Vol. 10 No. 1 An RRP Foundation Publication
2001 Summer
P.O Box 6643,
Lawrenceville, NJ 08648-0643
_____________________________________________________________________________________________________________________
Contents
Future Directions for the RRPF
In the last issue of the RRP Newsletter I discussed the continued growth of the RRPF network and organizational activities. I also indicated the need to entrain additional people to take over some of the responsibilities of running the RRPF. Unfortunately, there have not been any new volunteers who have come forward to help with running the organization. We did get an additional volunteer to assist with writing newsletter articles and editing, Jennifer Woo who is a young adult with RRP (you can read about her on page 11 of this newsletter). As I indicated previously, I plan to scale back my day-to-day level of involvement to spend more time with my family. As for how I see future directions for the RRP Foundation: 1) There is no doubt that the internet will play an ever increasing role in the RRPF, as it provides for very efficient, timely and global dissemination / collection of information. 2) I very much believe that RRP is a very treatable and potentially "curable" disease. I would like to see the RRPF being in a position to more directly support promising RRP research that furthers our understanding and leads to better treatments. I hope to remain involved in both expanding our web / Internet presence and RRP research efforts. However, in order for me to be able to do this, I am proposing some changes. First, the RRP Newsletter will continue to be published, but on an "as able to" basis and hardcopy mailings will be no more than once a year. This was not an easy decision for me, since the newsletter has been a major RRPF product and I know there are many people who still do not have Internet capability (But hopefully will in the near future.). I am also still looking to hand off much of the financial record keeping and correspondence before the end of FY2001 (i.e., Oct. 31 2001). These changes will hopefully allow me to focus more on the RRPF website, databases, scientific issues and RRP research, as well as allow for more time with my family. So, I am once again asking for volunteers to assist/replace me as the treasurer for the RRPF and proposing that we create a new corresponding secretary position. Please contact me (see page 2 for contact info.) if you have any interest in these positions or if you can help in other ways. Thank you.
Warm regards,
Bill Stern
P.S. Thanks to Lindsay and her friends Megan, Allison, Sadie and Katie, who helped stamp, address and stuff these newsletter mailing envelopes.
We are most grateful to all those
individuals, medical professionals and corporations who have
supported the RRPF. Although it is impossible to publish the
names of all that contribute, we extend our sincere thanks to
everyone who has supported our efforts. Future donations from
individuals, professionals or from the business community will be
very much appreciated. Tax-deductible contributions may be made
to:
RRP Foundation
P.O. Box 6643
Lawrenceville, NJ 08648-0643
Do you donate to the United Way through your employer? You can select a "Donor Choice" option, which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice. Since the RRP Foundation is a 501(c) 3 foundation, you may specify the RRP Foundation directly by writing in the name and address of the foundation as follows' RRP Foundation, P. O. Box 6643, Lawrenceville, NJ 08648. If you should need to add our 501(c) 3 number it is 521798693. Thank you for your support.
We want to acknowledge a generous donation by the Medtronic Xomed Corporation in honor of RRP patient Leia Peeden.
To physicians and nurses: Please distribute copies of this newsletter to your RRP patients. If you are not registered with the RRPF, please do so by completing the Practitioner Questionnaire enclosed.
RRPF Officers, Directors & Advisors
Marlene Stern
President
P.O. Box 6643
Lawrenceville, NJ 08648-0643
(609) 530-1443
marlenelin@aol.com
Bill Stern
Treasurer and Director
P.O. Box 6643
Lawrenceville, NJ 08648-0643
(609) 530-1443
bills@rrpf.org or rrpf@aol.com
Henry Woo, Esq.
Secretary
Medtronic International Inc.
Suite 2002, C.C. Wu Building
308 Hennessey Rd.
Wanchai
Hong Kong
henry.woo@medtronic.com
Chris Neuberger
Director
13001 Burlingame Ave.
Oklahoma City, OK 73120
(405) 749-8499
cneuberger@eti1.com
Susan Woo
Director
101 Repulse Bay Road
Apt. A3/1st floor
Hong Kong
852-2812-7379
Writeushere@aol.com
[Please see the enclosure for a complete list of the RRPF regional and state coordinators]
Scientific Advisory Committee
Thomas R. Broker, PhD, University of Alabama at Birmingham Schools of Medicine & Dentistry
Haskins K. Kashima, MD, Johns Hopkins University School of Medicine
Linda Miller, RN, MSN, Children’s Hospital of Philadelphia
Robert J. Ruben, MD, Albert Einstein College of Medicine
Keerti V. Shah, MD, DrPH, Johns Hopkins University School of Hygiene and Public Health
Bettie M. Steinberg, PhD, Long Island Jewish Medical Center
Kathleen Sullivan, RN, Children’s Hospital of Boston
Voice Specialist/Advisor
Julie Bowne, M.S., CCC-SLP
RRP Newsletter Editors
Other RRP Newsletter Contributors
Toni Barringer
Dale Barringer
Marlene Stern
Bill Stern
RRP Reference Service Editor
David Wunrow
RRPF Fundraising Coordinator
Ed Weiner
(703) 691-1922
maura.weiner@serviceimpact.net
The RRPF produces two publications, the RRP Newsletter and the RRP medical reference service. The RRP Newsletter focuses mainly on the human and clinical aspects of recurrent respiratory papillomatosis and in this regard targets a broad readership, including patients/families, attending physicians/nurses, as well as researchers and the general public seeking to stay in touch with RRP from a clinical perspective. The RRP medical reference service serves those in the community seeking a more comprehensive understanding of this disease. Please help us by supporting these publications and other RRP services including patient outreach, support and advocacy.
Subscription Policy and Minimum Annual Donations
RRP Newsletter
Professional/Corporate - $25
Individual - $15
RRP Newsletter plus Medical Reference Service
Professional/Corporate - $40
Individual - $25
[Note: Back issues of the RRP Newsletter and Medical Reference Service are available on the website, see RRP Web News.]
by Toni and Dale Barringer; Marlene and Bill Stern
These very brief patient profiles are intended to let you know that some of those with RRP are doing quite well.
John who is nine years old and from Missouri, was diagnosed with RRP before the age of one. He had 17 surgeries until the age of seven when he went into remission. John’s parents attribute his remission to interferon, which he had been on for four years, and prayer.
Mitchell, from Pennsylvania, was diagnosed with RRP at the age of 11 months. After 10 surgeries in about one year, he appears to have gone into remission. His mom credits the remission to intralesional cidofovir injections during his last 5 surgeries. Mitchell is now 27 months of age.
