Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.

The impact of provider surgical volumes on survival in children with primary tumors of the central nervous system--a population-based study.

BACKGROUND: Provider volume is often a central topic in debates about centralization of procedures. In Norway, there is considerable variation in provider volumes of the neurosurgical centers treating children. We sought to explore long-term survival after surgery for central nervous system tumors in children in relation to regional provider volumes. METHOD: Based on data from the Norwegian Cancer Registry we analyzed survival in all reported central nervous system tumors in children under the age of 16 treated over two decades, between March 1988 and April 2008; a total of 816 patients with histologically confirmed disease. RESULTS: There was no overall difference in survival between regions. In the subgroup of PNET/medulloblastomas, both living in the high-provider volume health region and receiving treatment in the high-volume region was significantly associated with inferior survival. CONCLUSIONS: In this population-based study of children operated over a period of two decades, we found no evidence of improved long-term survival in the high-provider volume region. Surprisingly, a subgroup analysis indicated that survival in PNET/medulloblastomas was significantly better if living outside the most populated health region with the highest provider volumes. One should, however, be careful of interpreting this directly as a symptom of quality of care, as there may be unseen confounders. Our study demonstrates that provider case volume may serve as an axiom in debates about centralization of cancer surgery while perhaps much more reliable and valid but less quantifiable factors are important for the final results.

Transsellar Ultrasound in Pituitary Surgery With a Designated Probe: Early Experiences.

BACKGROUND: Anatomic orientation in transsphenoidal surgery can be difficult, and residual tumors are common. A major limitation of both direct microscopy and endoscopic visualization is the inability to see below the surface of the surgical field to confirm the location of vessels, nerves, tumor remnants, and normal pituitary tissue. OBJECTIVE: To present our initial experience with a new forward-looking, custom-designed ultrasound probe for transsellar imaging. METHODS: The center frequency of the prototype tightly curved linear array, bayonet-shaped probe is 12 MHz. Twenty-four patients with pituitary adenomas were included after informed consent. RESULTS: With the use of transsellar ultrasound, we could confirm the location of important neurovascular structures and improve the extent of resection in 4 of 24 cases, as rated subjectively by the operating surgeons. Image quality was good. In 17 patients (71%), biochemical cures and/or complete resections were confirmed at 3 months. CONCLUSION: We found the images from our custom-designed ultrasound probe to be clinically helpful for anatomic orientation during surgery, and the technology is potentially helpful for improving the extent of resection during transsphenoidal surgery. This quick and flexible form of intraoperative imaging in transsphenoidal surgery could be of great support for surgeons in both routine use and difficult cases. The concept of transsellar intraoperative ultrasound imaging can be further refined and developed.

Cyclooxygenase inhibitors attenuate endothelin ET(B) receptor-mediated contraction in human temporal artery.

It is well documented that endothelin ET(B) receptor-mediated contraction develops in artery segments incubated in culture and that the reaction is augmented by proinflammatory cytokines, but little is known of the mechanisms involved. Segments of human temporal artery were incubated in organ culture for 2 days in the absence or presence of interleukin-1 beta (IL-1 beta), with or without nonsteroidal anti-inflammatory drugs, glucocorticoids or a nitric oxide synthase inhibitor. Thereafter, contractions were induced by the selective endothelin ET(B) receptor agonist, sarafotoxin S6c. Acetylsalicylic acid, indomethacin, nimesulide and rofecoxib were all effective in eliminating the increase in endothelin ET(B) receptor-mediated contraction induced by interleukin-1 beta, but only indomethacin and rofecoxib significantly reduced the spontaneous development of this reaction in cultured arteries. Dexamethasone and methylprednisolone augmented the reaction, and the nitric oxide synthase inhibitor had no effect. The results clearly indicate a role for cyclooxygenase, most likely cyclooxygenase-2, in endothelin ET(B) receptor-mediated contraction in this preparation.

