Recurrent Respiratory Papillomatosis

NEWSLETTER

Vol.5 No.1 An RRP Foundation Publication 1996 Spring

____________________________________________________________________________________________________________This This issue of the RRP Newsletter is dedicated to a patient in the support group who passed away in October of last year, Ruth Ellen Berke, who was 53 years old. A memorial is included on the back page of this issue.

Contents

• Opening comments - p. 1

• RRPF organizational information - p. 2

• RRP Remission and Network News - p. 2

• RRP National Issues - p. 3

• Patient Statistics - p. 3

• Update on Adjunct Therapies and new protocols - p. 4-6

Adjunct Therapy Survey Update - p. 4

indole-3-carbinol - p. 4-5
Mumps vaccine and RRP - p. 5

• RRP Perspective - p. 6

• Patient profile - p. 7-8

• Editorial comment - p. 8

• Award announcement - p. 8

• Patient memorial - p. 8

• RRPF Mission Statement, Information/Support Centers, subscription form - enclosure

From the Editors

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). Additional help is needed to continue and build on the efforts of the RRPF (please see additional comments on page 8). Specifically:
1) We need at least one additional volunteer to help us maintain and expand our informational databases.
2) We need people to help us gather information, write articles and serve as editors for the RRP Newsletter.
3) Additional help would also be welcome in conducting literature searches and coordinating RRP Medical Reference Service issues.

If you would like to help in any way, please contact me at the address and phone number listed on page 2.

Thank you.

Bill Stern

RRPF Publication and Subscription Policy

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

(see RRPF subscription form enclosed)

[Note: Back issues of the RRP Newsletter and Medical Reference Service ($10/issue) are available upon request, subject to availability]

We are most grateful to all those individuals, medical professionals and corporations who have supported the RRPF. In this regard we would like to take this opportunity to acknowledge a special grant to the RRPF from the Cheryl A. Levantini Fund in honor of RRP patient Adam Kotler. Although it is impossible to publish the names of all who 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
50 Wesleyan Drive
Hamilton, NJ 08690

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.

We would like to take this opportunity to acknowledge donations received from the following local United Way chapters during the past year: San Diego County, CA., Washington, DC. and Mercer County, NJ. We thank all those individuals who contributed in this way. Your help is very much appreciated.

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

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, NW., Suite 301

Washington, DC. 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 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

Bettie M. Steinberg, PhD, Long Island Jewish Medical Center

Kathleen Sullivan, RN, Children's Hospital of Boston

[ Please see the enclosure for a complete list of the RRPF regional and state coordinators]

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RRP Remission News

These very brief patient profiles are intended to let you know that some of those with RRP are doing quite well.

Emily from Michigan, almost eight years old, is now experiencing her second remission from RRP. After being diagnosed at age 2 she had approximately 12 surgeries in a year and then went into a 2 year remission. At age 5 Emily came out of remission, had 12 more surgeries through October 94, when she began I3C, and has been free of papillomas since then.

Andy from California, now almost 9 years old, has been clear of papillomas since November of 94. He was diagnosed at 3 1/2 years old and had surgeries regularly spaced 5-8 weeks apart. In 1992 he began interferon therapy and in 1995 acyclovir was added, but now both adjunct treatments have been stopped.

Kaitlyn from Tennessee has been in remission since her 5th surgery in March of 1995. She has had two more direct laryngoscopes since then at which no papilloma were found and has not pursued any adjunct treatments.

Talia from Colorado has been free of papillomas since the fall of 1995. She had a very aggressive history of RRP and was treated with mumps vaccine earlier in 1995 (more details can be found on page 5 of this newsletter issue).

Others still in remission include: Leah from New Hampshire who is now 16 years old; Steph from Florida, age 22; Melissa from New York, now age 6 1/2; Smokey from Virginia, age 24; Ariel from California, now 4 1/2 years old; Jeff from Illinois, age 48; and Lindsay from New Jersey, now age 6 1/2 (see patient update for more details).

RRP Network News

Our international support network has grown to approximately 300 respiratory papilloma families. Patients range in age from 1 to over 78 years and are located in 40 states, the District of Columbia, two Canadian provinces, the United Kingdom and Macedonia.

