Recurrent Respiratory Papillomatosis 

Vol.5 No.2
1995 Fall

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Contents

• Opening comments - p. 1
• RRPF organizational information - p. 2
• RRP Remission and Network News - p. 2
• Report on the RRP Workshop at the 14th International Papillomavirus Conference - p. 2-4
• Patient Statistics - p. 4
• Update on Adjunct Therapies and new protocols - p. 4-6
Adjunct Therapy Survey Update - p. 5
Indole-3-Carbinol - p. 5
Ribavirin trial update - p. 5-6
PDT with m-THPC - p. 6
• RRP Perspective - p. 6-7
• Patient profile - p. 7-8
• 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.

Thank you.

Bill Stern

Welcome to the fall 1995 edition of our newsletter. In this issue, we have status updates on indole-3-carbinol (I3C), interferon, and ribavirin clinical trials as well as a plethora of other information presented at a workshop associated with the 14th International Papillomavirus Conference held in Quebec City, Quebec, Canada.

This first-ever workshop, focusing solely on RRP was organized by Thomas R. Broker, along with Louise T. Chow and Bettie M. Steinberg. It was designed to bring those people directly working on the research and clinical aspects of the disease together to increase the flow of information. Many thanks to Drs. Broker, Chow, and Steinberg for such a successful workshop.

As for my role in all of this, I would like to extend my heartfelt thanks to Bill and Marlene Stern of the RRP Foundation and William Lazar of the American Laryngeal Papilloma Foundation, for their generous support in allowing me to attend this conference.

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 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 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 Foundation50 Wesleyan DriveHamilton, 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: Washington, D.C. and Mercer County, N.J. 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.f you are not registered with the RRPF, please do so by completing the Practitioner Questionnaire enclosed.

RRPF Officers, Directors & Advisors

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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RRP Remission News

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

Jerry age 45 from New York has been free of respiratory papillomas for more than 2 1/2 years. He was going for surgery twice a year. He used several adjunct therapies, including cruciferous vegetables, I3C and Acyclovir. He continues to follow the I3C therapy today.

Leah from New Hampshire is now 15 1/2 and was diagnosed with RRP at the age of 2. At the age of 5 1/2 her disease spontaneously went into remission and is still in remission today.

Steph from Florida, age 22, has not had a surgery in nearly two years. She had been requiring surgeries every 5-6 months. This is the second spontaneous remission she has had since she was diagnosed at age 2.

Others still in remission include: Melissa from New York, now age 6; Smokey from Virginia, age 24; Ariel from California, now 4 years old; Jeff from Illinois, age 48; and Lindsay from New Jersey, now age 6.

RRP Network News

Our national support network has grown to approximately 235 respiratory papilloma families. Patients range in age from 1 to 78 years and are located in 35 states, two Canadian provinces and the United Kingdom.

We have received questionnaires from about 160 families in the support group and adjuvant therapy surveys from 69. 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. 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. In addition we hope to have a page on the World Wide Web (WWW) shortly. For now, please refer to the WWW home page of the University of Alabama, Birmingham, Department of Biochemistry & Molecular Genetics (http://www.bmg.uab.edu). A directory of people working in the HPV field can be found under the heading Papillomavirus Society and additional HPV information is planned for the future.

The 14th International Papillomavirus Conference took place in July, 1995, in Quebec City, Quebec, Canada. For the first time ever, a workshop specifically dealing with RRP issues was created by Drs. Thomas Broker, Louise Chow and Bettie Steinberg. There were approximately 30 presentations related to HPV of the head and neck. The talks were divided into three sessions: 1) Basic Biology, 2) Clinical and Molecular Manifestations, and 3) Epidemiology, Patient Registry, Clinical Protocols. It was quite encouraging to see such a collective research interest in RRP. From a clinical therapy perspective, it was perhaps somewhat disappointing that there were no major announcements of new therapies for treatment of HPV, although, Indole-3-Carbinol (I3C) certainly appears to be helping some people with RRP.

It is beyond the scope of this newsletter to report on all the presentations. In the paragraphs that follow we will attempt to summarize a few.

