Włodzimierz Liebert

Genomic Instability in Pituitary Adenomas

Pituitary adenomas most commonly are identified as small, incidental microadenomas. They however may progress to macroadenoma forming intra and later suprasellar tumors which in about 1/3 of cases invade surrounding structures at the time of diagnosis. Mechanism of pituitary tumorigenesis remains still elusive. Because the value of karyotyping is limited by the technical problems related to cytogenetic methods, we studied the spectrum of chromosomal imbalances associated with pituitary adenoma using comparative genomic hybridization (CGH). Copy number aberrations on all 22 autosomes were evaluated by CGH using advanced computer software. In total, fifteen patients were included in the study of 9 non-invasive, 4 invasive and two recurrent adenomas. The mean age of the patients were 48 years ranging from 36 to 68 years. Five tumors showed hormonal activity. The histogram of all 15 cases representing the DNA imbalances as an incidence curve along each chromosome showed losses particularly for chromosomes 1p, 2q, 4, 5, 6, 11q, 12q, 13q and 18q as well as overrepresentation on 9q, 16p, 17p, 19, 20q. Functioning adenomas carried more imbalances than non-functioning, specifically deletions on chromosome 4 and 18q as well as overrepresentations of chromosomes 17 and 19. Invasive adenomas carried more overrepresentations at 1p34 than non-invasive tumors. Recurrent adenomas harbored more alterations than primary tumors, particularly DNA gains. The primary data is accessible at our CGH online tumor database at http://amba.charite.de/cgh. Reviewing the existing literature on the genetics of pituitary adenoma and discussing our results in this context, we hope that our study will contribute to the knowledge of this neoplasm.

Short-term pre-surgical treatment with somatostatin analogues, octreotide and lanreotide, in acromegaly

Eighteen patients with symptoms of active acromegaly were treated with somatostatin analogues for 4 weeks before surgery. Both before and after the treatment, levels of growth hormone (GH), prolactin (PRL), insulin growth factor -I (IGF-I), luteotropin (LH), folliculostimulin (FSH) and subunit α of glycoprotein hormones were estimated. Glucose tolerance test, magnetic resonance imaging (MRI) examination, sight acuity and field of vision tests were also performed. The same tests were performed on ten control patients with clinically and biochemically active acromegaly, subjected to surgery but not treated with somatostatin analogues. In six patients treated with somatostatin analogues GH levels decreased significantly to less than 5 ng/ml and in two patients remained elevated while in 10 patients GH level decreased and ranged from 6.1 to 42.9 ng/ml. In 13 patients we observed a decrease in IGF-I to normal levels (<400 ng/dl) and in 3 patients we noted a decrease to levels slightly higher than normal. There was also a slight decrease in α subunit concentration. In the glucose inhibition test 4 patients demonstrated normalized GH levels. In patients with elevated PRL and TSH levels, treatment with somatostatin analogues induced their decrease. No changes were observed in levels of LH and FSH. After therapy MRI examination disclosed a decrease in tumor volume in two patients (by 20 and 25%, respectively) and no changes in tumor size in 16 patients. The two patients with a decreased tumor volume also showed normalized glucose tolerance tests. All patients manifested an improved clinical condition. Neurosurgeons disclosed a decreased tumor consistency which greatly facilitated surgical procedure. Our studies documented favourable effects of somatostatin analogues on the assayed hormone levels, and on the general condition of the patients as well as on the course of the surgical procedure itself.

Ten years of experience in endovascular treatment of ruptured aneurysms of the posterior inferior cerebellar artery

