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otolaryngology, Patient Care, Pediatrics, Research

A serendipitous save that changed treatment of the most common tumor of infancy

A serendipitous save that changed treatment of the most common tumor of infancy

IsabellaManley1stgrade-cropAt research institutions like Stanford, we often talk about the value of evidence-based medical care, the kind based on careful scientific comparisons of which treatments work best.

But sometimes, even the best-studied treatments fail. That’s what happened in 2008, when a baby named Isabella Manley was brought by her parents from their Sacramento, Calif., home to Lucile Packard Children’s Hospital Stanford because of a tumor in her trachea that threatened to block her breathing. Her case illustrates that serendipity sometimes plays a key role in medical success.

Isabella had a hemangioma, the most common tumor of infancy. Most hemangiomas, which consist of extra blood vessels, create harmless red marks on a baby’s skin that fade with time. Isabella’s was much more serious. Although her doctors tried all the hemangioma treatments then reported in the medical literature, including high-powered steroid drugs and two types of surgery, her breathing problems persisted. Pediatric otolaryngologist Kay Chang, MD, who oversaw her care at Stanford, ordered an MRI to find out why. A story I wrote about her case explains what happened next:

“We found, to our horror, that this hemangioma was massive, surrounding her entire windpipe and also her heart,” Chang said.

“It was becoming tangled into every structure in her neck and crawling down into her chest,” said Mai Thy Truong, MD, a pediatric otolaryngologist now with the hospital’s vascular malformations clinic.

… The tumor was too extensive for surgery and was still growing. Truong and Chang feared that it would soon block Isabella’s airway. They were not sure they could save her.

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otolaryngology, Patient Care, Pediatrics, Stanford News

Hearing clearly helped Down syndrome toddler develop on track

Hearing clearly helped Down syndrome toddler develop on track

joshua-copen-mom-stanford-childrens

For children who are deaf or have hearing disabilities, cochlear implants can make it possible to hear sounds. Unlike hearing aids, which simply amplify sounds, cochlear implants stimulate the auditory nerve directly. If young children get the implant and the intense follow-up therapy, they are able to “develop language skills at a rate comparable to children with normal hearing, and many succeed in mainstream classrooms,” according to the National Institutes of Health.

But for children with other developmental disabilities, that training and therapy follow-up can be even more challenging, so many doctors don’t advocate for implants for them. That was the experience of Joshua Copen, who has Down syndrome, and his mother, Iara Peng. Notably, children with Down syndrome are more likely than the rest of the population to have hearing problems.

Peng’s efforts to get Joshua a cochlear implant ran into frustrating roadblocks until she met Kay Chang, MD, a pediatric otolaryngologist and otologic surgeon at Lucile Packard Children’s Hospital Stanford. Chang described the challenges of cochlear implants for children like Joshua in a post on Packard’s Healthier, Happier Lives Blog:

“Traditionally, developmentally delayed patients haven’t been seen as ideal candidates for cochlear implants,” said Chang, associate professor of otolaryngology – Head and Neck Surgery at the Stanford University School of Medicine. “The electrical stimuli delivered by the implants have no resemblance to regular hearing. The brain has to adapt itself to learn the electrical patterns. Someone who is developmentally delayed isn’t going to progress as fast as a child who is developing normally. However, just because it’s a lot tougher to rehabilitate a child with developmental delay doesn’t mean they won’t benefit from it.”

For Joshua, an added stumbling block was getting his family’s insurance providers to cover the surgery and follow-up classes. But that issue was resolved, and now, at five years old, Joshua has had no problems with his learning comprehension.

Evidence is mounting that although more challenging to implement, cochlear implants for children like Joshua are worth the effort. John Oghalai, MD, head of the Children’s Hearing Center at Packard, is conducting a study looking into how cochlear implants help developmentally delayed children. The blog post also highlights a 2012 study by Oghalai:

Oghalai found that the use of cochlear implants in deaf children with developmental delay can help them from falling further behind their peers and shouldn’t be so easily dismissed. And the earlier the child gets the implants – 12 months is the minimum age allowed by the FDA – the better.

