Glowing cancer tool illuminates benign, but dangerous, brain tumors during pituitary surgery

University of Pennsylvania School of Medicine

PHILADELPHIA – An experimental imaging tool that uses a targeted fluorescent dye successfully lit up the benign brain tumors of patients during removal surgery, allowing surgeons to identify tumor tissue, a new study from researchers at the Perelman School of Medicine at the University of Pennsylvania shows. The tumors, known as pituitary adenomas, are the third most common brain tumor, and very rarely turn cancerous, but can cause blindness, hormonal disorders, and in some cases, gigantism.

Findings from the pilot study of 15 patients, published this week in the Journal of Neurosurgery, build upon previous clinical studies showing intraoperative molecular imaging developed by researchers at Penn’s Center for Precision Surgery can improve tumor surgeries. According to first author John Y.K. Lee, MD, MSCE, an associate professor of Neurosurgery in the Perelman School of Medicine at the University of Pennsylvania and co-director of the Center for Precision Surgery, this study describes the first targeted, near infrared dye to be employed in brain tumor surgery. Other dyes are limited either by their fluorescent range being in the busy visible spectrum or by lack of specificity.

“This study heralds a new era in personalized tumor surgery. Surgeons are now able to see molecular characteristics of patient’s tumors; not just light absorption or reflectance,” Lee said. “In real time in the operating room, we are seeing the unique cell surface properties of the tumor and not just color. This is the start of a revolution.”

Non-specific dyes have been used to visualize and precisely cut out brain tumors during resection surgery, but this dye is believed to be the first targeted, near infrared dye to be used in neurosurgery. The fluorescent dye, known as OTL38, consists of two parts: vitamin B9 (a necessary ingredient for cell growth), and a near infrared glowing dye. As tumors try to grow and proliferate, they overexpress folate receptors. Pituitary tumors can overexpress folate receptors more than 20 times above the level of the normal pituitary gland in some cases. This dye binds to these receptors and thus allows us to identify tumors.

“Pituitary adenomas are rarely cancerous, but they can cause other serious problems for patients by pushing up against parts of their brain, which can lead to Cushing’s disease, gigantism, blindness and death,” Lee explained. “The study shows that this novel, targeted, near infrared fluorescent dye technique is safe, and we believe this technique will improve surgery.”

Lee says larger studies are warranted to further demonstrate its clinical effectiveness, especially in nonfunctioning pituitary adenomas.

A big challenge with this type of brain surgery is ensuring the entire tumor is removed. Parts of the tumor issue are often missed by conventional endoscopy approaches during removal, leading to a recurrence in 20 percent of patients. The researchers showed that the technique was safe and effective at illuminating the molecular features of the tumors in the subset of patients with nonfunctioning pituitary adenomas.

The technique uses near-infrared, or NIR, imaging and OTL38 fluoresces brightly when excited by NIR light. The VisionSense IridiumTM 4mm endoscope is a unique camera system which can be employed in the narrow confines of the nasal cavity to illuminate the pituitary adenoma. Both the dye and the camera system are needed in order to perform the surgery successfully.

The rate of gross-total resection (GTR) for the 15 patients, based on postoperative MRI, was 73 percent. The GTR with conventional approaches ranges from 50 to 70 percent. Residual tumor was identified on MRI only in patients with more severe tumors, including cavernous sinus invasion or a significant extrasellar tumor.

In addition, for the three patients with the highest overexpression of folate, the technique predicted post-operative MRI results with perfect concordance.

Some centers have resorted to implementing MRI in the operating room to maximize the extent of resection. However, bringing a massive MRI into the operating room theater remains expensive and has been shown to produce a high number of false-positives in pituitary adenoma surgery. The fluorescent dye imaging tool, Lee said, may serve as a replacement for MRIs in the operating room.

Co-authors on the study include M. Sean Grady, MD, chair of Neurosurgery at Penn, and Sunil Singhal, MD, an associate professor of Surgery, and co-director the Center for Precision Surgery.

Over the past four years, Singhal, Lee, and their colleagues have performed more than 400 surgeries using both nonspecific and targeted near infrared dyes. The breadth of tumor types include lung, brain, bladder and breast.

Most recently, in July, Penn researchers reported results from a lung cancer trial using the OTL38 dye. Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients with the dye using preoperative positron emission tomography, or PET, scans. Penn’s imaging tool identified 60 of the 66 previously known lung nodules, or 91 percent. In addition, doctors used the tool to identify nine additional nodules that were undetected by the PET scan or by traditional intraoperative monitoring.

Researchers at Penn are also exploring the effectiveness of additional contrast agents, some of which they expect to be available in the clinic within a few months.

“This is the beginning of a whole wave of new dyes coming out that may improve surgeries using the fluorescent dye technique,” Lee said. “And we’re leading the charge here at Penn.”