Background The aim of this study is to present our 10 years of experience in endovascular treatment of ruptured posterior inferior cerebellar artery (PICA) saccular aneurysms and to compare clinical presentation and outcome after endovascular treatment between patients with PICA aneurysms and patients with aneurysms in different locations. Methods and findings Out of 932 patients with a ruptured intracranial aneurysm treated endovascularly in our institution, 38 aneurysms were located at the posterior inferior cerebellar artery. Clinical presentation, mean aneurysm diameter and outcome of the therapy in this group were compared with the same for ruptured aneurysms in other locations. Patients discharged with favourable outcomes were checked angiographically in the follow-up period. Thirty-four patients with ruptured PICA aneurysms were treated by selective endovascular coiling. Two patients with wide-necked aneurysms had endovascular stents implanted. In two cases, the parent vessel was occluded due to failure to catheterise the target aneurysm. The evaluated variables did not differ significantly between two groups, but significantly more ruptured aneurysms in the PICA group were under 6 mm in diameter. 29.4% of controlled aneurysms needed additional reembolisation in the follow-up period. Conclusions Clinical presentation, extension of subarachnoid haemorrhage and outcome after endovascular treatment did not differ significantly between patients with ruptured aneurysms located on the PICA and patients with aneurysms located elsewhere intracranially. Endovascular treatment is an effective method of therapy in patients with ruptured PICA aneurysms. In our experience, even when sacrificing of the PICA is required, the results of treatment are favourable.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

Unusual Presentation of Traumatic Pseudoaneurysm of the PosteriorAuricular Artery Manifesting by Massive Bleeding from the External AuditoryCanal: A Case Report

Background: This report describes the unusual case of massive bleeding from the external auditory canal. Results: We present a very rare mechanism of potentially fatal bleeding. We describe presentation, differential diagnosis, anatomy considerations and management options for this case. Conclusions and relevance: Posttraumatic pseudoaneurysm is almost always a result of blunt trauma. When the pseudoaneurysm is bleeding, it requires urgent angiogram and occlusion.

Decreased expression of survivin 2B in human pituitary adenomas. A preliminary study

INTRODUCTION We aimed to investigate survivin and its splice variants DEx3 and 2B expressions in pituitary adenomas and normal pituitary glands using immunohistochemistry. MATERIAL AND METHODS The study group consisted of eight pituitary adenomas: five of non-functional tumors, two of GH-secreting tumors, and one PRL-secreting tumor. Eight healthy pituitary tissue samples obtained after autopsy served as controls. RESULTS Survivin expression was found in 87.5% of the study group and 100% of the controls. A positive staining of survivin 2B was found in 62.5% of pituitary adenomas and 100% of controls. Survivin DEx3 was recognized in 25% of pituitary adenomas and 12.5% of normal pituitary glands. There was significantly lower immunoreactivity of survivin 2B in pituitary adenomas when compared with normal pituitary glands (p = 0.0498). CONCLUSIONS Survivin and its splice variants might be involved to some extent in benign tumor growth of pituitary adenomas. However, survivin cannot be regarded as a candidate for targeted therapy or molecular biomarker of pituitary adenomas.

Embolisation of internal carotid artery aneurysm using the double microcatheter technique - a case report.

Summary Background A wide-necked aneurysm is defined as the one with a neck greater than 4 mm in diameter. Embolisation of wide-necked aneurysms is a great challenge for neuroradiologists. To overcome possible complications of endovascular treatment of this type of aneurysms, methods like intracranial stents, balloon remodelling, the double microcatheter and the microcatheter protective technique have been developed. Case Report We report a case of embolisation of a 63-year-old woman with a wide-necked aneurysm using the double microcatheter technique. Introduction of the second microcatheter into the aneurysm allowed for crossing two coils and prevented protrusion into the parent vessel, which resulted in successful treatment without postprocedural complications. Both postembolic and follow-up angiography showed complete exclusion of the aneurysm. Conclusions The double microcatheter technique, owing to creation of a stable coil frame across the neck of the aneurysm, is suitable for treatment of aneurysms with an adverse dome-to-neck ratio. This technique is easy to perform for an experienced neuroradiologist.

Very late in-stent thrombosis 9 years after double stent treatment of fusiform basilar artery aneurysm

Endovascular treatment seems to be the best approach to posterior circulation fusiform aneurysms. Double stent techniques are frequently used to occlude basilar artery dilations. Unfortunately, there is a limited number of studies that have followed up with patients over prolonged periods of time in order to evaluate delayed complications, such as stenosis, thrombosis or migration of stents. We present an unusual case of in-stent thrombosis 9 years after basilar artery aneurysm treatment to caution about complications associated with double stent implantation.