Previously: Cochlear implants could help developmentally delayed infants, says Stanford/Packard study and Baby steps: Therapy that helps the deaf to hear

Infectious Disease, otolaryngology, Public Health, Research, Science, Stanford News

New version of popular antibiotic eliminates side effect of deafness

New version of popular antibiotic eliminates side effect of deafness

About five years before he died, my father was prescribed gentamycin, one of the most commonly used class of antibiotics called aminoglycosides, for a heart infection of unknown origins. The antibiotic successfully cured him of the life-threatening infection, but it also left him with a life-changing side effect, one with the strange-sounding name of oscillopsia.

Oscillopsia is a balance disorder that creates the illusion of an unstable visual world in its patients that can be quite disabling. For my father, it messed with his tennis game in the remaining years of his life and forced him to sit on the couch when he would rather have been running around with his grandchildren. But he was lucky. In addition to balance disorders, side effects from these cheap and extremely effective antibiotics that have been used for decades worldwide, include high rates of deafness and kidney damage.

ChengNow, Stanford researchers led by otolaryngologoist Alan Cheng, MD, (pictured at left) and Tony Ricci, PhD, have made a modified version of these drugs that successfully treats infections without the side effects of deafness and kidney damage. In a press release on the study, which was published Friday in the Journal of Clinical Investigation, I wrote about a boy (whose story is also told in this Stanford-produced video) who lost his hearing from these antibiotic treatments during his battle with cancer:

On Christmas Eve, 2002, Bryce Faber was diagnosed with a deadly cancer called neuroblastoma. The 2-year-old’s treatment, which, in addition to surgery, included massive amounts of radiation followed by even more massive amounts of antibiotics, no doubt saved his life. But those same mega-doses of antibiotics, while staving off infections in his immunosuppressed body, caused a permanent side effect: deafness.

“All I remember is coming out of treatment not being able to hear anything,” said Bryce, now a healthy 14-year-old living in Arizona. “I asked my mom, ‘Why have all the people stopped talking?’ He was 90 percent deaf.

These are extremely important life-saving drugs, Ricci, a basic scientist and expert on the biophysics of the inner ear, told me. But they could be so much better if patients didn’t have to risk their toxic side effects. So far, the new versions of the drug that he and colleagues developed have only been tested in mice, but the hope is to conduct clinical trials as soon as is safely possible. “If we can eventually prevent people from going deaf from taking these antibiotics, in my mind, we will have been successful,” Ricci said. “Our goal is to replace the existing aminoglycosides with ones that aren’t toxic.”

The new drugs have not yet been tested as to whether they still cause balance disorders. That’s on the docket for the future. But my article describing this wedding of basic science with clinical treatment is a hopeful reminder of the importance of modern-day scientists to public health.

Previously: Listen to this: Research upends understanding of how humans perceive sound; Stanford developed probe aids study of hearing and Studying the inner ear and advancing research in developmental biology

Chronic Disease, In the News, otolaryngology, Patient Care

A look at one woman's long journey to diagnosis and treatment of rare disorder

VertigoThis week’s Medical Mysteries column in The Washington Post tells the story of a woman who lived with debilitating vertigo and odd tinnitus. Baltimore’s Rachel Miller lived with dizziness, the exaggerated sound of her heart and breathing and even anomalies with her vision for five years before she was diagnosed and treated. Many of the doctors she saw dismissed her symptoms as psychosomatic and Miller even went through a period when she stopped seeing doctors for her condition. Miller described her travails this way:

“I had started to feel like a person in one of those stories where someone has been committed to a mental hospital by mistake or malice and they desperately try to appear sane,” recalled Miller, now 53. She began to wonder if she really was crazy; numerous tests had ruled out a host of possible causes, including a brain tumor. Continuing to look for answers seemed futile, since all the doctors she had seen had failed to come up with anything conclusive.

But then she went to see David Zee, MD, who diagnosed her strange symptoms as a rare disorder called superior canal dehiscence syndrome (SCDS), when a small hole or a thin area of the temporal bone allows the fluid of the inner ear to touch the brain, transmitting sounds from the rest of the body, like our heartbeat or breathing, or even the movement of our eyeballs. John Carey, MD, operated on Miller, filling the small hole with bone and other tissue from the skull. As the piece notes, both Carey and Zee trained with Lloyd Minor, MD, now dean of the Stanford School of Medicine, when he was at Johns Hopkins University. Minor discovered SCDS in 1995 and developed the surgical treatment that Miller subsequently received in 2012.

