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

Robin Young’s 6th annual Stem Cell Summit was held on March 1, 2011 in NYC. In attendance were scores of public and private stem cell companies. Presentations included: 21 adult stem cell companies, 3 embryonic companies, 7 device/ instrumentation companies, and a panel of medical experts discussing Spinal Cord Injury. Each company gave a 10-15 minute presentation.

For the past few years, Arnold Caplan, Ph.D, a leader in the world of stem cell therapy, has presented the keynote address to the conference. Dr. Caplan is professor of biology at Case Western and has authored more than 300 publications. Not only is he well known in academic circles, but he is no stranger to the biotech financial community, as he was the founder of Osiris Therapeutics (Nasdaq: OSIR), a publicly traded cell therapy company. According to his own disclosures, Dr. Caplan no longer has financial ties with Osiris, but he is involved with other cell therapy start ups. Here are some highlights from Caplan’s keynote entitled, The State of MSC’s in 2011.

Changing the way we think about stem cells

“We are in a new era of how we should be thinking about stem cells.” Dr. Caplan described that we should think of the stem cell industry in two realms:

1. Tissue Engineering
2. Regenerative Medicine

He emphasized that the first phase of the cell therapy revolution has been focused on tissue engineering, whose main premise is using manufacturing processes to make stem cells differentiate into various lineages like bone, heart, or brain.  However, Dr. Caplan proposed that the next phase of the Cell Therapy Movement, known as Regenerative Medicine, will come from natural healing responses from the stem cell, not from the actual differentiation of stem cells into various cell lineages.

adipose tissue is an enormously potent source of autologous regenerative therapy.

- Arnold Caplan, PhD

More specifically, the REGEN revolution will come from your body’s own natural healing response which occurs when stem cells mechanically separate from blood vessels and release therapeutic molecules that your body takes cues from. Caplan stated that therapeutic uses would come from both cultured and uncultured  stem cell sources, and cited uncultured adipose tissue as a potent source of autologous regenerative therapy.

What are Mescenchymal Cells (MSC’s)?

Mechencymal stem cells, also known as MSC’s, are specific cells within a population of stem cells with certain surface markers. These “MSC’s are the cells that are doing all the business of healing”. Dr. Caplan described how Mesenchymal cell population is largely a function of the number of blood vessels.

MSC stem cells in their native state, resting within the wall of blood vessels.

The natural niche of mesenchymal cells is within the blood vessel wall. Thus, the more blood vessels, the more MSC’s–and vice versa. In the scientific community, this thesis is largely expressed as: All MSC’s are pericytes. Recent publications by Dr. Caplan have been devoted to this theme of how all MSC’s are pericytes and helps one understand why stem cells provide vascularity to damaged tissue. In simplified terms–they are a source of vascularity or blood supply.

How do you activate MSC’s?

MSC’s are attached to the blood vessels. According to Dr. Caplan, the healing mesenchymal cells activate when they become detached from the blood vessel wall. This can occur with mechanical force, chemical force, or signaling mechanisms. In previous blog posts, we have described some mechanical conditions where MSC’s become activated as they detach from the blood vessel wall.

What is magical about MSC activation?

When MSC’s detach from the blood vessel wall they release a TON of cytokines and growth factors that, in essence, become a  personalized drug store for your own body. What this means is that Big Pharma may need to rethink how they are doing things and get onboard the REGEN train.

The arrogance of bone marrow

Caplan recounted how bone marrow had been the defacto source of mesenchymal adult stem cells for decades. As was mentioned earlier, Dr. Caplan was involved in one of the first cell therapy start ups–Osiris. Dr. Caplan said that it always bothered him that “even though stem cells could be derived from other sources such as muscle, fat, heart, and brain- these other sources went largely ignored for years.”

Adipose fat has 300-500 fold more stem cells compared to bone marrow.

- A. Caplan, PhD

In a moment of jest, he referred to “the arrogance of those working with bone marrow.” Caplan explained that “as it turns out, the winner of MSC population is adipose tissue” explaining that per ml, adipose fat tissue has 300-500 fold number of healing mesenchymal stem cells compared to bone marrow. Adipose tissue can be derived from liposuctioned fat.  He also detailed that a concentrated pellet of uncultured fat tissue, known as the stromal vascular fraction (SVF) of adipose tissue, is an ‘enormously potent source of autologous stem cell therapy’.

Existing Clinical Trials using MSC’s

Dr. Caplan listed the many diseases which are currently in clinical trials with adult stem cell therapy. It’s an impressive list to say the least:

Potential treatment of sepsis

When the body doesn’t respond to antibiotics, a condition called sepsis can occur. This condition causes the body to shut down and often results in loss of peripheral limbs, shock, or even death. Dr. Caplan cited a recent publication which discovered the ability of MSC’s to kill gram positive and gram negative bacteria. If this plays out therapeutically, it would mean MSC’s could cure sepsis!

MSC’s – a new meaning for the acronym

This new era is not about stem cell lineage, but what the stem cell does naturally in different tissue environments. Since MSC’s are therefore site regulated, natural multi-drug delivery systems, they essentially become your body’s personal drug store. Dr. Caplan then proposed the following:

MSC = Mesenchymal Stem Cell => for tissue engineering
MSC = Medicinal Signalling Cells => for REGEN industry

Considering Dr. Caplan’s history, this promises to be a very interesting era for medicine and health care! We welcome your comments about this fantastic new era of regenerative medicine.

