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Aging, Imaging, Orthopedics, Research, Stanford News, Stem Cells, Surgery

Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees

Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they're making new knees

kneesAs a population ages, so do its knees. Americans undergo 700,000 knee-replacement operations annually – a number expected to quintuple within two decades.

Prosthetic implants, for the most part a godsend for those with knee problems, come with problems of their own. They can induce fractures in nearby bone. They can gradually loosen over time. Even in the absence of complications, they can wear out – their average lifetime is around 10 years – and a second surgery is technically tougher going than the first was.

In a fortunate development for the creaky-kneed among us, a study just published in Radiology and led by Stanford pediatric radiologist Heike Daldrup-Link, MD, PhD, promises to expedite clinical trials of  a class of “adult” stem cells with great potential for knee repair.

These cells, known as mesenchymal stem cells (which I’ll call MSCs), ordinarily reside in bone marrow. Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), MSCs can’t differentiate into all the 200-plus tissues in the physiological rainbow that is our body. That’s good: A major concern about using ESCs or iPSCs for regenerative medicine is their capacity to form tissues wildly inappropriate for the job at hand or even to spawn tumors.

MSCs pretty much generate only bone, cartilage, muscle or fat, in response to cues from their immediate environment. Plus, they can be easily extracted from bone marrow of patients who are going to undergo the knee-repair procedure.

The trouble is, just shooting MSCs into a knee-injury site doesn’t automatically mean they’ll generate the wanted tissues, in the wanted amounts, right where they’re wanted. They might migrate away. They might die, refuse to engraft or fail to replicate and differentiate. They might develop into, say, scar tissue instead of cartilage or bone.

But how would you know? One way to see how newly transplanted MSCs are behaving requires labeling them, by loading them up with iron in the laboratory, between their extraction and their injection into the knee.  This makes them visible via magnetic-resonance imaging (MRI), so they can be monitored afterwards.

But, as I wrote in my news release on the study:

Upon extraction, the delicate cells have to be given to lab personnel, incubated with contrast agents, spun in a centrifuge and washed and returned to the surgeons, who then transplant the cells into a patient.

Regulatory agencies and opinion leaders rightly look askance at the potential contamination that can be introduced when stem cells are manipulated in lab glassware. Besides, MSCs in a lab dish have scant appetite for iron particles.

Daldrup-Link’s team showed that – for whatever reason – the very MSCs that eschew iron in a dish munch it right up when they’re hanging out in the bone marrow. They gave rats an injected “snack” of  ferumoxytol, an FDA-approved supplement composed of iron-oxide nanoparticles. When they later harvested MSCs from those rats’ bone marrow and infused them into other rats’ injured knees, they could track the the iron-stuffed MSCs for weeks afterward because they gave off a powerful MRI signal.

Stanford orthopedic surgeon Jason Dragoo, MD, plans to conduct a clinical trial this fall using the new MSC-labeling method. MSCs extracted from feroxytol-supplemented knee-damaged patients’ bone marrow will be delivered to those same patients in a single procedure, eliminating the delay and greatly reducing the contamination risk associated with lab-based labeling.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, FDA audit of Texas stem cell clinic revealed by Houston Chronicle and From college football player to team physician: A look at the career of Stanford’s Jason Dragoo
Photo by Jesse.Millan

Research, Stanford News, Surgery, Technology

Study shows tele-health effective for postoperative care of select patients

Study shows tele-health effective for postoperative care of select patients

talking_phone_071013Past studies have shown that virtual medical visits, those conducted via telephone or Internet, are a cost-effective way to, among things, monitor low-risk newborns after they leave the hospital, decrease health disparities between rural and urban areas, deliver care to Parkinson’s patients, and reduce pediatric visits to the emergency department.

Now findings published in JAMA Surgery show that tele-health can be safely used as a substitute for standard postoperative visits for select ambulatory patients. The study was conducted by Sherry Wren, MD, a general surgeon at Stanford, and Kimberly Hwa, MMS, PA-C, a general surgeon with the Palo Alto Veterans Administration Health Care System.

The 10-month study involved a group of patients who underwent open herniorrhaphy or laparoscopic cholecystectomy and opted to enroll in a tele-health follow-up program instead of returning to the clinic for a postoperative visit. A physician assistant called participants two weeks after surgery and assessed their condition using a scripted evaluation. Overall, complications in the tele-health program were zero for cholecystectomy patients and 4.8 percent for individuals recovering from herniorrhaphy.

