Many diseases and injuries damage normal tissues. In the male, there are 2 diseases I commonly treat that are associated with damage to normal tissues leading to considerable disability – urethral stricture disease (including Balanitis Xerotica Obliterans) and Peyronie\’s Disease.
A urethral stricture is an area of hardened, sclerotic and narrow urethral tissue. Urethral strictures can be induced by many factors, including trauma, (e.g. blunt force or penetrating trauma, urologic procedures or urethral catheterization), infection, hypospadias surgery (hypospadias is a birth defect characterized by diminished development of the urethra), Lichen Sclerosus (also called Balanitis Xerotica Obliterans) and the treatment of prostate cancer with surgery and/or radiation. Urethral strictures can occur anywhere along the urethra, and range in length from less than 1 inch to over 10 inches. Patients with urethral strictures experience difficulty with urination often associated with a decreased quality of life. Other complications of urethral stricture disease include a complete inability to urinate, prostate infections, bladder damage, and kidney failure.
There is no effective medical treatment for urethral stricture disease. Surgical treatment options include dilations and internal incisions. These approaches are minimally invasive techniques that increase the size of the urethra and relieve symptoms. Unfortunately, these options generally provide only a temporary improvement and are considered a way to manage rather than cure the disease. In many cases, patients are managed with self-catheterization at a frequency ranging from weekly to several times every day in order to maintain adequate urethral patency and avoid total urinary retention. Currently, open urethral reconstruction offers the most effective definitive treatment for urethral stricture disease.
However, this surgery is only associated with a very high success rate when preformed by a urologist who has completed a fellowship in male reconstructive urology and is specialized in urethroplasty. When the stricture is short, excision of the diseased segment and a primary rejoining of healthy tissue can be accomplished; this procedure is performed at our Center for Reconstructive Urology and and has an extremely low recurrence rate (less than 2%). However, in cases of distal or long strictures or hypospadias, the reconstructive management often requires the transfer of local skin as a skin flap, or the free transfer of distant tissues to supplement or replace the damaged urethra. In current clinical practice, penile skin flaps and both buccal mucosa (tissue from inside the cheek) and thigh skin tissue grafts are the most widely used materials for urethroplasty (i.e. repair of the strictured urethra). However, graft harvest can lead to significant pain at the donor site and other complications, and requires additional operative time.
This is a particularly cruel disease. Balanitis Xerotica Obliterans is a chronic inflammatory disorder that, in men, affects the penile skin and/or urethra. The cause of BXO is not known. It is not sexually transmitted, infectious, or contagious. Those who suffer from the disease often experience whitish discoloration of the penile skin and/or urethral stricture disease that can progress and destroy the urethra. The current standard of care includes topical steroids to treat the penile skin changes and urethral reconstruction using grafts to augment the diseased urethra. However, this does not cure the underlying disease. This disease can be particularly debilitating, and even when surgery to repair the urethra is a technical success, there is a high risk of late recurrence due to disease progression. It is our hope that through research, we will not only develop improved treatment methods, but also an understanding of what causes the Balanitis Xerotica Obliterans so that it can be prevented and/or cured.
Peyronie\’s Disease is an acquired disorder of penile curvature. For unclear reasons, an inflammatory and subsequent scarring process involving the substance of the penis (tunica albuginea) occurs, and this leads to shrinkage and curvature of the penis during erections. In severe cases, the curvature can be disabling, completely preventing sexual intercourse. The surgical treatment options include shortening the longer side to straighten the penis, but this can lead to significant foreshortening of the penis and can also cause an “hourglass” deformity with associated buckling. Alternatively, the scarred area can be incised-excised and augmented with a graft to lengthen the shortened side and correct the curvature. Current graft materials used include dermis (tissue between the skin and fat from the abdomen) and veins from the legs (saphenous veins). The harvest of these grafts can be associated with severe scarring and pain at the donor site, and these grafts are structurally inferior to normal native penile tissue (tunica albuginea). Moreover, these grafts do not function as well as normal penile tissue. In particular, grafts may not “hold” the blood within the confines of the tunica albuginea during erections, and this is called a “venous leak”, resulting in rapid loss of an erection or complete failure to have an erection.
When I use penile skin flaps or dermal, buccal mucosa, or skin grafts, it requires damage and injury to completely normal and healthy tissues. Although I do this on purpose because these tissues are needed to replace or supplement damaged urethral and/or penile tissues, I would rather be able to instead use off-the-shelf sterile materials structurally and functionally identical to the urethral and penile tissues that require repair. This is the promise of tissue engineering.
The goal of tissue engineering is to supplement and assist the normal regeneration process of damaged or diseased tissues as an alternative to the use of tissue grafts and flaps; generally this is accomplished with synthetic or naturally occurring materials with or without cellular constituents. In the field of urology, tissue engineering is emerging as a viable option for replacement of ureters, bladders and urethras, obviating the need for harvesting grafts, a process that injures normal donor sites to obtain tissues that are different from the tissues being replaced and therefore these tissues may be prone to deterioration over time.
With the generous support of several donors, a Urologic Tissue Engineering laboratory was established at the UC, Irvine Medical Center. Through the efforts of Ph.D.s, Research Fellows, and others, we successfully developed scaffolds that support cell growth in the laboratory. This research was awarded a “Best of Session” award when presented at the Annual Meeting of the Western Section of the American Urological Association. This research offers the promise of improved care for patients who suffer from urethral strictures and Peyronie\’s Disease if and only if we can further refine our laboratory generated tissue constructs and eventually pursue human trials.
Unfortunately, Government support for research is extremely limited at this time. Therefore, your donations are needed if the promise of our initial efforts is to become a reality. As a physician specialized in male urethral and penile reconstructive surgery, I would love to witness the advancement of Urologic tissue engineering. I know that my patients would benefit tremendously. Moreover, those who are not my patients may benefit even more as very few Urologists in the country have true expertise in this complex surgery, and advances in tissue engineering may enable those less specialized to achieve excellent surgical outcomes.
This is an area of research that does not benefit from society and foundation support, unlike many other diseases. In general, those who have supported our efforts are my patients as they have personally experienced the suffering these disorders cause and want to contribute. If you are reading this, perhaps you or someone you know has suffered from urethral stricture disease or Peyronie’s Disease and would be willing to support our research efforts to that others in the future will suffer less, or not at all. All donations are tax deductible. I personally receive no direct or indirect salary support from donations or a salary from UC, Irvine for my participation in this research. Therefore, all contributions will be used exclusively for laboratory and clinical research and education. A contribution of any amount will help and be greatly appreciated.
It is my dream to help establish an endowed chair in Urologic Research at UC, Irvine. An endowed chair is a funded and supported University faculty position. A $2,000.000 gift is required to establish and fully fund an endowed Chair in Urologic research. With this support, we can recruit and retain a talented researcher (Ph.D.) who can pursue tissue engineering full-time indefinitely, as the interest generated from this gift insures that the position will be supported in perpetuity. I am fortunate to be able to generate my income from my clinical activities. However, Ph.D.s who devote their lives to medical research depend on government and/or private funding for their support. When a chair is endowed, the formal academic title of the individual holding the position can be named after the benefactor or a person being honored or remembered by the benefactor. That designation continues indefinitely. I think this is a very thoughtful and special way to honor a loved one such as a mother, father, spouse, or sibling. If you are blessed with the resources to make a generous donation of this nature, please contact me as Dr. Ralph Clayman (Dean of the UC, Irvine School of Medicine) and I would welcome the opportunity to personally provide you a tour of our University and facilities, and would be most interested to answer any questions. Thank you for your consideration.
Joel Gelman, M.D.