A number of investigators discussed aspects of the p53 gene and HPV. Below is a simplified summary of some of the talks.

Some interesting research presented suggests that a majority of RRP cases contain p53 over expression and may be responsible for the proliferative nature of laryngeal papillomas. p53 is a protein expressed at low levels in all cells and functions to maintain the normal cell cycle. As such, p53 has been dubbed a "tumor suppresser" protein. However, HPV makes a protein that has the ability to interfere with p53, thereby disrupting p53's true function. In the high-risk HPVs, namely HPV-16 and -18, this HPV protein binds to p53 and targets it for degradation. This complete loss of the p53 protein is believed to be the main reason for the formation of cancer when these types of HPV are present. In the low-risk HPVs, namely HPV-6 and -11, however, this HPV protein does not destroy p53. It's not known exactly how the low-risk HPVs and p53 interact, but as suggested by the above research, p53 is over expressed in many cases, thereby disrupting the cell cycle and generating benign growths.

Data presented from one study indicated p53 over expression in 14 of 16 juvenile and 33 of 36 adult laryngeal papillomatosis cases. When these same cases were examined for the presence of HPV, approximately 31% showed HPV infection. Out of these HPV positive cases, 86% showed concurrent p53 gene over expression when re analyzed.

What does all this mean? If p53 is indeed the major player in the formation of laryngeal papillomatosis, then as researchers unravel the peculiarities of the p53 protein, drugs may be developed that can block the HPV-p53 interaction, thereby allowing p53 to function normally.

Dr. Craig Derkay, who heads the Task Force on Respiratory Papillomas, presented an update on the multi-disciplinary task force at the workshop. The following is excerpted from his RRP Workshop abstract.

The Multi-Disciplinary Task Force on Recurrent Respiratory Papillomas (RRP) is comprised of otolaryngologists, gynecologists, virologists, epidemiologists, and patient advocates involved in research and treatment of HPV infections affecting the human respiratory tract. The Task Force is currently embarking upon Phase II of its three phase mission.

Phase I consisted of a comprehensive survey of otolaryngologists and pediatric otolaryngologists regarding their experience with this disease entity, current surgical, medical, and anesthesia management, and the role of cesarean section in the prevention of vertical transmission (mother-to-baby) from this disease entity. It is estimated that there were approximately 2,500 new pediatric cases and 3,200 new adult cases in the United States last year. Surgical procedures for RRP totaled nearly 25,000 last year at a health care cost exceeding $150 million.

Phase II represents a coordinated effort between the Centers for Disease Control and Prevention (CDC), the National Institutes of Health, and 22 geographically diverse clinical centers active in treating papilloma patients with a goal of establishing a national registry of RRP patients. This is planned as a three year project with the database implemented and managed by CDC.

Phase III consists of the development of clinical protocols utilizing the national registry to assess the efficacy of treatment modalities and to further investigate the risk factors involved with transmission and severity of the disease.

Dr. William Reeves, from Division of Viral Diseases at the CDC, presented information regarding the proposed RRP Patient Registry. Below is a summation of what was discussed:

The objective of the RRP Registry is to establish a representative cohort of juvenile-onset RRP patients which can be followed for at least three years according to a standard protocol. (The cohort will include all active cases - those requiring surgery at least once in the last three years - as well as newly diagnosed patients identified at 22 US tertiary care centers.)

Several specific aims of the registry are explained below. The first goal of the registry is to estimate the prevalence/ incidence of RRP in the general population. This will allow a more precise estimate of the numbers of children affected by RRP and will also provide descriptive epidemiological data and begin to identify risk factors for occurrence of the disease. The second aim is to describe the clinical course of RRP. Information regarding the presentation, sites involved, extent of disease, as well as surgical, anesthetic, and medical management will help clinicians determine the progression of the disease. In addition, risk factors for recurrence will also be determined. The last goal of the registry is to facilitate multi-site collaboration. At this time, many clinical trials are not considered significant in that there are not enough participants in the study to draw a reliable conclusion. With collaboration, trials will be larger and more meaningful data can be gathered.

