Endoscopic and Microscopic Surgery Equally Effective in Cushing’s Disease

Using endoscopic or microscopic techniques to surgically remove the pituitary glands leads to similar remission and recurrence rates in Cushing’s disease patients, a review of 24 studies shows.

The study, titled “Outcome of endoscopic vs microsurgical transsphenoidal resection for Cushing’s disease,” was published in the journal Endocrine Connections.

In endoscopic transsphenoidal surgery, a surgeon uses a tiny camera as a guide, allowing for a panoramic surgical view with increased illumination of anatomic structures. In microsurgical transsphenoidal resection, a surgeon views through a microscope and uses minute instruments or lasers. Both procedures are used in transsphenoidal (TS) surgery to remove pituitary gland tumors, the root cause of Cushing’s disease. In transsphenoidal surgery, a surgeon accesses the pituitary gland through the nose and sinuses.

While endoscopic surgery seems to lead to better patient outcomes, it was unclear before this study if it has any advantages in patients with Cushing’s disease.

To gain more insight into the remission and recurrence rates of both techniques, researchers examined a total of 24 studies that included 1,670 adult patients with Cushing’s syndrome. Of these patients, 702 underwent endoscopic TS, and 968 underwent microsurgical TS.

The study’s authors found that remission rates were similar in both groups. In the endoscopic group, an average of 79.7 percent of patients experienced remission versus 76.9 percent in the microscopic group.

Patients who underwent endoscopic surgery experienced recurrence less often than those who underwent microscopic surgery, with recurrence rates of 11 percent and 15.9 percent, respectively. But researchers pointed out that follow-up times in the studies varied, making comparisons unreliable.

When recurrence rates were calculated by person per year, which takes follow-up time into account, both groups had a recurrence rate of approximately 4 percent per person per year.

Previous studies have shown that complications following either type of surgery occurred at comparable rates. These complications include hypothyroidism (underactivity of the thyroid gland), diabetes insipidus (a condition characterized by increased thirst), CSF leakage (leakage of fluid that normally bathes the brain and spinal cord), visual defects, hypocortisolemia (low cortisol blood levels), and hypogonadism (little or no hormones produced by the sex glands).

“We found that overall remission proportion was the same in CD patients who underwent endoscopic TS compared to patients who underwent microscopic TS. However, patients treated with the endoscopic approach for micro-adenomas were more likely to achieve remission than those treated microsurgically. Patients treated endoscopically were less likely to experience recurrence; however, when follow-up time is taken into account, this advantage disappears,” the researchers concluded.

 

From https://cushingsdiseasenews.com/2018/02/01/cushings-disease-transsphenoidal-surgery-study-finds-endoscopic-microscopic-procedures-equally-effective/

Temozolomide May Partially Improve Aggressive Pituitary Tumors Causing Cushing’s Disease

The chemotherapy temozolomide partially improved a case of an aggressive pituitary tumor that caused symptoms of Cushing’s disease (CD), according to a new study in Poland. However, after tumor mass and cortisol levels were stabilized for a few months, the patient experienced rapid progression, suggesting that new methods for extending the effects of temozolomide are needed.

The study, “Temozolomide therapy for aggressive pituitary Crooke’s cells corticotropinoma causing Cushing’s Disease: A case report with literature review,” appeared in the journal Endokrynologia Polska.

Aggressive pituitary tumors are usually invasive macroadenomas, or benign tumors larger than 10 mm.

A very rare subset of pituitary adenoma — particularly corticotropinoma, or tumors with excessive secretion of corticotropin (ACTH) — exhibit Crooke’s cells. These tumors are highly invasive, have a high recurrence rate, and are often resistant to treatment.

Information is not widely available about the effectiveness of treating aggressive pituitary tumors, particularly those that cause Cushing’s disease. The management of these tumors usually requires neurosurgery, followed by radiotherapy, and pharmacotherapy. However, the chemotherapy medication temozolomide has been increasingly used as a first-line treatment after initial evidence of its effectiveness in treating glioblastoma, the most common form of brain cancer.

In this study, researchers at the Jagiellonian University, in Poland, discussed the case of a 61-year-old man with ACTH-dependent Cushing’s syndrome caused by Crooke’s cell corticotropinoma.

The patient first presented with symptoms of severe hypercorticoidism — the excessive secretion of steroid hormones from the adrenal cortex — in December 2011. He also showed advanced heart failure, severe headaches, and impaired vision, which had started two or three years before diagnosis. Examinations revealed osteoporosis and a fracture in the Th5 vertebra.

