Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

BACKGROUND: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. METHODS: A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. RESULTS: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. CONCLUSION: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

Endoscopic vs. microscopic transsphenoidal pituitary surgery: a single centre study.

Endoscopic pituitary surgery has shown promising results. This study reports the experiences of experienced microscopic pituitary surgeons changing to the endoscopic technique, and the beneficial effects on the postoperative outcomes. 45 transsphenoidal endoscopic-assisted surgeries performed in 2016-2017 were compared with 195 microscope-assisted surgeries performed in 2007-2017 for pituitary adenoma. Tumour size, hormonal status and vision were assessed preoperatively and 3-5 months postoperatively. Cases were identified through electronic patient records. GTR was achieved in 39% of the endoscopic operations vs. 22% of microscopic operations, p = 0.018. Mean duration of surgery was 86 min (77-95) with the endoscopic technique vs. 106 min (101-111) with the microscopic technique, p < 0.001. New hypothalamus-pituitary-adrenal axis deficiencies were observed after 3% of endoscopic vs. 34% microscopic operations, p = 0.001, and overall fewer postoperative pituitary deficiencies were observed in the endoscope-assisted group. Complications within 30 days of surgery occurred in 17% of endoscopic operations vs. 27% of microscopic operations (p > 0.05). Normalization of visual impairment occurred in 37% of the cases with preoperative visual impairment in the endoscopic group vs. 35% of those in the microscopic group (p > 0.05). The endoscopic technique performed better as a surgical procedure for pituitary adenomas. We found no statistically significant differences in complication rate or visual improvement between the two techniques.

[Pituitary adenoma].

In this review, we discuss pituitary adenomas (PA), which account for 10-25% of the intracranial tumours. Despite their benign nature, PA often show invasive growth. Pressure on neighbouring structures may cause hypopituitarism or vision field impairment. For PA, except prolactinomas, surgical treatment is first choice. The primary surgical technique is transsphenoidal surgery. Pituitary function, vision and post-operative magnetic resonance imaging scan is evaluated in a multidisciplinary team of neurosurgeons and endocrinologist 6-8 weeks post-operatively. Follow-up and treatment of pituitary adenomas is highly specialised and requires a team of dedicated endocrinologists and neurosurgeons.

Intraoperative low field MRI in transsphenoidal pituitary surgery.

BACKGROUND: Intraoperative low field MRI (iMRI, 0.15 T) during transsphenoidal surgery on pituitary adenomas (PAs) may significantly improve tumor removal. However, extensive surgery can lead to pituitary hormone deficiency. Furthermore, introduction of iMRI will prolong duration of surgery, which may elevate risk of postoperative infections. METHODS: Overall, 180 transsphenoidal surgeries for PAs from 2007 to 2015 were included. IMRI was available from 2011 to 2015, during this period 67/78 (86%) surgeries were with iMRI (iMRI, n = 67). A total of 113 surgeries were performed without iMRI (controls). All surgical procedures were performed by microscopic technique. Tumor size, hormonal status and vision were assessed before surgery and 3-5 months postoperatively. RESULTS: Gross total resection (GTR), mean tumor remnant volume and ∆-volumes were comparable between iMRI and controls: 15% (10/66) vs 23% (26/109) (P = 0.17), 2.97 cm3 (0.9-5) vs 2.1 cm3 (1.6-2.6) (P = 0.3) and 4.5 cm3 (3.6-5.5) vs 5.1 cm3 (4.2-6) (P = 0.4), respectively. Duration of surgery was significantly longer during iMRI vs controls: 126 min (117-135) vs 98 min (92-103) (P < 0.001). New pituitary-adrenal deficiency in iMRI vs controls was seen in 35% (17/48) and 35% (23/66) of surgeries, respectively (P = 0.95). New thyroid deficiency was found in 33% (13/29) and 41% (28/69) and visual field deficiencies improved in 44% (19/43) and 38% (23/60) in iMRI vs controls, respectively (P > 0.1). CONCLUSION: Tumor remnant after pituitary surgery was not significantly reduced using intraoperative low field MRI. Duration of surgery was increased in iMRI, but was not associated with increased infection rate. Pituitary hormonal function and vision were comparable between iMRI and controls.