CosmeticSurg Admin
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)

A reader of our blog posed a very interesting question having to do with stem cell activation. Briefly put,

“why do you need to inject stem cells into an area if the normal tissues in that area already have some stem cells present?”–Charles

To understand why, we will talk about two concepts with adipose derived stem cells: the stem cell niche, and stem cell activation . Adipose stem cells are stem cells that are derived from your own fat tissue. They will play a big role in the new field of Regenerative Medicine.

The Stem Cell Niche

Stem cells usually exist in a low grade resting state in a controlled environment called a niche. The niche contains mesenchymal stem cells, also known as MSCs. The mesenchymal stem cell niche is usually located in the blood vessel wall itself.

stem cell niche: stem cells attached to blood vessels

The status quo for a niche is not full blown stem cell activity, but a level of activity finely attuned to its surroundings. These cells like to keep a stable environment  (on the vessels) within the niche. They will only respond in a very specific way, to certain kinds of stimuli.

In a chronic disease state such as scar tissue or aged skin, the stem cells present in that tissue are responding in many small and measured ways to whatever is happening in the tissue. Stem cells like to maintain balanced conditions, also known as homeostasis. With chronic conditions there are no big changes, just a low-grade adaptation to aging or scar process. This is why the stem cells in the local tissue are not doing what you would like them to do. To get a stem cell to do what you want it to do, something else needs to happen. It needs to get activated.

Stem Cell Activation

How do adipose stem cells get activated? For a stem cell to shed its Clark Kent persona and become the activated Superman cell we need, there has to be a major signal. This major signal can be chemicals present in the tissues (cytokines) or coming from afar (hormones), or a mechanical force.

The cell then literally flies out of Clark Kent’s desk (niche) in its shiny new Superman uniform to do whatever is to be done, wherever it is needed. Fat harvesting, centrifugation and fat injections provide such a signal. The liposuction used to obtain tissue is a huge disruption signal, which in turn releases cytokines that augment the signal to activate. After fat is extracted with liposuction, the adipose tissue is then processed with centrifugation techniques. The centrifugation process is a mechanical stimulus that helps separate healthy cells from injured ones, but may also stimulate stem cells.

When you finish processing your fat graft you have a psyched up, ready to go, super-powered population of stem cells ready to go to town. As you inject them to the tissues, they literally do whatever is needed, wherever it is needed.

Fat harvesting, centrifugation, and fat injections provide an activation signal for stem cells.

- Dr. Rodriguez

The challenge for us practitioners and researchers is to understand how this process works. But make no mistake; stem cells are very effective in reversing chronic scarring processes and making skin look younger. My particular research interest is one of the small cytokine molecules that stem cells use to communicate with each other and stimulate growth.

Once stem cells have done their repair and rejuvenation job, they like to revert to their Clark Kent persona and settle into a new niche in the improved tissue environment. And that is a beautiful thing.

Ricardo L Rodriguez, MD
Board Certified Plastic Surgeon
©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)

As if you didn’t know it already–big, prominent, perky butts are in! The February issue of Juicy Magazine featured a story on Brazilian Butt Lifts. Our own Dr. Rodriguez was interviewed for the story and is quoted with a pink shout out next to Kim Kardashian!

Dr. Rodriguez specializes in the Brazilian Butt Lift, a type of butt augmentation that uses your own fat to enhance your buttocks.

Juicy Magazine article on Brazilian Butt Lifts

The article does a good job of explaining what the procedure is and why Dr. Ricardo Rodriguez loves performing the procedure. Dr. Rodriguez believes that using your own fat for buttock enhancement is far superior to using butt implants. Butt implants carry risks of complications and rupturing.

Additionally, the brazilian butt lift procedure involves a complete resculpting of the body with the goal of achieving a perfect waist, butt, hip ratio. Fat is first carefully extracted from several areas of the body, processed using special techniques, and then carefully reinjected into the buttocks.

if somebody is telling you they can perform this surgery in two or three hours they are taking shortcuts 

- Dr. Rodriguez

In the article, Dr. Rodriguez is clear to point out that the brazilian butt lift  is not a quick and easy procedure, and “if somebody (a surgeon) is telling you they can perform this surgery in two or three hours they are taking short cuts.”

Dr. Rodriguez injects the purified fat very slowly into the buttocks at various depths to ensure that the fat grafting will take. This is the only way to ensure that the fat cells remain viable and get adequate blood supply to produce a prominent buttocks that will give a long lasting result.  Our office gets many calls from patients who have had ‘quick procedures’ done with other surgeons, only to see their new enhanced buttock diminish in size after a year.

The Juicy article also rightly points out the dangers involved with silicon injections into the buttocks. Dr. Rodriguez is firmly against the use of silicon or hydrogel injections into the buttocks. Many distraught patients come to Dr. Rodriguez for help after having the misfortune of buying into these injections. Unfortunately they are marketed with the promise to plump up the buttocks for a cheap cost. Not! Please be sure to read Dr. Rodriguez’s cautionary advice from his 2007 blog post advice against buttock hydrogel injections.

If you would like to learn more about the brazilian butt lift, check out Dr.Rodriguez’s blog posts:

• What is the recovery period  for the Brazilian Butt Lift?
• Can a tummy tuck be combined with a brazilian butt lift?
• Recipe for permanent Fat Injections

To see Dr. Rodriguez’s actual patient results please view our collection of Brazilian Butt Lift Before and After Photos.

CosmeticSurg Admin
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)