His morning ACTH levels were high. The same was observed for mean cortisol levels even after dexamethasone treatment, which was suggestive of a pituitary tumor secreting ACTH. MRIs showed the existence of a tumor mass, later identified as a macroadenoma with high cell polymorphism, the presence of Crooke’s cells, and ACTH secretion.

The patient was referred for transsphenoidal nonradical neurosurgery, performed through the nose and the sphenoid sinus, and bilateral adrenalectomy, or the surgical removal of the adrenal glands, in 2012-2013. However, he developed fast, postoperative recurrence of hypercorticoidism and tumor regrowth. This led to three additional transsphenoidal neurosurgeries and radiotherapy.

The patient’s clinical status worsened as he developed severe cardiac insufficiency. Doctors began temozolomide treatment in April 2015, which did not result in adverse effects throughout treatment.

The initial standard dose (150–200 mg/m2) was given once daily in the morning for five consecutive days, in a 28-day cycle. The patient also received 600 mg of ketoconazole, an antifungal medication. Ondansetron was administered to prevent nausea and vomiting.

Subsequent examinations revealed clinical and biochemical improvements, including a reduction in ACTH and cortisol levels. In addition, the patient also showed reduced cardiac insufficiency, less frequent and less severe headaches, visual field improvements, and better physical fitness and mood.

However, clinical symptoms worsened after the eighth temozolomide cycle. The tumor size also suddenly increased after the ninth cycle, reaching the inner ear. Temozolomide was then discontinued and ACTH levels increased by 28 percent one month later. The patient also demonstrated deteriorated vision, hearing loss, and strong headaches.

Clinicians then decided to start treatment with the Cushing’s disease therapy Signifor (pasireotide), but a worsening of diabetes was observed, and the patient died in February 2016.

“The most probable reason for death was compression of the brainstem, which had been observed in the last MRI of the pituitary,” the researchers wrote, adding that “due to the very short duration of treatment, any conclusions on the treatment with Signifor cannot be drawn.”

Overall, “the results of the presented case suggest that [temozolomide] treatment monotherapy could have only partial response in aggressive corticotroph adenoma causing Cushing’s disease, followed by sudden progression,” the investigators wrote. This contrasts with mostly responsive cases reported in research literature, they noted.

“Therefore, further research on the factors of responsiveness and on novel methods to extend the duration of the effect of [temozolomide] should be carried out,” they wrote.

From https://cushingsdiseasenews.com/2018/02/08/cushings-disease-case-study-poland-shows-temozolomide-temporarily-effective-treating-aggressive-pituitary-tumor/

For Pituitary Tumors, Gamma Knife™ Radiosurgery Offers Better Tumor Control

For many patients with pituitary tumors, initial surgical intervention is followed quickly by Gamma Knife™ radiosurgery. The benefits of using this radiosurgical intervention are many, and can offer better tumor control and a more positive long-term prognosis compared to surgery alone.

San Diego, CA (PRWEB) July 03, 2017

Worldwide, up to 20% of all brain tumors—those confined within the skull—are identified as pituitary adenomas.(1) Each year, almost 10,000 new pituitary tumors are diagnosed in the United States alone, with the vast majority of these tumors being pituitary adenomas. As efforts to improve treatment for patients with pituitary tumors continue, researchers are discovering just how powerful treatment with Gamma Knife™ radiosurgery can be, at facilities like the San Diego Gamma Knife Center® (SDGKC).

Recent studies have shown compelling results for patients who received treatment with Gamma Knife™ radiosurgery following traditional surgery for pituitary tumor removal. Overall, tumor control was achieved with Gamma Knife™ treatment in up to 94% of patients studied.(1) For up to 85% of these patients, tumor control was still achieved 10 years after treatment with the Gamma Knife™.(6)

Pituitary adenomas are typically benign, but they can still cause significant problems for patients due to their location in the brain.(3) Many of these tumors also secrete certain hormones, which can ultimately change the way patients’ bodies function.(3) In most cases, the first line of defense in dealing with pituitary tumors involves surgical removal of as much of the tumor as possible; however, residual tumor tissue can exist in the brain after this process.(4)

Even though many physicians choose surgery as an initial treatment, Gamma Knife™ radiosurgery can be either a primary or secondary choice for the management of pituitary tumors. Most often, Gamma Knife is used as a secondary treatment following surgery.(5) A growing number of studies show that treating patients with the Gamma Knife™ after surgical removal of pituitary tumors is extremely beneficial for patients and can dramatically improve their long-term tumor control results.

Dr. Kenneth Ott, neurosurgeon of SDGKC®, said, “The extreme accuracy of Gamma Knife radiosurgery allows effective treatment of residual pituitary tumors following surgery to remove much of the tumor volume. In my practice, residual tumors which I have operated on are treated with Gamma Knife radiosurgery which almost always stops further growth.”