Beyond showing that tele-health can be safely and effectively used for the postoperative care of low-risk surgical patients, the findings identified additional benefits for patients and clinics. As Wren told me in a phone interview:

The tele-health program is very patient centered, and patients expressed great satisfaction with the telephone follow-up method. Patients’ time and travel expenses were significantly reduced because they could schedule the calls at their convenience and didn’t have to go anywhere. If patients had visited the clinic, the average round-trip distance traveled would have been about 140 miles and the average driving time, which we measured using Google Maps, would have been about 148 minutes.

Another benefit to the tele-health program was that the clinic was able to open up 110 spots, which could be used for new patients, and reduce patient wait times. This was all accomplished using a very low-tech method: telephone calls. Often tele-health approaches require patients to go to a clinic where there is provider and use a videoconferencing system to be evaluated virtually by another provider. In comparison, our approach is much simpler and easier to implement, yet still safe and effective.

Wren and Hwa have expanded the program at the Palo Alto VA to include patients undergoing appendectomies and laparoscopic inguinal hernia.

Previously: Can Internet monitoring of healthy newborns replace conventional post-discharge practices?, Examining the clinical benefits of “virtual” house calls for Parkinson’s patients, FCC allocates $400 million in funding to develop and expand telemedicine and Telemedicine takes root in the Midwest
Photo by Kelvin_Kevin Gan

Cancer, In the News, Patient Care, Surgery, Technology, Videos

Stanford surgeon uses robot to increase precision, reduce complications of head and neck procedures

Stanford surgeon uses robot to increase precision, reduce complications of head and neck procedures

In today’s San Francisco Chronicle, writer Kristen Brown highlights how surgical robots are simplifying head and neck procedures. Known as transoral robotic surgery, or TORS, Stanford is one of the few places in the country using the da Vinci surgical robot to remove tumors or scar tissue from patients such as 70-year-old John Ayers, who is featured in the story (subscription required).

Edward Damrose, MD, chief of the division of laryngeal surgery at Stanford Hospital & Clinics, describes the procedure to Brown:

The da Vinci’s most frequent use in transoral procedures is in head and neck cancers. By operating through the mouth, surgeons can remove tumors in places that previously might have required much more complex procedures, such as breaking the jaw to get a good enough look.

The robot has four arms – three that can hold typical surgical tools, and a fourth that holds an endoscopic camera, giving a surgeon a full view of the patient’s insides.

“You get an almost panoramic view,” said Damrose. “It’s as if you were miniaturized and in someone’s throat looking around.”

The da Vinci was first used on a human for a head and neck procedure in 2005 at the University of Pennsylvania. An update to the robot made the experiment possible, when slimmer tools were developed for the robot that might more easily fit inside the mouth. (Even with the smaller tools, working inside someone’s throat can be a tight squeeze, depending on the patient.)

“If we’re able to operate through the mouth, we can avoid a lot of downsides to different approaches,” Damrose said, pointing to surgeries that involve breaking the jaw.

“Patients recover faster. They look better. They can swallow better,” he said. “It’s helping us a lot to accomplish procedures endoscopically where a few years ago these things would likely not have been possible.”

Ayers’ story is also captured in the Stanford Hospital video above.

Sleep, Stanford News, Surgery

How effective are surgical options for sleep apnea?

How effective are surgical options for sleep apnea?

A recent entry on the Stanford Center for Sleep Sciences and Medicine blog on the Huffington Post examines the effectiveness of surgical options for obstructive sleep apnea (OSA), from which an estimated two in 10 Americans suffer.

Robson Capasso, MD, director of sleep surgery and a clinical assistant professor of otolaryngology at Stanford, writes:

Many patients, family members, and even physicians are skeptical and question the efficacy of surgery to treat OSA. This uncertainty arises from somewhat low success rates associated with uvulopalatopharyngoplasty (UPPP), the most commonly performed surgical procedure for OSA in the U.S. In this procedure, the surgery targets only the soft palate, without improving potential collapses in other areas of the upper airway. However, recent developments in this field — in great part pioneered at Stanford University by Drs. Nelson Powell and Robert Riley — provide the opportunity for more complex techniques to evaluate the upper airway and to treat obstructions at sites other than the palate. These cutting-edge approaches maximize airway improvement by reducing the anatomical obstruction or decreasing the collapse of tissue causing the obstruction in the nose, throat, or tongue — or, which is more common, in all of these sites. Currently, these procedures are offered by a limited number of surgeons in the country.

