Vol.9 No. 2 An RRP Foundation Publication
2000/2001 Winter
P.O Box 6643,
Lawrenceville, NJ 08648-0643
______________________________________________________________________________________________________________________
Contents
From the Editor
The second RRP focus session, hosted by the RRPF, was held September 23, 2000 in conjunction with the American Academy of Otolaryngology meeting in Washington DC. We had an outstanding turnout that consisted of RRP patients and families as well as a number of RRP doctors and researchers. A significant portion of this newsletter contains information from the focus session.
I would like to take this opportunity to thank those that made presentations as well as others that contributed to an active discussion following the presentations. While there is a great deal that is not known about this disease, it is the active interest that was displayed by the doctors and researchers as well as familes and patients in the meeting that have lead to improved treatment strategies. I would also like to acknowledge Marlene and Bill Stern for organizing the meeting and doing a great job with the second RRP focus session.
Chris J. Neuberger
(405) 749-8499
Email: Cneuberger@ETI1.com
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 tax id #, it is 521798693. Thank you for your support.
We once again want to acknowledge the generous efforts of Ed and Maura Weiner along with their friends. They turned an an annual golfing event among a close group of friends into a successful fundraiser for RRP.
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
Vice President, 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 1602, 16/F, Manulife Plaza
The Lee Gardens, 33 Hysan Ave.
Causeway Bay
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
[See 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
Diane Burke, RN, The Univ. of Iowa Hospitals and Clinics 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, Speech-language pathologist
RRP Newsletter Editor
Chris Neuberger
Other RRP Newsletter Contibutors
Wayne Barringer
Toni Barringer
Dale Barringer
Marlene Stern
Bill Stern
RRP Reference Service Editor
David Wunrow
RRPF ListServe Manager
Ed Beck, PhD.
RRPF Fundraising Coordinator
Ed Weiner
(703) 691-1922
serviceimpact@msn.com
The RRPF produces two publications semi-annually, 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.
Ryan from California who just turned 8 years old, has been in remission for nearly 5 years. After 7 surgeries in 1995, he suddenly went into remission without any adjunct treatments.
Between 1994 and June 1998, Jonathan (now in California), had 14 surgeries for RRP. Just before his 14 th surgery, he started taking DIM. Although there was no immediate response, after about 3 months of taking DIM his voice improved and he went into remission. He continues to take DIM and remains in remission today.
Nancy from Texas, who is now 34, had about 13 surgeries for RRP between the ages of 1 and 7. At that time she went into spontaneous remission and despite some residual scarring, remains in remission now (approximately 27 years).
Others still in remission (from 2 to
15 years) include: Nine year old Ariel and fourteen year old Andy
from California; from California; Christie age 12, 26 year old Julie
and 27 year old Steph from Florida; Mike from Georgia at age 48; Jeff
, age 53 and William age 76, from Illinois; Jessica from Kansas who
is now 10; Thirteen year old Anthony from Kentucky; Cara from
Michigan at age 18; Leah from New Hampshire, age 21; 11 year old
Lindsay from New Jersey; Joe from Ohio at age 33; Ralph from
Pennsylvania at age 74; and from Virginia, Alison age 10 and Smokey ,
age 29. Of this group still in remission, about 2/3 have attributed
their remission to some form of adjunct therapy, the most common
being I3C and/or DIM. Other therapies included interferon, 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 over 540 respiratory papilloma families. Patients range in age from about 2 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 14 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 (http://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 has provided a valuable mechanism of information exchange for the RRPF. Our website (http://www.rrpf.org) contains a wealth of information relevant to patients, families, doctors, nurses and researchers. 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 Listerve that currently has 170 subscribers with over 1000 postings. The RRP Listerve, maintained by Dr. Ed Beck, is a secure web based environment for communicating RRP based information. If you haven’t joined yet, please feel free to do so by sending a blank email to: rrpf-subscribe@egroups.com. Over the past few months we have seen some very interesting information exchanged via the listerve. We have devoted an article in this newsletter to summarizing some of the information from this forum.
We also maintain links with other sites relating to RRP including the RRPwebsite and the ALPF.
If you have some experience/expertise with the WWW and would like to help us improve our website, please contact Bill Stern.