Dr. Ott continued to explain that Gamma Knife radiosurgery is more effective than prior external beam methods of radiation and avoids complications to near-by sensitive structures. Tumors within a few millimeters of the optic nerves can be safely treated because of the frame-based fixation and software advantages of Gamma Knife. Tumors which are slowly growing can also be effectively treated without the need for surgery, as long as there is no visual loss from tumor compression of the optic nerves.

Patient outcomes can also be influenced by how soon after brain surgery they receive treatment with the Gamma Knife™. In many cases, patients benefit the most from early intervention with radiosurgery; some studies have suggested that patients who receive Gamma Knife treatment more than six months after their initial surgery are at a significantly greater risk of pituitary tumor progression nearly six years post-surgery.(7)

“Pituitary tumors, in general should be treated before the tumor compresses the overlying optic nerves,” said Dr. Ott. “The earlier the treatment begins, the better. The final decision regarding Gamma Knife should be made on a case-by-case basis by a surgeon who is experienced in surgery and radiosurgery.”
About San Diego Gamma Knife Center:
Since its opening, the San Diego Gamma Knife Center® has treated over 4,000 patients with various brain disorders from around the world. The facility is equipped to provide advanced radiosurgical treatment for a variety of conditions, including metastatic brain tumors, primary brain tumors, arteriovenous malformations, and functional disorders such as trigeminal neuralgia and cluster headaches.

On the campus of Scripps Memorial Hospital, the Center offers the use of its facilities to some of the top neurosurgeons and radiation oncologists in Southern California. It’s also a proud partner of the Neurosciences Department of Scripps Memorial Hospital La Jolla, helping to provide accurate diagnoses, treatment and support for a range of neurological conditions and disorders. To learn more about the San Diego Gamma Knife Center®, please visit http://www.sdgkc.com.

Sources:
1.    Sheehan J, et al. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study. Journal of Neurosurgery. 2013;119:446. http://thejns.org/doi/full/10.3171/2013.3.JNS12766. Accessed June 20, 2017.
2.    What Are the Key Statistics About Pituitary Tumors? American Cancer Society. https://www.cancer.org/cancer/pituitary-tumors/about/key-statistics.html. Accessed June 20, 2017.
3.    What Are Pituitary Tumors? American Cancer Society. https://www.cancer.org/cancer/pituitary-tumors/about/what-is-pituitary-tumor.html. Accessed June 20, 2017.
4.    Radiation—Gamma Knife Radiosurgery for Pituitary Adenomas. Pituitary Network Association. https://pituitary.org/medical-resources/pavilions/diagnostics-scanning-and-radiological-pavilion/diagnostics-scanning-and-radiological-archive/radiation-gamma-knife-radiosurgery-for-pituitary-adenomas. Accessed June 20, 2017.
5.    Gamma Knife Radiation Therapy for Pituitary Tumors—Candidates for Gamma Knife Treatment. The Pituitary Society. http://pituitarysociety.org/patient-education/pituitary-disorders/gammaradiation/candidates. Accessed June 20, 2017.
6.    Lee C, et al. Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas. Journal of Neurosurgery. 2014;120:647. http://thejns.org/doi/full/10.3171/2013.11.JNS131757. Accessed June 20, 2017.
7.    Gamma Knife Radiosurgery Safe in Early Pituitary Tumor. Medscape. http://www.medscape.com/viewarticle/879250. Accessed June 20, 2017.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/07/prweb14478413.htm

Endoscopic Surgery on a Pituitary Adenoma

Philip Theodosopoulos, M.D. is Professor and Vice-Chair of Neurological Surgery at the University of California, San Francisco. He is the Director of the Skull Base Tumor Program and has extensive experience performing endoscopic transsphenoidal pituitary surgery for pituitary tumors (over 1000 operations) and other disease processes as well as tumors of the base of the skull.

In this video Dr. Theodosopoulos illustrates portions of an endoscopic resection of a pituitary adenoma.

 

To learn more about Dr. Theodosopoulos and to schedule an appointment for consultation please copy this link:
neurosurgery.UCSF.edu/index.php/about_us_faculty_theodosopoulos.html

Imaging Technique Measures Tumor Stiffness to Aid Surgical Planning

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Important steps in planning tumor surgery include identifying borders between tumor and healthy tissue and assessing the tumor stiffness, e.g. hard and calcified or soft and pliant. For decades, tumors near the surface of the body have been evaluated for stiffness by simple palpation—the physician pressing on the tissue. Because tumors within the skull cannot be palpated, researchers used Magnetic Resonance Elastography (MRE) to assess pituitary tumor stiffness by measuring waves transmitted through the skull into pituitary macroadenomas (PMAs). MRE reliably identified tumors that were soft enough for removal with a minimally-invasive suction technique versus harder tumors requiring more invasive surgery.