We have received questionnaires from about 180 families in the support group and adjuvant therapy surveys from about 75. Included with this newsletter issue is a revised more comprehensive RRP patient/therapy questionnaire which is designed to replace both our earlier patient questionnaire and adjuvant therapy survey. This questionnaire follows a format developed by RRPF Scientific Advisor, Dr. Haskins Kashima, for his RRP patients at Johns Hopkins. Even if you have filled out all earlier questionnaires, please take a few minutes to fill out the accompanying forms. Please note that Dr. Kashima has requested that 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. 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. If you are not included in the directory and would like to be, please notify Bill or Marlene Stern.

Communication and information exchange throughout the support group and the RRP community remains a primary focus of the foundation. The RRPF maintains an account with America-On-Line (AOL) and can arrange for you to have a limited amount of free time on AOL for RRP related communications; just get in touch with Bill Stern. We now have a page on the World Wide Web (WWW); the address is (http://members.aol.com/rrpf/RRPF.html) . In the near future it will be cross linked with the WWW home page of the University of Alabama, Birmingham, Department of Biochemistry & Molecular Genetics (http://www.bmg.uab.edu) and a papilloma page created at Tufts University by med. graduate student John Strasswimmer (http://WWW.healthsci.tufts.edu/microbiology/strass/JSpage.HTML) . The UAB page will link information about the international papillomavirus community plus other HPV related material.

RRP National Issues

Development of an RRP National Registry is now underway. It is being established by Dr. Lori Armstrong at the Centers for Disease Control and Prevention, who should be ready to provide a progress report for the Fall 96 issue of the RRP Newsletter.

A successful RRP registry will require continued funding. In addition, 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 need to contact our congressional representatives and senators to make them aware of RRP and mobilize their support. Regarding specific CDC funding of a National Registry for RRP, ask them to contact :

The director of CDC:

David Satcher, MD, Director

Department of Health and Human Services

Public Health Service

Centers for Disease Control

Atlanta, GA 30333

The director of the National Center for Infectious Diseases:

James Hughes, MD, Director
National Center for Infectious Diseases

Centers for Disease Control

Atlanta, GA 30333

Others for representatives & senators to contact:

The contract officer at NIH.:
Dr. Penelope S. Hitchcock
Chief, Division of Microbiology & Infectious diseases
National Institute for Allergy & Infectious diseases
Solar Bldg., Rm. 3A24

6003 Executive Boulevard
Bethesda MD 20892-7630

Phone: (301) 402-0443; Fax: (301) 402-1456

The director of the FDA:
David A. Kessler, MD
Commissioner of Food & Drugs
Food & Drug Administration
Park Lawn Bldg., Room 1471
5600 Fishers Lane
Rockville, MD 20857

Director of Nat. Inst. for Allergy & Infectious diseases:
Anthony Fauci, MD

Assistant Secretary for Health:
Philip 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 251 to 266.

Table 1. Total number of patients in support group

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

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

Table 4. Birth Statistics from Patient Support Network:

Cesarean birth in 9 cases - 173 responses

juvenile onset: 5 of 128 responses

adult onset: 4 of 45 responses

Patient is first born in 90 cases - 158 responses

juvenile onset: 75 of 115 responses

adult onset: 15 of 43 responses

Patient was adopted in 33 cases - 171 responses

juvenile onset: 32 of 130 responses

adult onset: 1 of 41 responses

Mother's ages - 61 responses (juvenile onset only)

20 or under = 36

20 -> 25 = 18
> 25 = 23
Total responses = 77

Thus far 70 medical centers/practices who are treating RRP patients have registered with the RRPF by completing practitioner questionnaires. They account for approximately 1143 patients, 598 pediatric and 545 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.

Adjuvant Therapy Survey Update

by Bill Stern

Adjunct therapy survey responses from 75 patients/families have been received. Of those responding 21 indicated that they have not used any adjunct therapies and 54 responded that they have tried adjunct treatments (many have tried more than one). The most reported therapy was indole-3-carbinol (I3C) with 31 users and next was interferon (IFN) with 21 users responding. The patient/parent assessed impact of some adjuvant therapies is summarized in the following table.

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

Some notes regarding the above table:

The therapies are abbreviated as follows, I3C = indole-3-carbinol, IFN = interferon, Acyc = acyclovir, PDT = photo dynamic therapy (using Photofrin), Ribvrn = ribavirin, Retin = retinoic acid or accutane. In the category of other therapies used, improvement was noted by 3 patients (or parents) using, respectively, mumps vaccine (see page 5 for more details), topical 5-flourouracil (5FU) and Thuya (a homeopathic anti-viral). One patient reported no impact when, a few years ago, they were injected with extracts of their own papilloma in an attempt to elicit a response to an autologous vaccine.

