Vol.4 No.1
1995 Spring

____________________________________________________________________________________________________________
This issue of the RRP Newsletter is dedicated to a patient in the support group who passed away in February of this year, Katherine Wessinger, who was 72 years old. A memorial is included on the back page of this issue.

Contents
• Opening comments - p. 1
• RRPF organizational information - p. 2
New editorial policy; RRP Video - p. 2
1994 AAO-HNS & HPV meetings - p. 2
• RRP Network News - p. 2-3
• RRP Task Force and RRP Registry - p. 3
• Patient Statistics - p. 3-4
• Update on Adjunct Therapies and new protocols - p. 4-6
Early results from Adjunct Therapy Survey - p. 4
Indole-3-Carbinol - p. 4-5
New PDT Therapy - p. 5
• RRP/HPV Typing - p. 6
• RRP Patient Perspectives - p. 6-7
• Voice Quality in RRP Patients - p. 7-8
• Patient memorial - p. 8
• RRPF Mission Statement, Information/Support Centers, subscription form - enclosure

From the Editors
I am pleased to announce that the RRP Newsletter now has a second editor, Ken Ueding. In the section below, Ken introduces himself and tells us why he is interested in RRP.
The RRP Newsletter is vital to our support services and networking efforts. We welcome your comments and suggestions. Your feedback will be very helpful in improving this publication. We continue to seek people from the RRP community to actively participate in the RRPF and the RRP Newsletter. This includes practitioners, researchers, patients and families. If you have any interest in this regard, please contact any of the directors or officers (see page 2 for addresses). Thank you.
Bill Stern

As the new co-editor of the RRP Newsletter, I would like to introduce myself to the patients, families, practitioners, and research community who are actively searching for a cure for RRP.
After graduating from the University of California, Berkeley in 1992 with a B.S. in Genetics, I have been employed at Gen-Probe, Inc., located in San Diego, for the last two years. I am currently working on the development of a novel test for the detection of HIV in afflicted individuals.
As for my interest in human papillomaviruses and RRP, I have a younger brother, Jeremy Spock, who was diagnosed with RRP when he was eight months old and is now twelve years old. (His story is detailed on p. 6) During my college days, I spent many hours searching Medline for any new treatment modalities that would alleviate Jeremy's condition. Any leads that I found were discussed with our mother, Susan Spock, who in turn, would call on physicians and nurse practitioners to find any additional information.
This example addresses the exact nature of this newsletter - bringing the most up-to-date information to you so that you can make an informed choice on available treatment options as well as keep you in contact with families and patients so we can all work together to bring an end to RRP.
Ken Ueding

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 RRP Medical Reference Service
Professional/Corporate - $40
Individual - $25
(see RRPF subscription form enclosed)
We are most grateful to all those individuals and medical professionals who have supported the RRPF. Future donations from individuals, professionals or from the business community will be very much appreciated. Tax deductible contributions may be made to:
RRP Foundation
50 Wesleyan Drive
Hamilton, NJ 08690
Do you donate to the United Way through your employer? There is now a "Donor Choice" option which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice.

To physicians and nurses: Please distribute copies of this newsletter to your RRP patients
Please register with the RRPF by completing the Practitioner Questionnaire



RRPF Officers, Directors & Advisors

Marlene Stern
President
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Bill Stern
Treasurer and Director
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Henry Woo
Secretary
2600 Virginia Avenue, N.W., Suite 301
Washington, D.C. 20037
(202)965-4150

Diane Burke
Director
Department of Otolaryngology
The Univ. of Iowa Hospitals and Clinics
E230 GH, 200 Hawkins Drive
Iowa City, IA 52242
(319)356-1765

Susan Woo
Director
7107 Georgia St.
Chevy Chase, MD 20815
(301)652-6826

Scientific Advisory Committee

Thomas 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
Bettie M. Steinberg, PhD, Long Island Jewish Medical Center
Kathleen Sullivan, RN, Children’s Hospital of Boston

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The RRPF Board has voted to welcome editorial participation in the RRP Newsletter. We feel that diverse perspectives on RRP issues should help to stimulate innovative and constructive discussion. The Foundation reserves the right to review editorial submissions and may not necessarily agree with the opinions expressed.