The questionnaire is quite extensive and has the following forms: basic registration, interview, surgical treatment, pharmacological treatment, tracheostomy (if present), pathology and lab, and exit. Surgical treatment, pharmacological treatment, pathology and lab data will be collected on an on-going basis over the three year period.

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As indicated in an RRPF special correspondence in June, the Task Force reported that the establishment of an RRP registry is now imminent. A full-time position has been created at CDC for an investigator to establish and manage a national registry. However, there is still a need for additional funding to augment CDC funding and for travel, which will play a critical role in establishing the registry. It is proposed that the investigator be able to make site visits to each participating center. This would allow implementation of CDC developed registry software so as to greatly facilitate the data entry and analysis process. In this regard we still need to contact our congressional representatives and senators to mobilize their support. Regarding specific CDC funding of a National Registry for RRP, ask them to contact :

The director of CDC:

The director of the National Center for Infectious Diseases::

Others for representatives & senators to contact:

The contract officer at N.I.H.:

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

Assistant Secretary for Health:Phillip Lee, MD

The following briefly summarizes some presentations on Clinical Trials and Adjunct Therapies for RRP.

Dr. Leon Bradlow, from the Strang Cornell Cancer Research Laboratory, reported on a correlation between the induction of 2-hydroxylation (i.e., the "good" estrogen metabolite) and a decrease in the re growth of respiratory papillomas. He was also interested in understanding why certain people do not respond, and hypothesizes that some people fail to convert I3C to the active drug and others may have a genetic defect preventing 2-hydroxylation.

Dr. Karen Auborn, from Long Island Jewish Medical Center Department of Otolaryngology, reported on results of their clinical trial using cruciferous vegetables as a natural source of I3C. Poor patient compliance resulted in greater than a 50% drop out rate. Of the limited sample remaining that could be evaluated for more than a year, three out of four patients were clear or had improved disease. Those cases with no improvement of disease were found to correlate with a failure of the vegetable diet to induce 2-hydroxylation, suggesting that induction of 2-hydroxylation will prevent recurrence of laryngeal papillomatosis.

[Look for an article in the December 95 or January 96 issue of Prevention magazine regarding some of the I3C studies of Drs. Auborn and Bradlow.]

Although Dr. Clark Rosen, now at the University of Pittsburgh Department of Otolaryngology, was not able to attend he did provide a video presentation of early results from an I3C trial at the University of Tennessee. These results and additional details regarding the clinical trial will be included in "Adjunct Therapy and Protocol Update" section of this newsletter.

Dr. Ronald McGlennen, from the University of Minnesota Pathology department, discussed the use of Ribavirin for the treatment of RRP in a double-blinded clinical trial now taking place at the University of Minnesota. See the "Adjunct Therapy and Protocol Update" section for more information.

Dr. Allan Abramson, from Long Island Jewish Medical Center Department of Otolaryngology, spoke about their new clinical trial involving photodynamic therapy (PDT) using an improved photosensitizing agent, meso-tetra(hydroxy)phenyl chlorin or m-THPC, More information about this study is included in the "Adjunct Therapy and Protocol Update" section.

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 217 to 231.

Table 1. Total number of patients in support group

	Females	Males
All Ages	109	122

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

Age Groups	Females	Males	Total
Under 10	61	52	113
10-20	16	19	35
20-30	9	11	20
30-40	8	8	16
40-50	7	15	22
over 50	4	12	16

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

Age Groups	Females	Males	Total
Under 10	79	78	157
10-20	3	3	6
20-30	9	8	17
30-40	3	12	15
40-50	6	12	18
over 50	1	3	4

Table 4. Birth Statistics from Patient Support Network:

Cesarean birth in 7 cases - 154 responses

juvenile onset: 4 of 115 responses

adult onset: 3 of 39 responses

Patient is first born in 80 cases - 141 responses

juvenile onset: 69 of 104 responses

adult onset: 11 of 37 responses

Patient was adopted in 30 cases - 153 responses

juvenile onset: 30 of 119 responses

adult onset: 0 of 34 responses

Mother's ages - 61 responses

20 or under: 27 of 61 responses

20 -> 25: 16 of 61 responses

Thus far 65 medical centers/practices who are treating RRP patients have registered with the RRPF by completing practitioner questionnaires. They account for approximately 1094 patients, 563 pediatric and 531 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.

