Narrowing in on Pituitary Tumors

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As many as 20 percent of people may have a benign cyst or tumor in their pituitary gland. The vast majority of pituitary tumors are noncancerous, but can cause headaches and profound fatigue, and can also disrupt hormone function.

Currently, surgeons rely on radiologic images and MRIs to gather information about the size and shape of the tumor, but the resolution of such imaging technologies is limited, and additional surgeries to remove more of the tumor may be needed if a patient’s symptoms persist. In a new study published in the Proceedings of the National Academy of Sciences on July 27, investigators from Brigham and Women’s Hospital (BWH) present a new technique that could help surgeons more precisely define the locations of tumors in near real-time.

The new strategy uses a visualization technique (matrix-assisted laser desorption/ionization mass spectrometry imaging – MALDI MSI) that can analyze specific hormones, including growth hormone and prolactin, in tissue. In the newly published study, the researchers find that it’s possible to use MALDI MSI to determine the composition of such hormones in a pituitary sample in less than 30 minutes. This could give surgeons critical information to help distinguish tumor from normal gland.

“Our work is driven by a clinical need: we’ve developed a test specifically tailored for the needs of our neurosurgeon colleagues,” said corresponding author Nathalie Agar, PhD, director of the Surgical Molecular Imaging Laboratory in the Department of Neurosurgery at BWH. “A surgeon may sacrifice half of the pituitary gland in an effort to get the tumor out. Without a tool to distinguish healthy tissue from tumor, it’s hard to know in real-time if the surgery was a success. With this technology, in under 30 minutes a surgeon will be able to know if a sample contains normal pituitary tissue or a pituitary tumor.”

“Patients show up with the clinical symptoms of a pituitary tumor, but the tumor itself may not be visible on an MRI,” said co-author Edward Laws, MD, director of the Pituitary and Neuroendocrine Center at BWH. “This technique, which maps out where excess concentrations of hormone levels are located, has the potential to allow us to confirm that we’ve removed the abnormal tissue.”

“Evaluating whether a piece of pituitary tissue is abnormal can be challenging on frozen section,” said co-author Sandro Santagata, MD, PhD, of BWH’s Department of Pathology. “This approach has wonderful potential for enhancing our diagnostic capabilities. It is clearly an important step toward providing intra-operative molecular characterization of pituitary tissues.”

To test the technique, the research team analyzed hormone levels in 45 pituitary tumors and six normal pituitary gland samples, finding a distinct protein signature unique to the normal or tumor sample.

Mass spectrometry, a technique for measuring chemicals present in a sample, is currently used in the operating room to help inform clinical decisions, but up until now, the focus has been on small molecules – metabolites, fatty acids and lipids – using a different type of approach. By analyzing proteins, MALDI MSI offers a way to visualize hormone levels.

Current methods used to detect hormone levels take too long to fit the time constraints of surgical intervention. Surgeons must either remove a larger amount of potentially healthy pituitary gland or perform follow up surgery if the tumor has not been fully removed.

“We’re hoping that techniques like this one will help move the field toward more precise surgery: surgery that not only removes all of the tumor but also preserves the healthy tissue as much as possible,” said Agar.

In the next phase of their work, Agar and her colleagues plan to test out the technique in BWH’s AMIGO suite and analyze the impact of the technique on clinical decision making.

Other researchers who contributed to this study include David Calligaris, Daniel R. Feldman, Isaiah Norton, Olutayo Olubiyi, Armen N. Changelian, Revaz Machaidze, Matthew L. Vestal and Ian F. Dunn.

This work was funded in part by US National Institute of Health (NIH) Director’s New Innovator Award (1DP2OD007383-01 to N.Y.R.A.), U.S. Army Medical Research/CIMIT (2010A052245), the National Center for Image Guided Therapy grant P41RR019703, NIH K08NS064168, the Pediatric Low Grade Astrocytoma Program at Dana-Farber Cancer Institute, the Brain Science Foundation and the Daniel E. Ponton fund for the Neurosciences at BWH.

Brigham and Women’s Hospital 2015 | 75 Francis Street, Boston MA 02115 | 617-732-5500

From http://www.healthcanal.com/cancers/65676-narrowing-in-on-pituitary-tumors.html

Pituitary adenoma growth rate influenced by multiple factors

Monsalves E. J. Clin Endocrinol Metab. 2013; doi: 10. 1210/jc.2013-3054.

The etiology of pituitary adenoma growth rate is multifactorial and may be influenced by patient age and gender, as well as adenoma subtype, hormonal activity, immunohistological profile and the direction of growth relative to the pituitary fossa, according to results of a retrospective study.

Researchers evaluated pre- and postoperative pituitary adenoma (PA) traits in relation to patient demographics, MRI specifications and histopathological factors. They examined 153 patients who underwent surgery for removal of a histologically-proven PA at Toronto Western Hospital between 1999 and 2011.

All patients had at least two preoperative and two postoperative MRIs to measure tumor volume doubling time. Both scans were completed a minimum of 3 months apart.

Patients all underwent a sella/pituitary imaging protocol, and volume was determined using partitioning and target volume software. Each patient was also reviewed by two endocrine pathologists, and standardized diagnostic synoptic pathology reports provided information on MIB-1 labeling index, p27 and N-terminally truncated fibroblast growth factor receptor 4 (FGFR4). Growth direction patterns were classified as superior, anterior, posterior and lateral in relation to the sellar fossa.

The researchers found a relationship between preoperative growth rate and age (P=.0001), as well as suprasellar growth (P=.003), existence of a cyst or hemorrhage (P= .004), the MIB-1 (P=.005), FGFR4 positivity (P=.047) and p27 negativity (P=.007).

Postoperatively, 34.6% of patients demonstrated residual volumes, while the remaining 100 patients did not. Residual volume was found to be associated with older patient age (57 vs. 51, P=.038), as well as growth patterns, including anterior, posterior, suprasellar and cavernous sinus extension (P=.001). There was a correlation between pre-and postoperative growth rates (r=0.497, P=.026). The rates of postoperative growth were linked with age (P=.015) and gender (P= .017).

“Due to the heterogeneity of PA, no single predictor of PA growth behavior can be taken in isolation as a means to predict its outcome,” the researchers wrote.  “These predictors must be combined in order to formulate the most accurate estimation of PA growth, which in turn will inform sound clinical management.”

Disclosures: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/neuroendocrinology/news/online/%7B7cb2ec5d-eaa6-42a3-b279-2c2436d0fbd0%7D/pituitary-adenoma-growth-rate-influenced-by-multiple-factors

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