Miller has recovered now, with only occasional problems when she gets a cold. But her story points out how difficult it can be to diagnose rare medical problems.

Previously: NIH network designed to diagnose, develop possible treatments for rare, unidentified diseases and Using crowdsourcing to diagnose medical mysteries
Photo by Mikael Tigerström

Humor, otolaryngology, Research, Stanford News

Pigs to the rescue: How salt pork stops nose bleeds

Pigs to the rescue: How salt pork stops nose bleeds

pig-214349_640With all the talk this week of Nobel Prizes, another recent prize won by a Stanford physician escaped notice. To secure this prize for inventive research in medicine, Stanford otolaryngologist Ian Humphreys, MD, didn’t need access to laboratories packed with MRIs and supercomputers or a team of never-sleeping postdocs. His experimental design couldn’t be called elegant or complex – or perhaps even an experiment at all.

He won for simply deploying a nasal pork tampon. Yes, you read that correctly: He stuck bacon in the bleeding nose of a small girl, and took home the 2014 IgNobel Prize in Medicine.

“We are squealing with pride,” Robert Jackler, MD, chair of Stanford otolaryngology department, wrote to me. “We only wish that the work for which he is so deservedly honored was actually done at Stanford, but we would not want to hog the glory [from] a distinguished university in Michigan.”

Oh, dear. Before your eyes glaze over with bad-piggy puns, here’s the thing: The nasal tampon worked — twice.

Humphreys was working with a team at Michigan State University when a 4-year-old girl came into the Children’s Hospital of Michigan with a bloody nose. The girl had a rare platelet bleeding disorder called Glanzmann thrombasthenia, which can cause fatal internal and nasal bleeding and bruising. To treat her nosebleed, the doctors applied pressure, gave her a clotting protein and sent her home.

She returned the next day, “a pale, ill-appearing child in moderate distress… with brisk bleeding” from the nose, according to the winning paper, “Nasal packing with strips of cured pork as treatment for uncontrollable epistaxis in a patient with Glanzmann thrombasthenia” from the Annals of Otology, Rhinology and Laryngology.

The team whisked her into surgery and inserted  a specialized dressing to control the bleeding. Two days later, however, the bleeding started again. The girl received a transfusion and they continued monitoring her. They took her back in surgery the next day, applying another type of packing material and a coagulating serum. They also gave another dose of coagulating proteins and a red blood transfusion. She remained intubated to allow her nasal cavity to heal.

Two days later, when doctors began to remove the packing material, bleeding began immediately. Quickly, they reapplied the high-tech gauze and upped her dose of coagulation protein. She remained hospitalized, sedated. Five days later, the team again tried to remove the packing. Again, the nosebleed returned.

“At this time, strips of cured salt pork were placed in both nasal vaults,” Humphreys and his colleagues wrote. Three days later, “the bleeding was significantly less evident than it had been on all previous postoperative evaluations.” Go pork!

About a month later, the little girl fell on her face, again causing a nose bleed. This time, the team whipped out the pork right away – bye, bye nosebleed.

It turns out this isn’t the first time salt pork has been used to control a nosebleed. “It’s a traditional therapy for hard to treat bleeding disorders,” Jackler told me. “When I was a resident in the 1980s, we would buy a lump of salt pork to use.”

The salt-packed pork is thought to work by inducing swelling, thereby blocking the bleeding blood vessel.

“It is not ignorant, even though they deem it ignoble,” Jackler said.

Previously: Ten-year-old YouTube star: Famous for her singing, not for her illness, Stanford physicians and engineers showcase innovative health-care solutions and Stanford chair of otolaryngology discusses future regenerative therapies for hearing loss
Photo by Mutinka

Addiction, FDA, Health Policy, otolaryngology, Public Health

How e-cigarettes are sparking a new wave of tobacco marketing

e-cig tip - smallFollowing the FDA’s announcement earlier this spring that it would regulate the sale – but not marketing – of electronic cigarettes, debate has continued on the safety of using e-cigarettes and the ethics of advertising them.