Others still in remission (who we were able to contact) include: Ten year old Ariel and five year old Jonathon from California; 27 year old Julie and 28 year old Steph from Florida; Mike from Georgia at age 49; William age 77, from Illinois; Thirteen year old Anthony from Kentucky; Cara from Michigan at age 19; Leah from New Hampshire, age 21; 11 year old Lindsay from New Jersey; Joe from Ohio at age 34; Ralph from Pennsylvania at age 74; Nancy, age 35, from Texas; and from Virginia, Alison age 10 and Smokey , age 30. Of this group in remission about 2/3 have attributed their remission to some forms of adjunct therapy, the most common being I3C and/or DIM. Other therapies included interferon, cidofovir, acyclovir and mumps vaccine. [Please let us know if you are in remission, we will happily add your name to our growing list.]
Our international support network has grown to about 570 respiratory papilloma families. Patients range in age from about 1 to 86 years. Domestically, patients are located in 47 states plus the District of Columbia. Outside the U.S. there are currently 28 patients from 13 countries.
Our thanks to all who have taken the time to fill out the RRPF Patient/Therapy Survey. Please make sure to alert us of changed addresses by checking the box located near the top of the front side. There is also a box below the name and address section, which we ask you to check if you do not want your name and address information to be included in the RRPF Patient Directory. We are requesting the information contained in this survey be made available for RRP research. In this regard there is a place in the survey to grant permission.
As our support network has grown, we have become more dependent on the patient questionnaires to maintain our mailing list and keep our database of RRP patient information up to date. So if you haven't completed a questionnaire in the past, please take a few minutes to fill out the form enclosed. If you have previously filled out a questionnaire, you need only identify yourself, mark UPDATE along the top front of the form and answer only those questions where you have new or updated information to provide. Please return the surveys to Marlene and Bill Stern. Alternatively, you may submit questionnaires via our website (www.rrpf.org) by filling out the online "patient survey". In addition, RRP families, please review the Patient Directory listings and notify us regarding any corrections, omissions or additions. If you are not included in the directory and would like to be (or vice versa), please notify Bill or Marlene Stern.
..................................................................................…………..
By Chris J. Neuberger and Bill Stern
The use of the Internet is serving more and more as a valuable mechanism of information exchange for the RRPF. Our website (www.rrpf.org ) contains a wealth of information relevant to patients, families, doctors, nurses and researchers. It now includes an online database of RRP practitioners. The website has an Interactive Discussion Forum which allows for the posting of questions, comments and replies to previous postings relevant to RRP. Occasionally, we have invited "expert" moderators who monitor the board and respond to the postings. In addition, we now have the RRP Patient/Therapy Survey on line, which allows RRP patients to update and submit their survey to the foundation. This is a very important aspect of the foundation in that this information is used in analyzing RRP treatment therapies, experiences, etc. We ask that patients update their survey once a year. Also, we maintain back issues of RRP Newsletters and the RRP Reference Service.
The RRP Foundation now sponsors an
RRP community Listserve that currently has 184 subscribers
with over 1200 postings. The RRP Listserve, maintained by Petra
Holmstrom, is a secure web based environment for communicating
information relevant to RRP. If you haven’t joined yet, please
feel free to do so by sending a blank email to:
rrpf-subscribe@egroups.com.
We also maintain links with many other sites relating to
RRP.
If you have some experience/expertise with the WWW and would like to help us improve our website, please contact Bill Stern.
By Bill Stern
[The following article was written to be part of a future (~2002) voice disorders website coordinated by Dr. Clark Rosen. The article describes current facts and treatment strategies regarding RRP, It also raises some additional questions in understanding and treating RRP. ]
Teaching points regarding Recurrent Respiratory Papillomatosis
1. Recurrent respiratory papillomas (RRP) are (mostly) benign viral growths in the respiratory tract.
2. The human papilloma virus causes RRP.
3. It affects both children and adults, but tends to be more aggressive in children.
4. The growths are most often recurrent and are controlled via repeated surgeries. Adjunct treatments may help to slow or stop the cycle of growths.
5. There is a great variability in disease severity among RRP patients, for some the disease will go into an extended or even permanent remission while in some others it may progress deep in the respiratory tract.
What is Recurrent Respiratory Papillomatosis?
Recurrent respiratory papillomatosis (RRP) is a rare disease (there are perhaps 20000 active cases in the U.S.) that is characterized by the growth of tumors in the respiratory tract caused by the human papilloma virus (HPV). Although they primarily occur in the larynx on and around the vocal cords, these growths may spread downward and affect the trachea, bronchi and occasionally the lungs. It is sometimes referred to as laryngeal papillomatosis and in the past was often called juvenile laryngeal papillomatosis, because it was thought to primarily affect only children. A distinguishing aspect of this disease is the tendency for the papilloma to recur after surgical procedures to remove them. Hence, the "recurrent" part of the name.
The tumors or growths can be wart-like, often have a cauliflower-like appearance, and are either pedunculated (attached only by a slim stalk), or sessile (closely adhering to mucosa).
Who gets RRP?
RRP occurs in both children and adults. In children, JORRP (juvenile onset RRP) is almost always diagnosed by age ten and usually before the age of five, showing no sexual preference. Statistics indicate that first-born children delivered vaginally to young mothers (under the age of 20) with active condyloma during pregnancy, are at greatest risk. However, even among this group the disease is still rare. The distribution of diagnosis ages is much broader for adult onset RRP (AORRP) than for children, as RRP may present at any age with some preference for occurrence seen in adult males in their 30s.
Although there is now an RRP registry documenting juvenile RRP cases at 23 medical centers in the U.S. (managed by the Centers for Disease Control), there is still a lack of a comprehensive epidemiological database of RRP patient information. Hence, it is difficult to determine incidence and prevalence statistics with a high degree of confidence. The best estimate of RRP incidence and prevalence in the U.S. is based on a study conducted in 1995 by the RRP Task Force. Their projected totals for recurrent respiratory papillomas among children were 2354 new cases per year, with a 95% confidence interval (CI) ranging from 1448 to 3260, and 5970 active cases, with a 95% CI ranging from 3465 to 8474. The projections for AORRP, were 3623 new cases per year (95% CI, 2359 to 4887) and 9015 active cases (95% CI, 6435 to 11,591). These estimates indicate an incidence among children of about 4.3 per 100,000 and among adults of about 1.8 per 100,000.