To answer the question if surgery really works for sleep apnea, we can say that if the goal is to decrease the cardiovascular risk associated with OSA and improve the symptoms associated with the disease such as daytime sleepiness, snoring severity, and poor sleep quality, there is convincing evidence showing good results for each one of these problems. There is also a substantial amount of data suggesting improvement in quality of life and, very gratifying for the treating surgeon, frequent restoration of a more harmonious bedtime routine with loved ones.

Previously: Stanford doc talks sleep (and fish) in new podcast, Catching some Zzzs at the Stanford Sleep Medicine Center, Ask Stanford Med: Rafael Pelayo answers questions on sleep research and offers tips for ‘springing forward’ and Catching up on sleep science
Photo by Rachel Kramer Bussel

Ask Stanford Med, Neuroscience, Research, Surgery

Ask Stanford Med: Neurologist answers your questions on drug-resistant epilepsy

Ask Stanford Med: Neurologist answers your questions on drug-resistant epilepsy

An estimated 3 million adults and children in the United States suffer from epilepsy or seizures, and approximately 200,000 new cases occur annually, according to statistics from the Epilepsy Foundation. A portion of these patients can control their seizures with prescription drugs, but when medication fails, repeated seizures can seriously impair their daily life.

In the Stanford Program for Intractable Epilepsy, Josef Parvizi, MD, PhD, an associate professor of neurology and neurological sciences, works with epilepsy patients who are not responding to medication to determine if they are good candidates for surgical intervention. The procedure he performs involves removing a portion of the patient’s skull to provide access to the brain’s surface near the spot thought to be responsible for initiating the seizures. Electrode leads are placed next to the brain, with each electrode separately monitoring electrical activity there, allowing the function of the brain areas being considered for removal to be mapped and ensuring the surgery will be safe.

Below are Parvizi’s responses to a selection of questions on drug-resistant epilepsy and the procedure that were submitted using the hashtag #AskSUMed and the comments section on Scope. As a reminder, his answers are meant to offer medical information, not medical advice. They’re not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and provide appropriate care.

Lisa K. asks: A recent study showed that surgery soon after the failure of two anti-epileptic drug trials offers the best chance for patients to prevent a lifetime of disability. How soon should patients seek a surgical intervention?

Yes, a study published in the Journal of the American Medical Association by Pete Engel, MD, PhD, and colleagues suggested that epilepsy surgery should NOT be considered as the last resort for intractable epilepsy. They selected patients who had been non-responsive to two consecutive antiepileptic medications for no more than two years before the trial. Some patients were treated with surgery and some continued taking their drugs without surgery. Patients were followed up for two years. Of those who received surgery, 73 percent experienced seizure freedom. By comparison, none of the patients who continued to take medications without surgery were seizure free. Moreover, quality of life was enhanced significantly in the surgery group. They could drive and spend time socializing with friends. How soon? Well, as soon as a patient fails two appropriately chosen and tolerated anti-epilepstic drug when used for an adequate period of time (greater than six months). If a patient has seizures and imaging studies show a clear lesion in the brain, then surgery should be considered immediately.

Matt asks: I have a 7 year-old girl with severe cognitive disabilities. She follows the Atkins for seizures diet; presented at 6 months, seizes once a week, duration 10 minutes unconscious, then 10-minute ‘tremors’. Would the procedure be considered ‘too late’ to affect her future learning? Also, her doctors believe the seizure focus to lie deep in her brain (not seen on MRI) – can this area be accessed if indeed this proves to be the location?

I am sorry to hear that your daughter is having so many seizures. It is important to monitor her seizures with video-EEG to characterize the type of events that she’s having. If these seizures are epileptic and focal, then yes, she should be considered for resection surgery, i.e., surgically remove the piece of the brain that is the focus of her seizures. If the seizures are multifocal, she could benefit from devices such as vagus nerve stimulator (VNS). One could also consider corpus callosotomy surgery if your daughter is having generalized seizures that cause her to fall and injure herself.