In case you missed it, today’s New York Times delves into the issue and highlights how Big Tobacco is now rolling into the world of e-cigarettes, which writer Matt Richtel calls an “overnight sensation.” A subsidiary of Reynolds American plans to begin distributing its Vuse e-cigarette line nationwide on June 23 with a campaign that includes television ads (forbidden for cigarettes) in major markets, and other tobacco companies have similar entries in the works. Questions about the potentially far-reaching effects advertising of e-cigarettes, including promoting smoking tobacco and reaching child audiences, concern public-health advocates and other critics – and a U.S. Senate hearing is planned for Wednesday.

From the article:

Matthew L. Myers, [JD,] president of the Campaign for Tobacco-Free Kids, who is scheduled to testify at the Senate hearing, said the fact that the F.D.A. did not limit marketing allowed tobacco companies to return to the airwaves with ads that make e-cigarettes sexy, rebellious, glamorous — “exactly the same themes we saw work with kids in the U.S. for decades with cigarettes.”

In the absence of marketing regulation, “they will set the agenda,” Mr. Myers said of the tobacco companies. “They will drive the evolution of the product in a way that serves their interests and not public health, and that’s exactly what’s happening.”

Robert Jackler, MD, chair of otolaryngology at Stanford Medicine, is an expert on tobacco marketing who studies it through his center, the Stanford Research Into the Impact of Tobacco Advertising. Like Myers, he has vocalized his concerns about e-cigarettes and tobacco companies’ aggressive marketing tactics – especially those targeted toward teens – and you can hear more about his views and research in this recent podcast.

Previously: E-cigarettes and the FDA: A conversation with a tobacco-marketing researcherE-Cigarettes: The explosion of vaping is about to be regulatedStanford chair of otolaryngology discusses federal court’s ruling on graphic cigarette labels and What’s being done about the way tobacco companies market and manufacture products
Photo by Li Tsin Soon

Applied Biotechnology, Cancer, Genetics, otolaryngology, Research, Stanford News

Stanford researchers identify genes that cause disfiguring jaw tumor

Stanford researchers identify genes that cause disfiguring jaw tumor

jawPatients with the rare jaw tumor ameloblastoma have few treatment choices. Radiation and drugs have failed to stop this slow-growing cancer, leaving jaw removal as the only option. The surgery also takes out facial nerves and blood vessels, and so patients need reconstructive surgery and rehabilitation just to smile and chew again.

In a new study, published in Nature Genetics, Stanford researchers discovered two gene mutations that cause this tumor. Their findings point to FDA-approved drugs that are effective against these mutations in other types of cancer.

To find the mutations, the researchers sequenced mRNA – messages copied from genes that tell the cell how to make proteins – from slices of preserved tumor. In 80% of the samples, they found a mutation in either the SMO or the BRAF gene. Interestingly, the SMO mutations occurred predominantly in the upper jaw, while BRAF mutations were found mainly in the lower jaw.

From our press release:

“These genes are essential for delivering signals of growth and development, particularly in developing organs,” said Robert West, MD, PhD, associate professor of pathology at Stanford and a senior author on the study. “But it’s increasingly apparent that they are often mutated in cancers.”

Perhaps most promising, researchers found that there are already FDA-approved drugs for cancers with mutations in the same developmental pathway. A drug called vemurafenib is toxic to ameloblastoma cell cultures that harbor a BRAF mutation, they found. This drug is effective against melanomas that carry the same mutant gene. Researchers also found that a compound called arsenic trioxide, an approved anti-leukemia drug, is affective at blocking the mutant SMO protein.

West and his colleagues, A. Cain McClary, MD, a co-author and chief pathology resident at Stanford Hospital, and A. Dimitrios Colevas, MD, an associate professor of oncology at Stanford, have already submitted an application to the biotech company Genentech, which manufactures the most popular brand of vemurafenib. Their pilot study would test whether the drug could shrink tumors in people with ameloblastomas.

Also from the release:

Throughout this project, McClary has engaged with an ameloblastoma Facebook group to hear members’ stories and to learn about what a patient goes through during the initial surgery and subsequent facial reconstruction. He plans to conduct a webinar with the group, and can’t wait to share his findings with them.

“It’s a great motivator,” he said about his involvement with the group. “Our face is a special place. I couldn’t imagine not smiling.”

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Gene panel screens for dozens of cancer-associated mutations, say Stanford researchers
Photo by Gray’s Anatomy Plates/Wikimedia Commons

In the News, Neuroscience, otolaryngology

Say that again? Tone deafness is inherited, study finds

Say that again? Tone deafness is inherited, study finds

singing2Can’t carry a tune? Don’t spend all your money on music lessons: Turns out tone deafness is an inherited non-talent.