What are the risk factors for RRP?
There is considerable evidence that RRP in children results from a vertical transmission of HPV from mother to child. Virology studies have substantiated the link between genital condylomas and JORRP. HPV types 6 and 11, which are responsible for 80-90% of the condylomas, are responsible for nearly 100% of JORRP. In a study using data collected by the RRP Foundation, it was found that the number of JORRP patients born via cesarean section was less than 25% of the statistically expected number based on national normals, suggesting that a cesarean birth might play a preventative role for RRP. Furthermore, as previously noted, it was found that mothers under the age of 20, who have condyloma during pregnancy and who deliver their first born child vaginally, appear to be at greatest risk of infecting their newborn.
In adults RRP is also caused by infection with HPV-6 and HPV-11. However, there does not appear to be a statistically significant relationship with birth factors as is seen in JORRP cases. This probably indicates that for AORRP the infection is not likely acquired at birth and there is some speculation that for many adults it may be sexually transmitted.
Why does RRP occur?
Beyond the previously noted risk factors regarding the transmission of HPV, it is still not very well understood why only certain individuals, present with RRP. It is estimated that approximately 5% of the U.S. population may have HPV in their respiratory tract, but less than 1 in 1000 of those infected ever develop RRP. This seems to invite the speculation that some subtle immunologic deficiency affects the respiratory tracts of those few who develop RRP. In this regard, there are some interesting research studies indicating that in RRP patients some amount of killer T cells may be missing a key surface protein that normally would allow them to recognize HPV cells.
What are the symptoms of RRP?
The most common symptom of RRP is a voice that is persistently hoarse, weak, low in pitch, breathy, or strained. Often dysphonia (i.e., difficulty in speaking) or aphonia (i.e., loss of voice) can occur as well. Tumor mass and location (i.e., how the growths interfere with normal vocal cord function) may explain the degree of voice quality defects. For lesions that form near the vocal folds, hoarseness can occur very quickly with small lesions. As the disease progresses, shortness of breath can occur as the airway becomes blocked by bulky lesions. Although this is more common in children, in some situations RRP can cause breathing difficulties in adults, especially during exercise. Young children often present with a weak cry, chronic cough, swallowing difficulties and stridor . Inspiratory stridor is noted by noisy breathing such as a high-pitched whistle or snore as a child strains during inhalation, usually as they sleep. This is indicative of an upper respiratory obstruction and warrants immediate attention by an otolaryngologist.
RRP related symptoms may develop gradually over months or even years in mild cases, but in very aggressive situations symptoms may emerge in a matter of days.
How is RRP diagnosed?
RRP is typically diagnosed by an ear, nose and throat physician (ENT) performing an examination of the larynx. Some physicians may start with a mirror examination, which is done using a mirror placed in the back of the throat reflecting light down the throat and onto the vocal folds. More typically a doctor or a trained speech-language pathologist diagnoses RRP via an indirect laryngoscopy in the ENT office. This involves the placement of a flexible fiberoptic camera through the nose to further visualize the vocal folds in the throat or the use of a straight, rigid camera placed through the mouth that shines down the throat onto the vocal folds. In addition to allowing the ENT to view the larynx, a video record can also be obtained with these instruments. Some otolaryngologists or speech pathologists may use a videostroboscopy to obtain an even more detailed look. However, to make an absolutely definitive diagnosis of RRP a direct laryngoscopy (usually in conjunction with surgical removal of papilloma growths) must be performed in an operating room with the patient under general anesthesia at which time a biopsy is taken and tested for HPV. In some cases the direct laryngoscopy is the only option, usually this involves young children in distress, where instrumenting the airway outside of the operating room might be hazardous. It is most desirable, however, to have a diagnosis of RRP before a surgical procedure so as to facilitate family awareness/expectations and so the anesthesiologist, surgeon and OR nurses will be properly prepared.
Pediatricians who are unfamiliar with this disease often misdiagnose RRP. Many times shortness of breath and stridor are mistakenly assumed to be the result of asthma or croup. The consequences of these errors may be serious as papillomas are at least partially obstructing the airway to cause these symptoms and should be removed immediately.
How is RRP treated?
1. Surgical Management
Currently, there is no known cure for RRP, with surgical excision under general anesthesia being the accepted method of controlling these viral growths. Although surgery is necessary to prevent airway blockage and may improve voice quality, it does not stop the growths from returning (and it has even been speculated that surgery might in some instances exacerbate re-growth, by activating latent virus in adjacent normal tissue). Since the primary means of treating RRP is a surgical management approach, the process of selecting a surgeon is quite important. In this regard, surgeon selection criteria are proposed as follows: 1) First and foremost it is crucial that the surgeon is familiar with RRP. 2) Young children should be treated by a surgeon who has experience dealing with small airways, i.e., a pediatric ENT. Either a laryngologist or a general ENT with RRP experience should be able to treat older children and adults. In those situations where voice issues are paramount, perhaps a laryngologist is preferable because of their specialization in voice. 3) It is important that a surgeon maintain a good rapport with the patient and family. There must be two-way communications. 4) Finally, geographic proximity to one’s surgeon is desirable. The stress, disruption and financial hardship to a family can be considerable when frequent extended trips to a surgeon are required. However , this criteria should not be allowed to override the necessity of using a surgeon with RRP expertise.
There are a number of surgical techniques in use by RRP surgeons. The most widely used is the CO2 laser, it has the advantage of being able to rapidly debulk a large amount of tumor growth. It is important that a surgeon be aware of the possibility of injury to deeper tissue layers with injudicious laser usage, which may result in unacceptable scarring and subsequent abnormal vocal fold function. Inappropriate and aggressive use of the laser may also cause injury to nonaffected tissues thus, creating an environment suitable for implantation of viral particles. Other laser devices that have had much more limited use for RRP are the KTP/ND and Yag laser.
Some surgeons prefer the cold steel surgical approach for removal of laryngeal papillomas. It involves the use of small microsurgical instruments and a high-powered microscope. Cold steel surgical removal also requires specialized skills and techniques.
Proponents argue that this approach works well for removal of laryngeal papilloma because it allows for removing the infected tissue from the epithelial layer without damage to deeper tissue.
Recently, there has been increased use of a micro-debrider developed by Medtronics Xomed for removal of papilloma. It seems to be able to debulk as fast as the laser but without the danger of heat trauma to deeper tissue. Other new technologies that are just coming available, with limited long-term follow-ups, include flash pump dye and 585-mm pulse dye lasers, argon plasma coagulation, and phonomicrosurgical resection techniques.
