Vol.2 No.2          An RRP Foundation Publication                   1993 Fall

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From the Editor

In this issue of the RRP Newsletter we discuss contagion of RRP in social and family settings. Can this disease be acquired through casual contact?

Some additional highlights include:

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 are now offering an RRP medical reference service. Upon request, we will provide RRP related lists of medical references updated semi-annually. All we ask for is an annual tax deductible donation of $25 or greater to the RRP Foundation.

We are asking for your help in supporting this newsletter and other RRP support services. Although all of our time is donated strictly on a volunteer basis, it costs money to publish and distribute this newsletter, to maintain a long distance telephone network, to run periodic medical literature searches, and to carry out additional support and awareness activities . Any donations from individuals or from the business community will be very much appreciated. We have been granted a 501(c)(3) tax exempt status by the IRS. Tax deductible contributions may be made to:

RRP Foundation
50 Wesleyan Drive
Hamilton, NJ 08690

Bill Stern

IS RRP CONTAGIOUS?

by Bill Stern

The fact that recurrent respiratory papillomatosis (RRP) are far from household words, speaks to the non-contagion of this disease

I believe most otolaryngologists agree that RRP is non-contagious in social and family settings. However, there appears to be a significant amount of concern regarding the contagiousness of this disease among many who are less knowledgeable. For example:

This last situation prompted the RRP Foundation to contact a number of medical experts who are quite knowledgeable about RRP. We described the classroom incident and posed the following questions:

Responses were received from eight medical experts. The following are selective quotes from comments in their personal correspondence:

Contagion, continued on page 4

To physicians and nurses: Please distribute copies of this newsletter to your RRP patients.

RRPF Officers, Directors & Advisors

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

Michael Green, MSW, ACSW
Vice-President and Director
12219 Phinney Ave. N.
Seattle, WA 98133
(206)361-8185

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

Henry Woo
Secretary
600 New Hampshire Ave., N.W.
Suite 720
Washington, D.C. 20037

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

Scientific Advisory Committee

RRP Network News

Patient/Family Support Network:

Our national support network has grown to over 80 respiratory papilloma families. Included are patients from 23 states and two Canadian provinces. Current ages of patients range from 1 to 75 years.

We feel that enough support group members have provided information to include an additional section (look for it in this issue) for tabulating statistics about RRP patients in the support group. It is called RRP Patient Stats. Additionally, information provided by RRP practitioners will also be included.

We have received questionnaires from about 60% of the families. If you have not filled out a questionnaire before or would like to provide updated information for the RRP Foundation Patient/Family database, please take a few minutes to fill out the accompanying form to the extent needed to bring the information about yourselves up-to-date. Please return them to Marlene and Bill Stern.

Encouraging communication among support group members remains a primary focus of the foundation. When providing your phone numbers also indicate your long distance carrier so as to take advantage of group discounts (i.e., MCIs Friends & Family). For those who have access to a computer and a modem or other networking capabilities, we continue to explore ways to make electronic mail, bulletin boards and/or electronic forums, generally available. The RRPF maintains accounts with two on-line services, Compuserve (Comp) and America-On-Line (AOL) as well as access to Internet (see page 7 for the specific address listings). Those support group members that have computer network capabilities - let us know about it. If you have a Macintosh computer and a modem, we now 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. Please let us know your ideas on additional ways to provide for cost effective communication among members of the RRP community.

RRP Practitioner/Researcher Network:

The RRP Foundation is actively participating as part of a group called the Task Force on Respiratory Papillomas. This group is comprised of a number of otolaryngologists, RRP researchers, RRP support groups, immunology/epidemiologists (including the CDC) and gynecologists. One of the short term goals is to develop a comprehensive questionnaire for RRP patients. We are hopeful that with significant input and backing from CDC (Centers for Disease Control) this will initiate the process of developing a national registry of RRP patients. When this questionnaire is ready, it will likely be distributed to patients and families through your practitioners. As soon as we have definitive information we will pass it along to the support group.