RRP Focus Session 2000 Highlights
On September 23, 2000, in conjunction with the American Academy of Otolaryngology meeting in Washington, D.C., the RRP Foundation sponsored a special meeting dedicated to RRP. It was the second focus session that the RRPF has organized. The first one took place in January of 1999 in Charleston at the HPV meeting.
There were approximately 55 - 60 attendees, including about 40-45 RRP patients/family members and 12-15 RRP doctors / researchers. In addition to the many RRP families from the Washington, D.C. area, some people traveled from more distant locations such as New York, Florida, Alabama, Georgia, South Carolina, Oklahoma and Sally Bryn came all the way from Oregon.
Bill Stern provided some welcoming and introductory remarks, followed by formal presentations from Dr. Bettie Steinberg, Dr. Tom Broker, Clark Rosen, MD and Vincente Villa-Gomez, MD. There was discussion following the presentations, including much interest in the pros and cons of various surgical approaches, i.e, laser, cold steel and the new laryngeal shaver. There was also much conversation about cidofovir efficacy and safety.
[The presentations focusing primarily on research related topics can be found starting on page 8 under the heading Research Activities Update.]
...............................................................................….
Introductory Comments and RRPF Goals
The objectives of the RRPF were outlined for the group and are listed as follows:
It is proposed that the future direction of the RRPF will focus on database enhancements as well as website improvements.
A distribution of the RRPF support network was presented as a function of current age and sex. Grouping patients in decades of age there is somewhat of a peak in the 10 and under group and somewhat of a minimum in the 20-30 group, but otherwise the distribution is fairly flat. Overall there are more male than female patients, which shows up as adults over the age of 40. A second distribution was presented as a function of age of diagnosis. In this case there is a huge peak in the under 10 grouping, a minimum in the age 10-20 group (which has also been noted in published studies in Denmark) and a secondary maximum in the 30-40 group, which is again dominated by males.
Some RRPF current activities that were noted include:
The RRPF Website, which has become a main focus of information dissemination. The listserve has proved to be a very valuable forum for communication. The RRPF continues to publish the RRP Newsletter, RRP Reference Service and a directory of RRP families. The RRPF also maintains patient and physician databases, and does statistical analyses with the data. The RRPF encourages and supports research and collaboration in the scientific community through its various forums for communication, participation in the RRP Task Force and meetings like this. The RRPF also shares non-confidential information with researchers and very much wants to continue focus on the databases and website.
The introduction was concluded by posing some unanswered question that are evident in the RRP Community. These questions are listed below:
"RRP Potpourri"
by Clark Rosen, MD, University of Pittsburgh Voice Center
Dr. Rosen could not be present at the RRPF Focus Session, however, he submitted a video presentation outlining his thoughts on RRP. The video presentation can be seen as a streaming video on the RRPF website.
After starting with some kind words for the RRP Foundation’s support efforts and a warning to proceed cautiously with regard to fad treatments and anecdotal therapies, Dr. Rosen presented his insights on a range of RRP related topics as follows:
Selecting a surgeon: 1) It is crucial that the surgeon is familiar with RRP. 2) Very young children should be treated by a pediatric ENT. For older children and adults, it is felt that a laryngologist may be somewhat preferable to a general ENT. A laryngologist has a specialization in voice and should be better suited to take care of adult RRP patients and older children. (It should be noted that Dr. Rosen is a laryngologist himself.) 3) It is important that a surgeon maintain a good rapport with the patient. There must be two way communications. 4) Finally, if possible, geographic proximity to one’s surgeon is desirable. One source for finding surgeons who specialize in voice, is a directory located on the voice foundation website, www.voicefoundation.org.
Ethical issues for experimental drug treatments: Before considering an experimental drug there should be a sound theoretical basis and the drug should have undergone some animal and/or cell culture testing. Studies involving the drug should be reported in literature, no matter what the results. Only RRP patients with moderate to severe disease should be considered. There is a risk-benefit analysis involved. The key risks are that these treatments are experimental and should be treated as such. There may be extra testing and extra surgery needed. The benefits are to the patient and the RRP Community.
Cold steel surgical removal for RRP: Involves the use of small microsurgical instruments and a high powered microscope. Cold steel surgical removal also requires specialized skills and techniques. Dr. Rosen argues 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. (A two minute segment of a cold steel RRP surgery is shown at the end of Dr. Rosen’s video.)