As indicated in the RRP Newsletter issue for the Spring of 95, there was significant variation in dosages, brands and types of IFN used. (Most clinical trials have been with interferon-alpha. Additional controlled studies of interferon-beta, interferon-gamma and imiquimod, an inducer of interferons, are still needed.) Almost all IFN users reported some side effects, with a low grade fever being the most common complaint, and headaches, nausea and fatigue also being reported. I3C does not generally produce any obvious side effects, although there was one report of some minor stomach upset upon starting the therapy and two reports of temporary dizziness when a significant overdose was consumed.

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. We do hope that this information can provide guidance for those patients seeking adjunct therapies as well as those pursuing RRP related research.

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indole-3-carbinol Update

by Bill Stern

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 as well as Newfield et al., 1993, Anticancer Research 13:337-342

Preliminary Results of the Use of indole-3-carbinol for Recurrent Respiratory Papillomatosis

by Clark Rosen, MD,
University of Pittsburgh, Children's Hospital

We report the preliminary results of a phase I trial usingindole-3-carbinol (I3C) for the treatment of recurrent respiratory papillomatosis (RRP). I3C is a chemical that is found to be in high concentration in cruciferous vegetables and has been shown to alter the growth pattern of RRP cell cultures and be effective in an in vivo animal model of RRP. Methods: Eleven patients (6 male) have been treated with oral I3C and have a minimum follow-up of 8 months with a mean follow-up of 10.3 months. All patients received I3C and outcome measures were the change in papillomagrowth rate and the need for surgery during treatment compared to each individual's own pre-treatment history. All patients had serial examinations with videoendoscopy to document papilloma location and growth rate. Results: Fifty-five percent (6/11) of the study patients experienced a cessation of their papilloma growth and have not required surgery since the start of the study. One patient has experienced a reduced papilloma growth rate and four (36%) patients have shown no clinical response to I3C. indole-3-carbinol affects the ratio of the two major hydroxylation products formed during the metabolism of estradiol; ratios of 2-hydroxylation and 16-a hydroxylation of estradiol in the urine will be presented in all the patients and correlated with their clinical response. No major complications or changes in the children's growth curve have been noted. Conclusions: The preliminary results of treating RRP with I3C holds promise. Longer follow-up of this patient group and a blinded, controlled trial are required. We conclude that I3C is an effective treatment in a majority of patients with RRP.

Dr. Rosen, is currently enrolling patients for the I3C study at the University of Pittsburgh and University of Tennessee.

If you are interested in obtaining more information about these clinical trials, please get in touch with one of the principal investigators as follows:

University of Pittsburgh:

Clark A. Rosen, MD. - (412) 647-2112

University of Tennessee:

Gayle E. Woodson, MD. - (901) 448-7677

Jerome Thompson, MD. - (901) 572-4400

I3C Scientific Study at University of Alabama (UAB)

Investigators at UAB are finalizing the details of their proposed I3C research project. The approach at UAB will involve a combination of clinical and basic molecular and cellular research studies. It will also involve a collaboration with the Department of Obstetrics and Gynecology concerning genital warts. 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 epithelial raft culture system in the lab of Tom Broker and Louise Chow .

For more details please contact:

Brian Wiatrak, MD - (205)939-9834.

Thomas R. Broker, PhD - (205)975-8200

Genetic Testing and indole-3-carbinol

Dr. Karen Auborn of Long Island Jewish Medical Center and Dr. Leon Bradlow of the Strang Cancer Prevention Center are currently collaborating on an investigation of why some persons fail to respond to indole-3-carbinol. (I3C) This study, involving genetic testing, is looking to evaluate and identify defects in the enzymes in persons with RRP. Swabs taken from the inside of cheeks are used in the analysis process. The ultimate goal of this study is to clearly identify genetic deficiencies in people who fail to respond to I3C and with this knowledge to be able to propose an alternative approach for inducing a response.