In 1988 the University of Iowa put together a video overview of RRP, entitled "Recurrent Respiratory Papillomatosis". After reviewing it, we found that most of this video is still quite relevant. The key narrator for this video is Steven Gray, MD, a notable RRP surgeon. Other participants in the video were the Dept. of Otolaryngology Nurse/Clinician at that time, Cynthia Shive, RN, and four RRP families, who are all currently part of our support network. The video is about 35 minutes long and should serve well as a learning tool for patients, families and health care providers. Also included on the video tape is a shorter segment on RRP from 1985 as part of the program "Healthbeat". We are offering it to subscribers for a donation of $15, which is our cost for the tape, copying and mailing ($25 for non-subscribers). However, if an RRP patient/family would like this video tape but is unable to afford it, we will consider a reduced price. Use the enclosed subscriber form to order the video.

Members of three support network families attended the 98^th Annual meeting of the American Academy of Otolaryngology - Head and Neck Surgery held September 18-21, 1994 in San Diego, California. Bill Stern, Susan Spock, Ken Ueding and the Garner Family all helped at the RRPF exhibit booth, with Susan and Ken handling the booth by themselves the last two days.
At least several hundred otolaryngologists stopped by our booth during the meeting; many were finding out about the RRPF for the first time. Our presence at this and future meetings should help to continue to expand the network of RRP families and their treating physicians.

The 13^th International Papillomavirus Conference took place in October 1994 in Amsterdam, Netherlands. RRPF scientific advisors, Drs. Bettie Steinberg and Thomas Broker, were in attendance. From a clinical therapy perspective, it was disappointing as there were no major announcements of new therapies for treatment of HPV.
There was an interesting difference in results from two studies regarding the prevalence of HPV in esophageal cancers. An Amsterdam study indicated that 30% of such cancer patients tested positive for HPV, while a study from a group in Paris found no HPV in the esophageal cancer patients they followed. This seems to indicate that lifestyle co-factors may play at least as important a role as HPV in esophageal cancers.


RRP Network News
Patient/Family Support Network:
Our national support network has grown to nearly 200 respiratory papilloma families. Patients range in age from 1 to 77 years and are located in 34 states, two Canadian provinces and Great Britain.
We have received questionnaires from about 130 families in the support group and adjuvant therapy surveys from 54. If you have not filled out a questionnaire or adjuvant therapy survey as yet or would like to provide updated information for the RRP Foundation Patient/Family database, please take a few minutes to fill out the accompanying forms to the extent needed to bring the information about yourselves up-to-date. Please return them to Marlene and Bill Stern. In addition, RRP families, please review the Patient Directory listings and notify us regarding any corrections, omissions or additions.
Communication among support group members remains a primary focus of the foundation. The RRPF maintains an account with America-On-Line (AOL). We can arrange for you to have a limited amount of free time on AOL to communicate your questions, comments and/or suggestions; just get in touch with Bill Stern.

RRP Remission News

To let you know that some of those with RRP are doing quite well, we are introducing this new section which includes some very brief patient profiles.

Melissa age 5 1/2 from New York has not had a recurrence of papillomas since late 1993. Prior to then she underwent PDT therapy. She had undergone about 40 surgeries by age 4.
Smokey from Virginia is now 23 and has not required surgery in more than 1 1/2 years. He had required 6 surgeries in 9 months when he was diagnosed at age 21. His remission began shortly after starting I3C therapy.
Ariel, age 3 1/2, from California had been having surgery nearly every month. July of 94 was the last time papilloma were found. She has been following the I3C therapy.
Jeff from Illinois is now 47. In 1993 he was having surgery about every 3 months. It has now been about 14 months since his last surgery. He has been taking I3C.
Lindsay from New Jersey is now age 5 1/2. Between November 1991 and May of 1992 she had nine surgeries. She had two more surgeries in 1992 where no papilloma were found and she has not had any RRP symptoms since. Lindsay started I3C therapy in April of 92 and continues with it today.