Adjunct therapy survey responses from 69 patients/families have been received. Of those responding 19 indicated that they have not used any adjunct therapies and 50 responded that they have tried adjunct treatments. The most reported therapy was Indole-3-Carbinol (I3C) with 29 users - 13 indicating improvement, 8 no positive impact and 8 others have not used it long enough to make a determination. The number two therapy appearing on the survey forms was Interferon with 18 users - 12 showing improvement and 6 indicating no positive impact. For details on other therapies and side effects, see the Spring 95 issue of the RRP Newsletter.

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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, Anticanc Res 13:337-342

I3C Clinical Trial at Univ. of Tennessee and Univ. Pittsburgh

In the Spring 95 issue of the RRP Newsletter, Dr. Clark Rosen reported on a clinical trial using I3C at the University of Tennessee. At the special workshop devoted to RRP this past July (see previous section), Dr. Rosen presented early results from this trial via video-tape.

He reported on nine RRP patients enrolled in the University of Tennessee trial who have been using I3C for more than three months, six juvenile cases and three adult. Preliminary findings indicate that seven of the nine are showing some positive response.

Dr. Rosen, who is now at the University of Pittsburgh, is currently enrolling patients for an I3C study there.

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

I3C Clinical Trial at University of Alabama

The University of Alabama (UAB) is currently presenting the details of their trial protocol to their research board for approval. As in the University of Tennessee/Pittsburgh 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. It will also involve a collaboration with the Department of Gynecology. 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

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 would like to pursue this therapy on their own, we are providing the following information and service:

1) How and where to get I3C (note: there is now a new supplier)

2) Dosing information

3) Urine analysis testing information and supplies

As many of you already know, Designed Nutritional Products is no longer selling I3C to retail customers.

I3C may now be purchased from:

THERANATURALS Inc.P.O. Box 344Orem UT 84059-0344

(801)224-8893 - Telephone and Fax[They should be able to handle phone credit card orders]

Theranaturals will be 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 bottlesadd $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)

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: 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 the recent workshop on RRP, Dr. Ronald McGlennen reported on the status of a clinical trial using Ribavirin to treat RRP. As indicated earlier, this study involves a double-blinded cross over trial in which patients are randomly selected to receive either Ribavirin or a placebo. (A more detailed summary of the protocol can be found in the Fall 94 issue of the RRP Newsletter.) Thus far, six patients have successfully completed one arm of the study (i.e., 6 months on either Ribavirin or the placebo) and now have "crossed over" to the second arm (i.e., 6 months of either the placebo or Ribavirin, whichever they didn't get in the first part). Because of the study design, Dr. McGlennen is not able to provide any preliminary results regarding the therapeutic impact of Ribavirin as yet, but has promised to do so in the near future.

Additional RRP patients are needed for this study. For more information contact:

or

Frank Rimmel

(612)625-5526

email: rimel002@gold.tc.umn.edu

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A new study of photodynamic therapy for recurrent respiratory papillomas has begun in the Department of Otolaryngology at Long Island Jewish Medical Center. This study will use a new photosensitizing drug, meso-tetra(hydroxy)phenl chlorin, or m-THPC, that when activated by red light (PDT), has been found to cause the disappearance of tumors in both humans and animals. In our animal studies, we found m-THPC selectively localized better in cutaneous rabbit papilloma tissue than the drug used in our previous PDT protocol. In addition, the side effect of photosensitivity is considerably shorter with this new drug, approximately 2-3 weeks.

This new study is FDA approved and to be eligible for the new treatment, patients must have undergone at least three surgical excisions within the twelve months prior to enrollment or have tracheal disease. Upon enrollment, a direct endoscopic procedure and laser excision of all papillomas will be done at our institution. Three months later, the same procedure will be repeated (since all direct endoscopic procedures must be done at LIJ, patient travel expenses will be defrayed).