As important as a skilled RRP surgeon, is an anesthesiologist who is familiar with the various techniques available to manage difficult airways. These include endotracheal intubation, spontaneous ventilation and jet ventilation.
Irregardless of surgical approach, it is most important that the surgeon be quite skilled in using the surgical tools of choice. Furthermore, there is a danger in being too aggressive in removing papilloma from the larynx around the vocal cords, as indicated by the following excerpt from the RRP Task Force Guidelines: "Since there is currently no therapeutic regimen that reliably eradicates the HPV, when there is a question about whether papilloma in an area needs to be removed, it is prudent to accept some residual papilloma rather than risk damage to normal tissue and producing excessive scarring. Even with the removal of all clinically evident papilloma, latent virus may remain in adjacent tissue, which may explain the recurrent nature of RRP. Therefore, the aim of therapy in extensive disease should be to reduce the tumor burden, decrease the spread of disease, create a safe and patent airway, improve voice quality, and increase the time interval between surgical procedures. Staged papilloma removal for disease in the anterior commissure is appropriate to prevent the apposition of two raw mucosal surfaces."
Some comments on the role of tracheotomies in the treatment of RRP. A tracheotomy is a surgical procedure where an incision is made in the front of the patient's neck and a breathing tube is inserted through a hole, called a stoma, into the trachea. Rather than breathing through the nose and mouth, the patient will now breathe through the trach tube. Because a tracheotomy often results in papilloma seeding downward into the trachea and around the stoma, it is contra-indicated for RRP except in the most extreme cases where tumor growth is so aggressive that a patient’s airway cannot be maintained. It is in the patient’s best interest that the trach be removed as soon as it is feasible.
2. Adjunct Therapies
The goal of these adjunct therapies is to reduce or eliminate the need for future surgeries. There are a variety of adjunct therapies for RRP. Typically most of these therapies can be described via one (or occasionally two) of four mechanisms of action: anti-viral, hormonal, immunological or chemotherapeutic. Currently there is no single treatment that has been found to be generally effective in controlling RRP. The following represent therapies that have proven to be effective in treating RRP. See Table 1 for a summary of patient/parent-assessed responses to a variety of adjunct treatments for RRP.
Indole-3-carbinol/Diindolylmethane (I3C/DIM) has shown significant efficacy based on preliminary results of an uncontrolled study and responses to the RRP Foundation adjunct therapy surveys, with about 55% to 60% of patients showing at least some reduction of disease activity. I3C is a phytochemical that is found in cruciferous vegetables (i.e., cabbage, broccoli, cauliflower, etc.) and DIM is the major active by-product of I3C when it is broken down by stomach acid. The primary mechanism of action for these compounds is hormonal, specifically they tend to induce an estrogen metabolite balance that discourages papillomavirus growth. With regard to RRP, this mechanism may be particularly effective in hormonally sensitive laryngeal tissues, such as the vocal cords (for both men and women). While the hormonal mechanism does appear to be the primary factor by which I3C/DIM helps to prevent RRP, these compounds also have additional beneficial properties that should help them oppose malignant conversion. The advantages of this therapy are that it is virtually without side effects or toxicity and it involves a simple protocol for patients (i.e., a daily dosage once a day taken orally).
Interferon has been used to treat selected cases of RRP for about two decades and has demonstrated some effectiveness in ameliorating RRP by slowing down the recurrence rate. In most cases some form of interferon a have been used, both natural and recombinant. (There is some reason to believe that a natural interferon product would have less of a tendency to induce neutralizing antibodies - and neutralizing antibodies may adversely affect effectiveness.) The exact mechanism by which interferon (IFN) exerts its effect is not well understood. It is believed that there is modulation of the host immune response with production of a protein kinase and endonuclease, which results in both the inhibition of viral protein synthesis and breakdown of viral RNA. Several other cellular genes are also modulated by IFN with varying effects, and these regulatory mechanisms still need to be understood. The most common side effects are flu-like symptoms, especially low-grade fevers, mild lethargy, fatigue and headache. Occasionally patients may experience an elevated liver function, which would require at least a temporary discontinuation of the therapy.
Cidofovir is a fairly new drug exhibiting a broad-spectrum of anti-viral activity. It is absorbed by papilloma cells, which then converts into an agent that kills cells that have HPV. Cells that do not have HPV should not absorb it. The first pilot study to treat RRP with Cidofovir was done in Belgium involving severe adult RRP patients. The results were very encouraging. Another pilot study that used Cidofovir to treat ten pediatric patients with severe RRP, resulted in a dramatic reduction in disease severity for most of the patients. Furthermore, Cidofovir is now being used by many doctors on a case-by-case basis to treat RRP. For RRP Cidofovir is usually injected directly into the lesions (or location of the lesions after removal), which should avoid most of the toxicity (kidney damage) associated with this drug. The only side effect that has commonly been associated with this intralesional administration of Cidofovir has been some irritation to the laryngeal tissue. However, this drug is still relatively new so follow-up of patients over extended periods of time will be necessary to determine if any longer term side effects associated with Cidofovir emerge.
Photodyanmic Therapy (PDT) has been in experimental trials for more than a decade. An RRP patient is given a photosensitizing dye. When the dye is exposed to a particular wavelength of light, a single oxygen reaction occurs resulting in killing of cells. The dye is preferentially taken up by tumors, including papillomas. Results using a dye called Photofrin were not particularly encouraging and with a long "washout" period for the dye, patients remained extremely photosensitive for up to two months. Recently a new agent called mTHPC has shown more encouraging early results, especially for laryngeal papillomas and the period of photosensitivity has been greatly reduced to only 2-3 weeks.
Another adjunct therapy, the mumps vaccine, appears to be responsible for improvement in a number of RRP patients. It is administered via intralesional injections and the reason for why it should be effective against HPV is not understood at this time. To date the mumps vaccine has only had limited use in an uncontrolled setting.
Other therapies that have been used to treat RRP patients include: Acyclovir, Accutane, Ribavirin and Cimetidine.
3. Other Considerations
The otolaryngologist should make a substantial time commitment to have a frank and open discussion with newly diagnosed patients and families regarding the nature of their disease and the proposed management/treatment approach. Surgical details should be discussed including the risk of problems such as possible scarring, airway edema and airway fire with the use of the laser.