Task Force and RRP Registry

Coordinator of the Task Force on Respiratory Papillomas, Craig Derkay, MD, has documented activities and preliminary data analysis results in an article entitled, "Task Force on Recurrent Respiratory Papillomas: A Preliminary Report". This paper has been submitted for publication in Archives of Otolaryngology - HNS.
The task force continues to work towards the initiation of a national registry of RRP patients. A comprehensive patient questionnaire has been developed and refined. The major obstacle to date has been the reluctance of the National Institutes for Health (NIH) to act on a request for funding of a researcher to be located at CDC for the purposes of collecting and analyzing data from RRP patients. We continue to urge you to let your congressional representatives and senators know about RRP and how a national registry could significantly help research and more clearly document the extent to which this disease represents a public health threat. Ask them to contact the director of CDC, regarding a national registry of RRP patients. His address is:
David Satcher, MD, Director
Department of Health and Human Services
Public Health Service
Centers for Disease Control
Atlanta, GA 30333

Others for representatives & senators to contact:
Director of Nat. Inst. for Allergy & Infectious diseases: Anthony Fauchi, MD
Assistant Secretary for Health:
Phillip Lee, MD
RRP Patient Stats

The statistics that follow are based on RRPF questionnaire responses. 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, early results from the adjuvant therapy surveys is presented on page 4.
Tables 1 - 4 provide a breakdown of the patients in the support group based on sex and age; the sample sizes for tables 1-3 range from 184 to 192 .

Table 1. Total number of patients in support group

	Females	Males
All Ages	84	108

Table 2. Distribution of patients based on current age brackets and sex

Under 10	44	47	91
10-20	15	18	33
20-30	5	7	12
30-40	7	6	13
40-50	7	14	21
Over 50	3	11	14

Table 3. Distribution of patients based on diagnosis age brackets and sex

Age Groups	Females	Males	Total
Under 10	64	71	135
10-20	3	3	6
20-30	7	5	12
30-40	2	11	13
40-50	5	10	15
Over 50	0	3	3

Table 4. Birth Statistics from Patient Support Network:

Cesarean birth in 7 cases - 123 responses
juvenile onset: 4 of 94 responses
adult onset: 3 of 29 responses
Patient is first born in 64 cases - 111 responses
juvenile onset: 57 of 84 responses
adult onset: 7 of 27 responses
Patient was adopted in 24 cases- 124 responses
juvenile onset: 24 of 100 responses
adult onset: 0 of 24 responses
Mother’s ages - 42 responses
20 or under: 20 of 42 responses
20 -> 25 : 12 of 42 responses

Thus far 55 medical centers/practices who are treating RRP patients have registered with the RRPF by completing practitioner questionnaires. They account for approximately 1012 patients, 512 pediatric and 500 adults.

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.
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With guidance from RRPF advisor Dr. Haskins Kashima, last summer we initiated a survey of patients and families in the RRPF support network regarding adjunct therapies for RRP. In this survey an adjuvant (or adjunct) therapy is defined as any treatment other than standard surgical procedures. Thus far 56 patients/families have responded, with 18 indicating that they have not used any adjunct therapies and 38 responding that they have tried adjunct treatments. Many of the 38 positive respondents have tried more than one therapy, which is why the total number of therapies indicated in the analyses that follows is 55.

Table 1. Patient/Family assessed impact of adjuvant therapies reported

Therapy	Users	Improve	Same	Worse	???
I3C	21	11	6		4
IFN	14	7	5	1	1
Acyc	7	2	5
PDT	7	3	4
Ribvrn	2				2
Retin	1		1
Others	3	2	1

Some notes regarding the above table are as follows:
The therapies are abbreviated as, I3C = Indole-3-Carbinol, IFN = Interferon, Acyc = Acyclovir, PDT = Photo Dynamic Therapy (using Photofrin), Ribvrn = Ribavirin, Retin = Retinoic Acid. Other therapies reported include Thuya (a homeopathic anti-viral), papilloma vaccine and Topical 5-Flourouracil. (5FU)
The column headings indicate (1) the total number of users for each therapy category who have responded to the survey, (2) those who have reported at least a partial positive response, (3) those who reported no response to the therapy, (4) those who reported that the therapy had a negative impact on their disease and (5) those who responded to the survey, but have not pursued the treatment long enough to determine what type of impact it would have. Typically anyone who had not been following a therapy for at least 6 months (or longer based on their RRP recurrence history) was classified in the “undetermined response category”. However, two of the four I3C users and the IFN user, that are currently classified as “undetermined”, have shown some encouraging early indications.
The users of 5FU and Thuya both report some improvement. The patient who had the papilloma vaccine reported no impact.
Regarding IFN therapies it should be noted that there was a significant variation in dosages and brands. Eight users report using Intron A, with two users of Wellferon and two users of Roferon; the others didn’t know the brand. Reported dosages varied from about 1 MU/M² every other day to 5 MU/M² every day. Almost all users reported some side effects, with fever being the most common and headaches, nausea and fatigue also being reported.
Finally, we remind our readers that these are early results based on patient perspectives. Although the survey encourages objectivity and quantitative assessment where possible, these analyses cannot replace well designed clinical trials and research. However, we hope that this information can still help those patients seeking adjunct therapies as well as those pursuing RRP-related research. .............................................................................