The RRP Foundation continues to gather general statistics regarding the population of RRP patients from practitioners. Thus far approximately 20 hospitals and/or

continued on next page

private practices with respiratory papilloma patients have returned the single page RRP Medical Practitioner Questionnaire. If you are treating RRP patients and haven’t filled this form out, please help us by completing the form and returning it to the address indicated at the bottom. Thank you.

We continue to urge you to let your congressional representatives 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 assistant director of CDC (Walter Dowdle, M.D.), regarding a national registry of RRP patients. His address is:

Walter Dowdle, M.D., Assistant Director
Department of Health and Human Services
Public Health Service
Centers for Disease Control
Atlanta, GA 30333

RRP Patient Stats

The statistics that follow are based on RRPF patient and practitioner questionnaires. There has been no attempt to determine statistical significance, so caution is urged in drawing conclusions from the numbers below.

Tables 1 - 3 provide a breakdown of the patients in the support group based on sex and age; the sample size for these tables is 87.

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

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

Birth Statistics:

Cesarean birth in 2 cases (1 adult onset) - 39 responses

Patient is first born in 24 cases - 34 responses

Patient was adopted in 11 cases- 34 responses

Thus far we have received practitioner questionnaires from about 22 otolaryngology departments who are treating RRP patients. There is a total of approximately 792 patients, 387 pediatric and 405 adults.

Table 5. Surgical interval (based on 419 patients)

Practitioner responses to date have indicated that 214 of the approx. 792 patients in their practices are following (or have followed) other therapies in addition to surgical removal of papillomas, with a breakdown as follows:

Table 6. Number of patients using alternative therapies

Interferon	Acyclovir	Cabbage	Acutane	PDT
97	11	17	4	84

In addition ultra-sound has been used on one patient.

Four and a half year old Cristie Tulko was diagnosed with RRP approximately two years ago. She’s quite active and doesn’t let this disease get in the way of enjoying life. Cristie had been averaging one surgery every other month; however, lately the interval appears to have extended to nearly four months. Her mother Mary feels that vitamin C supplements, which Cristie has been taking since early this year, may be helping. Cristie is being treated for RRP by Dr. Douglas Dedo at Good Samaritan Hospital in West Palm, Florida.

Contagion, continued from page 1

RRP is presumably acquired from genital HPV, but the "vector" of transmission appears to be one-way, as the empirical evidence provided by these experts clearly indicates. Hence, RRP is not contagious in social and family settings.

A New RRPF Scientific Advisor

We welcome Professor Brigid G. Leventhal to the RRP Foundation’s Scientific Advisory Committee.

Brigid G. Leventhal, M.D. is currently a Professor of Oncology and Pediatrics at the John Hopkins University School of Medicine. Dr. Leventhal is a pediatric oncologist who did her training in Boston and then spent 12 years on the Leukemia Service at the National Cancer Institute, NIH, in Bethesda, MD, before coming to Johns Hopkins in 1976. At Johns Hopkins she has collaborated with Dr. Haskins Kashima to develop chemotherapeutic approaches to the problem of recurrent respiratory papillomatosis. This includes an artificial interferon inducer, poly-ICLC and a randomized study involving Wellferon, a product developed by Burroughs Wellcome, which is a combination of apha interferons. Dr. Leventhal has been an author of over 200 research papers and chapters including a number on respiratory papillomatosis. She has served on many committees including, an NIH study section, the FDA oncology advisory committee and most recently, the Recombinant DNA advisory committee of the NIH, which considers all human gene therapy protocols in the United States.

RRP Research News

RRP is a disease that often extends over years, even over decades, and it is little wonder that many patients and families become somewhat cynical over time about what seems to work and what doesn't.

Until recently, interferon was the only adjunct to surgery that seemed to show any clinical effect. But interferon has many well-known side-effects. There is also concern that its use can cause a "rebound-effect."

