Atte Karppinen

Transition From Microscopic to Endoscopic Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas

OBJECTIVE At our institution, a total of 320 patients were operated on between 2000 and 2010 for a newly diagnosed pituitary adenoma. In an attempt to improve quality of tumor resection, the transsphenoidal microscopic technique was replaced by the endoscopic technique in June 2008. This retrospective single center study compares the outcomes after microscopic (n = 144) and endoscopic (n = 41) tumor surgery of all patients operated on for a nonfunctional pituitary adenoma. METHODS Tumor size and location, Knosp grade, prevalence of anterior hypopituitarism, diabetes insipidus, visual acuity/fields, complication rates, and operation time were compared between the groups. RESULTS At the 3-month follow-up, hypopituitarism had improved in 7% of patients in the microscopic group and in 9% in the endoscopic group, and had further impaired in 13% and 9%, respectively. At the 3-month follow-up magnetic resonance imaging, a total tumor removal was achieved in 45% versus 56% of patients, respectively (P = not significant [NS]). Visual fields had normalized or improved in 90% versus 88% of patients, respectively (P = NS). Postoperative cerebrospinal fluid leak occurred in 3.5% versus 2.4% (P = NS), and diabetes insipidus (transient or permanent) in 7.6% versus 4.9% (P = NS) of cases, respectively. Larger tumor size (P < 0.0005) and endoscopic technique (P = 0.03) were independent predictors of increased mean operative time. CONCLUSIONS Initial results with the endoscopic technique were statistically similar to those achieved with the microscopic technique. However, there was a trend toward improved outcomes and fewer complications in the endoscopic group.

Whole-Genome Sequencing of Growth Hormone (GH)-Secreting Pituitary Adenomas.

CONTEXT The somatic landscape of pituitary adenomas is largely unknown. Identification of somatic alterations aims at better understanding of tumor pathology. OBJECTIVE The objective of the study was a genome-wide characterization of somatic single-nucleotide variants, structural variants, and copy-number aberrations in somatotropinomas. DESIGN AND SETTING Whole-genome sequencing and single-nucleotide polymorphism array analyses were performed on 12 fresh-frozen somatotropinomas and their corresponding blood samples. All the coding somatic variants were confirmed by Sanger sequencing. PATIENTS Studied tumors were somatotropinomas. Apart from one AIP mutation-positive patient, all cases were mutation negative for the established germline mutations associated with pituitary adenomas. INTERVENTION(S) There were no interventions. MAIN OUTCOME MEASURES Somatic variants were identified with an established computational pipeline and filtered against germline data. Somatic copy number alteration analyses were performed using segmentation-based approaches. RESULTS A genome-wide analysis revealed on average 129 somatic single-nucleotide variants per tumor. Further analysis of coding regions showed on average 2.3 single-nucleotide variants per tumor. The only recurrent somatic events were the oncogenic GNAS mutation (p.Arg201Cys) and shared chromosome losses (chromosomes 1, 6, 13, 14, 15, 16, 18, 22). Analysis of somatic structural variants revealed one tumor with a complex chromosomal rearrangement. CONCLUSIONS Somatotropinomas showed a low number of somatic genetic alterations. Whereas no novel recurrently mutated genes could be identified, the somatic landscape has potential to affect the Ca(2+) and ATP pathways known to be involved in the pituitary tumorigenesis. Further studies, eg, methylome and transcriptome analyses, are needed to investigate possible interplay between the recurrent chromosome losses and epigenetic factors.

Normal long-term health-related quality of life can be achieved in patients with functional pituitary adenomas having surgery as primary treatment.

Previous studies report impaired health‐related quality of life (HRQoL) in patients with functional pituitary adenomas (FPA). We assessed HRQoL in FPA patients having undergone surgery at our University Central Hospital between 2000 and 2010, with combined adjuvant treatment given to achieve strict hormonal control.

Health-related quality of life in patients treated for nonfunctioning pituitary adenomas during the years 2000–2010

The published data on health‐related quality of life (HRQoL) after treatment of nonfunctioning pituitary adenomas (NFPAs) are conflicting. We evaluated HRQoL in a recent series of patients who had surgery for an NFPA.