The RRPF has already written extensively 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 as well as Newfield et al., 1993, Anticanc Res 13:337-342). In the Fall 94 newsletter the RRPF encouraged researchers to better quantify the therapeutic role of I3C for RRP via carefully controlled clinical studies. We are pleased with the response of the medical research community and the cooperation of the producers of I3C as a nutritional supplement. Two medical centers have announced clinical trials involving I3C and Designed Nutritional Products has offered to provide their product free of charge for these trials (see address on page 5).

I3C Clinical Trial at University of Tennessee
by Clark A. Rosen, M.D.

This study is a Phase One trial, in which all participants receive daily oral I3C free for one year. Patients of all ages with active laryngo-tracheal papillomatosis (LTP - which is synonymous with RRP), are being accepted. The two main inclusion criteria are: (1) The patient is not presently taking I3C, and (2) They can come to Memphis for an initial evaluation and follow-up. Arrangements can be made to allow patients from long distances to participate if they can come to Memphis at the start of the trial and an acceptable agreement with their local otolaryngologist can be worked out regarding follow-up procedures.
This study does not require mandatory surgeries at a prescribed interval. Criteria for surgery will be twofold: (1) standard clinical indications for the establishment of a safe airway or to improve voice or swallowing function and/or
(2) if office endoscopy and documentation of the LTP growth is impossible because of patient factors.
There will be a requirement for regular clinical examinations that will include a video-endoscopic examination, review of symptoms from the LTP and any possible adverse reaction to the I3C. All patients will also have pre-treatment, 6 and 12 month voice recordings obtained. Urine specimens from patients will be analyzed by H.L. Bradlow prior to the start, at 3-4 weeks and then at random intervals. The latter testing is to measure compliance.
The principal investigators in this study are Clark A. Rosen, M.D., a Laryngologist, Gayle E. Woodson, M.D., a Laryngologist and Pediatric Otolaryngologist and Jerome Thompson, M.D., a Pediatric Otolaryngologist; all are on staff at the University of Tennessee, Memphis. Participating hospitals include Baptist Memorial Hospital, Methodist Hospital of Memphis and LeBonheur Children’s Medical Center.
It should be noted that all participants in this study will receive I3C; there is no special control group. If you are interested in obtaining more information please get in touch with one of the principal investigators as follows:

Clark A. Rosen, M.D.
University of Tennessee, Memphis - (901)448-7677
Gayle E. Woodson, M.D.
University of Tennessee, Memphis - (901)448-7677
Jerome Thompson, M.D.
LeBonheur UT ENT Office - (901)572-4400

I3C Clinical Trial at University of Alabama

The University of Alabama (UAB) is currently formulating the details of their trial protocol. As in the University of Tennessee trial, I3C will be supplied free of charge to all participants. The approach at UAB will involve a combination of clinical and basic research studies. In addition to quantitative assessment of papilloma growth, the plan is to assay blood and tissue samples as well as urine for estrogen metabolites and to perform parallel experimentation with the Broker and Chow raft culture system.
For more details please contact:
Brian Wiatrak, MD - (205)939-9834.
Thomas Broker, PhD - (205)975-8200
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For those who are unable to participate in an I3C trial, but would like to pursue this therapy on their own, approximate dosing information is based on preliminary results of Dr. Leon Bradlow's estrogen metabolism studies, as follows,
Estimated dosages - Adults 200 - 400 mg, Children (under 50lbs) 100 - 200 mg (Please consult your doctor)
I3C may be purchased by mail from the following supplier:
Designed Nutritional Products
Accounts Receivable
PO Box 1242
Orem UT 84059-1242 (801)224-4518
( note the above is a new address)

Designed Nutritional Products produce nutritional products in bulk including pure indole-3-carbinol (catalog #2704). It can be purchased in 25 gram amounts (bulk powder, not capsules - a level 1/8 tsp holds approx. 350 - 380 mg) for $46.50 + $5 shipping. They are not equipped for credit card orders, so one must pay by check. The check should be made out to Designed Nutritional Products and mailed to the address above. Include a note explaining that you want to order indole-3-carbinol catalog #2704. For those interested in very large quantities, you can inquire about the price of a kilogram of indole-3-carbinol.