Another protocol using photodynamic therapy (PDT) seems to be somewhat effective with certain patients in lengthening the time between recurrence. But it does not work on everybody. It causes extreme photosensitivity, sometimes for weeks or even months at a time. Steinberg (1986) and Abramson (1988) have indicated that PDT causes oxygen radicals to be produced within cells exposed to light that have absorbed the photosensitive dye. It is essential that patients weigh potential side effects against potential benefits in selecting this treatment.

Radiation had been contraindicated in a variety of journal articles--it can cause RRP to undergo malignant change.

Two institutions (UNC, Drake and U of Iowa, McCabe/Smith) are currently experimenting with Acyclovir. Theoretically, Acyclovir should not work. It affects an enzyme active in the herpes virus that doesn't exist in the papilloma virus. But for some reason yet unknown, this drug is apparently having a clinical effect on at least some RRP cases. It should be noted, however, that in one recent study Acyclovir appears ineffective.

There is one very hopeful protocol with no side-effects that is currently being tested at Long Island Jewish Medical Center (L.I.J.)and also outside that institution. It's the so-called "cabbage juice" protocol.

It's easy to figure that if the heavy artillery (interferon, PDT, multiple laser surgeries) didn't control the disease without significant side-effects, no mere dietary supplement could. But early anecdotal reports of patients on this protocol (outside of L.I.J.) suggest that early optimism regarding this therapy might be justified.

This is more than just a "food fad diet," and the RRPF urges patients and families to contact L.I.J. about their study. If participation is not possible, then try this therapy on your own.

The theory runs as follows, as described in a recent publication (Newfield et al, 1993): Estrogens are known to exacerbate laryngeal HPV-induced lesions. There are two pathways for the metabolism of estrogen (16 alpha-hydroxylation versus 2-hydroxylation). There is a possibility that there is a concordance between 16-alpha-hydroxylation and RRP. Cruciferous vegetables contain a compound (indole-3-carbinol) that induces 2-hydroxylation (the "benign" pathway) and "shunts" it away from the 16-alpha pathway.

Several support group members have expressed confusion in interpreting the quantitative instructions from the L.I.J. protocol. Initially, adult subjects were told to take two cups of cruciferous vegetables a day, or juice therefrom. But since this is written to volume rather than mass, it can mean almost anything, depending on whether one shreds one's cabbage fine or thick. To clarify this, consider quantities specified in weight as follows: In order for adult subjects to obtain a clinically effective dose of indole-3-carbinol, they need to consume about a pound of cabbage a day (yields 8 ounces of juices). Children need about half a pound (yields about 4 ounces of juice). These amounts are for green cabbage, which appears to be the best source of indole-3-carbinol (It is claimed that green Savoy cabbage may contain more indole-3-carbinol than other cabbages - Bradlow, 1993, private communication).

In order to consume this much cabbage, one pretty much has to buy a juicer. Cabbage juice generally needs to be mixed to be palatable. (I usually buy organic cabbage, juice it, and mix it with an equal amount of organic apple juice. The apple juice masks the cabbage taste. Sometimes I also juice in some carrots.)

Cabbage oxidizes very quickly, and one needs to take this into account in planning. Although it is probably not a good idea to let the juice sit in the refrigerator for a day or two, freezing doesn't seem to hurt it. (You can make popsicles out of the mixed cabbage/apple juice: Put the juice in an ice tray, cover it to prevent air from reaching it, and in a few hours you'll have a tasty treat that even the dog will love.)

If you are participating in the L.I.J. clinical study (or otherwise seriously following this therapy) compliance is important. Let us know if you are following this therapy and whether or not you think it is working for you.

A note from the Editor -

As of this writing, according to researcher Dr. Karen Auborn at L.I.J., there were about 10 patients formally enrolled in their cruciferous vegetable clinical trial. They feel it is necessary to recruit additional patients for this study to be statistically significant.

