hormone receptor expression of insulinlike growth factor-1, growth hormone-releasing hormone receptor, growth hormone, progesterone, estrogen (ER-1, ER-beta), and leptins (Ra6.4, Ra12.1, Rb) on tumor recurrence, size, and proliferation using clinical, histopathological, and molecular genetic analysis. PATIENTS AND METHODS: cDNA expression analysis was obtained in a cohort of 20 patients suffering from a craniopharyngioma to systematically determine the expression of above-mentioned receptors. In addition, 51 tumor samples were available to immunohistochemically investigate the extent and distribution of estrogen and progesterone receptors. In 18 tumor specimens, both experimental paradigms could be performed. RESULTS: All hormone receptors under study, including leptins, were detectable in craniopharyngiomas with reverse-transcription polymerase chain reaction but did not reach significance regarding the tested parameters. However, a correlation was observed between tumor size and cell proliferation indexes, as well as with cDNA expression levels of ER-1 and growth hormone receptors. CONCLUSION: The present preliminary data point to a correlation between estrogen and growth hormone receptor expression and proliferation indexes with tumor size in craniopharyngiomas. Because of the small cohort of tumors, these data require expansion and validation. This is the first report about leptin expression in this tumor entity. These findings should prompt careful consideration of hormonal replacement therapy regimens in patients with tumor remnants and evidence of respective receptor expression.

Target gene activation of the Wnt signaling pathway in nuclear beta-catenin accumulating cells of adamantinomatous craniopharyngiomas.

Activating beta-catenin (CTNNB1) mutations can be identified in the majority of adamantinomatous craniopharyngiomas (adaCP), suggesting an aberrant Wnt signaling pathway in this histopathologically peculiar tumor entity. However, there is no proven evidence that nuclear translocation of beta-catenin is associated with CTNNB1 mutations and target gene activation. We performed a laser-microdissection-based study comparing beta-catenin accumulating vs. non-accumulating tumor cells. Mutational analysis and gene expression profiling using real-time polymerase chain reaction were conducted in adamantinomatous and papillary tumor specimens. Target gene activation, that is, over-expression of Axin2 could be detected in adaCP, especially in tumor cells with nuclear beta-catenin accumulation. In addition, increased expression of BMP4 was identified in the accumulating cell population, which supports the hypothesis of an oral ectodermal origin. Interestingly, accumulating and non-accumulating tumor cell populations carried CTNNB1 mutations within exon 3. We extended the analysis, therefore, towards genetic regions encoding for membrane linkage and active/passive nuclear transport mechanisms (exon 4 and exon 8-13), but could not detect any alteration. This is the first report demonstrating an association between nuclear beta-catenin accumulation and target gene activation in adaCP. The results confirm the Wnt signaling pathway as molecular basis of the distinct and challenging clinical and morphological phenotype of adaCP.

Silent ACTH cell adenoma in coincidence with granulomatous hypophysitis--a case report.

A 44-year-old male suffered from an inactive pituitary adenoma measuring 20mm in computed tomography (CT) scan and nuclear magnetic resonance tomography (NMR). The tumor was surgically resected via the transnasal-transsphenoidal route. Surgical specimens revealed a typical, sparsely granulated adrenocorticotropic hormone (ACTH) cell adenoma, but also a granulomatous inflammation mostly in the periphery of the tumor, corresponding to a granulomatous hypophysitis. This coincidence appears to be unique and has yet not been described in the literature. Therefore, the clinical data and the pathohistologic and ultrastructural findings are presented here.

Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach.