Impact of AIP and inhibitory G protein alpha 2 proteins on clinical features of sporadic GH-secreting pituitary adenomas

INTRODUCTION In sporadic acromegaly, downregulation of AIP protein of the adenomas associates with invasive tumor features and reduced responsiveness to somatostatin analogues. AIP is a regulator of Gai signaling, but it is not known how the biological function of the Gai pathway is controlled. AIM To study GNAS and AIP mutation status, AIP and Gai-2 protein expressions, Ki-67 proliferation indices and clinical parameters in patients having primary surgery because of acromegaly at a single center between years 2000 and 2010. RESULTS Sixty patients (F/M, 31/29), mean age 49 (median 50), mean follow-up 7.7 years (range 0.6-14.0) underwent primary surgery. Four adenoma specimens (6.8%) harbored an AIP and 21 (35.6%) an activating GNAS (Gsp+) mutation. Altogether 13/56 (23%) adenomas had low AIP protein levels, and 14/56 (25%) low Gai-2 staining. In regression modeling, AIP expression associated with Gai-2 (P = 2.33 × 10-9) and lower Ki-67 (P = 0.04). In pairwise comparison, low AIP protein predicted high GH at last follow-up (mean 7.7 years after surgery, q = 0.045). Extent of treatments given for acromegaly associated with higher preoperative GH (P = 7.94 × 10-4), KNOSP (P = 0.003) and preoperative hypopituitarism (P = 0.03) and remission at last follow-up with change in 3-month postoperative IGF1 (P = 2.07 × 10-7). CONCLUSIONS We demonstrate, for the first time, that AIP protein expression associates with Gai-2 protein intensities in sporadic somatotropinomas, suggesting a joint regulation on somatostatin signaling. Low AIP level associates with higher proliferative activity and predicts high GH concentrations after long-term follow-up. The AIP mutation rate of 6.8% is fairly high, reflecting the genetic composition of the Finnish population.

Chiari Malformation in otology practice.

The purpose of the study was to evaluate prevalence, characteristic symptoms, and management of Chiari Malformation 1 (CM1). A retrospective chat review was made in Otology Tertiary Department including 439 otologic patients referred to the Helsinki University Hospital Radiology Department for head magnetic resonance imaging (MRI) during 2005 and also among 42 patients seen at the Department of Neurosurgery in years 2001-2005 with a diagnosis of CM1. We made a structured analysis of medical records focusing on patient history, neurologic symptoms, and radiologic findings. For surgical patients, information was collected on symptoms, treatment, and operative outcome. The prevalence of CM1 in the 439 otologic patients was 0.9%. Most CM1 patients sent to the Neurosurgery Department were operated on. Two months postoperatively, 26 patients (68%) had benefited from the surgery, but 12 patients (32%) experienced no change to symptoms. The possibility of CM1 should be borne in mind in patients presenting with atypical benign positional vertigo or recurrent facial paresis.

Inheritance of nasal dermoid sinus cyst and evidence for association with third ventricle colloid cyst

PurposeThe purpose of this paper is to study the possible inheritance of nasal dermoid sinus cyst in the Finnish population.MethodsA patient questionnaire and interview were utilized for this study.ResultsWe identified nine patients with dermoid sinus cyst. Only one of them had familial nasal dermoid sinus cyst. We found no evidence for founder effect.ConclusionsWe report a pedigree with six affected individuals and an association of nasal dermoid sinus cyst and third ventricle colloid cyst. Whether patients or pedigrees with nasal dermoid sinus cyst (NDSC) and third ventricle colloid cysts represent a previously unrecognized syndrome or belong to the normal phenotypic spectrum of NDSC remains unclear. Our patient material suggests that only minority of NDSCs seem to be familial.

Molecular alterations in pediatric brainstem gliomas

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27‐mutated diffuse midline gliomas, and whether rare long‐term survivors also belong to this group.