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Cancer, Research, Stanford News, Surgery

Chemistry technique improves cancer surgery

Chemistry technique improves cancer surgery

mass spectrometer

For many cancers of the stomach and intestinal tract, removing the tumor is the best way of treating a patient. The problem is that the cancerous cells don’t necessarily look any different from the normal cells. I wrote recently about a new technique to pick out those cancerous cells and help surgeons completely remove the tumor.

What’s fun about this story is that the idea started with a chemist, Livia Eberlin, PhD, who’s a post-doc in lab of chemistry professor Richard Zare, PhD. Zare is a member of Stanford’s Bio-X and from that has experience working with colleagues across campus. He suggested to Eberlin that she find a surgeon who would be willing to collaborate with her and test her approach to identifying the cancerous cells.

Eberlin knew that surgeons rely on pathologists during a surgery to help them figure out if they’ve removed the entire tumor, but the initial results aren’t always accurate. In some cases, pathologists find out days later, when results of a slower, more accurate test are complete, that the patient might need to come back for another surgery to remove more tissue.

Eberlin called up surgeon George Poultsides, MD, to see if he’d like to collaborate on her idea. As I wrote in my piece:

Eberlin’s expertise is in mass spectrometry, a tool not commonly used in a hospital setting. It takes a sample in one end, turns the molecules into charged particles, then detects how long it takes each charged molecule in that sample to migrate down a vacuum tube. The result is a jagged mountain range of tens of thousands of peaks, each representing a single chemical in the sample. The height of the peak indicates how much of that chemical the sample contained.

The idea was that maybe some of those peaks would be different in tissue samples that had cancerous cells versus those that didn’t. If it worked, this mass spectrometry approach might end up being more accurate than the approach being used now.

It took a team of statisticians, pathologists, surgeons and chemists to develop and test Eberlin’s idea. In the end, their approach seemed to be more accurate than what’s being used now. They are going to try their approach on a larger group of stomach cancers and in other cancers to see if it can help improve the odds of completely removing all cancerous cells during surgery.

Previously: Good-bye cancer, good-bye stomach: A survivor shares her tale
Photo – of Livia Eberlin, PhD, at a mass spectrometer used to identify cancerous cells in tissue samples – by L.A. Cicero

Applied Biotechnology, Microbiology, Patient Care, Research, Stanford News, Surgery

Staphylococcus aureus holes up in upper nasal cavity, study shows

Staphylococcus aureus holes up in upper nasal cavity, study shows

nostrilsA posse led by Stanford microbe sleuth and microbiologist David Relman, MD, has apprehended Staphylococcus aureus, one of the most notorious sources of serious infections, lurking in formerly unsuspected nasal hideaways. The discovery may explain why attempts to expunge S. aureus from the bodies of hospitalized patients being readied for surgery often meet with less than perfect results.

About one in three of us are persistent S. aureus carriers, and another third of us are occasional carriers. This bacterial shadow, which abounds on skin (especially the groin and armpits) and is quite at home in the nose, does us no harm most of the time. But if it gets into the bloodstream or internal organs, it can cause life-threatening problems such as sepsis, pneumonia and endocarditis (infection of heart valves). That makes S. aureus not such a good thing to be coated with if you’re about to have your skin punctured by a catheter or pierced by a scalpel.

This is exacerbated by the all-too-frequent presence, particularly in hospital settings, of S. aureus strains resistant to an entire family of antibiotics related to methicillin. In 2011, more than 80,000 severe methicillin-resistant S. aureus infections and more than 11,000 related deaths occurred in the U.S. alone, along with a much higher number of less-severe such infections.

In a study just published in Cell Host & Microbe, Relman – who pioneered the use of ultra-high-volume gene-sequencing techniques to sort out the thousands of species of microbes that communally inhabit our skin, orifices and innards – and his team used this method to show that mucosal sites way up high in our nose, where standard S. aureus-elimination techniques may not reach, can serve as reservoirs for S. aureus. That may, at least in part, explain why efforts to rid patients of this potentially nasty bug have so often fallen short of the mark, as I noted in my news release about the new findings:

Rigorous and somewhat tedious regimens for eliminating S. aureus residing on people’s skin or in their noses do exist, but it’s typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

Previously: Cultivating the human microbiome, Anti-plaque bacteria: Coming soon to your toothpaste? and Eat a germ, fight an allergy
Photo by OakleyOriginals

Clinical Trials, Neuroscience, Research, Stanford News, Surgery, Technology

Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity

Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity

DBS team - 560

Mark down October 30 and November 20, 2013, as medical mileposts.