“The group developed brain MRE several years ago and is now successfully applying it to clinical diagnosis and treatment,” explained Guoying Liu, Ph.D., Director of the NIBIB Program in Magnetic Resonance Imaging. “This development of a new imaging technique followed by its practical application in surgical planning for better patient outcomes is an outstanding example of one of the main objectives of NIBIB-funded research.”

MRE is a special magnetic resonance imaging technique that captures snapshots of shear waves that move through the tissue and create elastograms—images that show tissue stiffness. John Huston III, M.D., Professor of Radiology at the Mayo Clinic in Rochester, MN, and senior author of the study, explains how MRE works. “MRE is similar to a drop of water hitting a still pond to create the ripples that move out in all directions. We generate tiny, harmless ripples, or shear waves, that travel through the brain of the patient. Our instruments measure how the ripples change as they move through the brain and those changes give us an extremely accurate measure–and a color-coded picture–of the stiffness of the tissue.”

MRE data enables non-invasive surgical planning

Ninety percent of PMAs are soft—nearly the consistency of toothpaste. Therefore, without MRE, surgeons would routinely plan for a procedure called transphenoidal resection that employs very thin instruments that are threaded through the nasal cavity to the pituitary gland at the base of the skull, where suction is used to remove the tumor. However, in about 10% of the cases, the surgeon will encounter a hard tumor. At that point an attempt is made to break-up the tumor—essentially chipping away at it with sharp instruments. If that is not successful, the surgeon must perform a fully-invasive craniotomy that involves removing a piece of the skull bone in order to fully expose the tumor.

The more extensive procedure means added risk and discomfort for patients, and up to a week-long recovery in the hospital compared to the transphenoidal approach that allows patients to leave the hospital in a day or two. Using MRE, hard PMAs can be identified and the more extensive craniotomy can be planned before starting the surgery, which makes the more invasive procedure less taxing for both the surgeon and patient. Similarly, MRE showing a soft PMA gives surgeons confidence that the nasal entry and removal by suction will be successful-eliminating the likelihood that the surgeon may need to perform a second fully-invasive craniotomy.

In the study of PMA reported in the January 2016 issue of the journal Pituitary, the group performed pre-surgical MRE evaluation of the PMAs of 10 patients.The MRE measurements were compared to tumor classifications made by inspection of the tumor during surgery. The surgeons categorized six tumors as soft and four tumors as medium. No tumors were deemed to be hard. The comparison of the MRE results and reports of stiffness by the surgeons when the tumor was removed and inspected were in close agreement, which was confirmed by statistical analysis.

Future plans

Although brain MRE is not yet widely available, Huston explained that the surgeons at the Mayo Clinic are now routinely using MRE to plan the best procedure for the removal of PMAs as well as several other types of brain tumor. And, even though this study of the 10 PMA patients is a very small set, Huston believes that as Mayo surgeons continue to use MRE in planning, the technique will likely begin to be adopted by other surgical centers.

Huston explained that an important aspect of some of the other brain tumor types, which the surgeons are finding extremely useful, is the ability of MRE to identify tumor adhesion to the brain. Adhesion refers to whether the brain tumor and healthy brain tissue are connected by an extensive network of blood vessels and connective tissue. This is in comparison with a tumor that is in the brain but is isolated from healthy tissue.

When MRE is used to analyze this aspect of the tumor, it clearly identifies those that are non-adhered, showing a border around the tumor through which there are no vascular connections. Conversely, MRE of adhered tumors show no border between the tumor and healthy brain, indicating extensive vascular and soft tissue connections between brain and tumor. Mutual blood vessels make removal of adherent tumors much more difficult, with a much higher chance of damage to healthy tissue and potential loss of function for the patient.

Huston and his colleagues are continuing to apply MRE, often called “palpating by imaging” to diagnosis of other brain disorders. In addition to characterizing focal brain disorders such as tumors, the group is testing the potential for MRE to provide diagnostic information about diffuse brain disease, and are currently using MRE brain stiffness patterns to identify different types of neural disorders including dementia.

This research was funded by the National Institutes of Health through the National Institute of Biomedical Imaging and Bioengineering grant EB001981.

Magnetic resonance elastography detects tumoral consistency in pituitary macroadenomas. Hughes JD, Fattahi N, Van Gompel J, Arani A, Ehman R, Huston J 3rd. Pituitary. 2016 Jun;19(3):286-92

From http://www.rdmag.com/news/2017/01/imaging-technique-measures-tumor-stiffness-aid-surgical-planning

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