Clinical and histopathologic differentiation of cystic lesions from the sellar region, that is, craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), is challenging and has paramount importance with respect to variable clinical manifestation and adapted surgical treatment strategies in both entities. Here, we retrospectively evaluated clinico-pathologic findings in 81 patients presenting with a cystic tumor located in the sellar region. All patients underwent transsphenoidal or transcranial resections. Microscopic inspection of surgical specimens identified CP in 51 patients, and RCC in 30 patients. Amongst the panel of immunohistochemical marker proteins used for histopathologic analysis, nuclear accumulation of beta-catenin was detectable only in CP. On the basis of the histopathologic and immunohistochemical analysis, clinical presentation (sex, age, ophthalmologic, and endocrinologic deficits), imaging (tumor location, size, and calcification), as well as a description of cyst contents obtained during operation were retrospectively evaluated. In purely cystic CPs, an isointense signal was more frequent in T1-weighted magnetic resonance images and calcification of the tumor capsule in computed tomography scans. In addition, the size of RCC was smaller and this tumor entity was more often located within the sella. Aberrant (nuclear) immunohistochemical staining for beta-catenin appeared, however, as most reliable factor for the differentiation between purely cystic CPs and RCCs, whereas tumor location, tumor size, and calcification of the tumor capsule were less consistent parameters. The data are compatible with distinct pathogenic pathways associated with these related histopathologic entities.

Surgical treatment of recurrent Cushing's disease.

OBJECTIVE: The aim of this study was to evaluate the role of transsphenoidal selective adenomectomy alone or in combination with adjuvant therapy in treatment of recurrent Cushing's disease. METHODS: A total of 16 patients with recurrent Cushing's disease underwent reoperation, 15 via a transsphenoidal approach and one via a combined transsphenoidal/transcranial approach. Selective adenomectomies were performed in 13 patients and hemihypophysectomies were performed in three patients. Endocrinologically, recurrence was diagnosed by an overnight 2-mg dexamethasone suppression test. All patients underwent a 1.5-T magnetic resonance imaging scan, and eight patients underwent inferior petrosal sinus sampling. RESULTS: After selective adenomectomy, six of the 13 patients went into remission. Recurrence always occurred at the localization of the original tumor. In three patients without intraoperative tumor detection, hypophysectomy did not lead to remission. In 10 patients with persistent disease, adjuvant therapy (radiotherapy, adrenalectomy) led to normalization of basal cortisol levels in eight patients and clinical remission in one patient. One patient was lost to follow-up. In 10 patients, no evidence of an adenoma was visible on the preoperative magnetic resonance imaging scan. Inferior petrosal sinus sampling allowed correct prediction of the tumor localization in two of eight patients. CONCLUSION: By performing repeated selective adenomectomy, patients with recurrent Cushing's disease can be cured without the risk of endocrine deficits or major complications. Dynamic endocrine tests are of paramount importance for surgical decision making. Imaging and inferior petrosal sinus sampling are not helpful in locating the recurrent tumor. If normalization can not be achieved, adjuvant therapy is mandatory.

Treatment of Cushing's disease: a retrospective clinical study of the latest 100 cases.

We evaluate the current role of microsurgery for Cushing's disease (CD) and the efficacy of adjuvant treatment modalities. The standard treatment for primary CD remains transsphenoidal surgery followed by adjuvant therapy in cases with persisting hypercortisolism. Moderately severe cases are treated with radiotherapy, while in the very severe adrenalectomy is performed. In our series of primary CD (March 1997 to September 2004, mean observation period 18.8 months) adenomas were confirmed intraoperatively in 84.0% of the cases. Remission was achieved in 75.0% and recurrence was observed in 4.8% of the patients. Complications occurred in 2.0% of the cases and all resolved without resulting in permanent morbidity. In the literature, the rates of intraoperative confirmation of an adenoma vary between 59.1 and 100%, remission rates between 42 and 100%, and recurrence rates between 3.0 and 63.2% depending on the experience of the surgeon and on the definition of remission. These rates have not improved significantly over the years. In experienced hands selective adenomectomy remains the least damaging and most effective treatment modality since it results in rapid clinical improvement if performed successfully. Therefore, it remains the treatment of choice. Patients not cured by surgery alone benefited from a combination of adjuvant treatment tailored to their specific needs using medications, radiation and/or adrenalectomy. In this fashion, we achieved normalization of cortisol levels in 79% and improvement in another 18% of the patients. We expect these rates to increase further once patients treated with radiotherapy begin to experience its full effect within the next few years.