Three months after the second endoscopic procedure, the patient will undergo photodynamic therapy. As an outpatient, in our office, the drug m-THPC is given intravenously. Six days later, a special laser is used in the operating room to shine the red light on the larynx to activate the drug. The anesthesia given is the same used during routine laser surgery. Each patient will remain in the hospital at least 24 hours following the PDT procedure.

Following the PDT, the patient will undergo direct endoscopic procedures, at LIJ, every three months for the next twelve months, unless an indirect scoping indicates that the patient is clear of papilloma.

The only major side effect of the m-THPC is skin photosensitivity, which is currently estimated to last for approximately 2-3 weeks. As a result, following the injection of the drug, the patient must avoid exposure to direct or indirect sunlight, and any bright indoor lighting, such as office fluorescents, dental lights, etc., to avoid experiencing a bad sunburn reaction. Patients may also experience some throat discomfort over the next few weeks after the red laser light therapy is given.

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:

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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

It was a cultural and moral dilemma. Should she uproot her small son to go to the United States to seek medical treatment or take the risk that his disease would remain the same or remiss and leave him in an environment where he knew love and security? She decided to go. Thus was the decision that a young mother from Guyaquil, Ecuador, Irene Cruz made for her young son, Alex.

He had been in and out of medical facilities since he was born. No one knew for sure what was wrong. He had difficulty in breathing at times and was constantly hoarse. Around age 1 he was labeled "mute". He took a turn for the worse when he was 1-1/2 and ended up with a tracheotomy. He stayed in the hospital for "routine" care for the next 1-1/2 years. He knew all his health care providers like his own family, and his parents were just glad he was alive, but his doctors felt that his disease was going into his lungs and the family knew they needed to find experts to help their son survive.

Mr. Cruz was a field hand of the Continental Grain Co. in Ecuador which has its headquarters in New York City and branch offices throughout the United States, including Iowa (Wayne Feeds). A Mason City, Iowa manager for Wayne Feeds was sent to their town for business. While there, he met Alex's father and learned of their plight. After a few contacts were made, the company decided to sponsor them and bring them to the United States for medical treatment.

The issue of leaving their homeland to come to the United States was overwhelming. If he came alone, human resources informed the family it would be grounds for abandonment. His mother knew no English. She would leave behind her husband and small daughter which was a cultural taboo. Knowing the native customs, she knew she may even face being "ousted" from her village when they returned. Alex was a sick child and that was how it was to be. But the family refused to accept this philosophy and against many odds they made their arrangements and Alex and his mother set off for the United States.

Through the plans that were arranged, their first stop was in New Orleans where Alex underwent his first surgery. At this time, the diagnosis of Recurrent Respiratory Papillomatosis was finally made. While being treated in New Orleans, some of Alex's attending physicians had heard about a new treatment for this disease in Iowa led by Dr. Brian McCabe and after much deliberation, decided this would be the best option to treat Alex's condition. So once again they geared for a new place and new faces.

It was October 1982 when they first set foot in our community. They were greeted by a kind woman named Sharon Sorenson who spoke some Spanish and worked for Wayne Feeds in Coralville. They became instant and lifelong friends.

Iowa City was very sympathetic to the young mother and her son's plight. The Otolaryngology Dept. did everything they could to make them feel at home in a very unfamiliar setting. Alex spent most of his time in the Oto in-patient unit. His mother at his side, the team of nurses, doctors, social workers, and many others, "adopted" them as one of their own. Undergoing multiple laser surgeries to remove the lesions that were trying to take over his airway, did not dampen the spirit of this cheerful, happy child. When Alex was well enough to be an outpatient, they rented a room at Lalla's Guest House which was within walking distance from the University Hospital. The nurses taught his mother how to give Alex injections of a drug called Interferon which was to help slow down or even stop the growth of the papilloma-virus. This was a difficult task for Irene who had no medical background and was missing some fingers from her hand, but she was determined and overcame one more obstacle.