A final I3C note: the digestive process is important to properly breakdown I3C (see RRP Newsletter - Spring 94 ). In this regard, try to avoid taking antacids and it would probably be best to take I3C at meal time. ..............................................................................

At this time, the proposal (by Haskins Kashima, MD) is pending review by several federal funding agencies.
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A new study of photodynamic therapy for recurrent respiratory papillomas is beginning in the Department of Otolaryngology at Long Island Jewish Medical Center. This study will use a new drug, meso-tetra(hydroxyphenl) chlorin, or mTHPC, that has a much shorter period of photosensitivity for patients than Photofrin (approximately 2 weeks as compared to 12-16 weeks). It also shows much more specificity for papillomas in our laboratory studies, with an absorption ratio of 10:1 for papilloma tissue compared to normal tissue, while Photofrin was usually only 2:1 (Lofgren, L.A., et al., Arch, Otolaryngol Head Neck Surg 120:1355-1362). Our previous study of photodynamic therapy, using Photofrin as the sensitizer, showed an average 50% reduction in recurrence rate, and several patients remain free of disease. We hope that this new sensitizer will be much more effective, with fewer photosensitivity problems for the patients.
This new study is FDA approved and to be eligible for the new treatment, patients must have had at least three surgeries to remove papillomas within the past year. The protocol will involve a six month observation period prior to PDT surgery and a one year follow-up period after the PDT. It is anticipated that funding will be provided to cover travel expenses for those participating in this trial. Patients interested in participating should contact Ms. Ginny Mullooly, Research Nurse Clinician, at (718) 470-7011. They can also arrange to send their medical records for evaluation to the following address:
Dr. Allan Abramson
Dept. of Otolaryngology
Long Island Jewish Medical Center
270-05 76^th Ave.
New Hyde Park, NY 11402
(718) 470-7555

.

Dr. Leon Bradlow has noted in cell culture studies (no human trials as yet) that another way has been found to induce 2-hydroxylation (the “ tumor suppressor” estrogen metabolism pathway). They have used Omega-3 fatty acids, or fish oil (capsules of which are readily accessible). We will continue to follow this with much interest.
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The RRPF invites patients and doctors to learn more about these and other experimental therapies. Before entering or recommending any experimental trial we suggest that you make inquiries regarding details of the protocol, all possible side effects, expected impact on papilloma growth, etc. The applicability of any treatment must be assessed within the context of each individual situation. The information given above is intended to provide some guidance.

RRP/HPV Typing
Some comments by Bill Stern

In the Fall 94 issue we wrote of HPV typing studies being conducted by Frank Rimell, MD, at Children's Hospital of Pittsburgh. He has informed me that his grant for these studies has ended and also that he will be moving to the University of Minnesota in July. He extends his thanks to all those who had samples sent to him and the results of his study has been submitted for publication. Comprehensive HPV typing of RRP samples is still being done at Children's of Pittsburgh by Dr. Garth Ehrlich; however, there would be a charge of $175.
With regard to HPV analysis and typing, I would like to take this opportunity to share some of our own experiences. Stimulated by some recent work in HPV typing and disease course, we resurrected a papilloma biopsy taken from our daughter, Lindsay, in November of 1991. The pathologist's report claimed that it was HPV 16/18 with no evidence of HPV 6/11 and moderate dysplasia was noted. Because HPV 16/18 is quite rare in respiratory papillomas, we were suspicious. In addition, later biopsy samples analyzed at places with known expertise in HPV typing, indicated that Lindsay’s tissues were type HPV 6. We are still awaiting final results on the reanalysis of this November 1991 tissue, but thus far the moderate dysplasia has been disputed and the HPV type has been narrowed down to HPV 6/11. How can there be such a discrepancy between laboratory analyses? In talking to experts such as Drs. Thomas Broker and Frank Rimell, many places use packaged kits which can often lead to inaccurate and sometimes misleading results. Furthermore, microscopic determination of dyplasia is subjective and is best done by one who has significant experience. HPV typing of respiratory papillomas should be done by pathology departments with state-of-the-art molecular genetic capabilities, experienced and specifically equipped to do it accurately. They should have customized probes for HPV types 6, 11, 16, and 18. They should be able to perform the analysis at high enough “stringency” to clearly discern an HPV 6/11 signal from an HPV 16/18 and preferably be able to separate HPV 6 and HPV 11. Some of the pathology labs that I know have this capability are: Univ. of Alabama at Birmingham, Univ. of Pittsburgh, Johns Hopkins, Long Island Jewish, to name a few. The lesson that we have learned is that if you are requesting an HPV typing analysis, make sure it is going to be done correctly by asking a few well placed questions.