In an effort to make it easier to participate and comply with their clinical trial, the L.I.J. study guidelines have been revised as follows:

Given the revised structure of this program, we encourage RRP patients to participate in the L.I.J. study. For more details, please contact:

Currently there are at least seven patients in the support network who have been following this therapy for nine months or longer. In four of the seven cases that we know about, there appears to be significant positive responses, based on the patient or parent’s assessment.

For more general information regarding the cruciferous vegetable therapy, please contact Michael Green or Bill Stern (addresses on page 8).

RRP Patient Update

This issue features the case history of RRP patient Christina Lancaster who offers her personal experiences and perspectives on this disease to the RRP community.

I am a thirty-six year old Recurrent Respiratory Papillomatosis patient who was diagnosed at Yale New Haven Hospital at the age of three.

I am writing to you with the hope that I can succinctly and concisely explain the impact of this disease on not only each patient but each family member: parents, siblings, spouses and children of the RRP patient.

The disease is virus caused and usually affects the larynx and vocal cords. Respiratory papillomas are benign tumors which have a distinctive quality of cluster growth. Their location often changes and may "travel" within the respiratory tract and therefore can become more complicated to treat if the disease is found to be reoccurring in such areas as the trachea and even more seriously into the bronchial tree.

Children are often considered severe sufferers from the disease as the airway is of constant concern. A child's airway is less developed, smaller than an adult's, and therefore can become easily blocked by the papilloma growths. Growths seem to have their own timetable in terms of reoccurrence and each patient's progression varies from other patients. It is difficult to find a trend or to help parents cope with some sort of description of the anticipated course of the disease. Families are therefore always alert for signs of reoccurrence: labored breathing, or a voice which becomes more and more hoarse.

My own case began on a camping trip with my parents, two brothers and younger sister. My mother thought I had caught a cold due to the inclement weather and upon returning from our trip she took me to see our family pediatrician. The pediatrician diagnosed the condition as laryngitis, reassuring my mother that it would run its course and I would be fine in a matter of days. My throat and my voice have never returned to that three year old's playing on Cape Hatteras.

I began to have trouble breathing and my voice continued to decline. Fortunately, my parents were persistent with my medical care, traveling to New York City to see several different otolaryngologists who all recommended a tracheostomy. My parents were relentless and finally found a wonderful otolaryngologist at Yale who was familiar with respiratory papillomas, and began treating me surgically immediately. The papillomas were cut with a scalpel under general anesthesia and required several days in the hospital for treatment of pain and a constant oxygen tent. Those treatments continued for 12 years at least once a year, if not every couple of months as the growths reappeared. I was spared severe breathing emergencies but lived with no speaking voice. I had to adapt to traditional education and was placed in private school for classes with smaller student/teacher ratios. I had a small group of friends who were understanding and would help me by ordering a hamburger for me or asking for a movie ticket at the box office. I wore a whistle around my neck night and day in case I needed help and couldn't scream. I was restricted from swimming and other physical activities for fear of breathing difficulties. My brothers and sister had to bear the loneliness and the responsibility of the household when my mother was attending to my needs. My parents were separated for long periods of time as my mother remained with me through every medical treatment. Travel and medical expenses seemed infinite, but I vividly remember looking forward to my hospital gifts after each ordeal, the blood tests, the medication, post operative pain and restriction to the oxygen tent.

I was referred to Boston University for CO2 laser surgery at age fifteen. I was a rather reserved teenager as I was not able to talk on the phone or be involved in social events. I was too self conscious. The laser changed my life as it caused less trauma to the cords and for the first time since age three, I could squeak out a hoarse speaking voice. It offered some hope for the future. I went on to college at American University and my first job after school was as a receptionist.

It seems to me that the emotional hardship of the disease varies with life's passages. I am now married with two wonderful sons who are healthy and happy and bring me more joy and feeling of success than the commercial real estate career I was pursuing. I was cautioned, however, about becoming pregnant because there is some theory that hormonal changes in pregnancy reactivate the aggressiveness of the disease. Unfortunately, there is so little research on Recurrent Respiratory Papillomatosis that even after searching the national computerized medical library, I haven't been able to find any publications on adult women, childbearing and the effect on papillomas.