RRPF I3C Research Coordination Efforts

The RRPF continues to encourage research studies involving I3C as an RRP adjunct therapy. In this regard we suggest that those patients who are interested in I3C as an adjunct treatment for RRP become part of a clinical trial. For those who are unable to participate in an I3C trial, but who would like to pursue this therapy on their own, we have been providing information regarding how and where to get I3C and how much to take. In addition, last fall we began supplying urine analysis testing information and supplies to RRP patients upon request. Thus far we have had requests for and have mailed out 19 test kits. Twelve kits have been sent to Strang Cancer Prevention Center for analysis and two patients have since decided to enroll in a clinical trial. To date, urine assay results have been received for 6 of the 12 sets of samples submitted and this information has been passed along to the patients and/or families. In this regard we ask for your patience. These analyses are being performed as part of a research program by a limited number of scientists, not by a fee for service laboratory that receives a direct payment for each test completed.

How to get I3C and How much to take

As indicated in the Fall 95 newsletter issue, Designed Nutritional Products is no longer selling I3C to retail customers.

I3C may now be purchased from:

THERANATURALS Inc.
PO. Box 344
Orem UT 84059-0344

(801)224-8893 - Telephone and Fax
[They are able to take orders by phone]

Theranaturals is selling I3C in capsule form, each capsule will be guaranteed to contain 100 milligrams of I3C*. Each bottle will contain 100 capsules.
Pricing (which includes surface UPS shipping) : $35.00 for one bottle; $95.00 for a package of 3 bottles
add $10.00 to above prices for Fed X shipping.

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 (Please consult your doctor)

* [ Please let us know if the change in supplier or the change from powder to capsules presents any problems (perhaps for children who cannot swallow pills). In addition to the 100 mg of I3C guaranteed to be in each capsule, there is considerable “filler” which we are told in no way should compromise the ability of a person to induce the desired estrogen metabolite changes. We very much welcome your feedback on this issue.]

The RRPF will provide urine sampling and mailing kits to those people not enrolled in an I3C trial who would like to have their urine tested for the ratio of estrogen metabolites. Contact Bill Stern (609-890-0502) for more details.

A final I3C note: We want to remind all those patients currently taking or proposing to take I3C, that 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.

Can Mumps Vaccine be used therapeutically for RRP?

by Bill Stern

Late last year I was contacted by a member of our support network, Lisa Talve, to tell me of a dramatic improvement in her daughter (Talia) since she had received mumps vaccine therapeutically for her RRP. I made a note of this, but did not investigate any further until recently, when the mother of a second RRP patient called with a similar account. A recent update on Talia Talve indicates that she had approximately 30 surgeries between ages 2 and 4 1/2, with the longest interval between any surgery being 7 weeks. She had been treated with the mumps vaccine during the past year and now at age 5 1/2 appears clear of respiratory papillomas as determined by two direct laryngoscopes in the past three months.

These phone calls motivated me to contact their treating Otolaryngologist, Dr. Nigel Pashley. Dr. Pashley indicated that he first heard of using mumps vaccine to treat RRP during a presentation at an Otolaryngology meeting in the early 80s. He doesn't believe that there is any published article on this therapy. (I also could not find any references involving mumps vaccine for papillomas via a medline search back to 1966.)

He first tried this therapy in 1983 on a girl with fairly aggressive RRP. His approach was to remove the papillomas and then inject the vaccine locally into the sites where the papilloma growths previously had been. In this case he administered the vaccine only once. Following treatment the interval between surgeries extended until the patient went into a remission. He lost contact with this patient for 3 years after the vaccination was applied, but he does know that she has been disease free for at least the last 4 years.

In recent years Dr. Pashley has used the vaccine more regularly. He has given this vaccine to seven juvenile RRP patients, who had regular recurrence intervals ranging from 2 to 6 weeks. His approach in these cases has again been to inject the vaccine locally following excision of papillomas, but now he is re-vaccinating each time the patient returns until no new growths appear. Six of the seven cases are now in some stage of “remission” or at least a no new growth status and the seventh case has seen the interval between surgeries more than double.

Dr. Pashley is cautiously optimistic about this RRP treatment approach. He readily admits that his methodology here would not nearly satisfy rigorous, controlled scientific research standards. However, these anecdotal successes are highly suggestive of some real cause and effect. Since all of his patients should have mumps virus antigens as per early childhood inoculations, one might speculate that introduction of a new mumps vaccine booster shot in the larynx could trigger some locally elevated inflammatory response which, in a non-specific fashion, may suppress HPV reactivation during the process of healing from surgery.