Cidofovir: Cidofovir has been used to treat RRP (primarily in severe patients) for approximately two years at the University of Pittsburgh. The protocol has been to do standard removal of RRP and then inject the papilloma sites (5mg/cc) typically every 3-4 weeks. Several patients have had a remission. The majority have had small recurrences. Patients are having more time between surgery and less surgery involved. Complications include airway difficulties that are temporary, several have developed a web from bilateral injection. There has been no change seen in the histologic nature of papilloma, nor has any kidney toxicity been seen. The future for cidofovir appears optimistic. Controlled studies including long term follow-up are needed.
by Wayne Barringer
The RRP email discussion forums continue to be
highly active and informative. Over the past six months, the topics
have included HPV acquisition and transmission, the question of "To
rest or not to rest voice after surgery," follow-up reports on
cidofovir and speculation of vitamin D deficiency associated with
I3C. Marlene Stern also clarified how anyone can specify the RRPF
when donating to the United Way (see front page of this newsletter
issue). Here are some samples of the discussion. If you’d
like to join the list, simply send a blank email to:
RRPF-subscribe@egroups.com Any subscriber to the list serve may post
a message to all of the list serve subscribers simply by sending the
message to RRPF@egroups.com Subscribers may reply individually to
posts on the list.
"Latent" HPV and boosting immunities
"Regarding… possible ways to get HPV besides at birth or oral-genital contact, we just don’t know. It’s probably not from the air (like flu or measles)… We researchers don’t have all the answers… So don’t be afraid to discuss anything that is bothering you or that you think might be of interest. It could give us clues. We are testing the hypothesis that irritation or injury (probably so mild it isn’t noticed) may be the trigger for activating latent HPV, but that in order for the full symptoms to occur the immune system must not be able to stop the diseases. Therefore, the immune system is probably the most important factor in having the disease. If we could make a vaccine to boost the immune response, maybe many patients would go into remission. Experimental trials of such a vaccine are in progress…"
Bettie Steinberg, PhD, Chief, ENT Research, LIJ
DIM, I3C and estrogen
"(Recent studies) tend to confirm my suspicion that estrogen metabolism mediation isn't I3C's only mechanism of action (which raises an interesting question about whether DIM does, in fact, do everything that I3C does.) To view these abstracts, which are quite technical and more for doctors than lay people, go to http://www.rrpwebsite.org/index.html#New, and then scroll down and click on: "Recent (2000) I3C and DIM-Related Abstracts Dealing with Estrogen, Cancer Prevention, Killer Cell Activity, P-450 Activity and the Immune Function."
Michael Green
Voice rest, or not?
"For 43 years, I have had papillomas bilaterally. This time (as in 1992), I also had a polyp with the papilloma, on the right vocal cord. That was the side the doctor removed first. Last year was the first time I was informed to use my voice only to find out there was no voice at all. It took four weeks then it came back very clear. Two years ago, I was informed to use my voice minimally, and no voice came back in four weeks. But, during a post op follow-up, the papillomas had returned on both sides. I had not had back to back surgeries like that since I was 10 years old."
Gail Faulkner
Until very recently, my docs have prescribed voice rest for 24-48 hours post-op. However, my current doctor, Allen Hillel at Univ. of Washington in Seattle, recommends that voice rest isn't necessary. And, in fact, after my last surgery, I finally decided to trust this advice (after 30 years to the contrary) and began talking immediately after surgery. My voice has come back stronger than ever.
It's very likely that the voice improvement is a coincidence. What is relevant, I think, is that the immediate post-op talking didn't cause voice problems for me."
Wayne Barringer
The statistics that follow are based on RRPF questionnaire responses. Although suggestive trends are apparent, there has been no attempt to determine statistical significance, so caution is urged in drawing conclusions from the numbers below. In addition to these data, results regarding adjuvant therapies are presented on page 7. Tables 1 - 3 provide a breakdown of the patients in the support group who have reported to us, based on sex and age; the sample sizes range from 444 to 503 for tables 1-3.