RRP Patient Perspectives
The following perspective comes from Susan and Bob Spock and relates parental experiences on finding that a child is stricken with RRP:

My husband and I adopted Jeremy, our 12 year-old son, when he was eight weeks old. He has a very aggressive case of Recurrent Respiratory Papillomatosis. We have endured the trials of this dreadful disease (with surgeries now in excess of 200) and would like to share some aspects of learning to cope with this illness.
When Jeremy was first diagnosed at age eight months, we were overwhelmed and in denial -- how could our darling little baby be afflicted with such a disease. One could not see these growths, as it was not a visible disability. This led to anger over the unfairness of this illness, to both family as well as our child. Finally, we experienced a grieving period for the loss of what could have been, a child we thought was the picture of good health. As time marched on, we accepted the situation and began to look at just how we could best help our son. This entailed a search for the surgeon best known in the field, which would lead to our many trips to Children's Hospital in Los Angeles. For myself during this learning process, I needed to know as much as possible about the disease and asked a multitude of questions. In the beginning, the surgeon would draw a picture and score the growth areas, and later, he videotaped the surgical area before and after surgery to give us a better visual perception.
Have you ever been hospitalized?? Beside fear, did you also feel powerless?? We not only treat Jeremy's physical well-being, but also the ongoing emotional distress of each hospital visit as well. Children like a routine. Jeremy feels better if he knows just what to expect and the nurses play a vital role in maintaining this coping process. They greet him warmly and then give him as many options as possible, such as "Would you like flannel PJs or scrub greens like the doctor wears?" and "Would you like to ride on the gurney or walk to the OR?" Jeremy has always been frightened of the mask used to administer the anesthesia, so the anesthesiologist starts an IV first so that he need not worry about the mask. Jeremy expects the staff to remember these details, since this routine is what encompasses his comfort level. The nurses save baseball cards and pogs for Jeremy (we have enough of both to sink a battleship!!), and he has grown to anticipate these treasures. We have incorporated lunch at McDonalds and, often, a visit to the cousins on the way home. The nurses tell me that Jeremy gives them his McDonalds order as he is rolled into the recovery room.
At twelve, Jeremy is involved in those sports that are within his physical limitations. He loves to bowl and is on a bowling team. He loves to roller blade and go boogie-boarding at the beach. We watch our son grow bigger, stronger and more confident each day and know that this is truly a team effort. Through it all, the best thing to do is to step back now and then and make some time for yourselves.
The RRP Foundation is part of the team, offering support and keeping everyone informed. Please feel free to reach us if you need a good listening ear.

Susan and Bob Spock
1553 Via Allondra
San Marcos, CA 92069 (619) 744-5022

This next perspective was written by Jerry Boone discussing the benefits of a positive attitude when dealing with RRP:

As you read this article, please keep in mind that I write this from the viewpoint of someone with a milder form of RRP. When I was first diagnosed with RRP at 39 years of age, I was devastated. I required two operations per year and everyone remarked on the hoarseness of my voice. I needed two operations per year, but to me, it was two too many. My voice affected both my job and my hobby, singing and playing in a rock n' roll band. Initially, I focused on the things I couldn't do and felt I did not have much control over my future.
My turnaround came when I reasserted control over my life. First, I refocused my energies by thinking of all the other parts of me that did work. I worked around my hoarseness and pushed myself to do everything I normally would do. My band is still going strong. I sing when I can and play saxophone when I am unable to sing. I have minimized any insecurity I have about my voice at my job.
I believe a positive attitude affects our immune system, which in turn affects RRP regrowth. I have tried self-hypnosis, under a credentialed physician, to boost my immune system and slow RRP regrowth. Basically, I took control of my situation by doing something positive. Now, I am having great success with indole-3-carbinol (I3C).
Every time I take I3C I feel I am doing positive things for myself. It has been nearly 2 years since my last operation and I credit a positive attitude as much as I do the I3C. RRP does not control me anymore, and in fact, I believe RRP has made me enjoy what I have much more. My advice is to stay positive and make the best of your situation.