It seems that after the birth of my second son in May of 1991, I have taken a turn for the worse. I am unable to fight the disease as successfully, and reoccurrence has increased to as often as every 6 weeks, requiring laser surgery each time. I have begun to try interferon therapy which is likened to chemotherapy, and its side effects are quite debilitating. At the time of this writing, I am preparing to travel to Johns Hopkins to meet with Dr. H. Kashima who has become a highly respected surgeon and researcher of the respiratory papilloma virus.

I am tired and depressed with living with this disease. My husband, a clinical psychologist and Assistant Professor of Psychology recently confessed his anger at the disease and the overwhelming circumstances financially as we have to live on one income and I have so many extraneous bills due to the surgeries, and the emotional turmoil and physical pain that disrupts our young family. We are concerned about our medical insurance as we have a one million dollar lifetime benefit and my medical bills in the last 2 years have reached $50,000. My four year old son tells me that he doesn't want me to leave him to go to the hospital any more and my two year old can't understand Mommy's pain or inability to rock him and sing him to sleep.

I tell you these most personal and agonizing accounts only because I feel it is so vitally important that Recurrent Respiratory Papillomatosis receive acknowledgment and recognition in the medical community for accurate diagnostic purposes, and in the hope that research can become more available for finding the cause and possibly a cure for the disease, if not in my lifetime, then within the lifetime of those children who are only now beginning to cope with the magnitude of the disease.

Christina Lancaster

The following additional comments were written by Christina’s mother.

Dealing with disabilities was not new in our family; Christina’s father lost his leg in World War II and one of her older brothers is profoundly deaf. She saw them coping and leading as normal lives as possible. I think she was aware of our deep love and concern - and how much we enjoyed her.

As I look back I’m impressed by how much she did and how hard some of it must have been - and still is. I also think that her sisters and brothers shared more of the burden than we realize, but are the better for it.

As for me, my heart is full of grief that she has had to cope with this - that my love could not make it all better. And yet I feel blessed that we’ve shared so much of our lives.

Anne Young

RRP Practitioner Perspectives

Johnnie came to the hospital in the middle of a cold winter night. His purple color gave me the immediate adrenaline booster that I needed to keep going. Mom told me that he has been breathing with a lot more difficulty in the past few days. Her husband has left her and she was struggling with little Johnnie and her two other children. She apologized for not bringing her son to the follow up appointments but on the other hand she was discouraged by the increased frequency that Johnnie was needing the laser surgery to get rid of his ever growing papillomas. After giving him Heliox therapy, his breathing improved to the point that I was able to examine him. We had no choice, tracheotomy was life saving for little Johnnie. His papillomas were growing from the mouth to the lower trachea, and certainly compromised his airway very dramatically.

During my residency years, I have seen quite a few little Johnnies. There is an incredible magic bond to the chronically ill child. I have seen them grown up and continue battling for a cure. You may think that after 40 or 50 procedures it should become second nature; that is not the case. Christina (Lancaster) has battled laryngeal papilloma for many years and has been treated all over the country. I remember her shivering in the pre-op area with some fear and frustration in her eyes; it reminded me of little Johnnie’s eyes. I covered her with a warm blanket, bringing back her nice smile to her face.

These days we take a lot of things for granted. Going back into the history of medicine, we learn how inadequate treatments were for lethal conditions that these days we just treat with a 10-day course of antibiotics. I very frequently find myself browsing through medical journals hoping for a better answer for the treatment and cure of papillomas. From my uncomfortable clinical position, I cannot wait to hear great news from our researchers.

I am very optimistic for the future and I know there will be a breakthrough soon. For the time being, we will keep chasing these relentless papillomas with the laser and comforting these brave patients with a warm blanket and a big heart.

(note: Dr. Stolovitsky is Christina Lancaster’s otolaryngologist)

.