Jim Abrahams asks: I’ve read that since 1921 the ketogenic diet has improved over 50 percent of the thousands of children and adults with drug-resistant epilepsy and that as many as 20-30 percent become seizure and drug free. In addition to almost 100 years of published data, a randomized controlled study published in 2009 supported its efficacy in children. Could you comment?

A Cochrane analysis showed that the diet results in short to medium term benefits in seizure control – like the effect of any other medication. However, the long-term outcome of the diet is questionable. Many patients find the diet difficult to tolerate, and many drop-out from using this diet because of gastrointestinal side effects and dislike for the diet.

Nolan asks: I read that an experimental implantable device may benefit epilepsy patients who don’t respond to medication. What are the advantages of a surgical intervention compared to something like this type of implantable device?

Devices are only partially helpful. They reduce seizure frequency by ~35 percent (almost like a medication). Very rarely does a patient become seizure free. Removing the brain focus of seizures, on the other hand, can result in 100 percent seizure freedom.

@EpilepsyBlogger asks: Are there any new surgeries or implants being released in the future for patients who suffer with drug-resistant epilepsy?

Two new devices are waiting for approval in the U.S. One is made by NeuroPace and the other by NeuroSigma.

Previously: Ask Stanford Med: Neurologist taking questions on drug-resistant epilepsy, Positive results in deep-brain stimulation trial for epilepsy and Brain implant designed for patients with difficult-to-treat epilepsy
Photo by Hey Paul Studios

Pediatrics, Stanford News, Surgery, Transplants

Record number of organ transplants saves five lives in a day

Record number of organ transplants saves five lives in a day

For most of us, a change of heart takes some time. But for the team of Stanford medical professionals at Lucile Packard Children’s Hospital, a change of heart – plus two livers and two kidneys – can happen in less time than it takes to ease into the workweek.

Five organ transplants in twenty-four hours is no typical feat for this Stanford hospital. Though medical teams at Packard Children’s Hospital perform about 70 liver and kidney and 15 heart transplants a year, they had never attempted this many organ transplants in a single day.

Since donor organs are scarce, medical teams must be ready to perform an organ transplant (or five) at a moment’s notice. In the most recent issue of Inside Stanford Medicine, Robert Dicks explains the extraordinary circumstances and determination leading to this surgical marathon. From the piece:

“This was the ultimate demonstration of the passion we have for healing children through transplant,” said [Waldo Concepcion, MD, professor of surgery], who once led five kidney transplants in two days. “Care teams throughout the hospital immediately got into it. Experience matters, and they all put in lots of extra hours in order to ensure everything would go smoothly.”

Concepcion also noted that other surgeons postponed scheduled cases to make room for the transplants. “It was impressive but not surprising,” he said. “Everyone was thrilled to see so many transplants save so many lives in such a short period of time.”

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.

Previously: The mystery surrounding lung transplant ratesFilm about twin sisters’ double lung transplants and battle against cystic fibrosis available online and Pediatric social worker discusses the emotional side of heart transplants
Photo of members of the transplant teams by Robert Dicks

Cardiovascular Medicine, Research, Stanford News, Surgery, Videos

Creating organ models using 3D printing

Creating organ models using 3D printing

A recent segment on local ABC affiliate KGO-TV examined how Stanford cardiologist Paul Wang, MD, and colleagues are using a new technique to create three-dimensional models of the heart. In the above video, Wang discusses the process for printing the replica organs and how the technology could be used to aid surgeons:

Wang says the models are so accurate that surgeons could potentially scale and fit devices ranging from catheters to coronary stents to the precise dimensions of an individual’s heart. The technology could allow doctors to test different surgical strategies in advance, before a patient ever enters the operating room.

“There’s a lot of different ways we could do it,” he explains. “We can have different tools that deliver new valves and other devices to different parts of the heart. They’re all different approaches that we’re going to see an explosion of in the future.”

Previously: 3D printer uses living cells to produce a human kidney and Regenerating organs from scratch

Sports, Stanford News, Surgery

From college football player to team physician: A look at the career of Stanford’s Jason Dragoo

From college football player to team physician: A look at the career of Stanford's Jason Dragoo

To call Jason Dragoo, MD, a busy guy would be an understatement: The orthopedic surgeon divides his time between clinical work, the surgery suite, research, his work in the Human Performance Lab, and the care of Stanford athletes. He has served as head physician of Stanford’s football program for the past six years, and he’s a team physician for the U.S. Olympic Committee and the U.S. Ski Team. Oh, and he’s also dad to two small children.