Voice Quality in RRP Patients
The following has been excerpted from an unpublished article written by Steven D. Gray, M.D, et. al., in the late 1980's.

Histologically, RRP is an epidermal disease that is confined to the epithelial layer and does not break through the basement membrane into the lamina propia or deeper tissue.
Papilloma growth may become so extensive that normal laryngeal anatomy, such as vocal cords, false cords, and ventricle, may be unrecognizable. This airway obstruction demands surgical treatment to remove the papillomatous growth before the patient suffocates. Precise laryngeal surgery is difficult because the surgeon may not be able to determine where the vocal cords are located in the mass of papilloma that needs to be excised. Inaccurate identification leads to inadvertent surgical injury to the vocal cords.
It can be difficult for the surgeon not only to discern where the vocal cords are located, but also to determine where papilloma growth in the epidermal layer ends and normal cord tissue begins. Vocal cord webbing, partial vocal cord excision, and glottic stenosis have been encountered. Following remission, the vocal cords may appear normal on mirror examination, but stroboscopy shows that the vocal cords are adynamic and stiff. This is most likely due to scarring that has occurred from previous surgeries.
The University of Iowa has treated 28 patients with severe RRP. To determine the effect of this disease and surgical treatment, four patients in remission were studied.
Patient #1 was diagnosed at age one and had 49 microlaryngoscopies with the minimum interval being three weeks. The patient had visible disease for 7.5 years. His voice is described as coarse, rough, like esophageal speech or false cord speech. However, when he sings, a clear sound with normal voice is produced.
Patient #2 was diagnosed at 1.5 years and had 46 microlaryngoscopies with the minimum interval being one month. The patient has had visible disease for 44.5 years. His voice is described as extremely high pitched - first impression being a "falsetto", very strangled-strained voice with some aphonia.
Patient #3 was diagnosed at ten months and had 34 microlaryngoscopies with the minimum surgical interval being 1.5 months. The patient had visible disease for ten years. His voice is described as mild breathiness, moderately hoarse, but okay pitch.
Patient #4 was diagnosed at age one and had 27 microlaryngoscopies with the minimum interval being one month. The patient had visible disease for 5.75 years. His voice is within normal limits.

Each patient represents a difference in severity of disease and type of surgical treatment experienced. For many years, the surgical treatment was to totally remove the papilloma. It was felt total removal could 1) cure or eradicate the disease, 2) prevent early regrowth of the papilloma, and 3) lengthen out the surgical intervals required to prevent papillomatous obstruction of the airway. This approach emphasized that all papilloma be removed and frequently resulted in the vocal cord epithelium being stripped.
As can be heard from the patients presented, some of them have residual scarring of their vocal cords; however, these tend to be the older patients who have been subjected to the total removal surgical approach. We have recently taken an active approach to preventing vocal injury in these patients. We advocate subtotal removal of papilloma in areas prone to vocal injury as well as important for vocal function, such as the vocal cords and the anterior commisure. At these sites, care is taken to prevent deep tissue injury. Additionally, to allow maximum identification of laryngeal structures during the surgery, patients are brought in to have their papillomas removed before the papilloma have obscured these important laryngeal structures.