In some cases speech therapy may be helpful. Vocal function exercises (i.e., gentle stretching) may reduce stiffness. Establishing a balanced use of respiration, phonation (e.g., loudness and pitch), and resonation may be appropriate.
The patient should be informed about avoiding certain medications or products and treated for situations that are known to exacerbate RRP such as gastro-intestinal reflux disease (GERD). Prolonged use of medications containing steroids should be avoided as they tend to compromise immune function, which may allow for more aggressive growth of the papilloma. Other products such as tobacco smoke, drying agents, or other mucosal irritants may exacerbate the disease.
Finally, the patient and family should be made aware of support organizations such as the RRP Foundation (www.rrpf.org).
What if I do not have treatment for RRP?
Ignoring RRP symptoms and refusing treatment could result in airway blockage and eventual suffocation. Breathing difficulties should not be ignored!
What is the expected disease course for an RRP patient?
The disease course may vary greatly from one RRP patient to the next. Since the factors controlling this variability are not well understood, there is very little predictability of how many surgeries a particular patient may need and whether they will experience distal spread of papillomas beyond the larynx. However, some broader statistical assessments of RRP disease course can be made based on epidemiological data obtained from clinical research studies and the RRP Foundation database. JORRP is typically more aggressive than AORRP and this greater severity appears to be more than just an issue of the size of the airway. Another factor that may influence RRP aggressiveness is the specific HPV type. From a few limited case studies and data available in the RRP Foundation database, there is a suggestion that HPV 11 is involved in more severe RRP cases than HPV 6. In Table 2 it is seen that 18 of 305 patients (~5%) report some papilloma in the lungs, of those 18, five know their specific type to be HPV 11, the other 13 do not know their specific type.
An ability to make an estimate of "lifetime" surgeries that an RRP patient might anticipate, could be a useful part of the disease prognosis process. As previously noted the great variability in disease presentation makes this nearly impossible to do for any individual RRP patient. An attempt to estimate a "lifetime" of surgeries that a group of RRP patients might expect to experience has been made based on data from the RRP Foundation patient database. Estimates of 95% confidence ranges for JORRP at 60 to 100 and for AORRP patients at 13 to 35. It is felt that these estimates may be high for application to newly diagnosed patients today, since they are based on information from patients who have been dealing with RRP for one to two decades or more. The impact of new adjunct treatment options that have emerged recently plus those anticipated in the near future should help to significantly reduce future "lifetime" surgery numbers.
Challenges and Frontier Techniques for RRP
Some of the remaining challenges in understanding and treating RRP may be summarized as follows:
1) Why is there such a tremendous variability in how RRP affects one patient versus another? Some patients (mostly JORRP) suffer from aggressive papillomatous growth, resulting in extreme voice disorder and frequent surgeries over many years, while some others experience spontaneous remissions after only a few surgeries. What makes them different?
2) Why do some patients respond to some therapies and yet others, often those aggressive cases with distal respiratory involvement are unresponsive? Perhaps one of the greatest RRP therapeutic frustrations is the lack of any effective way of treating patients with pulmonary papillomas. It represents a significant challenge to the RRP clinical research community.
3) Why is it that RRP disease expression is so low despite much higher estimates of HPV transmission. There are estimates that approximately 5% of the U.S. population may have HPV positive normal laryngeal tissues, but the prevalence of RRP is estimated to be less than .005%. Why is expression so limited despite a much higher incidence of HPV in the general population? - is it an immunological issue?
4) Can JORRP be prevented? Children born to HPV positive mothers are at risk of developing JORRP. Although the risk is small, it appears to increase significantly when condylomas are present during pregnancy and if the child is first born, delivered vaginally and the maternal age is under 20. A prospective study coupled with a cost-benefit analysis is needed so that the gynecological community will be able to provide better treatment options for expectant mothers presenting with HPV.
It is hoped that in the near future some new immunotherapeutic treatment options for RRP will become available. Despite slow progress and some disappointments, there have been some encouraging early results involving vaccines for HPV. In clinical trials at least one HPV vaccine has shown encouraging effectiveness in treating patients with HPV related anal dysplasia and HPV6/11 genital warts. A clinical trial involving RRP patients is anticipated in the not too distant future.
I would like to thank RRPF voice specialist Julie L. Bowne M.S. CCC-SLP for her insights regarding voice therapy and RRP. I also am most grateful to Marlene Stern for her assistance in proofreading this manuscript.
For a complete list of references and
resources see the web version of this article located at:
www.rrpf.org/rrpf/publications/RRP.htm
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N=575 |
4.1 N=525 |
4.7 N=519 |
19.7 N=575 |
|||
The foregoing table summarizes information obtained by the Centers for Disease Control and Prevention (CDC) for their RRP National Registry. Site coordinators at 22 medical centers have submitted data on children with active RRP aged 17 years and younger. As of March 19, 2001 there were 575 children in the registry.
Adjunct Therapy and Protocol Update
The following reports of statistics and clinical research involving RRP therapies, represents a best effort to make an accurate and objective presentation of information from surveys, articles submitted by investigators, personal communications and reference to literature. Where appropriate, the RRPF has provided its input in a constructive manner, which we hope will best serve the RRP community.
by Bill Stern
Table 1. Patient/family assessed impact of adjuvant therapies reported.
|
Therapy |
Users |
None |
Improve |
Comp |
Partial |
|
I3C/DIM |
125 |
57 |
68 |
23 |
45 |
|
IFN |
60 |
26 |
34 |
4 |
30 |
|
Acyc |
31 |
20 |
11 |
4 |
7 |
|
PDT* |
19 |
13 |
6 |
1 |
5 |
|
Retin |
16 |
10 |
6 |
0 |
6 |
|
Mumps |
15 |
6 |
9 |
3 |
6 |
|
Cidofovir |
15 |
1 |
14 |
3 |
11 |
Some notes regarding the above table:
The therapies are abbreviated as follows, I3C/DIM = indole-3-carbinol (I3C) or Diindolylmethane (DIM), IFN = interferon, Acyc = acyclovir, PDT = photo dynamic therapy (*thus far 3 patients have reported who have used the new agent) , Cidof=cidofovir, Retin = retinoic acid or accutane, Mumps = mumps vaccine.