By now, Alex was nearly 4. His disease was stable enough for his trach to come out, but his language development was still not adequate for his age. Speech pathology worked diligently with him and in no time he was talking in sentences. Child psychology and social services worked with Alex closely to help him adjust to "cultural shock" changes. He became "Americanized". He loved hamburgers and hot dogs. He learned to ride a bike and dress like "the Merican kids". He enrolled in first grade. And still they lived at Lalla's Guest House and made the trip back and forth to the hospital cafeteria for their meals. In between all his care here, they made a couple of trips back home, each time it became harder for them to return and home-sickness set in for them both. Medical Visa status was also a concern so the medical health team explored all areas to see if the same level of care could be continued in Ecuador. They had no laser in which to do his surgeries to remove the papillomas. They were unfamiliar with Interferon and did not have it available in any of their facilities. Again, through the efforts of many professional and caring people, the impossible was done. Wayne Feeds would purchase a used laser. Dr. McCabe and nurse Jan Mixon located one. Extensive research and calls were made and the Hoffman La Roche Drug Corporation agreed to make Alex their "Mission Project" and supply all his Interferon free to him. Plans were finalized, good-byes were said, and the return trip home was made. Dr. McCabe flew to Ecuador also to teach the local otolaryngologist, Dr. Alfonso Espinel, on proper usage of the laser machine.

This amazing story continues to happily evolve today. Alex is now 15 years old. Our hospital still receives Alex's surgical reports and monitors his care via mail. The Hoffman La Roche Drug Company still supplies his Interferon medication at no cost. Although Alex has not "outgrown" the disease as many children do in the adolescent years, he leads a relatively healthy and happy life. For a child that was never supposed to live at all, Alex has proven a lot of people wrong. But only by the concern, love, and care of a group of people who made a difference!

RRP Patient Profile

[ Ed. Comment: The following patient profile was written by Kim McClellan, who, after more than 180 surgeries, tells of her ongoing battle with RRP. Kim's situation is distinguished by a particularly severe occurrence of stenosis, i.e., scar tissue build up. This unusually severe situation is likely the result of a combined lack of available technology and surgical expertise 25 years ago. With technological advances and much greater surgical expertise regarding laser excision of papilloma on and around the vocal cords, a repeat of Kim's situation is an extremely unlikely event today. However, care in following an appropriate surgical approach when removing respiratory papillomas, cannot be over stressed. Finally, an important function of the RRP Newsletter is to provide a forum for people with RRP to share their experiences. It is in this spirit that Kim, whose voice is significantly impaired, is able to communicate her case history and feelings.]

As I sit here trying to decide what to write concerning my history with RRP, I am somewhat confused as to where to begin. I have had the disease since I was five years old (1971), so I have no point of normalcy to refer back to.

I read of patients having remissions-the longest I have ever gone without papilloma is 18 months. I was told as a child that the papilloma would go away with puberty-onset of menstruation-it did not. I was told pregnancy would stop the disease-it did not. I think the best way to tell my story, is to begin where I remember - 1971.

Dr. Grant of Memphis TN was the ENT who first diagnosed my disease. Being only five, I was treated to popsicles, ice-cream, and toys every operation - I thought it was fun! Not only did I get everyone's attention, but toys and no school too! Shortly after diagnosis, my family moved back to my father's hometown of Baytown TX. I then started having surgery at Texas Children's in Houston. I remember that I missed a lot of school, at one point I was having procedures every two weeks. The novelty had worn off, this was no longer fun. They still gave those awful pre-op shots before every surgery - I am sure there is a nurse out there who still remembers the time I slapped her. I do think God makes children stronger than we give them credit for - if not, I don't know how I would have survived those long years of procedures as well as I did. By the time I was about 12, my parents heard of a doctor in New Orleans that was performing laser procedures. It was decided that I would change facilities for my treatment. I was going to New Orleans for about two years, having procedures about every 3-6 months. My voice by now was very raspy, and often just a whisper. My name at school was Donald Duck.