I first became involved with papilloma patients in 1983. I was introduced to them because the Children's Hospital of Philadelphia was participating in an interferon research study. I never realized 10 years ago how much these families would become part of my life,

Dealing with RRP children and their parents can be rewarding and frustrating at the same time. In pediatric otolaryngology where most of the patients have short term problems, like infected ears or enlarged tonsils, an opportunity to know families well rarely exists. The children with RRP, however, are a group that I can follow for many years. The reward is the development of relationships and watching the children grow and flourish. The frustration is the disease and the chronicity that often requires frequent surgeries.

Nurses, too, can feel frustrated when the disease recurs at an unpredictable rate. Sometimes I feel all I can say to parents is, "I don't know when your child will be better; I don't know what the future holds."

Since these patients are never seen in the office, I can only see them in the operating room. While I don't go to the OR with every child, I am able to go to the operating room with some of my more chronic children. I feel this provides some sense of continuity for them and their families. It also allows me to see the progress of the disease.

This extension of my practice into the OR has allowed me to become a patient advocate. We now try to shorten the time that the families have to wait between their arrival at the hospital and the actual surgery.

I look forward to continuing my interaction with RRP families.

RRPF Information and Support Centers:

Main Info. Center and Northeast

Marlene and Bill Stern
50 Wesleyan Drive
Hamilton Square, NJ. 08690 (609)890-0502
weekday phone - (609)452-6545, (609)258-2751
e-mail (AOL): billslins@AOL.com
(bitnet): mstern@lindsay.princeton.edu

West Coast

Michael Green
12219 Phinney Ave. North
Seattle, WA 98133 (206)361-8185
e-mail (Comp): 75450.2252@compuserve.com

Mid-Atlantic

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

Mid-West

Carol Motley
1820 Brookview
Arlington, TX 76010 (817)261-1023

Southeast

Wendy Bodner
4800 S.W. 64th Ave., Suite 110
Davie, FL 33314-4449 (305)581-3400

California

Susan and Bob Spock
1553 Via Allondra
San Marcos, CA 91606 (619)744-5022

Georgia

Christina Lancaster
186 Pine Knoll Lane
Eatonton, GA 31204 (706)485-1016

South Carolina & North Carolina

Tami Elsey
2 Hill Trace Trail
Irmo, SC 29063 (803)781-2442

Recurrent respiratory papillomatosis (RRP) is a disease in which tumors grow inside the larynx, vocal cords and trachea. It affects both children and adults. Research has determined that the Human Papilloma Virus (HPV), is present in these respiratory tumors. These growths are often associated with two specific types of the virus (HPV6 and HPV11) which are also found in genital and cervical warts.

There is no known cure for RRP, with CO2 laser surgery under general anesthesia being the accepted method of controlling theses growths. If left untreated these respiratory tumors will continue to grow, blocking the patient’s airway with suffocation being the likely result.

The Recurrent Respiratory Papillomatosis Foundation was created to provide family support, promote public awareness, and aid in the prevention , cure and treatment of RRP.

Our organization is primarily focusing on the networking of the RRP community, including patients (both juvenile and adult), families, medical practitioners and researchers.

By coordination of the RRP community and enhanced awareness of this disease, our goal is to stimulate more RRP related research, which will hopefully lead to more effective treatments and ultimately a cure for this disease.

The Recurrent Respiratory Papillomatosis Foundation is pleased to publish this issue of the RRP Newsletter. We hope that this and future issues will serve to enhance the support network among laryngeal papilloma families and also help to provide accurate medical and scientific information about this disease.

Please help us with our RRP work, including this newsletter and other publications, networking RRP patients families and physicians, and creating greater public awareness of RRP. In order to succeed we need your support. We are a completely volunteer organization.

An annual tax deductible contribution of $15 or more will assure that you continue to receive the RRP Newsletter. In addition our RRP medical reference service, providing semi-annual updates of RRP related references, is available to those contributing $25 or more. For further information on our goals and objectives, please send a self-addressed stamped envelope to:

We are most grateful to those who have contributed to this cause, either financially or by volunteering their time.