November 08, 2004
Arm Transplant Preserves Ovary During Cervical Cancer Treatment

Scientists have moved an ovary to an arm so that it would not be damaged by pelvic radiation treatment used against cervical cancer.

A new study finds surgery to transplant an ovary to the upper arm is feasible and preserves hormonal function in women undergoing treatment for cervical cancer. The report details the technical procedure and outcome of only the second successful human ovarian autotransplantation in the world. The study will be published in the December 15, 2004 issue of CANCER, a peer-reviewed journal of the American Cancer Society. A free abstract of this study will be available via the CANCER News Room upon online publication.

While treatment for cervical cancer, including systemic chemotherapy and regional administration of ionizing radiation, improves survival and cure rates, it can also cause permanent ovarian failure. Since cervical cancer is diagnosed during reproductive years, ovarian failure can be a severe blow to a patient's quality of life. While protecting a patient's fertility has often been studied, there have been no effective options.

Hormonal regulators, such as gonadotropin-releasing hormone, have demonstrated ovarian protection in rats but conflicting data in nonhuman primates. Cryopreservation of embryos has been successful, but there have been no reported successful cryopreservation and transplantation of oocytes or primordial follicles, which are necessary for future fertility. Attempts at ovarian tissue autograft or xenograft without blood vessel anastamoses in animal models and human cases have been promising but hampered by large follicle loss due to ischemia. However, animal models with anastamoses have demonstrated success, but there has been only one prior successful human autotransplant.

In this second successful human trial, C. Hilders, M.D., Ph.D., and a gynecologic surgical team of the Leiden University Hospital, The Netherlands developed a new method of ovarian autotransplantation to preserve ovarian function in a woman treated for cervical cancer. This method does not require developing a donor site with an implant over several months and utilizes a donor site that is easily accessible to noninvasive monitoring and has suitable vasculature.

Autotransplantation of a healthy ovary into the upper arm using brachial vessels to establish blood supply resulted in a functional ovary. Blood flow to and from the ovary was adequate to maintain cyclical follicular growth as verified by ultrasound and clinical examination. Moreover, the surgery did not result in additional operating time.

The authors conclude, "it seems likely that ovarian autotransplantation will be a realistic goal to achieve for women facing cancer, treated by high dose pelvic radiation, to preserve reproductive and hormonal function, thereby substantially improving the quality of life post-treatment."

Note that this is a case of autotransplantation, meaning transplantation between locations in the same body. However, the approach taken here opens up the possibility of temporary transplantation of ovaries between people as well. One can imagine a woman with cervical cancer asking all her friends to volunteer for tissue type compatibility testing so that one of them can keep an ovary alive for her during some more severe form of cancer treatment where the use of chemotherapy would pose a hazard to the ovary even if the organ was placed on the woman's own arm.

But ovary transplants onto arms is still mighty inconvenient and obviously a temporary measure. Another future possibility is that cryopreservation techniques might be improved enough to make cryopreservation a viable option. Cryopreservation would be useful as a way to allow a woman to more reliably reproduce in her late 30s, 40s, and even later ages. Take just one ovary out of a woman when she is, say, 20 years old, cryopreseve it for 20 years, and then transplant it back into the woman to serve as a much younger ovary. This might not only raise the fertility of middle aged women but might also reduce the rate of birth defects for women who reproduce later in life since a cryopreserved ovary would presumably produce a younger egg that would be less likely to contain genetic mutational damage.

Since growth of replacement ovaries will most likely become feasible in two or three decades the long term cryopreservation of ovaries is likely at most to be a transitional technique. Better to just grow a new pair of ovaries for a woman in her late 30s and throw in some genetic engineering to remove a few harmful genetic variations that she doesn't want to pass on to her kids along with adding a few genetic variations that she does want to pass along (e.g. I predict natural blondness will be incredibly popular).

However, there is another potential use of organ cryopreservation: provide a supply of key organs in event of traumatic injury. Combine the ability to grow replacement organs with the ability to freeze them. Anyone with enough money and fear of death from injury could have organs grown from their own starter cells to ensure immunocompatibility Then in event of an injury an organ could be thawed and transplanted to supply a heart, liver, or other needed replacement part.

Even cryopreservation for emergency replacement organs is likely to be a transitional technology at most. If immuno-suppressive techniques improve enough then it will not be necessary to store emergency replacement organs for each individual. If each replacement organ can be made compatible with a large range of people then a much smaller stock of recently grown organs could be constantly replenished to provide replacements to the small subset of the population that needs them. In that scenario organs there would still be a place for organs that are grown for individuals since people will want to replace organs as they age as part of a regular maintenance regime of rejuvenation therapies.