At about fourteen years old, my family once again moved. It was back to Memphis. I would have to agree that being a teenager is a lot harder than having RRP, but at least you do outgrow your teens - RRP just doesn't seem to leave, at least in my case. From the age of fourteen to nineteen, I would have procedures at three to six month intervals. My parents thought it would be good for my self esteem to enter pageants. I did, and much to my surprise I was winning. This did make my life somewhat normal, but every now and then, the papilloma would come back, affecting my voice and airway, and reality would pop back in. I graduated high school, and went to college, which is where I met my husband Lee. We were married in 1987 (yes, I was young), and now have a beautiful family. Megan is eight, and Joshua is 18 months.

During my first pregnancy, the papilloma did not grow for almost eighteen months. I fooled myself into thinking it was all finally over. It came back more aggressive than ever, but it did not come back alone. I am sure that many of you with RRP have some type of webbing across the vocal cords - so did I. The difference is that mine had decided to grow stronger. With a fairly new family, I found myself having procedures every month not for papilloma, but to keep the webbing from closing my airway. The papilloma were still there, but not in quantities to warrant procedures that often. The webbing would simply envelop my vocal cords, blocking my airway. I endured this monthly cycle for one year. I had no choice but to agree to a laryngeal stent. Being cut open on my neck did not bother me as much as knowing I would have a tracheotomy. That would make my disease noticeable to everyone - something I had tried very hard to avoid. For six weeks I had a tube in my neck, and a large piece of plastic suspended by strings and buttons inside my vocal cords. At six weeks the stent came out, and two weeks later the tracheotomy was removed. I once again could talk! (I was not able to communicate verbally during the entire six weeks.) For almost a year, I had no papilloma, and my airway stayed open. Just as I was letting my guard down, the papilloma returned, and the cycle began again. I only let it go on for about two months this time. I had another stent procedure. I was not as fortunate with the second stent. It had to be removed after about four weeks, when I had to be rushed into emergency surgery on a Friday night because I could not breath. In January following the second stent, we tried a third stent. The tracheotomy was still in, as no one was willing to risk taking it out. In May 1993, following this procedure, Lee took a position in Bentonville Arkansas. I don't know what is worse, moving away from friends and family, or changing doctors at such a critical time.

After much searching, I located a doctor at the Univ. of Missouri that would take my case. At this same time I found out that I was pregnant with Joshua (yes, antibiotics do make a difference in family planning). I was not only ecstatic to be pregnant, but since Megan gave me such a wonderful remission, I could only wish for the same. It was not to be. The papilloma grew very quickly during my pregnancy. I had four procedures during my pregnancy and I was put to bed rest at seven months after starting to go into full labor during a procedure. Joshua was born four weeks early, but very healthy. Given the distance to U of M, I decided to locate a doctor closer to my home. I found Dr. Marvel in Fort Smith AR. He had his studies at Texas Children's and was very familiar with RRP. It has been 15 months since I first began going to him. I have had three more stents, one of which stayed in seven months. I am at a crossroads. I did go to UT in Memphis to enter the I3C trial for the papilloma. Three months with no new growths. My concern now is that the stenosis is stronger, and that my voice is all but gone. My children have learned a new language - "kimish". I hope to see someone at Univ. of Alabama soon, but even they think there is not much that can be done.

I will be having another laser procedure to open my cords back up in the next two to three weeks. The procedure should give me about three weeks worth of airway before I am closed again. I try to postpone procedures until I cannot stand not smelling and talking any longer.

Emotionally this ordeal has taken its toll. To be 29 years old and not have a voice, and be trach-dependent, seems like a cruel joke. Financially, I am just thankful that some of my providers have looked the other way after receiving payment from the insurance company. I think that I will be paying 25 dollars a month for the rest of my life to each and everyone of them. Physically, the disease has been tiring. I cannot swim, run, shower safely, or talk.

I pray that someone will give me a cure to the stenosis, and to everyone a cure for RRP. I do think that we as a group are just at the tip of the ice-berg, and I am confident that as a group we can turn the ice-berg into a mere ice-cube. Too many procedures have taken their toll on my cords, but young people are lucky today in that there is much more known regarding prevention of such horrific scarring. This is not the whole story, but that would be a novel and I'm not sure anyone would believe it.

Closing Thought

Lindsay Stern at dinner on her sixth birthday, " I wish good health for everybody who has 'bumps'."