On Oct. 30, a Stanford surgical team led by neurosurgeon Jaimie Henderson, MD, implanted a next-generation deep-brain-stimulation (or DBS) device into a Parkinson’s disease patient’s brain. On the order of 100,000 nearly but not quite identical procedures have been performed worldwide in the past decade or so, to relieve symptoms of not only Parkinson’s but epilepsy, chronic pain and more. Making what took place just over a month ago unique wasn’t the surgery itself but, rather, the nature of the device that was implanted – the first time ever in the United States. (In August, a patient in Germany received such a next-generation DBS device, although for a different indication.)

With current DBS technology, a fine, insulated wire is threaded into the brain so that its lead, containing four electrodes, impinges on the relevant brain area. (In Parkinson’s, for instance, the targeted area would be key brain regions that participate in the generation of spontaneous involuntary tremors characteristic of that disease). In a second procedure, a pacemaker-like device called a neurostimulator is placed under the skin, typically near the collarbone. The neurotransmitter transmits signals – at frequencies, amplitudes and durations programmed by a neurologist – to the leads, which accordingly fire electrical impulses counteracting the aberrant brain signals producing the physical symptoms in question. Over time, the neurostimulator’s impulse-transmission pattern is optimized via a trial-and-error process involving extensive patient-neurologist interaction.

Stanford neurologist and Parkinson’s specialist Helen Bronte-Stewart, MD, routinely sees patients a few weeks after their DBS devices have been implanted. They come in having not taken their medications for a while, so she can observe their symptoms and watch how they respond to different DBS frequencies and intensities.

But the new device, manufactured by the same company (Medtronic, Inc.) that makes the existing one, has an additional capability. It can not only transmit signals to the brain but, in addition, monitor and record the brain region of interest’s electrical output.

This will let Bronte-Stewart remotely capture vast amounts of information about a particular patient’s brain-firing patterns to discern that patient’s “neural signature” – and ultimately, it is hoped, be able to develop algorithms for automating the device’s signaling program so that it changes in response to changes in brain activity. (The goal, in engineering vocabulary, is a “real-time negative-feedback loop.”)

On Nov. 20, after recovering from the surgery, the patient and Bronte-Stewart, a noted expert in movement disorders, embarked on the first of a series of groundbreaking sessions during which Bronte-Stewart will download data from the implanted device for thorough analysis. While brain-activity data has been downloaded from Parkinson’s patients while they’re lying still on the operating table after the initial electronic-lead implantation, the recorded data has by necessity reflected only activity in the brain while the patient is at rest. Now Bronte-Stewart will be able to identify the neural signatures of not only the resting state but also voluntary movement, task performance and the tremor itself, and to see how those neural signatures change in response to her manipulations of DBS frequency and voltage output.

Stanford has received 10 of the new “two-way” DBS devices from Medtronic, and is recruiting Parkinson’s patients who, while they may not benefit directly from the ongoing study, wish to make a difference in how this disease’s symptoms are treated.

Previously: Revealed: The likely role of Parkinson’s protein in the healthy brain, Mind-reading in real life: Study shows it can be done (but they’ll have to catch you first), Positive results for deep-brain stimulation trial for epilepsy and Stanford neurologist discusses advances in research on movement disorders
Photo courtesy of Jaimie Henderson

Medical Education, Stanford News, Surgery, Technology

SICKO web-based game helps surgeons practice decision making

SICKO web-based game helps surgeons practice decision making


Simulation in various forms has become an accepted form of medical education, especially for those techniques needed for surgical procedures. It’s obviously safer to practice on a mannequin than a real person. But one Stanford physician, surgeon James Lau, MD, was struck by a distinct absence of similar practice techniques for pre-surgical decision-making – those questions whose answers help a doctor decide whether to conduct a surgery. In fact, Lau knew, the only time a doctor is tested on those non-surgical skills is during the board certification process that takes places years into actual practice.

With the help of a grant designed to nurture innovative approaches to medical education, Lau collaborated with a Stanford medical student and a third-year Stanford surgical resident to build upon and expand the technology behind last year’s Stanford CME hit, Septris, a web-based game designed to teach doctors how to better identify and treat sepsis. The new game, SICKO (Surgical Improvement of Clinical Knowledge Ops), aims to duplicate what doctors face every day: the pressure of time and multiple patients.