Experimental therapies for which the RRPF has no documented patient supplied statistics:
Cimetidine (Tagamet)
HPV Vaccines
Omega-3 Fatty Acids (Fish Oil)
Some notes regarding the above table:
The therapies are abbreviated as follows, I3C/DIM = indole-3-carbinol (I3C) or Diindolylmethane (DIM), IFN = interferon, Acyc = acyclovir, PDT = photo dynamic therapy (*thus far only 1 patient has reported who has used the new agent mTHPC and they have indicated a complete response) , Ribvrn = ribavirin, Retin = retinoicacid or accutane, Mumps = mumps vaccine. In the category of other therapies used, improvement has been noted using the following treatments: Echinacea and Thuja (homeopathic anti-virals), a mixture of vitamins including vitamin C and vitamin A, ShapeRite immune formula, topical 5-flourouracil (5FU), bleomycin and cobalt. (Please see the I3C Update in this issue and previous newsletter issues, regarding side effects for some of these treatments.)
Finally, we continue to remind our readers that these results are based on patient perspectives. Although the survey encourages objectivity and quantitative assessment as much as possible, these analyses cannot replace well-designed clinical trials and research. Furthermore, since sample sizes are generally small and no statistical significance tests have been applied to data in the above table, one must interpret these numbers cautiously, especially when considering the natural variability of RRP. However, we do hope that this information can provide some guidance for those patients seeking adjunct therapies as well as those pursuing RRP related research.
For background information about the impact of indole-3-carbinol (I3C) on estrogen metabolism and how this subsequently may act to reduce the growth rate of respiratory papillomas, see the RRP Newsletters Fall 93 through Fall 94 and Fall 97, Winter 2000-01 for DIM, as well as Bradlow et al., 1996 J. of Endocrinology 150, S259-S265; Newfield et al., 1993, Anticancer Research 13, 337-342.
To patients enrolled in Dr. Rosen's I3C study:
Over the next two months, Paul Bryson, a medical student working with Dr. Rosen, will be calling patients in regard to:
1) Their current I3C use
2) Their surgeries post-I3C
3) The interval between surgeries post I3C
4) Reasons for discontinuing I3C
5) Other treatments since discontinuing I3C
If patients know this information, they may call the Voice center in Pittsburgh at 412-647-8094 and leave a message or speak to Jaime Osborne.
Additionally, Patients or their physicians may send or fax their follow-up sheets to:
Dr. Clark Rosen
Suite 500
Eye and Ear Institute
200 Lothrop St.
Pittsburgh, PA 15213
fax: 412-647-6274, 412-647-2080
Phytosorb-DIMTM products containing DIM are available from:
BioResponse
L.L.C. at P.O. Box 288
Boulder, CO 80306
Email at etzeligs@bio-response.com
303-447-3841 - Telephone; 303-938-8003 - Fax
Credit card orders (Visa and MasterCard) are being accepted
Phytosorb-DIM is available in two forms:
1. Phytosorb-DIM Capsules; 150 mg; 60 capsules per bottle or 75 mg; 90 capsules per bottle.
2. Phytosorb-DIM Flavored* Sprinkles; 9.0 grams per bottle with directions indicating dosage per teaspoon.
At the suggested dosing below, 1 bottle should provide a two-to-four month supply for a child about 50 lbs.
* Now available in orange as well as chocolate flavors.
Shipping : US priority mail ($3.20 up to 2 lbs.) , or global priority : small envelope ($5.00 up to 4 lbs; large envelope flat rate $9.00 up to 4lbs.)
Estimated dosages; BioResponse now recommends that individuals with RRP choose a daily dose which is close to 5-8 mg/kg/day. A typical man weighing 70-85 kg (where kg. = 2.2 lbs.) would take approximately 350 to 600 mg per day. A typical woman weighing 60-70 kg would take from 300 to 500 mg per day.
BioResponse has reformulated its "Sprinkles". These new formulations require lesser amounts of the powder to deliver the increased suggested dose. Detailed dosing instructions are included on the bottle label. Guidelines for children are as follows:
Weight in Pounds (lbs)
Amount of Sprinkles in Teaspoons (tsp.) up to 25 lbs. 1/8 tsp 25 to 50 lbs 1/4 tsp, 50 to 75 lbs 3/8 tsp, 75 to 100 lbs 1/2 tsp 100 to 150 lbs 3/4 tsp
(Please consult your doctor, especially for young children.)
Call or e-mail for pricing
Special Note: Unlike I3C, Phytosorb-DIM does not require activation by stomach acid. Individuals who use antacids or H2 blockers like Zantac can take Phytosorb-DIM.
For scientific inquiries contact Michael Zeligs, MD at zeligsmd@bio-response.com
I3C may be purchased from:
Theranaturals Inc.
PO. Box 344
Orem UT 84059-0344
e-mail: theranat@itsnet.com
(801)224-8893 - Telephone; (801) 226-6064 - Fax
www.theranaturals.com
[Credit card orders may be placed by phone, fax, web or e-mail]
Theranaturals I3C product pricing as of 9-1-99 (includes shipping via USPS priority mail):
1 bottle - 100 capsules @ 100 mg -$20
3 bottles - 100 capsules @ 100 mg - $55
add $16.00 to above prices for Fed X shipping.
Medical Center Compounding Pharmacy
3675 S. Rainbow Blvd, #103
Las Vegas NV 89103
e-mail: mccp@mccpharmacy.com
Tel: 1-800-723-7455
Local: 702-873-8455
Fax: 702-873-6845
www.mccpharmacy.com
[Credit card orders may be placed by phone, fax, or web ]
For more detailed information ask to speak with Richard Fura.
Medical Center Compounding Pharmacy I3C product pricing as of 9-1-99 :
1 bottle - 100 capsules @ 400 mg - $59.50 + shipping
1 bottle - 100 capsules @ 200 mg - estimated ~ $33.95 + shipping
SHIPPING: UPS 3rd Day Service ($5.00) or Airborne Overnight ($8.00)
Approximate dosing information is based on preliminary results of Dr. Leon Bradlow's estrogen metabolism studies, as follows:
Estimated dosages - Adults approx. 400 mg, Children (under 50 lbs.) 100 - 200 mg
The digestive process is important to properly break down I3C (see RRP Newsletter - Spring 94 ). In this regard, try to avoid taking antacids and it is probably best to take I3C at mealtime. It has also been suggested that taking ascorbic acid (vitamin C) along with I3C will produce ascorbigen, which some investigators (Preobrazhenskaya, et al., 1993, Food Chemistry, 48,48-52) speculate may be an even more important anti-carcinogen than I3C.
If you do not appear to be responding to I3C, you might want to give DIM a try.