Table 1. Total number of patients in support group reporting.
|
|
Females |
Males |
|
All Ages |
219 |
284 |
Table 2. Distribution of patients based on current age brackets and sex.
|
Age Groups |
Females |
Males |
Total |
|
Under 10 |
63 |
56 |
119 |
|
10-20 |
45 |
50 |
95 |
|
20-30 |
22 |
22 |
44 |
|
30-40 |
33 |
32 |
65 |
|
40-50 |
15 |
37 |
52 |
|
Over 50 |
19 |
50 |
69 |
Table 3. Distribution of patients based on diagnosis age brackets and sex.
|
Age Groups |
Females |
Males |
Total |
|
Under 10 |
150 |
140 |
290 |
|
10-20 |
12 |
7 |
19 |
|
20-30 |
22 |
31 |
53 |
|
30-40 |
9 |
38 |
47 |
|
40-50 |
8 |
28 |
36 |
|
Over 50 |
5 |
15 |
20 |
Table 4. Distribution of respiratory papilloma sites of involvement based on responses from 305 patients.
|
respiratory site |
no. of patients |
|
above cords |
141 |
|
at cords |
300 |
|
below cords |
117 |
|
tracheal |
53 |
|
bronchial |
27 |
|
lung |
18 |
Table 5. Distribtion of surgeries for RRP
|
|
JO-RRP |
AO-RRP |
ToT |
|
1-10 |
57 |
89 |
146 |
|
11-25 |
36 |
32 |
68 |
|
26-50 |
30 |
20 |
50 |
|
51-75 |
12 |
1 |
13 |
|
76-100 |
13 |
0 |
13 |
|
>100 |
19 |
3 |
22 |
|
>200 |
5 |
2 |
7 |
|
tot responses |
172 |
147 |
319 |
Table 6. Answers to some RRP research questions.
|
|
Was patient nursed? J-O / A-O |
Was patient exposed to smoking? J-O / A-O |
|
Yes |
63/66 |
72/90 |
|
No |
96/55 |
74/40 |
RRP National/ International Issues
by Tom Broker
There is now an international papilloma virus society &emdash; which is an officially incorporated (non-profit) biomedical society for the study papilloma viruses. Tom Broker is the President and Bettie Steinberg is the secretary. The web site is www.IPVSoc.org. The society is in the process of a membership drive. The RRPF as well as a number of RRP families/patients are members as well. Membership cost is $25. A large member base is important as it creates greater credibility for the society which enables the society to secure larger contributions from the pharmaceutical industry, furthering papilloma virus research. If you are interested in joining please see the website.
.................................................................................…………...
A number of proposed scientific and clinical studies involving promising therapies for the treatment of RRP are in need of funding. Government agencies are a very significant source of support for these RRP research efforts. In this regard we continue to urge you to contact your congressional representatives and senators to make them aware of RRP and mobilize their support. For names and addresses of specific key governmental officials see the RRP Newsletter Spring 97 issue.
................................................................................…………..
The table that follows 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 December 8, 2000 there were 535 children in the registry.
|
Site # |
per site |
|
|
|
|
|
|
|
|
101 |
|
|
|
|
|
|
|
|
|
601 .2 |
|
|
|
|
|
|
|
|
|
602 |
|
|
|
|
|
|
|
|
|
1101 |
|
|
|
|
|
|
|
|
|
1201 |
|
|
|
|
|
|
|
|
|
1301 |
|
|
|
|
|
|
|
|
|
1901 |
|
|
|
|
|
|
|
|
|
2401 |
|
|
|
|
|
|
|
|
|
2501 |
|
|
|
|
|
|
|
|
|
2701 |
|
|
|
|
|
|
|
|
|
2901 |
|
|
|
|
|
|
|
|
|
3602 |
|
|
|
|
|
|
|
|
|
3701 |
|
|
|
|
|
|
|
|
|
3901 |
|
|
|
|
|
|
|
|
|
3902 |
|
|
|
|
|
|
|
|
|
4201 |
|
|
|
|
|
|
|
|
|
4701 |
|
|
|
|
|
|
|
|
|
4702 |
|
|
|
|
|
|
|
|
|
4801 |
|
|
|
|
|
|
|
|
|
4901 |
|
|
|
|
|
|
|
|
|
5101 |
|
|
|
|
|
|
|
|
|
5301 |
|
|
|
|
|
|
|
|
|
Total |
|
|
|
|||||
|
Overall Mean |
10.3 N=564 |
N=515 |
N=519 |
N=564 |
||||
.................................................................................…………...