But, to Lau’s goal of improving patient safety, none of SICKO’s patients are real – and practice might make perfect. I explain more in an Inside Stanford Medicine story today.

Previously: A conversation about digital literacy in medical educationThe data deluge: A report from Stanford Medicine magazine and Can battling sepsis in a game improve the odds for material world wins?
Image from Zak Akin

Cancer, Events, Stanford News, Surgery, Women's Health

Discussing trends in breast reconstruction choices

Discussing trends in breast reconstruction choices

Women are choosing silicone implants twice as often for breast reconstruction after mastectomy than using their own natural tissue for the reconstruction, a Stanford plastic surgeon says. Both methods have their advantages and drawbacks, Gordon Lee, MD, told an audience at a Stanford Health Library lecture last week.

Implant surgery is simpler, shorter and produces good results, but the implants “don’t last forever,” said Lee, an assistant professor and director of microsurgery in the Division of Plastic and Reconstruction Surgery. Tissue surgery takes longer and requires more recovery time, but it can provide natural-touch breasts that last long-term, with the “two-for-one” benefit of a tummy tuck for some women as well, he said.

Given the 1-in-8 chance that a woman in the U.S. will get breast cancer, reconstruction is an important topic to many

Given the 1-in-8 chance that a woman in the U.S. will get breast cancer, reconstruction is an important topic to many. “Patients should get a choice,” said Lee, who does both kinds of surgery.

Tissue surgery has been refined and improved for more than 30 years, with multiple options available to women now, Lee said. The most recent improvements enable surgeons to build new breasts using fat and skin tissue removed from the belly while leaving most or all of the belly muscles in place. Refined microsurgery techniques have also let surgeons connect arteries to the transplanted tissue with more precision, improving results.

Still, about two-thirds of U.S. women have decided to get implants in recent years, while one-third have had reconstruction using their own body tissues.

Many women choose implants because the procedure is simpler, they can recover in 1 to 2 weeks and get good-looking results sooner. Implants are made with a filler of either silicone or saline. About 95 percent of Lee’s patients who get implants choose silicone because they have a more natural feel and don’t flatten if the implant shell breaks.

Manufacturers estimate that implants last 10 years, on average, before rupturing, whether they are silicone or saline, Lee said. For any one woman, though, the rupture can occur much earlier or later – as soon one year or as long as 15 years after reconstruction, for example. Even if an implant shell ruptures, a woman may not notice it,  Lee said, because the silicone filler is likely to stay in place given that it is a cohesive material.

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Aging, Orthopedics, Stanford News, Stem Cells, Surgery

Stanford study shows protein bath may rev up sluggish bone-forming cells

Stanford study shows protein bath may rev up sluggish bone-forming cells

Fractures that are complex, pose a significant health risk, or don’t heal properly are repaired using bone grafts. The surgical process involves transplanting whole marrow, which is rich in stem cells that form bone, blood and the cells of the immune system, into a fracture site.

Although it’s preferable to use a patient’s own tissue to avoid rejection, elderly patients (whose older marrow forms bone less robustly), often require the use of donor bone marrow from younger people or the use of drugs to stimulate bone growth.

Now researchers at Stanford have identified a simple way to stimulate old marrow to form bone, which could allow the use a patient’s own cells without medications. My colleague explains the findings in a release:

In studies involving mice and rabbits, the researchers found that a quick dip in a bath of a signaling protein called Wnt3a can rev up sluggish bone-forming cells in older animals that would normally be unable to heal a fracture. If the simple treatment is eventually found to be effective in humans, it may significantly improve the success of bone grafts, which are performed more than 500,000 times every year in the United States.

“We’re very focused on designing a treatment that could be easily employed by orthopaedic surgeons in the normal course of bone grafting,” said professor of surgery Jill Helms, DDS, PhD. “We’ve shown that when we temporarily treat bone marrow from aged animals with Wnt before transplanting the cells into a fracture site, we see really robust bone formation.”

“Hip fractures in elderly people nearly triple the risk of dying within a year of the injury, and a rapidly aging population demands more effective treatments for this type of trauma,” said Helms.

Previously: Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees and Biomarker can predict graft-versus-host disease in men after transplants from women donors

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

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