Finally, no matter what product one is using the best way to extend the shelf life is to keep them in a cool dark location such as the refrigerator.
I3C/DIM reported side effects:
• Occasional gastro-intestinal upset
• A couple of instances of dizziness
To date three RRP patients who are using I3C and DIM have reported varying degrees of low bone mineral density (BMD). Unfortunately, in none of these cases was a baseline BMD taken before the I3C/DIM therapy began, so it is impossible to say that I3C/DIM is solely responsible. Furthermore, in a study sponsored by the RRPF it was shown that I3C did not cause bone loss in mice (see summer 2000 issue of the RRP Newsletter). Nevertheless, the possibility still exists that I3C or DIM could result in some of the adverse effects associated with less estrogen such as osteoporosis in humans. After consultation on this subject with Dr. Clark Rosen, the RRPF recommends the following:
Anecdotal BMD report from an RRP patient
[RRP patient John Reiss asked if we would pass along news of his encouraging BMD test results.]
His correspondence follows:
" First a little background. I am a 66 year old white male. I was diagnosed with Laryngeal Papillomas in April, 1994. I have had nine surgeries, most performed in Long Island Jewish Hospital on Long Island, NY. In April, 1996 I had a photo dynamic therapy procedure performed by Allan Abramson, MD. At this time I began taking I3C caps, 200 mg. to start and after about six months I went up to 400 mg. per day. In 1998 I changed to Phytosorb Dim, 300 mg. per day and also increased that to 450 mg. I went about three years without having a recurrence. This past March I had laser excision surgery by Dr. Abramson once again. As of a month ago I am still clean. I am hoping that I can go another three years without surgery but only time will tell.
The main reason for my writing is that I decided to follow your advice and went for a bone density test at Orthopedic Surgery Associates in Delray Beach, FL, where I now live. I will give you a brief description on the interpretation of the scan:
T SCORE: compares your results to the ideal bone density, which is generally around age 35 - 40. A plus score means that your bones are harder than average. A minus means softer.
Z SCORE: compares your results to people in your age and gender. Again plus is good and minus is bad.
My results are as follows:
Spine - T Score +1.27 - 113% --- Z Score +2.05 - 122%
Left Forearm - T Score +0.44 - 103% --- Z Score +1.45 - 112%
Left Hip - T Score + 0.59 - 109% ---Z Score +1.12 - 118%
As you can see, my scores show that I have strong bones. I have been taking I3C and DIM for over five years. Presently I take 400 mg. of I3C caps every other day. On the opposite days I take 450 mg. of DIM. Just recently I began taking a Dietary Supplement Calcium 500 pill once a day because of my age. Obviously I do not need it.
Perhaps this information will persuade some other people to take the (Dexa Scan) test. I was afraid to take it for fear that my results would give me something else to worry about. I will take the test again in a year from now to see if my results change. At least now I have a base line to go by."
HPV vaccine news:
On March 29, 2001 Stressgen Biotechnologies announced that it had been granted orphan drug status by the FDA for an immunotherapeutic drug to treat RRP called HspE7. In clinical trials the drug has shown encouraging effectiveness in treating patients with HPV related anal dysplasia. In these trials it was also shown to regress genital warts.
The drug is administered via 3 injections &emdash; an initial dose followed by two more injections 30 days apart. The company is definitely planning a trial with RRP patients, and is currently
involved in extensive discussions with RRP experts regarding the detailed clinical trial design, but no specific timetable for this trial is yet available. A complete press release can be viewed at: http://biz.yahoo.com/cnw/010329/stressgen_hspe7.html
I3C/DIM research:
Karen Auborn PhD was an invited speaker at the Functional Foods Section of the 11th World Congress of Food Science and Technology in Seoul Korea on April 27, 2001.
Excerpts from an extended abstract of her presentation follows:
Indole-3-Carbinol and Diindolymethane, a New Treatment and Prevention Strategy for Human Papillomavirus Associated Tumors
K.J. Auborn, D-Z. Chen, M. Qi, K. Liu, and T.H. Carter
BoasMarks Biomedical Science Research Building, 350 Community Drive, Manhasset, NY, USA
Introduction:
There is mounting evidence that the onset and progression of many cancers are affected by diet and that diet can affect existing tumors. Unfortunately, modern diets - especially in Western countries - are increasingly deficient in vegetables, the very components that seem to be protective. Among the many beneficial components of plant-based diets, cruciferous vegetables (broccoli, cabbage, brussel sprouts, cauliflower, etc.) contain indole-3-carbinol (I3C) and its congeners, which appear to be natural prophylactic and anticancer agents against a variety of estrogen-enhanced and other neoplasms. It is increasingly apparent that this phytochemical has multiple effects on cells. This dietary component has the potential to not only prevent many tumors and also to be useful in the treatment of certain tumors.
We have been investigating whether cruciferous vegetables and specifically whether dietary I3C and its condensation product diindolymethane (DIM) would be useful for preventing and treating certain papillomavirus associated tumors, namely laryngeal papillomatosis and cervical cancer. We had made the observation that infection with papillomavirus adversely alters estrogen metabolism (1), and were able to reverse the adverse estrogen metabolism with I3C (2,3,4,5). Our molecular and animal studies (2,3,4,5,6) have translated into the treatment of laryngeal papillomatosis (4,7,8) and cervical pre-cancerous lesions with I3C (9).
Our current studies focus on mechanisms whereby I3C and DIM can induce apoptosis of existing tumors.
Results and Discussion:
We investigated how I3C and its major metabolite DIM kill pre-malignant and malignant cervical cells. Both I3C and DIM induced apoptosis. in cervical cancer cells in vitro by all apoptotic assays. DIM was the more potent cytotoxic agent, consistent with I3C being converted slowly into DIM in culture medium but rapidly in acid (as in stomach). The induction of apoptosis was independent of expression of papillomavirus oncogenes. In vivo, dietary I3C induced apoptotic changes in the cervical epithelium of transgenic mice receiving chronic estradiol. The mechanism by which I3C/DIM causes apoptosis was not via p53 because papillomavirus oncogenes cause the degradation of p53, and the cervical cell line without the viral oncogenes has mutant p53.
The apoptosis activity of I3C/DIM shown in these study is likely to be a major activity of I3C/DIM that enables these compounds to be effective in the treatment of tumors that have already developed. Our observations in vivo support in our vitro studies on apoptosis.