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This study was supported in part by the National Institutes of Health (R01 CA193556), the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania, and the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000003).

Editor’s Note: Dr. Singhal holds patent rights over the technologies presented in this article.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

From https://eurekalert.org/pub_releases/2017-09/uops-gct090517.php

(For the General Public) Are there any advantages to human growth hormone?

Harvard Men’s Health Watch

Ask the doctor

Q. I’ve heard about the benefits of human growth hormone (HGH) for older individuals. Is this something I should try?

A. The benefits of HGH supplementation for older adults are unproven, and perhaps most telling is that these products have a negligible effect on HGH levels. In addition, there are concerns about potential side effects.

HGH comes in two forms: injections and pills. Since HGH injections are difficult to administer, pills are often preferred. Yet, these supplements do not actually contain HGH like injections do, because the hormone would quickly break down in the digestive tract. Instead, they contain amino acids that are absorbed by the body, which raises HGH levels. (They are also more expensive and can cost $100-plus for a month’s supply.)

HGH levels naturally decline as people age, which makes sense since our bodies stop growing during the late teenage years. So why would you need higher HGH levels later in life? The hype around HGH comes from a few studies that showed HGH injections can increase lean body mass and shrink body fat, which led to claims of HGH as an “anti-aging” hormone. However, the effects on strength and body weight are quite minimal. In addition, HGH can increase the amount of soft tissues in the body, which can lead to swelling, joint pain, carpal tunnel syndrome, and breast tenderness in men.

There is also a concern that HGH might promote cancer growth. (MaryO’Note:  I always mentioned this to doctors when I was diagnosed with kidney cancer.  Even though I couldn’t take HGH for the first 5 years after diagnosis, none of my doctors would confirm a connection between HGH and my cancer)

If you want to improve your strength, forget about HGH and increase your exercise. Some studies suggest this alone may be more effective than HGH supplementation for raising growth hormone levels in the body.

—William Kormos, MD
Editor in Chief, Harvard Men’s Health Watch

Originally published: July 2016

Adapted from http://www.health.harvard.edu/mens-health/are-there-any-advantages-to-human-growth-hormone

Day 27, Cushing’s Awareness Challenge 2016

I first saw a similar image to this one with the saying Life. Be in it at a recreation center when my son was little.  At the time, it was “Duh, of course I’m in it”.

The original image was one a couple males, a couple females and a dog walking/running.  No folks in wheelchairs, no older folks and certainly no zebras.

It would be nice to have everyone out there walking or running but that’s not real life, at least in the Cushie world.  It’s been a long time since I’ve really been In My Life – maybe it’s time to get back.

A dear friend who has not one, but two forms of cancer was traveling throughout Europe for the first time after her husband’s death wrote:

Some final words before I turn in for the night. If there is a spark of desire within you to do something which is not contrary to God’s Holy Law, find a way to make it happen. All things are possible and blessings abound for those who love Him. Life is such an adventure. Don’t be a spectator – live every single moment for Him and with Him.

Somedays, it’s hard even getting up in the morning but I’m trying.  I’ve tried Water Aerobics for People with Arthritis and I actually went to class twice a week, I got a “part-time” job four years ago, my son and I will play at Steinway Hall in NYC again in June, we have plans for another trip to Scotland to see/hear the Edinburgh Tattoo again.  This year, we plan to go to Lockerbie, as well!

This is the one and only life I’ll ever have and I want to make the most of it!

 

Day 24, Cushing’s Awareness Challenge 2016

sunday-glitter

 

It’s Sunday again, so this is another semi-religious post so feel free to skip it 🙂

I’m sure that many would think that Abide With Me is a pretty strange choice for my all-time favorite hymn.

My dad was a Congregational (now United Church of Christ) minister so I was pretty regular in church attendance in my younger years.

Some Sunday evenings, he would preach on a circuit and I’d go with him to some of these tiny churches.  The people there, mostly older folks, liked the old hymns best – Fanny Crosby and so on.

So, some of my “favorite hymns” are those that I sang when I was out with my Dad.  Fond memories from long ago.

In 1986 I was finally diagnosed with Cushing’s after struggling with doctors and trying to get them to test for about 5 years.  I was going to go into the NIH (National Institutes of Health) in Bethesda, MD for final testing and then-experimental pituitary surgery.

I was terrified and sure that I wouldn’t survive the surgery.

Somehow, I found a 3-cassette tape set of Readers Digest Hymns and Songs of Inspiration and ordered that. The set came just before I went to NIH and I had it with me.

At NIH I set up a daily “routine” of sorts and listening to these tapes was a very important part of my day and helped me get through the ordeal of more testing, surgery, post-op and more.

When I had my kidney cancer surgery, those tapes were long broken and irreplaceable, but I had replaced all the songs – this time on my iPod.