[Hormonally inactive pituitary adenomas]. / Ikke-hormonproduserende hypofyseadenomer.

BACKGROUND: This paper surveys hormonally inactive pituitary tumours on the basis of the current international literature; it also reflects the experience of the authors. INTERPRETATION: Pituitary tumours are frequently diagnosed and usually show a low potential for growth. Although benign they may invade adjacent structures such as the cavernous and sphenoid sinuses. The diagnosis is usually made on the basis of pituitary failure or visual problems, or incidentally. Tumour debulking or removal, usually by transsphenoidal surgery, is indicated if there is a compression of the optic chiasm or if the tumour shows signs of growth on consecutive MRI scans. Surgery is an effective treatment of these tumours, with little risk of complications. Repeated surgery, either transsphenoidally or by craniotomy, is indicated if chiasmal decompression is not achieved initially. Fractionated single beam irradiation or stereotactic radiosurgery is indicated in cases where there is a residual of growing tumours that may not be removed surgically.

Acute endovascular repair of iatrogenic right internal carotid arterial laceration.

Carotid arterial bleeding is a feared and possible life-threatening complication of transsphenoidal surgery. We present a case of a meningioma that during resection had a serious complication with laceration of the internal carotid artery (ICA). These patients rarely undergo endovascular treatment, with indications mainly due to the development of pseudoaneurysms or penetrating trauma. However, endovascular treatment with covered stents of carotid arterial bleedings is a feasible alternative due to technical advances and smaller sized stentgrafts that expand treatment options.

Intrasellar ultrasound in transsphenoidal surgery: a novel technique.

OBJECTIVE: Residual tumor masses are common after transsphenoidal surgery. The risk of a residual mass increases with tumor size and parasellar or suprasellar growth. Transsphenoidal surgery is usually performed without image guidance. We aimed to investigate a new technical solution developed for intraoperative ultrasound imaging during transsphenoidal surgery, with respect to potential clinical use and the ability to identify neuroanatomy and tumor. METHODS: In 9 patients with pituitary macroadenomas, intrasphenoidal and intrasellar ultrasound was assessed during transsphenoidal operations. Ultrasound B-mode, power-Doppler and color-Doppler images were acquired using a small prototype linear array, side-looking probe. The long probe tip measures only 3 x 4 mm. We present images and discuss the potential of intrasphenoidal and intrasellar and ultrasound in transsphenoidal surgery. RESULTS: We present 2-dimensional, high-resolution ultrasound images. A small side-looking, high-frequency ultrasound probe can be used to ensure orientation in the midline for the surgical approach to identify important neurovascular structures to be avoided during surgery and for resection control and identification of normal pituitary tissue. The image resolution is far better than what can be achieved with current clinical magnetic resonance imaging technology. CONCLUSION: We believe that the concept of intrasellar ultrasound can be further developed to become a flexible and useful tool in transsphenoidal surgery.

[Hyperprolactinemia and prolactinemia--investigation and treatment]. / Hyperprolaktinemi og prolaktinom--utredning og behandling.

BACKGROUND: Prolactinoma represents the most commonly occurring hormone-secreting pituitary adenoma. The majority of prolactinomas are small, only rarely do we find larger prolactinomas, so-called macroadenomas. They are almost exclusively benign. The symptoms are mainly caused by elevated prolactin levels and result in changes to the reproductive and sexual function. In cases of macroprolactinomas, symptoms caused by local mass effects can be seen. A variety of other conditions may also cause hyperprolactinaemia; the goal of the examination is to identify the cause. MATERIAL AND METHODS: We have reviewed recent literature and compared findings with current management of hyperprolactinaemia and prolactinoma in Norwegian university hospitals. RESULTS AND INTERPRETATION: The primary treatment is medical, intended to normalize prolactin levels, restore gonadal function, and reduce tumour size. With the new selective dopamine agonists, the treatment is often simple and efficient, but not all patients are in need of treatment.