RRPF Activities:
Support research proposal - We are pleased to announce approval a research grant to Children’s Hospital of Alabama in support of a study to investigate biases against children with juvenile RRP.
Scientific meeting participation &emdash; The RRPF has accepted an invitation to the 5th International Conference of the European Society of Pediatric ORL (ESPORL). A presentation, "RRP Foundation: Activities and Objectives", will be made by the RRPF European representative Jan Schneider-Eicke on 10 July 2001 at the ESPORL meeting in Graz, Austria.
[Jennifer Woo is a young adult with RRP who is making her debut as an RRP Newsletter editor. She is hoping her story of successfully coping with RRP will inspire other young adults to tell how they are coping with this disease.]
Gritty As My Voice
By Jennifer Woo
That which doesn’t kill you only makes you stronger.
Growing up with RRP since my diagnosis at 10 months, that’s been a solid mantra to live by, and it often rings especially true to teenage ears. None of us needs to be reminded that RRP challenges patients in our everyday lives &emdash; large-scale difficulties, like getting that instinctive feeling that it might be time for another surgery, or smaller inconveniences, like remembering to pop some Indoleplex caplets before heading out the door in the morning. But sometimes it doesn’t hurt to reflect on the strength these challenges have forced us to develop, for the better.
As a little girl, emerging from my shyness around strangers became slightly thornier when it was assumed that my raspy voice was caused by strep or something equally contagious and undesirable. I can recall the times I was taunted at parties or called names by kids delighting in school bus bullying. I remember the odd glances in response to remarking that I’d undergone a dozen or so operations on my vocal cords, from those whose sole experience with anesthesia was a shot of Novocain to get a tooth pulled.
While those trials have made my skin a little thicker, they have also instilled in me fortitude for situations that might cause others to sweat a bit harder. Gently informing people that I have laryngeal scar tissue, not some lethal airborne throat condition, teaches tolerance; finding ways to overcome magnitude of volume with a choice quality of words nurtures an appreciation for language; overcoming bullies with the grace of an adult fosters grit; coping with post-surgery rawness and the plasticky scent of sterilized anesthesia masks heightens the threshold for physical pain. Memories of comforting moments in pre-op or the heartening words of a confident doctor are easy sources of inspiration for RRP teens looking into possible careers in medicine, research, or, in the ultimate twist of poetic justice, finding the cure to this gosh darned "disease."
Indeed, RRP can be seen not as an obstruction to, but as a springboard for great things to be accomplished as much in the spiritual domain as the physical for RRP teens. Last winter I joined 10,000 other runners in Hong Kong for the annual Standard Chartered Marathon and placed 5th in my division &emdash; exhausted and glowing with perspiration, my shortness of breath had less to do with my RRP than with the sheer exhilaration of completing the race. Trekking through knee-deep snowdrifts in the Himalayas caught me gasping for air, but only because oxygen is scarce at 15,000 feet above sea level. I’ve served as a class president and sung unabashedly in karaoke lounges, read at the altar of our Catholic parish, and tutored local Chinese girls in colloquial American English. These were the girls who started out regarding me with a strangely familiar fear of hearing the awkward sounds coming out of their mouths &emdash; a fear that was instantly recognizable to anyone who has ever been ill at ease with having an unusual voice.
It is a voice that has come to define me ever more clearly, to the point where I have qualms about undergoing any surgery that would change it too dramatically. Just as our voices help define young adult RRP patients, so do the successes achieved with the strength of learning from our condition. We gratefully acknowledge our parents, family and friends who have dotingly watched over us and stood up for us when we were literally or figuratively voiceless, and I thank God for bringing us this far into our lives in the face of the danger RRP can impose on our bodies. Health is not something to be taken for granted, nor are these precious years that some would consider the peak of our lives. We are young adults grown ever more resilient tackling the various levels of gravity of this moody condition, from the most acute diagnosis to steady remission. Like it or not, this very condition that has helped define us will ultimately reveal its place in preparing us for all the worlds of blessings and burdens that are somewhere, out there, still ahead.
Contact
RRPF Local Support Network Coordinators
Main Info. Center and Northeast
Marlene and Bill Stern
P.O. Box 6643
Lawrenceville, NJ. 08648-0643 (609)530-1443
Bill’s e-mail: bills@rrpf.org or
rrpf@AOL.com
Marlene’s e-mail: marlenelin@aol.com
Mid-West
Diane Burke, R.N.
University of Iowa Hospital, Dept. of Otolaryngology
200 Hawkins Drive
Iowa City, Iowa 52240-1009
(319)356-1765
diane-burke@uiowa.edu
Southeast & Florida
Wendy Bodner
4800 S.W. 64th Ave., Suite 110
Davie, FL 33314-4449 (305)581-3400
e-mail: wsbcpa@email.msn.com
West Coast & California
Susan and Bob Spock
1553 Via Allondra
San Marcos, CA 91606 (760)744-5022
e-mail: sspock@mail.adnc.com
Asia
Susan and Henry Woo
101 Repulse Bay Road
Apt. A3/1st floor, Hong Kong 852-2812-7379
e-mail: writeus@attmysite.com
Europe
Jan Schneider-Eicke, MD
Sonnwendstr.19
82152 Krailing, Germany 49-89-85661486
e-mail: nuklearmedizin@klinik-schindlbeck.de
California
Cheryl Downey
2520 Pearl Street
Santa Monica CA 90405
(310)581-6690
e-mail: cheryl_downey@paramount.com
Georgia
Bill Widmayer, Atlanta Area Support Group
744 Hickory Ridge Rd. SW
Lilburn, GA 30047 (404)313-8965(days); (770)921-9497
e-mail: widmayer@mindspring.com
Christina Lancaster
186 Pine Knoll Lane
Eatonton, GA 31204 (706)485-1016
e-mail: 75230.1612@Compuserve.com
New York
Barbara Kotler
2545 Navy Pl.
Bellmore, NY 11710 (516)679-5160
Oregon
E. Susan Bates
614 W. Second St.
Medford, OR 97501 (541)779-9233
e-mail: esbates@hotmail.com
South Carolina & North Carolina
Tami Shirley
206 Charlwood Rd.
Irmo, SC 29063-2303 (803)487-6484
------------------------------------------------------------------------------------------------------------------------------------------------------------------
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and families trying to cope with Recurrent Respiratory
Papillomatosis and to help find a cure for this
disease.
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The RRPF is a 501 (c) (3) non-profit corporation as determined by the Internal Revenue Service. Fed. Id #: 52179869