Dr. Pashley is happy to discuss his work with other RRP practitioners and RRP researchers. He can be contacted at:

Nigel Pashley, MD
1601 East 19th Ave.
Suite 5500
Denver, CO 80218
phone: (303) 839-7900
fax: (303) 839-7930

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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 Perspective

My Experience with RRP

by

Jennifer Woo

I'm only twelve years old, but I'm like many kids with RRP. I'm not blind to the horrors of this disease, and to be perfectly honest, it's come pretty close to taking everything, including my life, away from me. How could I not see the trouble it causes?

I was diagnosed when I was nine months old or at least somewhere around there. I was too little to remember. But my first head-on experience with the reality of my disease came when I was only about three years old. At daycare, one would only hear me speak once and would assume I had strep throat, causing slight unpopularity amongst many on my part. A teacher or two even veered away from me at first.

By the time I turned five, I realized that I wasn't very much like the others in the area of health. That was because, by July 1989 nearly my entire airway had been overtaken by papillomas; and when I was rushed to the Georgetown University Hospital in the middle of the night, it was almost too late. I spent two weeks in intensive care, sucking on ice chips and wishing desperately to go home. My earliest hospital memory was that of me sitting in the ICU, holding a cup of ice chips and watching a James Bond movie with my dad, unable to speak. The day I checked out, my stitches were removed (where a special arterial oxygen monitor had been inserted), and I remember the pain as though it happened this morning at breakfast. A nurse approached my bedside and promised that it would burn only a little bit but my entire wrist felt like it had been torched.

But as they say, you get older and wiser every year. As I grew up, I had more and more hospital encounters. All of my subsequent operations were at Children's in Philadelphia, which is renowned for its spectacular service, but how much does that mean to a seven-year-old in pain? I didn't know that I was being poked and stitched in order to save my life. I only knew that I was being separated from my parents, forced to have an IV shot into my vein and it hurt unbearably.

Fortunately, I haven't been on the operating table in two years. But that doesn't mean that the consequences of RRP have ended for me. Just today I went on a field trip to the Washington Post and National Geographic. The first thing my chaperone said when we introduced ourselves was a curt, "You sound horrible. Are you sure you should be here?" Of course I told her I was fine, but even then she looked skeptical. At the beginning of the school year, my teachers were hugely protective of me - if I didn't have a water bottle in my hand, I would be grilled.

It's such a long story to explain what's behind my unusual voice, so when people ask, I simply go with, "I normally talk this way." If they want more, I'll add, "I've had a lot of operations." And if they keep probing in an inexcusably rude way, a cold stare will usually do the job. It's not friendly, but aren't we guaranteed the right to privacy when it is desired? I might not be able to speak loud, but there's no doubt that I can speak out. And, to quote a line from the film PHILADELPHIA, "I wasn't raised to sit in the back of the bus."

I am lucky that I have a voice at all, even though it may not be booming or loud. So maybe I'll never be a cheerleader. I might never be the next Kathleen Battle. But I've learned that RRP can't take over you unless you let down your guard. My friends have learned that, too, and even they have become somewhat protective of me. Being twelve is hard enough without the complications of the disease, but if you get used to it and stay healthy, you won't be touched by it until you let it. You've got to be normal. I consider myself anything but different. My passions are animal rights, swimming and living life to its fullest. My slight vocal handicap is one thing that will never stop me. And to those out there who share the wisdom carried by RRP... I have already refused to become a victim of this disease. I am, and always will be, a survivor.

RRP Patient Profile

[In this issue we are exercising our editorial prerogative and presenting the case history of Lindsay Stern, daughter of RRPF officers Marlene and Bill Stern. The following article will attempt to combine our RRP experiences as parents of a child with this disease, as coordinators of an RRP support organization and a few excerpts from a scientific case history about Lindsay written by Clark Rosen, MD, et al. ]