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
268 RRP patients/families have reported using at least 1 adjunct therapy. The most reported therapy was I3C/DIM with 180 users and next was interferon (IFN) with 86 users responding. The patient/parent assessed impact of some adjuvant therapies is summarized in the table that follows. In this table the sample sizes include only the subset of adjunct therapy users who indicated some response to a treatment, either some improvement (Improve) or no impact (None). If some improvement is noted, it is further broken down into either a complete response (Comp, i.e., no new growths seen for at least two typical surgical intervals) or a partial response (Partial).
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.
Table 1. Patient/family assessed impact of adjuvant therapies reported.
|
Therapy |
Users |
None |
Improve |
Comp |
Partial |
|
I3C/DIM |
121 |
54 |
67 |
23 |
44 |
|
IFN |
56 |
24 |
32 |
4 |
28 |
|
Acyc |
31 |
20 |
11 |
4 |
7 |
|
PDT* |
19 |
13 |
6 |
1 |
5 |
|
Retin |
16 |
10 |
6 |
0 |
6 |
|
Mumps |
14 |
6 |
8 |
2 |
6 |
|
Cidof |
12 |
1 |
11 |
3 |
8 |
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 3 patients who have reported, have used the new agent, Foscan®) , Cidof = cidofovir, Retin = retinoic acid or accutane, Mumps = mumps vaccine. Other therapies for which improvement has been reported: Echinacea and Thuja (homeopathic anti-virals), a mixture of vitamins including vitamin C and vitamin A, ShapeRite immune formula, ribavirin, topical 5-flourouracil (5FU), bleomycin and cobalt. (Please see the I3C Update in this issue and previous newsletter issues, such as the RRP Newsletter Spring 97 issue 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 for DIM, as well as Bradlow et al., 1996 J. of Endocrinology 150, S259-S265; Newfield et al., 1993, Anticancer Research 13, 337-342.
Phytosorb-DIMTM products containing DIM are available from:
BioResponse
L.L.C. at P.O. Box 288
Boulder, CO 80306
Email at zeligsmd@sni.net
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.
See the RRP Newsletter summer 2000 issue for more details regarding dosages for Phytosorb-DIM.
(Please consult your doctor, especially for young children.)
Call or e-mail for pricing
Special Note: Unlike I3C, DIM does not require activation by stomach acid. DIM can be taken by individuals
who use antacids or H2 blockers like Zantac.
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
http://www.theranaturals.com
[Credit card orders may be placed by phone, fax, web or e-mail]
Theranaturals I3C product pricing (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
http://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:
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
[The following updates were presented at the RRP Focus Session 2000.]
LIJ has a grant from the NIH to study all aspects of RRP, including molecular studies, immunology and the possible efficacy of photodynamic therapy (PDT) in treating RRP. Some other collaborating centers in the PDT study include the Univ. of Iowa, Univ. of Seattle and Southwest Medical Center, Dallas.
This PDT study currently has 17 patients enrolled, 8 children and 9 adults with follow-up on 7 patients for at least a year. Patients are enrolled with direct scoping, biopsy and scoring of disease before PDT. Patients are randomized to one of two treatment times, so that the study is controlled in agreement with an FDA-approved study design, but all patients receive the PDT. All patients receive the same dose of the new photosensitizing agent Foscan®, intravenously. Drug levels in the blood are monitored. After a 6-day waiting period, which allows the sensitizer to selectively accumulate in the papillomas, a non-burning red-light laser is used to activate it and kill tissue that has high concentrations of the drug. The biggest side effect is photosensitivity, but the period of photosensitivity with Foscan® is a few weeks as compared to a few months with an earlier drug.
Results from the first six patients, some with follow-up out to two years, indicate a consistent delayed response: initially they are not better, if anything they might be slightly worse, but five out of six were free of disease at a year. Only one has not gone into a complete remission. In these cases, the RRP was confined to the larynx. In cases where there both laryngeal and tracheal disease occur, it appears that PDT is more effective on the laryngeal disease but there still was improvement in tracheal disease.