Leonard Bernstein (no, not that one) writes in The Checkup:

Finnish researchers say they have found genes responsible for auditory response and neuro-cognitive processing that partially explain musical aptitude. They note “several genes mostly related to the auditory pathway, not only specifically to inner ear function, but also to neurocognitive processes.”

“Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested,” the researchers note in the study. Using a genome-wide scan, researchers evaluated 767 individuals “for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception.” The study was published in Molecular Psychiatry.

Previously: Music that comes straight from the soul…er, DNA
Photo by Kathleen Tyler Conklin

otolaryngology, Research, Stanford News, Stem Cells

Understanding hearing loss at the molecular level

Understanding hearing loss at the molecular level

baby earDeep inside the ear, specialized cells that are confusingly called “hair cells” – they have nothing to do those hairs protruding from your Uncle Fred’s ears – detect vibrations in the air and translate them into sound. Without them, you can’t hear. Unlike non-mammalian species, in humans, there are a limited number of these cells, and if enough of them get damaged or killed off, hearing loss occurs.

Hair cells are the key to understanding the process of hearing. By figuring out how these cells work at a molecular level, scientists believe they can eventually develop better treatments and possible cures for deafness. Key to this goal is figuring out how to regenerate these cells if they get damaged or die off.

A new Stanford study published in the journal Development takes one more step along this pathway by showing that these early hair cells can be grown back in newborn mice.

“The study builds on the hypothesis that younger cochlea – that portion of the inner ear where the hair cells are located – can regenerate,” said Alan Cheng, MD, one of the senior authors of the study, which was done in collaboration with St. Jude Children’s Research Hospital.

“No spontaneous auditory hair cell regeneration has been observed in postnatal mammals prior to this study,” Cheng, an assistant professor of otolaryngology and pediatrics, told me. “Extensive efforts from laboratories around the world have focused on understanding mechanisms that can drive mammalian hair cell regeneration.”

In their study, the scientists induced hair cell loss in their mouse models at birth and then observed there was “spontaneous regeneration of hair cells.” One week after birth, there was no much regeneration.

The research also showed, interestingly, that most of these regenerated hair cells in the young cochlea didn’t ultimately survive. “This lack of survival posits a new challenge to regenerating hearing,” Cheng said.

Previously: Battling hearing loss on and off the battlefield, Stanford researchers gain new insights into how auditory neurons develop in animal study, Stanford hearing study upends 30-year-old belief on how humans perceive sound and Stanford chair of otolaryngology discusses future regenerative therapies for hearing loss
Photo by boltron-

otolaryngology, Podcasts, Research, Stanford News

Listening to elephants, communicating science, and inspiring the next generation of researchers

Listening to elephants, communicating science, and inspiring the next generation of researchers

Caitlin O’Connell-Rodwell, PhD, is an instructor in Stanford’s Department of Otolaryngology and a scientist who studies, among other things, how elephants hear. In this just-published Neurotalk podcast, Rodwell discusses her studies from the field, including how elephants use foot stomping and low-frequency vocalizations to communicate. “If you think of the earth as a trampoline and you have this 10-ton animal on the earth running, you’re going to create a huge wave,” she said of the seismic vibrations they create. Elephants can also use their big ears, and comparatively large malleus middle-ear bone, to hear, and draw still to listen, she noted.

The podcast details O’Connell-Rodwell’s contributions to science as a writer and instructor of science communications at Stanford and for the New York Times, as well as her mission to encourage girls to pursue the hard sciences. She said:

As a woman in science, especially doing a little bit of physics, if you don’t have a role model it’s very difficult to try to imagine yourself [there]. So I got interested to get girls interested in the hard sciences because there’s no reason why they shouldn’t be there.

You have to get kids excited about science… One of the things that got me interested in entymology to begin with was that childlike enthusiasm for the miniature and the unknown.

She added, “In our minds it’s a story, but it’s not obvious to everyone else.”

Previously: Elephants chat a bit before departing water hole, new Stanford research shows and Researcher dishes on African elephant soap opera
Photo in featured entry box by Caitlin O’Connell-Rodwell and Timothy Rodwell

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