Radiosurgery for pituitary adenomas: evaluation of its efficacy and safety

<p>Abstract</p> <p>Object</p> <p>To assess the effects of radiosurgery (RS) on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas.</p> <p>Methods</p> <p>Retrospective analysis of 42 patients out of the first 48 consecutive patients with pituitary adenomas treated with RS between 1999 and 2008 with a 6 months minimum follow-up. RS was delivered with Gamma Knife as a primary or adjuvant treatment. There were 14 patients with non-secretory adenomas and, among functioning adenomas, 9 were prolactinomas, 9 were adrenocorticotropic hormone-secreting and 10 were growth hormone-secreting tumors. Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization. Radiological control was defined as stasis or shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes. Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS.</p> <p>Results</p> <p>The median follow-up was 42 months (6-109 months). The median dose was 12,5 Gy (9 - 15 Gy) and 20 Gy (12 - 28 Gy) for non-secretory and secretory adenomas, respectively. Tumor growth was controlled in 98% (41 in 42) of the cases and tumor shrinkage ocurred in 10% (4 in 42) of the cases. The 3-year actuarial rate of hormonal control and normalization were 62,4% and 37,6%, respectively, and the 5-year actuarial rate were 81,2% and 55,4%, respectively. The median latency period for hormonal control and normalization was, respectively, 15 and 18 months. On univariate analysis, there were no relationships between median dose or tumoral volume and hormonal control or normalization. There were no patients with visual deficit and 1 patient had hypopituitarism after RS.</p> <p>Conclusions</p> <p>RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature.</p

MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

<p>Abstract</p> <p>Background</p> <p>Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas.</p> <p>Methods</p> <p>Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated.</p> <p>Results</p> <p>MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level.</p> <p>Conclusion</p> <p>MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus or had other neuropathies related with gamma knife. MASEP GKRS may serve as a primary treatment method in some or as a salvage treatment in the others. However, treatment must be tailored to meet the patient's symptoms, tumor location, tumor morphometry, and overall health. Longer follow-up is required for a more complete assessment of late radioreaction and treatment efficacy.</p

Research in progress: report on the ICAIL 2017 doctoral consortium

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences

Induction and transmission of oncogene-induced senescence

Senescence is a cellular stress response triggered by diverse stressors, including oncogene activation, where it serves as a bona-fide tumour suppressor mechanism. Senescence can be transmitted to neighbouring cells, known as paracrine secondary senescence. Secondary senescence was initially described as a paracrine mechanism, but recent evidence suggests a more complex scenario involving juxtacrine communication between cells. In addition, single-cell studies described differences between primary and secondary senescent end-points, which have thus far not been considered functionally distinct. Here we discuss emerging concepts in senescence transmission and heterogeneity in primary and secondary senescence on a cellular and organ level

Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages

Refinement of Light-Responsive Transcript Lists Using Rice Oligonucleotide Arrays: Evaluation of Gene-Redundancy

Studies of gene function are often hampered by gene-redundancy, especially in organisms with large genomes such as rice (Oryza sativa). We present an approach for using transcriptomics data to focus functional studies and address redundancy. To this end, we have constructed and validated an inexpensive and publicly available rice oligonucleotide near-whole genome array, called the rice NSF45K array. We generated expression profiles for light- vs. dark-grown rice leaf tissue and validated the biological significance of the data by analyzing sources of variation and confirming expression trends with reverse transcription polymerase chain reaction. We examined trends in the data by evaluating enrichment of gene ontology terms at multiple false discovery rate thresholds. To compare data generated with the NSF45K array with published results, we developed publicly available, web-based tools (www.ricearray.org). The Oligo and EST Anatomy Viewer enables visualization of EST-based expression profiling data for all genes on the array. The Rice Multi-platform Microarray Search Tool facilitates comparison of gene expression profiles across multiple rice microarray platforms. Finally, we incorporated gene expression and biochemical pathway data to reduce the number of candidate gene products putatively participating in the eight steps of the photorespiration pathway from 52 to 10, based on expression levels of putatively functionally redundant genes. We confirmed the efficacy of this method to cope with redundancy by correctly predicting participation in photorespiration of a gene with five paralogs. Applying these methods will accelerate rice functional genomics

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions