While Friday the 13th may be bad luck for some, such was not the case for the U.S. stem cell industry. On Friday, April 13, the Texas Medical Board (TMB) approved the first set of regulations which will allow physicians to offer autologous adult stem cell therapies. These are stem cells from your own body for your own usage.

The Texas bill was drafted over the past year and the final version was released for public comment in March. After the 30 day public comment period, the bill went for final vote on April 13.  The TMB passed the new regulation by a vote of 10 to 4.

Current FDA Regulations

Although the FDA has published regulations for embryonic stem cells and allogeneic stem cell therapies, there has not been a clear cut FDA pathway for autologous adult stem cell therapies. After years of waiting, some physician practices (ours included) recently received FDA guidance on adipose stem cells, but the rules are not written in stone. Regulations are not official until they become part of the Federal Register.

The resulting ‘time out’ and lack of guidance by the FDA created uncertainty among doctors and forced many patients to seek autologous stem cell therapy abroad. To help bridge the gap, the Texas Medical Board created regulations for autologous adult stem cell therapies, the area not yet formalized by the FDA.

Unlike embryonic stem cells, adult stem cell therapies have no ethical issues. Adult stem cells can be extracted from bone marrow, adipose fat, umbilical cord blood, dental pulp and other adult tissues. These stem cells have been used to treat a wide range of diseases and injuries. Over 3000 clinical trials using adult stem cells have taken place over the past few decades.

 Texas Stem Cell Regulations, Chapter 198

With the new Texas regulations, known as Chapter 198, physicians will be able to perform autologous adult stem cell therapies if they conduct therapies under the supervision of an IRB, or Investigational Review Board. In addition to monitoring patient outcomes, IRB’s also have very strict protocols for informed consent which tell the patients that the procedure is experimental and that results are not yet known. In summary, Texas Medical Board 198 regulations include:

• The regulation applies only to stem cell therapies that are not currently regulated by the FDA. Thus, this regulation applies to certain types of autologous adult stem cell therapies. Allogeneic therapies (donor cells) and embryonic stem cell treatments are not applicable as they are already delineated as HCT/P 351 drugs by the FDA.
•  Texas physicians must file an IRB which is affiliated with a hospital or academic institution.
• Texas physicians are NOT required to file an IND (Investigational New Drug Application) with the FDA.
• Informed Consents must be IRB approved and state to the patient that the stem cell therapy is experimental.
• Patient results and follow up care must be reported to the IRB, and doctors must be able to respond to information requests by the Texas Medical Board within 14 days of inquiry.
• A physician can charge a fee for the therapy as long as there are no placebos in the therapy.

Reaction to Texas Stem Cell Regulations

While some members of the stem cell research community are unhappy over the Texas Medical Board’s decision, many practicing physicians view the new regulations as a positive step in innovation and patient treatment. The difference of opinion between researchers and doctors has to do with each side’s tolerance for risks and benefits.

throughout history much medical innovation has come outside of randomized clinical trials

Many scientists assess risks and benefits primarily via prospective ‘randomized clinical trials’ (RCT), a process which is common place for the testing of drugs that will be manufactured and distributed to thousands of people. Scientists do not interact with the patient and therefore must control as many variables as possible (randomized clinical trials) in order to be assured of the highest possible evidence of safety and efficacy.

But practicing physicians communicate with their patients on a one-to-one basis and are comfortable assessing levels of risk/benefits during their patient’s therapy. They do not need every external parameter to be controlled in order to see meaningful levels of safety and efficacy with a therapy. Therefore, throughout history much medical innovation has come outside of prospective randomized clinical trials. Physicians validate findings of safety and efficacy via case reports, non-randomized clinical trials, and a peer review mechanism well established by the medical community. Non randomized clinical trials performed outside of the FDA purview can show safety, proof of concept, and enough information about risks and benefits to allow for patients to make informed choices.

The Tug of  War between the FDA and ‘Practice of Medicine’

Traditionally, the FDA’s purview has been the safety of “one-to-many” manufactured products.  These are drugs, devices, and donor/allogeneic tissues which are dispensed to many people.  On the other hand,  autologous stem cell therapy is a ‘one-to-one relationship’. This is because the cell or product is only distributed to one person, the patient himself. The risks and benefits of “one-to-one therapy” have traditionally fallen under the purview of  ’Practice of Medicine’.  Following such precedents, the risks and benefits for autologous therapy should be an issue of consent between you (the patient) and your doctor.  And therein lies another reason why the Texas Medical Board has exercised it’s authority over autologous stem cell therapy.

The Practice of Medicine is primarily regulated by each state’s Medical Board , but doctors are accountable  on many levels to many organizations. In addition to the State Medical Board, there are layers of peer review organizations that include professional societies, peer review journals, malpractice insurance carriers, hospital boards, licensing and accreditation agencies, the community, and ultimately a courtroom with a jury.

Equally as important is the fact that the patient interacts with their doctor face to face, and doctors get informed consent from every patient before every procedure. Whether it is a traditional procedure or an experimental procedure, the informed consent is part of the process. During the informed consent process doctors give you an idea about the safety and efficacy of the procedure. If your treatment is experimental, the informed consent outlines that fact.

Wall Street Journal’s OpEd on the FDA and Stem Cells

But last week there was even more good news for the stem cell sector! A few days after the Texas announcement the Wall Street Journal posted an Op Ed piece written by the former FDA commissioner in support of stem cell therapy.

In the Op Ed piece the former commissioner, Dr. Andrew von Eschenbach, called for a move toward a 21st-Century FDA.

He noted the need to overhaul the current FDA regulations and process for evaluating new technologies such as Regenerative Medicine.  Furthermore he called attention to the lawsuit of the FDA against a Colorado physician’s right to perform autologous stem cell therapy.  In a hat tip to the seriousness of Dr. Centeno’s case, the former FDA commissioner pointed out how ‘lawyers–many lawyers are  trying to resolve the dispute’.   We have previously written about the issues surrounding U.S. vs. Regenerative Sciences  here on this blog. The outcome of this case will no doubt be a landmark decision for the stem cell industry.

Dr. Von Eschenbach further impassioned the stem cell cause when he wrote:

When I was commissioner of the FDA from 2005 to 2009, I saw firsthand how regenerative medicine offered a cure for kidney and heart failure and other chronic conditions like diabetes. Researchers used stem cells to grow cells and tissues to replace failing organs, eliminating the need for expensive supportive treatments like dialysis and organ transplants. But the beneficiaries were laboratory animals…..the FDA doesn’t have the scientific tools and resources to review complex innovations more expeditiously and pioneer regulatory pathways for state of the art therapies that defy current agency conventions.

In conclusion, this is a tipping point for stem cell therapy.
We salute the Texas Medical Board and all the hard work it took to get to this point! It’s your own cells and you deserve the right to use them.  In Texas, patients now have a choice. You don’t have to risk being a placebo in a randomized clinical trial, you can have the therapy, as long as you understand the risks.

We would love to hear your thoughts and comments on the topic.

Leeza Rodriguez
CosmeticSurg Staff Writer
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

Related stem cell blog posts:

FDA Regulation and the English Language: Switched at Birth

FDA: Stem Cells From Your Own Fat are a Drug

What are the most common sizes of breast implants used in breast augmentation?

To find out, we did an analysis of the last 125 cases of breast augmentation procedures performed by Dr. Rodriguez in our surgery center located in Baltimore, Maryland. So what styles and sizes of implants were most popular? Glad you asked!

Saline vs. Silicon

The comparison of silicon implants to saline implants was a landslide win for silicon. After more than a decade of breast implant hysteria in the 1990′s, silicon implants are solidly back as king of the mountain.

• Approximately 80% of our patients choose silicon implants over saline implants.

High Profile vs. Moderate Profile Breast Implants

The next criteria we compared was moderate profile implants vs. high profile implants. Each size of silicon implants can be either moderate profile or high profile. High profile implants give more projection and have a smaller base diameter. The implant also has a slight oval shape compared to the moderate style. Moderate profile implants do not give as much fullness and are completely circular, which means they occupy more space horizontally on the chest wall compared to high profile implants.

High Profile Breast Implants – 86% : Moderate Profile Breast Implants – 14%

• High profile implants trounced moderate profile implants by a 6 to 1 margin.

Top 5 Breast Implant Sizes

Breast Implant Sizes: 400 cc vs. 500 cc

Breast implants come in a wide range of sizes which go from 200 cc to 800 cc. They are generally sized in increments of 25 cc, which is about the size of a kitchen serving spoon. Since 1 cc= 1 ml, you can use a kitchen measuring cup to get an estimate of size. Fill the cup with water up to the number of ml’s (cc’s) and pour the water into a plastic baggie. Voila! You have a quick rough estimate of your new implant size. However, to get the best idea of implant size, you should ask your plastic surgeon for the sample size.

Here at CosmeticSurg we let all of our breast augmentation patients try on every size that is manufactured. The photo above is the actual display cabinet of various implant sizes. During consultation, patients can try on as many implant sizes as needed to help them make the best selection.

• The winners of the most popular breast implant size contest are:

Our most popular implant is a high profile, 400 cc, silicon implant.

Dr. Rodriguez

Looking back at breast implant choices over our latest 125 breast augmentation procedures, it’s clear that our most popular breast implant is a high profile, 400 cc, silicon implant.

Every body is unique and beauty is in the eye of the beholder. To determine what’s best for you, be sure to discuss the important decisions you’ll need to make to ensure the type of implant and surgical approach will garner the results you desire.

Leeza Rodriguez
CosmeticSurg Staff Writer
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

The 7th annual New York Stem Cell Summit was held on February 21, 2012. The conference was sponsored by Robin Young, former Wall Street Biotech analyst, and featured presentations by numerous public and private companies involved in the stem cell industry. After attending last year’s Stem Cell Summit, we reported on the industry awareness that adipose tissue has more stem cells than bone marrow .

This year Robin Young presented his 2020 U.S. sales forecast for stem cell therapies. Likewise, he took everyone through a look back on what happened in 2011. A total of 27 companies each gave top level overviews of their products, clinical trial statuses, and business models. The majority of the companies are developing allogeneic stem cell therapies, which are based on cells from a donor and scaled up in the manufacturing process.

2011: The Darkness Before the Dawn

It is no secret to biotech investors, that stem cell stocks suffered dramatic declines in 2011. To be more specific, they were taken out to the woodshed and beat to smithereens. Robin Young summarized that the market capitalization of all the public stem cell sectors declined by 25% in 2011 compared to the previous year. In 2011, total market cap of the entire publicly traded stem cell sector was only $ 3.4 Billion. Every single publicly traded stem cell stock declined in value, except for one company, Mesoblast (ASX: MBX).

Robin Young attributed the steep sector decline to ‘FDA regulatory pushback‘ – which is code speak to mean that the FDA reversed some of the previous favorable decisions from the past. In one example, an allograph product from Allosource was already approved, but now the FDA was reclassifying the product from tissue to drug, causing major upheaval in the industry.

However, the good news is that 2011 is now over! The thinking is that the stem cell space is emerging from the ‘valley of death’, or the’ trough of disillusionment’, which is commonly seen in new industries years after their initial hype period. Several cell therapy manufacturing companies are reporting increased commercial activity and clinical trial activity is ramping up.

contract activity in the cell therapy space is heating up

Lonza, a huge Swiss cell therapy company, reported that contract activity is brisk and that they are expanding cGMP manufacturing capacity based on existing and extrapolated demand coming out of clinical trials. In fact, many companies presenting at the conference appeared to be using Lonza as their manufacturer.

According to conference host Robin Young, Mesoblast is now considered the largest and most prolific stem cell company in the industry as measured by clinical trial activity. Mesoblast is actively involved in phase I, II and III clinical trials. Mesoblast is so positive about the future marketplace for commercial stem cell therapy that it has contracted with Lonza to make it’s own separate manufacturing facility. And Gamida, an Israeli company, detailed how, by manufacturing their approved StemEx® product with Lonza, they reduced the cost of goods sold (COGS). StemEx® is the first approved allogeneic stem cell product to get FDA approval for the marketplace.

Based on the number of times ‘Lonza’ was mentioned during all the presentations, it appears that Lonza will be ready to scale up manufacturing and assist the vast majority of cell therapy companies to get their products out to the marketplace. If this were the railroad industry, Lonza would be the supplier of the train tracks.

MSC’s as a Cure : Curing Disease vs. Managing Disease

Arnold Caplan, PhD, a prolific publisher of stem cell research and an Osiris founder, presented the keynote address to the group. Caplan is largely responsible for coining the term MSC, or Mesenchymal Stem Cells, in the late 1980′s. MSC’s are one of the prominent types of stem cell cells responsible for healing and curing disease.

Caplan reiterated that stem cells usher in a new era of Regenerative Medicine.

Regenerative medicine is a new paradigm because stem cells will cure diseases, and not just manage them.

Up to now, diseases have only been managed by drugs mass produced by the pharmaceutical industry. Regenerative medicine is a new paradigm because stem cells will cure diseases, and not just manage them. As an example, Caplan reminded the group that diabetes has been managed with insulin for 60 years, but that insulin has not been able to cure diabetes. In another example, nitroglycerin has been used since the 1880′s to treat heart disease, but it has not been able to cure heart disease. According to Dr. Caplan, stem cells will do the curing!

MSC’s: Mesenchymal Stem Cells Medicinal Signaling Cells

Dr. Caplan called for a name change for the stem cell acronym ‘MSC’, which he created back in the late 80′s. He said that since he created the term, he should have the right to change the wording based on what we have learned since then. The current MSC term is widely known to mean “Mesenchymal Stem Cells”. However, Dr. Caplan feels that a better description of MSC is Medicinal Signaling Cells. This term much better reflects the cells ability to become your own personal medicine cabinet to heal and cure disease.

How do MSC’s work their magic?

Much of the original work in the stem cell world over the past decades focused on what stem cells can differentiate into, or turn into. Dr. Caplan believes that while differentiation does occur, we have largely been missing the boat on the magical part of what stem cells do. The magic of stem cells occurs when they leave their niche and secrete a medicine chest of cytokines and other molecules which are capable of healing the body.

According to Dr. Arnold Caplan, all MSC’s sit on blood vessels as pericytes. Every blood vessel has pericytes. MSC’s are pericytes. Whenever a blood vessel is inflamed or broken, the pericyte/MSC will leave the blood vessel and travel, (or ‘home’) to the site of injury. As MSC’s leave the blood vessel, they release tons of cytokines and molecules. These cytokines and molecules become your own personal drug store eligible to treat and cure over 40 diseases. Even more exciting is Caplan’s belief that the medicine chest is self renewing—it is capable of restocking itself! After an MSC has performed its duty to repair or cure, the MSC returns to its native niche on the blood vessel, capable of performing its magical healing all over again.

Animal studies point the way to success

There are basically three phases of clinical trials: Phase I, Phase II, and Phase III. Prior to embarking on any Phase I trial, clinical investigators must show results using animals. We are happy to report that the animals are doing great! Vet Stem has treated over 5,000 animals for tendinitis with MSC’s derived from adipose fat. The cure rate is an amazing 89%.

Mindblower for MSC applications: Use as an Antibiotic

Dr. Caplan said the mindblower of all applications is MSC’s use as an antibiotic. When MSC’s upregulate, they secrete a molecule called hcap18-LL37, which acts like an antibiotic. Antibiotics treat infections. There is currently a clinical trial on the condition known as ‘sepsis’ which is a life threatening form of infection in the blood stream. Caplan stated that early trial results using MSC’s are extremely encouraging. Speaking to the point of MSC’s inherent capability as an antibiotic, Caplan pointed out that if you were to go back and look at the databases for allographs, which are simply a matrix seeded with adult stem cells, you would see that these have incredibly low, nearly zero, infection rates. According to Dr. Caplan, this is due to the antibiotic properties of MSC’s.

FDA regulatory guidelines

Dr. Arnold Caplan called on the FDA to create a new category in the regulations for stem cell therapy with MSCs. He suggested that stem cells are neither tissues, nor drugs (in the pharma sense), but their own unique category. Additionally the idea of performing phase I, II, and III drugs trials for each indication is not realistic because stem cells are multi functional multi purpose, multi reactive agents, as opposed to single agent drugs that have been the standard in the pharma industry. He called for a distinct new classification in the FDA regulations to help mobilize the stem cell sector. He emphasized that we can not shape the new era of stem cell therapy to the existing FDA regulatory code. This sounded like an awesome idea to me, but inquiring minds want to know who has the authority to make that change? How do we put that in motion?

Market Projections and Crystal Ball Gazing

The total U.S. stem cell market is projected to be $6 Billion by year 2020. However, this assumes less than a 3% penetration rate for nearly all indications and is based on 44 million procedures. By all accounts, this 3% projection is an extremely conservative estimate of penetration. Top level category breakdowns for the US market in 2020 include orthopedic, cardiovascular, dental, diabetes, nerve repair, and others. An interesting application from the ‘others’ category included a presentation by Celtigen whereby stem cells repair the hair shaft and restore hair growth.

2012: Looking forward
After a year of contracted growth in 2011, according to Robin Young, this is the inflection point in the growth curve.

In 15 years, stem cell therapies will eliminate 80% of all spine surgery.

In 2012 the stem cell sector will embark on its prolific and steady rise, resulting in higher market caps and stock price for stem cell companies. The sector will not look back.

Top Treatment Category for Year 2020: Neurological diseases
Robin Young predicts that in 2020, cell therapy treatments for neurological diseases will be the biggest sector of the stem cell economy. The sector will command the highest prices per treatment. He estimates that pricing for neuro treatments will be $35K-$40K.

Orthopedic Applications: Stem Cells to trounce Spine Surgery
How do you spell disruptive? According to one orthopedic surgeon involved in a clinical trial for lower back pain, cell therapy will one day own the orthopedic market. Dr.Kenneth Pettrine of the Spine Institute has teamed with SpineSmith and they are using Mesoblast’s mesenchymal precursor cells (MPC’s). Dr. Pettrine predicts that in 15 years, stem cell therapies will eliminate 80% of all spine surgery.

Stem Cell Clinical Trials

Number of stem cell trials: According to Dr. Caplan, there are currently 182 active clinical trials using MSC’s for over 40 different applications.

Conditions being treated: heart attack, ischemia, stroke, asthma, Crohn’s disease, acute renal failure, tendon and meniscus repair, diabetes, arthritis, Lupus, ALS, MS, sepsis.

Tissue sources used to isolate stem cells: adipose fat, bone marrow, cord blood.

Stem Cell Delivery Methods: In the marketplace, stem cells will be delivered by two methods. Many companies will be distributing products in both categories.

1. Direct Delivery to the injury site by injection or placement of a matrix. This method of cell delivery is used in orthopedics and cardiac.
2. IV infusion delivery. Disease indications using this delivery method include asthma, osteoporosis, inflammatory joint disease, multiple sclerosis, and acute radiation syndrome.

Dosing and timing of injections matter: Mesoblast reports that there is a clear dose response curve in cardiac applications. In their phase II trial they reported that a single dosage of 150 Million MPC cells in their Revascor project significantly reduced hospitalization and death rates for congestive heart failure patients, compared to lower dosages of 25 Million, or 75 Million cells.

one week after injections with MSC’s patients are euphoric

In orthopedic applications, Dr. Pettine reported using dosages of 6 Million and 12 Million  stem cells for disc repair. He reported that one week after injection with MSC’s, patients are euphoric.

Jason Kolbert, a former Wall Street Biotech analyst and now VP of Neostem, stated that dosing must be given with enough time for the cells to migrate to the site of injury or disease. Neostem has identified that period as day 4 or 5 for one of its cardiac applications.

Are stem cell therapies safe?

On the topic of safety, Allosource, a maker of allographs, which is a matrix seeded with stem cells, reported that there have been NO reported adverse events with over 4,000 procedures.

The Future of Healthcare

In closing remarks to the conference attendees, Robin Young noted that he believes stem cell therapy will ultimately be less expensive for the healthcare system. He gave an example whereby a $40K orthopedic procedure will be replaced with a single session $5K cell therapy injection.

Best soundbite heard

If Don Draper of Mad Men were hired to run a PR campaign for public awareness of stem cell therapies, he would likely have zoomed in on this sound bite spoken during the course of the conference. It’s quite simple, yet accurate:

“Stem cells are a way to naturally heal your body.”

Nuff said. Onward with the revolution!

Leeza Rodriguez
CosmeticSurg Staff Writer
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

One of the biggest concerns patients have with any surgery is the amount of pain they will have to endure afterwards. This is especially true in cases of breast augmentation and other cosmetic surgery procedures since the patient is undergoing elective surgery and wants the best experience possible.

Pain itself can have a negative impact following surgery. In fact, it’s the main cause for re-admission to a hospital after cosmetic surgery. When patients are in pain, they tend to breathe in short, shallow gasps which results in poor oxygen delivery tot he tissues that, in turn, affects healing. Besides, when the lungs don’t fully expand, patients are more prone to additional complications such as pneumonia.

To prevent this, patients need pain relief. The traditional way is pain pills. The first problem with pills is that the effect of the pill goes up and down, so patients experience waves of pain. Secondly, too much of a dosage can depress the breathing urge, which can be very damaging to healing tissues. Thus a patient can get caught into a dangerous pattern cycle: a wave of pain, followed by taking more than the prescribed amount to control the pain because the pain pill takes time to take effect, followed by the danger of not breathing well enough due to the dosage taken.

Pain pills also have the unfortunate effect of causing nausea. If the patient is having pain, then takes a pain pill she may get pain relief, but a lot of nausea which means she’s not able to drink as many fluids as she needs to replenish the loss of fluids during surgery. This dehydration can also be dangerous. And it only worsens if the patient actually vomits, because she gets even more dehydrated and can’t get pain relief because she can’t keep the pills down.

So what is the solution to the pain problem?

The solution? Pain pumps, not pain pills!

Dr. Rodriguez, Baltimore Plastic Surgeon

Pain Pumps. Not pain pills. Unlike pain pills that affect your brain and your gut, the pain pump just pumps minute amounts of numbing medication to the operated area. This means your mind remains clear. You have no nausea so you eat well and remain well hydrated.

Pain Pump used after Breast Augmentation

Here at CosmeticSurg, when a patient comes in for drain removal after a breast augmentation, I can tell whether she’s wearing a pain pump from the minute she opens the door. To begin with, she actually grabs the door handle and gives it a push.

Post Op patients without a pain pump

Over 95% of my breast augmentation patients opt for the pain pump! Furthermore, patients who have undergone a tummy tuck do even better. Without a pain pump, every single breath hurts because you use your abdominal muscles to breathe. In my Baltimore practice, the abdominoplasty patients who opt for the pain pump get up faster, move around more, and thus recover better. If you’re planning on having breast aug, or a tummy tuck, make sure you have the option to get a pain pump, too.

More about pain pumps…

To learn more, you might also want to read Improving the cosmetic surgery experience: Pain pumps to control pain and nausea and watch me explain how pain pumps can dramatically reduce post operative pain and shorten your recover time in my video post, Pain Pumps: Cosmetic Surgery with minimal pain.

Ricardo L Rodriguez, MD
Board-Certified Plastic Surgeon
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

FDA and Adipose Stem Cells

Several years ago we became fascinated with the potential of adipose stem cells for both cosmetic and medical purposes. However, we soon discovered that nothing in the written FDA guidelines specifically addressed the use of autologous adipose stem cells. Thus began our journey for an answer. In June 2009, we sent a letter to the FDA asking for a position statement on adipose stem cells. Our request focused specifically on autologous, freshly isolated, adipose stem cells for use in soft tissue reconstruction. These stem cells are from your own fat, for your own usage, and not culture expanded .

After a very long wait, we recently received a written response from the FDA. First, a little bit of background for any stem cell newbies….

Stem Cells 101

• There are three general categories of stem cells: embryonic, induced pluripotent (IPS), and adult stem cells.
• Stem cell treatments are either autologous or allogeneic. Autologous treatments use your own cells and allogeneic treatments use stem cells from donors.
• Adult autologous stem cells have a higher safety profile than both embryonic and IPS cells.
• Over three thousand clinical trials have taken place worldwide with adult stem cells.
• The adult stem cells in adipose tissue are mesenchymal cells (MSC’s), which are one of the cell types largely responsible for the healing properties of stem cell therapies.
• Compared to other adult stem cell tissue sources, adipose stem cells contain the highest number of healing mesenchymal stem cells (MSCs) per volume of tissue, by a factor of 500 fold. Due to their ease of extraction and highly abundant supply of MSCs, adipose stem cells hold great promise for stem cell therapy.
• Adipose stem cells are derived from fat, which is commonly collected via a liposuction procedure. There are various techniques used to isolate adipose stem cells, but they are generally classified as either freshly isolated or culture expanded. The typical method to freshly isolate adipose stem cells combines fat with collagenase to make a stromal vascular fraction (SVF). The process to obtain SVF can be done in a few hours.  Culture expansion is used to multiply the number of stem cells and takes days or weeks in a lab.
• SVF is a mixed population of cells containing a high proportion of MSC’s. Culture expanded refers to an SVF population of cells that has been allowed to grow and multiply under specific laboratory conditions. This results in a homogeneous population of MSC’s.

FDA classifications: tissues vs. drugs

Human cells and tissues intended for human transplant are regulated by the FDA. The FDA maintains two levels of classifications for cells and tissues: 1) HCT/P 361 and 2) HCT/P 351.

uncultured stem cells from my own fat…. a tissue or a drug?

 

Category 361 is summarized as a ’tissue’ . A subset of category 361 includes procedures that take place in the same operative session . These same session operative procedures are exempt from FDA regulation. These procedures fall under the jurisdiction of practice of medicine. Surgeons follow guidelines and laws established by state medical boards and their professional societies, but are not controlled by the FDA. The other category, 351, is the ‘drug/biologic’ category, which is completely regulated by the FDA. It is infinitely easier and faster to bring medical procedures which fall under 361 guidelines to a physician’s practice compared to the 351 category.

Examples of tissues and cell types in each of the two FDA categories are as follows:

• 361-TISSUES: skin, bone, ligaments, corneas, heart valve allographs, hematopoietic stem and progenitor cells derived from peripheral and cord blood, reproductive tissue (IVF procedures)
• 351- DRUGS: prescription drugs, biological products and devices, embryonic stem cells, allogeneic stem cells

Our request simply asked the FDA if SVF (not culture expanded) adipose stem cells for autologous usage in soft tissue reconstruction in the same operative session fall under the tissue or the drug classification.

The FDA response–adipose derived stem cells are a drug

Last month we finally received a response from the FDA. Close your eyes and imagine a train coming to a screeching halt. It was not the answer we were hoping for.

Your own autologous adipose stem cells from the stromal vascular fraction (SVF) used for reconstruction and repair in the same operative session are considered by the FDA to be a DRUG.

Is the FDA being consistent?

What is interesting to us is that hematopoeitic stem cells and IVF procedures are both not classified as drugs, but uncultured fat stem cells are. The FDA’s main consideration for classifying adipose stem cells as a drug was because the cells are more than minimally manipulated. So what about IVF procedures? Is creating a human from a sperm and an egg only a “minimal manipulation”?

What implications does this FDA letter have?

To make a long story short, the ‘drug’ classification will add several years to the equation for surgeons manually performing therapies with adipose stem cells. In our opinion, the FDA’s new position on adipose stem cells will likely have two effects:

1. Clinics offering therapies with adipose stem cells will be driven offshore
2. In the arms race for adipose stem cells, the power will shift to the device makers specializing in processing adipose tissue.

The new FDA position means that any surgeon who wishes to use the SVF fraction (centrifuged adipose tissue plus collagenase to yield higher numbers of stem cells) must now submit an IND (Investigational New Drug Application) to the FDA and have an approved IRB (Institutional Review Board) with a hospital. This submittal process is extremely time consuming, requires many resources, and is expensive. Some surgeons will simply move their trials, therapies, and clinics offshore.

This FDA position essentially takes surgeons performing manual processing with collagenase in their OR’s out of the physician practice equation for the near future. Therefore, this FDA position likely benefits adipose stem cell device makers who process adipose tissue as they are much further along in the approval process with the FDA. Device makers will likely be first to market with their autologous stem cell processes.

Does this FDA position affect plastic surgeons currently performing high density fat grafting?

No. But it is not out of the question that the FDA may put fat grafting under the magnifying glass in the future.

Fat grafting uses fat obtained from liposuction. The fat is harvested with a cannula, decanted, and processed via centrifugation techniques. A portion of the processed fat is then reinjected into areas for cosmetic enhancement. The enhancements primarily involve restoring volume and fullness.

Although fat grafting does not use collagenese to isolate the stem cells, the dirty little secret is that high density fat grafting does contain small numbers of stem cells. These stem cells are found in the ‘fat pellet’ separated via centrifugation after the tumescent liposuction procedure. The mechanical forces of the liposuction procedure act to separate the mesenchymal stem cells from the blood vessels. This is all within the great science of stem cell activation. Plastic surgeons have recently come to understand that the small population of stem cells in the fat pellet provide more vascularity to fat grafts. High density fat grafting results in long lasting fat grafts and healthier looking skin.

Copy of the FDA’s response, December 12, 2011

For the truly adventurous, below is a copy of the FDA response in its entirety. Your comments and thoughts are welcomed!

Leeza Rodriguez
CosmeticSurg Staff Writer
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

Click on the image of the letter enlarge it!

There have been several comments recently on one of my previous blog posts about swelling after a tummy tuck. Swelling is only one of the possible complications that can occur following a tummy tuck procedure. Other post-op abdominoplasty complications can be subdivided into a few major classifications: Infection, Wound Separation, and Fluid Collections (Hematoma and Seromas).

Infection after a tummy tuck

Most surgeons give patients pre-operative antibiotics so wound infection is not as big a problem as it used to be. Ask your surgeon if he will be giving you preoperative antibiotics and make sure you are not allergic!

Infections can be minor, such as a suture abscess. However, they can also be life threatening, like those of MRSA.

A suture abscess is typically not dangerous, and it’s caused by the body trying to dissolve away some of the absorbable sutures that are placed in the deep layers of tissue to hold the tissue together. It is easily taken care of by lancing the area under a local anesthetic, and packing the small puncture with a medicated gauze. Usually additional antibiotics are not needed unless the patient has fever and redness over an extended area.

With respect to MRSA, as a precaution I routinely ask patients if they, or anyone in their family, has had an episode of MRSA (Methcillin Resistant Staph Aureus). This can be a very dangerous infection after surgery. If the patient has a history of MRSA or exposure, we will do a swab culture of the nose (where MRSA frequently resides), and will give specific antibiotics against MRSA at the time of surgery.

Remedy: Taking active steps to prevent infection is the best remedy.

Wound separation after a tummy tuck

This looks dramatic to the patient, because the patient thinks that the separation is very deep. However, it is not, as the separation only goes to the muscle wall. Wounds can separate for the following reasons:

1) Excess skin tension if too much skin was taken out during the procedure. The best way to prevent this is for the surgeon to excise the skin in surgery not according to ‘the pre drawn pattern’, but by making sure the closure will be more than adequate well before the actual cutting is made!

2) The wound edge heals poorly because of poor blood supply. This is more common with techniques that elevate the skin all the way up to the skin margins.

The Lockwood technique that I use for the tummy tuck dissection is excellent because it does less undermining and preserves most of the blood supply.

Remedy: Small wound separations are easily taken care of by packing the wound with medicated gauze. Slightly larger wound separations, or those caused by tension, can be taken care of by a suction device called a “Vac Dressing” manufactured by KCI. Large wound separations caused by poor blood supply may need revision and re-approximation of the wound edges in a procedure room.

Fluid collections after a tummy tuck

Fluid collections are more common when there is a lot of space created between the abdominal skin and the underlying muscle. Fluid can easily accumulate in this space and complicate the healing process. For more detailed information, see my blog post about post operative tummy tuck swelling and seromas, Tummy Tucks and How To Reduce Swelling and Eliminate Fluid Collections.

In summary, the different type of fluid collections associated with tummy tucks are seroma and hematoma.

Seroma
A Seroma is a collection of wound fluid. It is mostly seen when the patient has a lot of activity in the post operative period or there is inadequate compression, and rarely happens when the Lockwood technique is used. It can easily be treated with a needle aspiration, but it is not unusual to have to do a series of aspirations spaced over a few days to take care of the problem.

Hematoma
A Hematoma is a collection of blood in the dead space. It usually needs to be evacuated because it can be painful, can lead to infection or cause excessive scarring. It is usually caused by a small blood vessel that opens up in the recovery period, and can happen up to a few days after surgery. Most of the time it can be evacuated with a needle, but sometimes it may need a small intervention in a procedure room.

Remedy: The best remedy against fluid collections is prevention. I am a firm believer in the right kind of compression garment with shoulder straps to keep the garment well placed. Foam pads over areas of potential fluid accumulation also help a lot.

All in all, the Tummy Tuck is a very safe operation. However, you need to be aware of the risks and potential complications prior to any surgery. When you go into your pre-operative tummy tuck consultation be sure to ask your plastic surgeon about these possible complications and how he or she handles them when they occur. Most importantly, get a commitment that the surgeon will be available after surgery within a short time period should you experience any problems. I give all of my post op patients my cell phone number so I can communicate immediately if any problems or concerns arise. Be sure you know how to get answers to post op questions prior to your surgery.

Have a great Thanksgiving!

Ricardo L Rodriguez, MD
Board-Certified Plastic Surgeon
© Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

Nearly everyone has heard of Groupon, the coupon site for daily deals. If you are on the receiving end as a consumer, it can be a great way to get some great deals. For over a year we have been seeing other plastic surgeons and dermatologists sell Botox® at huge discounts. Not wanting to be outdone by our competitors, we decided to explore our options for selling facial injectables such as Botox, Restylane, Juvederm and Sculptra via Groupon.

Our biggest dilemma about using the popular daily deal service was a legal one, rather than what price we could negotiate with Groupon. Our question was “Is it legal for our medical practice to give a percentage of the sales to Groupon based on the number of injectable procedures we sell?”

If you are scratching your head, you may not be aware that many states have anti-kickback and ‘fee splitting’ rules for doctors. These rules forbid medical doctors from giving a payment to anyone for a referral. In other words, awarding a commission to an advertiser based on the income generated or number of patients treated is illegal.

We first broached the question to one of our patients, who happens to be a well respected attorney here in Maryland. His short answer was that Groupon likely violates Maryland State laws on fee splitting. Having gotten his response, we next put in a phone call to the American Society of Plastic Surgeons (the ASPS) to hear their formal position on Groupon.

They pointed the way to a recent article about the use of Groupon for cosmetic services published in the June 2011 issue of Plastic Surgery News, the trade publication for plastic surgeons.

In summary, the ASPS article was written by the plastic surgeon who heads the ASPS Ethics Committee and a lawyer. They concluded that Groupon likely violates the laws for physicians in many states. In particular, they considered the use of Groupon to be in violation of laws in California, Florida, Illinois, and New York State. Lots of specific details were given about the regulations in these particular states. The State of Maryland was not discussed, but we are certain that the laws here are very similar, which means that kickbacks can not be given for referrals of patients.

According to the ASPS, the use of Groupon to promote cosmetic surgery procedures likely to be illegal in many states.

If that wasn’t enough to scare us away from using Groupon, the authors of the article also shed some light on how Groupon management is approaching the issue of the legality of doctors using their services to promote cosmetic services. Groupon has acknowledged that there may be issues with particular states and their licensing authorities, “Groupon advised [the ASPS] through its counsel that it has not independently done a legal analysis and assessment as to whether the Groupon program violates federal or state laws regarding flee splitting, kickbacks, and referral fees.”

Furthermore, the article stated that Groupon does not consider it their obligation to determine whether services are legal or not. According to ASPS, “Groupon is taking a ‘buyer beware’ position and assumes no responsibility for determining whether the program raises legal implications for the service providers (doctors).”

Haven’t done an assessment yet? Don’t consider it their obligation to determine legality? Has Groupon taken a new position since the writing of this article? Certainly an acknowledgement that including cosmetic services such as Botox injections within their daily deal offerings is illegal in many states would rain on the Groupon IPO parade. Halloween may be over, but for Groupon investors, this is a scary thing!

CosmeticSurg Staff Writer
©Cosmeticsurg.net (permission to copy article or part of article provided this notice is included and proper attribution is given, including a link to the original source URL)

Unless you are a science major, understanding the topic of stem cells can be daunting. The mainstream media has provided some good articles on the topic of Stem Cells, but there is a lot of misleading information out there. In an effort to give you a mile high view of the stem cell world, we made a graphic, Stem Cell Types – Debunking Misconceptions.

The truth is that adult stem cell therapy is much closer to therapeutic commercial reality compared to embryonic or induced pluripotent stem cells. In fact, adult stem cells are on the launch pad now. We’re not diminishing the importance of embryonic or IPS research/clinical trials. ALL stem cell research is important and findings in one field have helped the other fields. We hope to see all three types of stem cells in mainstream medicine!

Mainstream media often lumps all stem cells into one category and quotes doctors saying things like: Stem cell therapies are many years away; (All) stem cells cause cancer; Stem cells are highly risky; Clinical trials are only in early stages; etc. Those types of statements are simply not categorically true. In actuality, there’s a wide variation in stem cell risk profiles and clinical trial development. A big misconception is how far along adult stem cells are in their clinical trial development. In reality, the number of adult stem cell trials trounce the number of embryonic and IPS trials.

To summarize our illustration:

3 Types of Stem Cells
Adult, Embryonic, and Induced Pluripotent (IPS)

Autologous or Allogeneic
Autologous cells are your own stem cells. Allogeneic stem cells are donor cells from another human being.

Risk Profiles
The more stem cells are manipulated, the greater the risk they pose to the patient receiving them. Adult stem cells have the lowest risk profile. Embryonic and induced pluripotent stem cells have higher risk profiles. Furthermore, teratomas (tumors that originate from a group of normal cells) can form in embryonic and induced pluripotent stem cells. Teratomas do not form in adult stem cells.

The FDA regulates stem cells according to risk profiles and the potential to spread disease to the general population. For this reason, embryonic and pluripotent have more regulatory hurdles than adult stem cells. Likewise, autologous stem cell therapies have less regulatory burdens than allogeneic therapies.

Worldwide Stem Cell Clinical Trials
If you include all the trials that have been done over the decades with hematopoietic cells and bone marrow, the number of adult stem cell trials is in the thousands. Compare that number to just a handful of embryonic and induced pluripotent trials. Big difference right? So, why is the media obsessed with talking about embryonic and IPS stem cells, when adult stem cell therapies are right at our doorstep?

Click on the image below to see our graphic in its full glory!

Use the HTML below to embed this graphic

<br /> <a href="http://www.cosmeticsurg.net/blog/2011/09/16/stem-cell-types/"><img title="Adult, Embryonic, and Induced Pluripotent Stem Cells " src="http://www.cosmeticsurg.net/blog/wp-content/uploads/2011/09/stemcelltypes1.png" alt="" width="400" height="2817" /></a><br /> <br />Source:<a href="http://www.cosmeticsurg.net/blog/2011/09/16/stem-cell-types/"> Stem Cell Types – CosmeticSurg.net</a>

CosmeticSurg Staff Writer

©Cosmeticsurg.net (permission to copy article or part of article provided this bio is included and proper attribution is given, including a link to the original source URL)

Related posts:

• Adipose Tissue has more Stem Cells than Bone Marrow – March 17, 2011
• Cosmetic Surgery Trends for 2010 – Fat is phat! – January 1, 2010
• Plastic Surgery Predictions 2011: Fat Stem Cells 2.0 – January 5, 2011

In January, President Obama ordered federal agencies, such as the FDA, to search their books and strike any overburdensome regulations. Following this queue, in June, the FDA quietly posted a request for comments to any existing regulations that are burdensome or outdated by technology. To quote the FDA’s request to the public:

The “FDA is particularly interested in comments that identify regulations that may be impediments to innovation and suggestions for how they can be improved.”

We saw the request and passed the link on to a friend of ours who teaches healthcare law and has taken great interest in the fate of autologous stem cell therapies. Professor Mary Chirba holds a Ph.D. in Public Health from Harvard and is a Professor of Healthcare Law at BC College. She believes that it’s high time for the FDA to reclassify therapies in which patients use their own stem cells and decided to submit a comment. She’s graciously given us permission to post her comments here on our blog.

Her point is that therapies using your own adult stem cells are being held to the same rigorous regulations as allogeneic stem cell therapies (where tissues from a donor are used), despite each having very different risk profiles for patients. It’s a sentiment we’ve voiced ourselves. Keep in mind that the FDA’s primary mission is to protect the public from transmitted disease by regulating the manufacture and marketing of mass produced drugs or biologic tissue products.

Rather than ‘reinvent the wheel’ of regulatory apparatus, it can simply expand IVF oversight to include a broader category of cell and tissue products.

- Prof Mary Chirba

Autologous therapies pose no public health threat to the general population, as they are your own cells. However, allogeneic (donor) therapies do use cells from other human beings, and it is the proper role of the FDA to regulate those therapies.

In her submission to the FDA, Professor Chirba critiques changes made to the regulations by the FDA without public comment. In 2006, the FDA replaced the wording regarding the use of tissues “into another human” with the wording “into a human.” By doing so, replacing the word another with the word a, the FDA expanded the regulatory overview of allogeneic therapies to include autologous therapies. Although it involved only one tiny word swap, it completely redefined the circumstances which draws the line between practice of medicine, where a physician uses tissues from the patient being treated, and drug therapy, where a physician uses tissues from a separate donor.

Anyone who’s following the case filed in Federal Court, US Justice Department vs. Regenerative Sciences knows exactly what we’re talking about here. This will no doubt be a landmark case which will affect the entire cell therapy world.

Dr. Chirba’s suggestion to the FDA is to treat autologous stem cell therapies not as it treats drug therapies, but rather to treat them in the same capacity as IVF therapies. This would make regulations less burdensome and allow autologous adult stem cell therapies, using stem cells derived from a patient’s own body, to come to market much quicker.

Professor Mary Chirba is simply one of the smartest people we know and we think she’s hit a lot of nails on the head with her commentary. We take great pride in sharing her brilliance with you!

FDA’s Periodic Reviews of Existing Regulations
[Document ID FDA-2011-N-0259-0001]

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Cite: 21 CFR 1271
Agency Division: CBER

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From: Mary Ann Chirba, J.D., D.Sc., M.P.H.
Boston College Law School, 885 Centre Street, Newton Centre, MA 02459
chirbama@bc.edu
Date: June 24, 2011

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The Problem:

In 2005, the FDA stated that autologous cell therapies carried “minimal, if any risk.” See, e.g.,70 Fed. Reg. 29952 (May 25, 2005) (clarifying § 1271.90(b)(3) labeling requirements for autologous cells and tissues). Yet in 2006, the agency departed from the requirements of notice and comment rulemaking when it quietly but dramatically changed the basic definition of HCT/Ps that anchors the FDA’s three-tiered, risk based framework for regulating human cells and tissue products. With no notice and absolutely no opportunity for public comment – and, indeed, with no formal announcement beyond its routine, annual publication of regulations – the FDA substantively redefined autologous HCT/Ps by deleting the critical descriptor of transfer into “another” human from the regulation.

Thus, section 1271.3(d) now states that “[h]uman cells, tissues, or cellular or tissue-based products (HCT/Ps) means articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.” 21 C.F.R. § 1271.3(d) (April 1, 2006) (emphasis added). See also, 21 C.F.R. § 1271.3(d)(1) (April 1, 2010).

The White House’s own Cass R. Sunstein, current Administrator of the Office of Information and Regulatory Affairs, has written extensively and testified repeatedly before the U.S. Congress (most recently on June 23, 2011) regarding the need to evaluate the practical impact of regulations, and reject those that yield more costs than benefits. See, e.g., Cass R. Sunstein, Group Judgments: Statistical Means, Deliberation, and Information Markets, 80 N.Y.U.L. Rev. 962, 1042 (2005); Robert H. Frank & Cass R. Sunstein, Cost-Benefit Analysis and Relative Position, 68 U. Chi. L. Rev. 323, 324 (2001) (“The movement toward cost-benefit analysis of regulatory initiatives is generally desirable and . . . most of the conventional criticisms of it are unconvincing.”) And yet, in revising §1271.3(d) without the benefit of public input, the FDA has fashioned a regulation that imposes real and extensive burdens on patients and providers while achieving little if any benefit — at least with regard to low-risk, autologous adult stem cell therapies.

More specifically, the FDA’s CBER merged two previously distinct categories of products, i.e., autologous and allogenic, into one. In doing so, it removed autologous cells from minimal regulatory § 361 oversight and subjected them to § 351′s far more rigorous requirements (including the need to comply with BLA, IND, NDA, cGMP and other FDA premarket review and approval requirements that govern commercial manufacturers of medical drugs and devices).

Obviously, treating autologous and allogenic HCT/Ps as carrying comparable risks directly contravenes the FDA’s prior stance that autologous cells involve “minimal, if any, risk.” Moreover, making this change in such a covert manner – i.e., without following legally required process of notice and comment rulemaking – unfairly disadvantages the very actors who are most likely to develop and use autologous therapies, i.e., surgeons and physicians engaged in the (state regulated) practice of medicine. And it is no small matter that these actors, on the front lines of therapeutically and economically necessary innovation, are also the least likely to have the legal resources or prior awareness of the need to comb each year’s Code of Federal Regulations for subtle word changes.

As a direct consequence of reclassifying autologous adult stem cells as § 351 products, a physician’s normal ability to develop new therapies is now hampered by the administrative and economic burdens of having to file endless INDs. At a time when patients and the overall economy are desperate for innovation, and the FDA is already so seriously under-resourced, its determination to increase IND filings and to do so exponentially is, to put it mildly, difficult to comprehend.

One adverse, but predictable result is that patients must increasingly leave the country to obtain autologous adult stem cell therapies. Consequently, what should carry “minimal, if any, risk” now varies widely in terms of patient safety due to variability in: (a) the training and skill of the provider; (b) the information available to the patient trying to make informed decisions; and (c) the availability and quality of follow-up care and, if necessary, legal recourse in the event of serious complications or medical error.

In 2001, the FDA promised to regulate HCT/Ps in a manner that would promote consistency, efficiency, safety and “encourage the development of new products.” 66 Fed. Reg. 5447-5448 (Jan. 19, 2001). The FDA initiated its three tiered, risk-based framework for regulating HCT/Ps because it correctly recognized that regulating cellular products as if they were conventional drugs made no sense.

Regulating autologous adult stem cell therapies under section 351 and thereby treating physicians as if they are large, commercial pharmaceutical manufacturers similarly makes no sense. It is neither consistent nor efficient. Erecting regulatory barriers that limit access to existing therapies and impede the development of new ones creates an array of economic inefficiencies. It also compromises what should be the agency’s paramount objective: optimizing patient safety by increasing the availability of low-risk, minimally invasive therapies that harness the power of a patient’s own cells to cure or at least mitigate what ails them.

Physicians take an oath to do no harm to their patients. While not formally bound by the Hippocratic Oath, one would hope that the FDA aspires to the same. However, by surreptitiously changing the substantive content and impact of § 1271.3(d), the FDA did indeed do harm – and did it to patients and providers alike.

II. Proposed Solution:

1. The FDA should rescind its April 1, 2006 change to the wording of 21 C.F.R. § 1271.3(d) by replacing the current term “transfer into a human” with its predecessor, “transfer into another human….”
• The agency must respect and adhere to federal law concerning notice and comment rulemaking. As explained above, its April 2006 change was substantive and has a significant impact in terms of who is bound by the rule and what their obligations are. Consequently, any change of this kind is invalid and unenforceable unless preceded by giving the public notice of the opportunity to submit comments.
2. At a minimum, the agency should regulate minimally manipulated autologous adult, freshly isolated, Stromal Vascular Fraction, non-culture expanded stem cells under § 361.
• This is a necessary first step in relieving the economic costs and administrative log jam of INDs that currently lead too many clinicians to abandon this field or relocate to a more hospitable regulatory climate.
• Acknowledging that the HCT/P category is not homogenous more properly accommodates the agency’s multiple objectives of maximizing patient safety without unduly burdening economically viable and therapeutically necessary innovation.
3. Alternatively, the FDA can subject autologous adult stem cells and therapies to the same regulatory oversight currently employed for in vitro fertilization.
• The FDA presently subjects in vitro fertilization to less rigorous oversight than autologous stem cell therapies even though IVF is typically more invasive, involves more manipulation, and poses higher risks to the patient.
• Consequently, the agency should acknowledge and correct inconsistencies in its current regulation and enforcement efforts regarding autologous HCT/P therapies, at least with regard to autologous adult stem cells (or subsets thereof). Rather than “reinvent the wheel” of regulatory apparatus, it can simply expand IVF oversight to include a broader category of cell and tissue products.

Thank you for the opportunity to submit these comments.

Mary Ann Chirba

CosmeticSurg Staff Writer
©Cosmeticsurg.net (permission to copy article or part of article provided this bio is included and proper attribution is given, including a link to the original source URL)

Fat grafting, also known as fat transfers or fat injections, is a plastic surgery procedure which removes fat from unwanted areas of your body, carefully processes the fat, and then reinjects your own adipose fat tissue where more volume is desired. Fat injections can help rejuvenate your face, your buttocks, your hands, or your breasts. Fat injections are also being used in breast reconstruction surgery. Fat grafting will restore volume to the breast and can be performed with or without an implant.

Lately we have seen some plastic surgery blogs expressing concern regarding how fat injections to the breast affect mammograms. We feel that both sides of the story are not being told, so we would like to address that here.

When we wrote about fat grafting to the breast back in April of 2009, the conclusion from the ASPS position paper indicated no evidence that fat injections interfere with breast cancer detection and that results of fat transfers remain highly dependent on a surgeon’s technique and expertise. See our previous blog post, Fat Stem Cell injections to the breast- Risky?, for more detail.

Two years later it’s still being debated. The Plastic and Reconstructive Surgery Journal, a journal of peer reviewed studies from the plastic surgery community, recently published several papers that come to different conclusions about whether fat injections to the breast can interfere with cancer screening.

Let’s explore these publications to review the various findings.

The Chinese Study

April 2011, Plastic and Reconstructive Surgery

“Clinical Analyses of Clustered Microcalcifications after Autologous Fat Injection for Breast Augmentation”

The recently released paper, published in the April 2011 issue, put fat injections to the breast in a negative light. The study was conducted by Chinese plastic surgeons at Meitan General Hospital and Peking Union Medical College Hospital in Beijing, China. The Chinese study concluded that fat injections create issues with mammograms used to detect cancer in the breast. Based on these findings, the study recommended prohibiting all fat injections to the breast.

This study analyzed ‘digitized mammographic films’ from 48 patients who had received fat injections to the breast from July 1999 to December 2009.

The study focused on calcifications which occur after fat grafting is performed.

When a fat injection does not take well, the fat cells can die (fat necrosis), and take on the appearance of a calcification. The Chinese study concluded that mammograms cannot distinguish between calcifications formed from fat or calcifications that may be cancerous. The study’s abstract conclusion states “clustered microcalcifications found after autologous fat injection for breast augmentation, cannot be distinguished from malignancy.”

Even though all calcifications were biopsied to be non-malignant, the study also reached a grandiose conclusion that fat injections to the breast “should be prohibited.”

So–should fat injections to the breast be outlawed? Or is there another side to the story? If so, what is it? The heart of the matter is whether radiologists can distinguish if calcifications seen on mammograms are due to dead fat cells, or from malignant cancer cells. First of all, not all fat grafting produces calcifications. If a fat graft takes well, there will be fewer dead fat cells, or fat necrosis, thus resulting in fewer or no calcifications. However, a poorly performed fat graft will likely have lots of dead fat cells, likely resulting in more calcifications.

Let’s look at other recent articles that were published on the topic of fat injections and mammograms, all within the last month.

The Discussion Article about the Chinese Study

April 2011, Plastic and Reconstructive Surgery
Daniel DelVecchio, M.D.

The same April 2011 Plastic Surgery Journal issue included a ‘Discussion’ article about the Chinese study. If you had a hard copy of April’s journal, you would simply turn from the last page of the Chinese publication to read the ‘Discussion’ section that immediately follows written by Plastic Surgeon, Dr. Daniel DelVecchio. Dr. DelVecchio was an early adapter of fat grafting to the breast and has been published frequently in the Plastic Surgery literature.

Dr. DelVecchio brought up several excellent points as to why the Chinese publication conclusion was without merit. One point addressed concerned the issue of the resolution quality of the mammograms. What type of mammography did the Chinese use? The Chinese publications stated that they used ‘digitized mammographic films.’

screen film mammograms are inferior to direct digital mammograms

- Dan DelVecchio, MD

According to DelVecchio, this would imply that plain screen film mammograms were initially imaged, and later digitized. Per DelVecchio: “the quality of digitized screen film mammogram is only as good as the quality of the original mammogram, and it is common industry knowledge that screen film mammograms are inferior to direct digital mammograms.”

In other words–did the Chinese study simply digitize mammogram films with inferior resolution?

Dr. DelVecchio pointed to the work of other fat grafting pioneers, such as Dr. Emmanuel Delay, who have described the ability to distinguish between benign and malignant findings on post fat grafting mammograms. DelVecchio cited the radiologic literature which supported the general concept that calcifications and fat necrosis can be distinguished from the malignant signs of irregularly shaped, high-opacity microcalcifications when supplemental imaging modalities are considered.

Other notable points made by Dr. DelVecchio included the need for standardization of fat injection procedures in order to minimize fat necrosis, which result in calcifications. Deviation from ideal fat grafting techniques result in poor fat take because some of the fat dies. It is these dead fat cells that can result in calcifications. As standards emerge for the best fat grafting techniques, there will be less fat necrosis and calcifications to show up on mammograms as a result of fat injections to the breast.

In DelVecchio’s opinion, modern mammography techniques can distinguish between malignancy and benign fat deposits found on mammograms.

The French Study

March 2011, Plastic and Reconstructive Surgery

“Radiographic Findings after Breast Augmentation by Autologous Fat Transfer”

Exactly one month prior to the Chinese article publication, a group of French surgeons published an article in the March 2011 issue of Plastic Surgery Journal. The study compared mammograms pre and post operative mammograms on 20 patients who underwent fat grafting to the breast. The study’s goal was to determine whether the transfer of fat to the native breast hampers breast imaging.

Using guidelines stabled by the American College of Radiology classification, the study concluded that radiographic follow up of breast treated with fat grafting is not problematic and should not be a hindrance to the procedures. However, the study did recommend that techniques used for fat injection patients should become standardized, so that reproducibility could be insured.

Our Summary:

As more radiographers gain experience with fat grafting, we expect this mammogram issue to diminish, as happened with the case of breast implants and mammography.

Additionally, there is one important fact to remember–of all the thousands of fat grafts to the breast that have been done to present, there is yet to be a reported case of a cancer being missed on a mammogram because of a previous fat graft.

CosmeticSurg Staff Writer

©Cosmeticsurg.net (permission to copy article or part of article provided this bio is included and proper attribution is given, including a link to the original source URL)

Related posts:

• Stem Cell Enhanced Fat Grafting for Breast Reconstruction – Sept 21, 2010
• Lumpectomy Reconstruction: fat grafts to the breast – August 12, 2009
• Fat Stem Cell Injections to the Breast – Risky? – April 25, 2009
• Breast Lumpectomy Reconstruction Using Your Own Fat Cells – March 3, 2009