This lagged response suggests the possibility that although PDT does not get rid of the virus, it might alter immune response to papilloma viruses. This issue of immune response to papilloma viruses in patients with recurrent respiratory papillomas is the focus of a related study at LIJ. Some key questions being explored in this study, are whether there is a difference in the way RRP patients' immune systems respond to papilloma viruses, so that they cannot prevent recurrence of papillomas and whether the variation in immune response between patients explain the variation in clinical severity of disease? There are generally two ways of activating immune response, humoral immunity and cell-mediated immunity. It is the latter that needs to be active in RRP patients. But initial results show that in RRP patient's immune system T-cells respond to HPV proteins by making cytokines that stimulate antibody production, not cytotoxic T-cells that would destroy papillomavirus-infected tissue. This study also suggests that there may be some genetic differences in the immune system of patients, that could affect susceptibility to HPV infection. Virtually all of one category of T-cells from severe RRP patients do not appear to have a key protein which is necessary for them to recognize HPV. In mild to moderate patients this protein is apparent in about 45%-50% of that group of T-cells, while in a sample of people without RRP it is seen in about 90% of those T-cells.
"Clinical and Molecular Responses of RRP to Adjunct Therapies: A Seven Year Study with 55 Children at UAB" by Dr. Tom Broker, University of Alabama at Birmingham
Tom Broker and Louise Chow have done RRP research for at least 20 years. Their approach has been to maintain a close working relationship with otolaryngologists and patients/parents.
This study at UAB has followed the clinical course of 55 juvenile RRP patients who have been treated with a variety of adjunct therapies, including interferon, accutane, I3C, acyclovir and cidofovir. Each child is evaluated using a rating system with a score of 0 to 3 (with 3 indicating most severe) being assigned to describe voice quality, extent of airway obstruction and amount of papilloma coverage at a number anatomical sites. Dr. Brian Wiatrak developed this scoring system, which is based on an earlier system used by Dr. Haskins Kashima. A very similar RRP scoring system has been proposed by the RRP Task Force. Both the epidemiology and molecular biology of this group of patients are being analyzed, with hope of finding some associated trends and patterns.
The group of patients consists of 31 males and 24 females, with approximately two thirds being Caucasian and one third African American. No significant differences have been observed as a function of gender or race.
As in a number of other centers, there has been much interest in cidofovir as an RRP adjunct with some encouraging results. In one case a child who was enrolled in the FDA approved cidofovir protocol, was first just receiving a saline solution and then a very low dose of cidofovir. After the study broke down and doses were increased according to what was used in the Belgium study, cidofovir extended his surgical interval to the best he had been. Cidofovir works well in some but there are notable exceptions. An observation from this study is that no child can be guaranteed to respond to any therapy.
In an attempt to understand the great variability of clinical course among RRP patients, 550 biopsies from this patient group have been collected. Tissue samples are being evaluated for a variety of changes including DNA and RNA transcription of the virus. They are comprehensively typed &emdash; with HPV 11 associated with somewhat more aggressive RRP (this has also been observed in other studies). By working very closely with otolaryngologists, papilloma can be taken from the operating room and get it to the lab in just a few minutes to test it. Cells in the papilloma that are replicating may be seen with the aid of fluorescent tags. The goal here is to better understand the natural history of the disease.
Dr. Broker also noted that HPV viruses are very prevalent with between 150 &emdash;200 different HPV types. In most cases ,the immune system handles the presence of the virus. Previously HPV virus types were considered rare, but now many these different virus types are being discovered, mostly in immunosuppressed patients. It is speculated that perhaps some of these viruses are good and create antibodies that serve a purpose, and we may not want a cure, but perhaps a vaccine.
"Intralesional Cidofovir: A New Treatment for Laryngeal Papilloma"
by Steven Bielamowicz, M.D. and Vicente Villa-Gomez, M.D.(presenter) &emdash; George Washington Univ.
Laryngeal papilloma were first described in 17th century. Transmission is unknown. Children tend to be more aggressive with the growth rate usually slowing during adulthood. Adults have more indolent behavior and malignant degeneration is rare. The most common HPV types found in the respiratory tract are 6/11. Types 16/18 are found rarely and have been related to more malignant behavior.
Intralesional injection by cidofovir. Effective in treatment of any DNA virus, Cidofovir is approved for CMV Retinitis. Some complications include loss of pressure in eye, kidney and liver toxicity, but these have been associated with intravenous injection. No significant complications have been seen with intralesional injections of cidofovir.