Dragoo, who specializes in knee injuries, is the focus of a piece in the current issue of Inside Stanford Medicine. And as my colleague describes, his experience as a college football player (he played defensive safety) has benefited his professional life greatly:

“It really helps for sports medicine physicians to have experienced injuries themselves,” he said. “I understand how long it takes each of these athletes to get where they are, whether it’s an NCAA competitor, an Olympic hopeful or a professional athlete. It takes years of commitment and effort to get to their skill level, so if I can help them achieve their goals without injury, it’s very satisfying to me.”

Previously: Study shows men, rather than women, may be more prone to ACL injuries, Stanford physician discusses prevalence of overuse injuries among college athletes and When can athletes return to play? Stanford researchers provide guidance
Photo by Norbert von der Groeben

Cancer, Cardiovascular Medicine, Health Costs, Health Policy, Surgery

Check the map – medical procedure rates vary widely across California

Check the map - medical procedure rates vary widely across California


While many patients may think “doctor knows best” when choosing between different medical procedures, a new study from the California HealthCare Foundation found that some of these decisions may be driven more by local physician preferences rather than clinical evidence.

In some California counties, the local rates of elective procedures are dramatically higher than neighboring areas. For example, a man newly diagnosed with prostate cancer who lives in Tracy, Calif., is 479 percent more likely to undergo internal radiation, i.e., brachytherapy, than the state average. (Click on the map above for rates in other counties.)

To make this data more useful to medical consumers, the study authors published an online interactive map that allows Californians to quickly determine if their region performs elective procedures at disproportionately higher rates than the rest of the state.

“We’re hoping these maps can push along conversations about how to improve health-care delivery,” said Laurence Baker, PhD, a consultant on this study and a professor of health research and policy at Stanford. “One thing that is often important is better communication between patients and doctors, particularly in cases where patients can have different preferences. Getting this information out there might help some conversations happen that could lead to better treatment decisions and health outcomes.”

This new version of the procedure map adds breast cancer, prostate cancer, and spine procedure rates and expanded data to include Medicare patients and younger populations enrolled in commercial plans, Medicaid patients, and the uninsured.

Previously: Heart bypass or angioplasty? There’s an app for thatNew breast cancer finding suggests limiting surgery and Ask Stanford Med: Answers to your questions on prostate cancer and the latest research

Cardiovascular Medicine, Medical Apps, Research, Stanford News, Surgery

Heart bypass or angioplasty? There’s an app for that

Heart bypass or angioplasty? There’s an app for that

A new online tool can help seniors with advanced heart disease decide between two possible medical interventions - Coronary Artery Bypass Graft surgery or Percutaneous Coronary Intervention, a.k.a. angioplasty.

To use the tool, seniors enter in their age, gender, diabetes status, tobacco use and heart disease history. The tool then calculates a predicted five-year survival rate, based on outcomes of similar patients who underwent these procedures. These predictions are derived from data extracted from the medical records of more than 100,000 Medicare patients, and analyzed using a model recently published in a study led by Mark Hlatky, MD, professor of health research and policy and of cardiovascular medicine at Stanford.

I had the pleasure of working with the amazing team of health researchers and programmers who developed this medical decision tool in a little under a month. For me, it was a sneak preview into the future of personalized medicine, where a person can review surgical outcomes of real-world patients with similar health histories, to reach an informed decision on a treatment plan with their physician.

“Studies usually focus on the results for the average patient, and not on how much the results vary among individuals. This model is a step towards personalizing treatment recommendations, based on each individual’s unique characteristics,” Hlatky told me. “The other exciting thing about this new methodology is that with relative ease, it can be applied to other medical conditions such as cancer and stroke.”

Hlatky will present his model and findings at the Institute of Medicine workshop “Observational Studies in a Learning Environment,” which can be viewed via a webcast on April 24-25.

Previously: Is stenting or surgery better for diabetics? New study provides answer, New test for heart disease associated with higher rates of procedures, increased spending and To stent or not to stent: not always an easy answer
Illustration by Dawn Johnson/iStock

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