The following article is written by Jean Wunrow, M.S., CCC, and discusses the voice quality of her son, Gregory, from a speech pathologist's point-of-view:

Our son Gregory, now 40 months old, was diagnosed with juvenile laryngeal papillomatosis (JLP) at 20 months of age. My husband and I were alerted to a potential "problem" more so because of his hoarse and deeply toned voice, rather than to any airway obstruction or breathing difficulty. Because I am a Speech and Language Pathologist, I was somewhat more aware of some of the many laryngeal pathologies that could be present, but I never expected a diagnosis of JLP! My area of study is in the field of language development, so we requested a consult with a Speech Pathologist whose expertise was in voice disorders. The clinician wrote the following article about Gregory's case:
I first met and heard Gregory before the family had even seen an otolaryngologist. With my interest in this particular area, you could imagine how my ears perked up! Gregory's presenting vocal quality was severely harsh and hoarse with a decreased habitual pitch for age and sex. At times, he was even aphonic (without voice) and exhibited stridor when breathing. I knew immediately that something was wrong and it definitely wasn't the typical "vocal abuse" case. Gregory was then seen by an otolaryngologist at Marshfield Clinic who diagnosed laryngeal papillomatosis. Surgeries to remove the papillomas began, but because the lesions tend to recur, Gregory had a long road ahead of him. Following several surgeries at Marshfield Clinic, Gregory was then entered in a research protocol at the University of Minnesota.
After my initial meeting with Gregory, I continue to follow him to monitor any changes and progress of his voice. Following most of his surgeries, his breathing improved and less effort for vocal production was noted, but there remained a marked hoarseness and decreased habitual pitch. However, with his most recent surgeries, laryngeal quality and habitual pitch have significantly improved, but are not yet normal for his age and sex.
The recent improvement in laryngeal quality is surprising as one might expect trauma and damage to the true vocal folds from repeated surgical intervention. One must consider many variables to the recent improvement, but one aspect that I am interested in deals with the development of the layer structure of the vocal fold. Maturation of the layered structure of the vocal fold is not completed until around the end of adolescence. As I think about this, the long-term effects on the health of Gregory's laryngeal mechanism and perceptual quality of his voice could be minimal, but time will tell.
I cannot express enough the importance of early involvement of a speech pathologist trained in the area of voice. At a very young age, intervention with formal voice training is usually not indicated. However, the speech pathologist can be very helpful in providing education and information regarding vocal hygiene, vocal conservation, and the importance of avoiding vocally abusive behaviors to the family. Once the child reaches an appropriate age and the papillomas have ceased recurring, or perhaps between episodes of recurrence, voice therapy may be appropriate in order to maintain or restore the most efficient voice production and prevent and/or eliminate unwanted compensatory behaviors. The long-term prognosis for Gregory's voice will ultimately depend on the state of the vocal fold mucosa.

Lisa A. Polenz, M.S., CCC, Speech Pathologist
Marshfield Clinic (715) 387-5128

As of February, 1995, Gregory has had 18 surgeries and is enrolled in a ribavirin/placebo study at the University of Minnesota. As parents, we are not only concerned about his airway, but also about his vocal quality. We have already overheard other children refer to our son as the kid with the "monster voice." While he is still too young to be affected by any of this, we know it is only a matter of time.
It is possible, via a stroboscope, to obtain a visualization of the larynx during sustained phonation. Norms for these vibratory characteristics will vary from age to age. We have not yet elected to opt for this level of precision since this involves another invasive procedure.
As the above article stated, many internal factors affect voice quality. One external factor may be that of surgical technique. It has been our empirical observation that there is a difference among surgeons with regard to vocal quality post-surgical intervention. While the mainstay of the interventions must be to maintain an adequate airway, we feel there exists a need to somehow quantify which surgical techniques result in optimal outcomes for both vocal quality and time between interventions. Since it appears that, for the near future, laser excision will continue to be the standard of laryngeal papilloma treatment, it is our hope that some institution will conduct such a study with regard to vocal quality.
Jean Wunrow, M.S, CCC, is a Speech and Language Pathologist for the Marshfield Public School System in Wisconsin. Her husband David is a registered Pharmacist for an HMO. Gregory is an adopted Korean, who joins a biological sister, Lindsay, who is ten years old. The Wunrow's home phone number is (715) 387-8824.

In Memory of Katherine Wessinger
A member of the RRPF support network, Katherine Wessinger died on February 8, 1995, at the age of 72. Katherine, who was diagnosed with RRP about 25 years ago, experienced particularly aggressive disease for an adult. She had a tracheotomy, progressive involvement of papillomas in her lungs and had undergone approximately 200 surgeries. Yet despite all this, in recent conversations she seemed particularly interested in how RRP was affecting children, rather than expressing concern for her personal situation.
Surviving, are her husband, Murphy S. Wessinger, son, M. James Wessinger and daughter Sandra W. Titcomb.