At George Washington University a protocol involving monthly intralesional injections of cidofovir with laryngoscopy under general anesthesia with no removal, has been approved for adult RRP patients by George Washington human subject protection board. By not removing papillomas surgeries are shorter with a quicker recovery time. Injections with clinical evaluation are performed until resolution of disease is seen. Typically disease resolution is seen with 5 injections, but there was at least one case that required 15 injections. Two patients were discussed. The first patient was a 63 year old male who had 65 surgeries and 2 trachs over the course of his disease. After 15 injections of cidofovir, the papillomas resolved. The second patient was a 30 year old male who had 3 laser surgeries for papilloma removal. This patient required 15 injections in order for the papillomas to resolve.
Some possible caveats/unanswered questions are: potential airway obstruction due to post op edema; unknown longer term carcinogenic effect; may provide for only a temporary remission and not a cure. More time will help provide answers.
[The following case history is written by Julie Bowne, whose personal experience as an RRP patient motivated her to pursuer a career in speech-language pathology. Julie has also volunteered to serve as Voice Advisor for the RRP Foundation.]
Approximately eight months after I was born, I was diagnosed with juvenile papilloma. Prior to being diagnosed, the only symptom that my mother noticed was a weak/hoarse cry. The doctor did not have any suggested treatment at the time. When I was two years old, I underwent emergency tracheostomy because the papilloma had grown so large that they blocked my airway. From the ages of 2 to 13 I had approximately 30 operations, most of which were performed by cryotherapy. When I was 10, the papilloma stopped recurring, but I was left with a laryngeal web. The doctors attempted to reduce the web by using the CO2 laser, but were unsuccessful. Although I have been in remission for 16 years, I have been left with a web that blocks a portion of my airway and have a raspy voice.
Over the years, I began to realize that I became short of breath easily during exercise or when I tried to talk loud. Because of my experience with papilloma and the resulting voice, I pursued a career as a speech-language pathologist. During my undergraduate studies, I had the opportunity to work with a professor that specialized in voice disorders. Together, we pursued ways to reduce my shortness of breath. We found that a physical therapy professor was researching the effects of an "inspiratory threshold trainer" on patients with chronic obstructive pulmonary disease. The threshold trainer proved to have a positive effect on the breathlessness of this population, so we decided to research the effects of the trainer on a patient with a history of papilloma (specifically, me). A four-week training session was implemented using the one-way spring-loaded valve. Essentially, this device is similar to lifting weights, because as you inhale to close the valve, resistance is provided to the respiratory muscles. For the study, inspiratory muscle strength was measured by maximum inspiratory pressure (MIP). Over the four-week period, my MIP increased by 57%, indicating increased respiratory strength. My sensation of breathlessness decreased by 2 scale points during exercise and decreased from a moderate to a minimal rating during load speech.
It has been almost three years since I participated in that study, and since then, I have been able to participate in cardiovascular activities that I was unable to do before. I am able to project my voice more because I have increased respiratory strength. Overall, my life is more enjoyable even though the effects of the papilloma will remain with me always.
Reference for article: Sapienze, C.M. Brown, J., Martin, D., & Davenport, P. (1999) Inspiratory pressure threshold training for glottal airway limitation in laryngeal papilloma. Journal of voice, 13 (2), pp 382-388
Marlene, Lindsay and I would like to take this opportunity to wish all of you good health and happiness for this holiday season and throughout the new year.
Over the past few years the RRP Foundation has continued to grow in a number of ways. There has been growth in the number of RRP patients in our support network along with a significant increase in requests for information. Our databases of RRP patients and doctors/researchers continue to expand. In addition, the RRPF has been involved in more research related activities, has sponsored two national support group meetings and has participated in a number of scientific/clinical meetings. We have also experienced a growth in donations and we are most appreciative of this, since without these additional funds we would not have been able to participate in and sponsor RRP related activities to the extent that we have.
Today it seems that the most precious of all commodities is time. I am most grateful to those of you who are donating time to the RRPF (see page 2), as I know how valuable it is. My personal dilema is that the demands of continuing to run and grow the RRPF along with my primary occupation as a research meteorologist, are leaving me precious little family time. I am making a personal commitment to significantly scale back on my own involvement in the RRPF. My goal is to hand off most of the financial record keeping and correspondence before the end of FY2001 (i.e., Oct. 31 2001). This will hopefully allow me to focus more on the RRPF website, databases and scientific issues, as well as allow for more time with my family. So, I am asking for a volunteer to replace me as the RRPF treasurer and proposing that we create a new corresponding secretary position. Please contact me (see page 2 for contact info.) if you have any interest. Thank you.
Warm regards,
Bill Stern