We adopted Lindsay from Korea when she was 13 months old. From the first day that she was with us we noticed that she had a low cry and a faint deep voice. We often mentioned this to our pediatrician, who said that we were “lucky” that we didn't have a baby with an ear piercing scream. She seemed generally happy and healthy, except for an occasional cough, croup, and constant ear infections. Shortly before her second birthday she seemed to be breathing loudly and then began snoring loudly when sleeping. After more than a month involving many visits to the pediatrician, diagnoses ranging from post-nasal-drip to asthma to croup and 3 weeks of prescribed ventolin and prednisone treatment, we were referred to a local otolaryngologist, Dr. Stephen Farmer, in Princeton. After looking into Lindsay's larynx with a scope, he sat us down and told us what he knew about this disease, that we (and our pediatrician) had never heard of. He referred us to Mount Sinai Medical Center for emergency admission that evening, November 14, 1991. Lindsay was scoped again and the resident otolaryngologist suggested the possibility of a tracheotomy (at this point we barely knew what a trach was, let alone the implications when it is used in conjunction with RRP). The next day Dr. Peter Catalano performed a laser surgery; thankfully, he was able to avoid a tracheotomy, despite the fact that she was nearly 99% obstructed. ( We remembered the embattled and exhausted look on the face of the anesthesiologist after coming out of surgery. Lindsay was the most severely obstructed two year old they had ever seen!) She spent 9 days at Mount Sinai with a second laser surgery 6 days after the first.

We had many questions and received only a few answers. No one seemed to know much about RRP, only that it is rare. Were we all alone with this disease? What type of life did our little girl face and how many more surgeries will she have to endure? Will she live to go to college, get married and raise a family? Is there anyone doing any research to try to find a cure? No one knew of any support group. We scoured the Mount Sinai medical library for information. The little bit of literature about RRP that we found, told us that it was virtually certain to reoccur for some time. We very much needed to reach out and talk with others in similar situations. It was this deep need for emotional support that motivated us to seek others and develop a support network of RRP families.

We began the process of reaching out to others by contacting the otolaryngology departments of major medical centers in the Northeast US. In our search we found out that Children's Hospital of Philadelphia (CHOP) had a significant RRP patient population and the otolaryngology department clinical nurse, Linda Miller, provided a wealth of information (and if it wasn't for Linda's support and guidance, we might not be coping today). Over the next 6 months Lindsay had 7 more surgeries, all at CHOP.

During this brief but aggressive period we felt our emotions wax and wane as this disease went through its unexplained ups and downs. For example, Lindsay's 5th surgery since diagnosis occurred on February 13, 1992, it was her best to date. Her surgeon, Dr. William Potsic, told us that he found only a small amount of papilloma on the false and true cords (using the Kashima scoring system, my estimate was a score of 2, where 0 is none and 27 is total coverage and obstruction). He lifted our spirits by predicting that we should be able to extend the surgical interval to at least 5 weeks. Well, this fickle, uncaring disease gave us a significant emotional blow, when less than 3 weeks later Lindsay began snoring loudly and her nighttime breathing had become distressed (i.e., early stage stridor). Unfortunately, this was a Friday night, which meant an emergency room admission. In anticipation of some difficulties, we video-taped Lindsay's breathing while she slept that night. On Saturday morning we went to the CHOP emergency room and, as we feared, were presented with difficulties. The emergency room doctors didn't really have a clue regarding RRP, saying that she might have a touch of bronchitis and were going to send us home with ventolin. We insisted on having the otolaryngology resident on call examine her. He also was about to release her, not finding any significant respiratory problem in his exam. But she was awake now, and as parents of an RRP patient we knew that respiratory problems from papilloma always appear more noticeably at night while asleep. We insisted that he look at this video of her sleeping the night before. Reluctantly, he agreed, and 20 minutes later he came back saying that she was obstructed and would be admitted. Our difficulties in this situation did have some positive impact on emergency admission policy for RRP patients at CHOP. Based on our experience, Dr. Potsic, who very much believes that parents are the best judge of when their kids with RRP are ready for surgery, instituted a policy that a child with RRP will be admitted and surgery performed on their parent's say so.

Lindsay continued in an aggressive mode, requiring surgeries 7 and 8 over the next 5 weeks - we were starting to consider adjunct treatments, such as acyclovir or interferon. About a week after her eighth surgery, we received a call from Linda Miller. She had just spoken to someone from Long Island Jewish Medical Center (LIJ) and during the conversation a study involving indole-3-carbinol (I3C) and RRP was mentioned in passing. We quickly pursued this by contacting the LIJ department of Otolaryngology and were put in touch with the researcher, Dr. Karen Auborn. Dr. Auborn told us of encouraging results with a mouse study and suggested cruciferous vegetables as a source of I3C. She estimated that about 8 ounces of cabbage (or about 4 ounces of cabbage juice) might provide a sufficient amount of I3C to induce a shift in estrogen metabolism so as to suppress papilloma growth (see the RRP Newsletters Fall 93 through Fall 94 as well as Newfield et al., 1993, Anticancer Research 13:337-342). Lindsay's 9th surgery occurred several weeks after initiation of a daily regimen of between 4 and 6 ounces of cabbage juice ( The juice was made palatable by mixing approximately 2 oz. of cabbage juice with 5 oz. of apple juice.) In contrast to the 8th surgery, which (like most of the prior operations) involved laser excision of a large amount of papillomas from multiple sites, the ninth surgery revealed a very small amount of papilloma which could easily be removed with a micro laryngeal forceps.