Abide With Me was on this original tape set and it remains a favorite to this day.  Whenever we have an opportunity in church to pick a favorite, my hand always shoots up and I request page 700.  When someone in one of my handbell groups moves away, we always sign a hymnbook and give it to them.  I sign page 700.

I think that many people would probably think that this hymn is depressing.  Maybe it is but to me it signifies times in my life when I thought I might die and I was so comforted by the sentiments here.

This hymn is often associated with funeral services and has given hope and comfort to so many over the years – me included.

If you abide in Me, and My words abide in you, you will ask what you desire, and it shall be done for you.

~John 15:7

Abide With Me

Words: Henry F. Lyte, 1847.

Music: Eventide, William H. Monk, 1861. Mrs. Monk described the setting:

This tune was written at a time of great sorrow—when together we watched, as we did daily, the glories of the setting sun. As the last golden ray faded, he took some paper and penciled that tune which has gone all over the earth.

Lyte was inspired to write this hymn as he was dying of tuberculosis; he finished it the Sunday he gave his farewell sermon in the parish he served so many years. The next day, he left for Italy to regain his health. He didn’t make it, though—he died in Nice, France, three weeks after writing these words. Here is an excerpt from his farewell sermon:

O brethren, I stand here among you today, as alive from the dead, if I may hope to impress it upon you, and induce you to prepare for that solemn hour which must come to all, by a timely acquaintance with the death of Christ.

For over a century, the bells of his church at All Saints in Lower Brixham, Devonshire, have rung out “Abide with Me” daily. The hymn was sung at the wedding of King George VI, at the wedding of his daughter, the future Queen Elizabeth II, and at the funeral of Nobel peace prize winner Mother Teresa of Calcutta in1997.

Abide with me; fast falls the eventide;

The darkness deepens; Lord with me abide.

When other helpers fail and comforts flee,

Help of the helpless, O abide with me.

Swift to its close ebbs out life’s little day;

Earth’s joys grow dim; its glories pass away;

Change and decay in all around I see;

O Thou who changest not, abide with me.

Not a brief glance I beg, a passing word;

But as Thou dwell’st with Thy disciples, Lord,

Familiar, condescending, patient, free.

Come not to sojourn, but abide with me.

Come not in terrors, as the King of kings,

But kind and good, with healing in Thy wings,

Tears for all woes, a heart for every plea—

Come, Friend of sinners, and thus bide with me.

Thou on my head in early youth didst smile;

And, though rebellious and perverse meanwhile,

Thou hast not left me, oft as I left Thee,

On to the close, O Lord, abide with me.

I need Thy presence every passing hour.

What but Thy grace can foil the tempter’s power?

Who, like Thyself, my guide and stay can be?

Through cloud and sunshine, Lord, abide with me.

I fear no foe, with Thee at hand to bless;

Ills have no weight, and tears no bitterness.

Where is death’s sting? Where, grave, thy victory?

I triumph still, if Thou abide with me.

Hold Thou Thy cross before my closing eyes;

Shine through the gloom and point me to the skies.

Heaven’s morning breaks, and earth’s vain shadows flee;

In life, in death, O Lord, abide with me.

Day 22, Cushing’s Awareness Challenge 2016

This is a tough one.  Sometimes I’m in “why me” mode.  Why Cushing’s?  Why cancer?  Unfortunately, there’s not a thing I can do about either.  Cushing’s, who knows the risk factors?  For kidney cancer I found out the risk factors and nearly none apply to me. So why? But why not?  No particular reason why I should be exempt from anything.

Since there’s nothing to be done with the exception of trying to do things that could harm my remaining kidney, I have to try to make the best of things.  This is my life.  It could be better but it could be way worse.

One of the Challenge topics was to write about “My Dream Day” so here’s mine…

I’d wake up on my own – no snooze alarms – at about 8 am, sun streaming through the window.  I’d we well rested and not have had any nightmares the night before.  I remember my son is home for a visit but I let him sleep in for a while.

I’d get out for a bike ride or a brisk walk, come home, head for the hot tub then shower.  I’d practice the piano for a bit, then go out to lunch with friends, taking Michael with me.  While we’re out, the maid will come in and clean the house.

After lunch, maybe a little technology shopping/buying.  Then the group of us go to one of our homes for piano duets, trios, 2-piano music.

When we get home, it’s immaculately clean and I find that the Prize Patrol has visited and left a substantial check.

I had wisely left something for dinner in the Ninja so dinner is ready.  After dinner, I check online and find no urgent email, no work that needs to be done, no bills that need to be paid, no blog challenge posts to write…

I wake up from My Dream Day and realize that this is so far from real life, so I re-read The Best Day of My Life  and am happy that I’m not dealing with anything worse.

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