My guess is that by the time tissue engineering techniques have advanced far enough to make routine growth of replacement organs possible immunosuppression techniques will allow a fairly small stocks of organs to serve as the sources of emergency replacement organs. If there is a cost in terms of general suppressed immune response for such an approach then the emergency organs will be used to keep a patient alive until a custom and fully immune compatible organ can be grown up to provide a more compatible replacement for the temporary and less compatible organ.

There is of course one other option worth mentioning: artificial organs. Artificial heart technology is maturing with a number of promising products under development. The CardioWest Temporary Total Artificial Heart won US FDA approval in October 2004.

The CardioWest Temporary Total Artificial Heart (TAH) on Monday became the only device of its kind to be approved by the U.S. Food and Drug Administration.

"This takes the CardioWest TAH off of the Medicare 'experimental list,'" said University of Arizona cardiothoracic surgeon Dr. Jack G. Copeland, who led the study of the device. "It's a huge relief to know that 19 years of work with the device has been officially recognized and that a technology that we believed in has now been released for use by others."

The CardioWest TAH is not being pitched as a permanent solution but rather a tool to use to strengthen a body so that eventual donor heart transplantation has better odds of success.

Then there are cyborg-like bioartificial organs that blend artificial parts with human cells. A bioartificial kidney has recently been tested successfully at the University of Michigan.

ANN ARBOR, Mich. -- The first test in humans of a bioartificial kidney offers hope of the device's potential to save the lives of people with acute renal failure, researchers at the University of Michigan Health System report.

While the phase I/II study was designed primarily to look at the safety of using this device on humans, the results also suggest improvement in kidney function. The patients enrolled in the trial faced an average 86 percent likelihood of dying at the hospital. Six of those 10 patients survived more than 30 days after treatment with the bioartificial kidney. The study appears in the October issue of the journal Kidney International.

"These results showed this type of human adult progenitor/stem cell is well-tolerated by patients with acute renal failure, and resulted in some improvement of the patients' clinical conditions. It's a small study but it was compelling enough for us and the FDA to go forward with a full phase II study," says lead study author H. David Humes, M.D., professor of Internal Medicine at the U-M Medical School. Humes developed the renal tubule assist device, or RAD, the cell cartridge that is key to the bioartificial kidney.

The RAD is being developed for future commercial applications under license to Nephros Therapeutics Inc.

...

The bioartificial kidney includes a cartridge that filters the blood as in traditional kidney dialysis. That cartridge is connected to a renal tubule assist device, which is made of hollow fibers lined with a type of kidney cell called renal proximal tubule cells. These cells are intended to reclaim vital electrolytes, salt, glucose and water, as well as control production of immune system molecules called cytokines, which the body needs to fight infection.

Conventional kidney dialysis machines remove these important components of blood plasma, along with toxic waste products, and cannot provide the cytokine regulation function of living cells. Traditional therapy for patients with acute or chronic renal failure involves dialysis or kidney transplant, both of which have limitations.

While this device operates outside of the body its developers hope to eventually miniaturize it to allow implantation in the body for long term use.

There is a general thread running through all these reports and speculations: organs are going to become as manipulable and replaceable as auto car parts. The sooner this happens the better.

Share |      Randall Parker, 2004 November 08 12:25 PM  Biotech Organ Replacement


Comments
Engineer-Poet said at November 9, 2004 8:22 AM:

The autograft scheme for preserving an ovary from radiation can also work for chemotherapy.  Some (many?) chemotherapy agents have very short active lifespans in the body.  With the ovary in a place where it is much more accessible and with a blood supply chosen for its surgical suitability, it should be a simple matter to chill it with an ice pack on the arm and then cut off the blood supply for the duration of the chemotherapy session.  Even brain tissue manages short periods of anoxia without damage when its oxygen demand is reduced by chilling; I cannot imagine that ovaries would be more fragile.

Patrick said at November 9, 2004 11:24 PM:

Alternatively you could arrange a separate blood supply (using donated blood, or the patients own previously stored blood) for that one arm.

Of course this only works for cancers you know haven't spread to the arm, but that would be the usual case.

Misty said at January 14, 2008 7:31 PM:

I am a Cancer survivor & would be glad to perticipate in ovary transplants when they come about. Being I was 12 when I had Ovarian cancer and had to have a complete hysterectomy, it's hard to cope with sometimes. Being I am in my thirties now and would love to have children...sign me up. :)
Misty__age 31

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