Lindsay continued the cabbage juice regimen and had two more visual examinations of her respiratory tract under general anesthesia at which time no papilloma were found. The first was at the end of June 1992, six weeks after her ninth surgery and then again at the end of September 1992, shortly before her third birthday. At the beginning of 1994, when it was learned that we could obtain I3C in powdered form we gradually modified her sources of I3C to include approximately 190 mg of powdered I3C daily and reduced her cabbage juice intake to about 2 ounces per day. Today, at 6 1/2 years of age, Lindsay continues this therapy and has remained free of symptoms for a total of 47 months.

We are most thankful for Lindsay's apparent remission and wish the same for all RRP patients. It is our firm belief that I3C played a key role and this appears to be born out by the accounts of some others in the support group as well as the clinical work of Dr. Clark Rosen and Dr. Karen Auborn. We know that I3C does not work for everybody, but we are optimistic that progress is being made in a variety of treatment approaches.

This article would not be complete without noting that without the inspiration of a number of RRP practitioners and researchers (whose names are listed on the RRPF Scientific Advisory Committee and Board) we would not have been motivated to actively seek information, network and organize. In particular, we are indebted to an article in the New York Times early in 1992 which allowed us to contact Drs. Tom Broker and Louise Chow. Tom literally spent hours on the phone with us. His enthusiastic support for developing a close working relationship between RRP researchers and patients was critical in directing our efforts and creating the RRP Foundation.

Editorial Comment

The RRPF as a Community Effort

As implied in the case history of our daughter Lindsay, RRP has dramatically changed our lives. Our priorities in life went through a major restructuring, i.e., finding the best treatments and a cure for this disease was put at the top of our list. To this end the RRP Foundation (RRPF) came into existence. We feel that the RRPF's organizational goals of networking the RRP community and providing a forum for exchange and coordination of RRP related information have been achieved to a reasonable degree.

However, what we are finding is that the RRPF has grown beyond the point where Bill and Marlene Stern can effectively manage it without significantly more help. Those day to day operations which are fundamental to the RRPF are consuming so much of our time and energy that there is little or no time left to pursue other creative efforts. Furthermore, those other high priority items on life's list, i.e., quality time as a family and being actively involved with many other aspects of our daughter's journey through life, are not getting nearly the time they deserve. Although we plan to remain active in the RRPF, Marlene and I must reduce our level of involvement so that we may better address personal and family matters that very much need our attention. In this regard I appeal to the RRP community to help us. We welcome all offers of assistance, especially those which deal with the fundamental tasks of running the RRPF (as indicated on page 1).

We do very much appreciate the efforts of some individuals who have contributed their time to the RRP cause, but if the RRPF is to survive and continue to grow, it must be the result of a community effort. Its future success will depend on the collective energy, creativity and hard work of a much broader segment of the RRP community.

Thank you for your help,

Bill and Marlene Stern

Award Announcement

[ The RRPF congratulates Louise Chow and is quite pleased to include the following announcement, which is excerpted from the April 5, 1996 issue of the University of Alabama Birmingham publication Synopsis ]

American College of Physicians Honors
Louise T. Chow

Comprehensive Cancer Center Senior Scientist Louise T. Chow, PhD, will receive the prestigious 1996 American College of Physicians Award for Distinguished Contributions in Science as related to Medicine on April 25 at the annual meeting in San Francisco.

Dr. Chow is an internationally known researcher on the human papillomavirus (HPV) and its role in cervical cancer. Together with her husband, biochemist Thomas R. Broker, PhD (RRPF scientific advisor), she is the discoverer of the phenomena of interrupted genes and messenger RNA splicing in higher organisms, in collaboration with colleagues at the Cold Spring Harbor Laboratory in New York - work that was the foundation of a 1993 Nobel Prize.