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RRP ISA Survey Results
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    Treatment Strategies



    These are some of the treatment strategies that have been used with RRP:

    1. Surgery using cold steel
    2. Surgery using the laser
    3. Surgery using Microdebrider
    4. Gardasil and Artemisinin
    5. Indole-3-carbinol (I3C) and its derivative (DIM)
    6. Interferon
    7. Photo-Dynamic Therapy (PDT)
    8. 13-cis retinoic acid and other retinoids
    9. Acyclovir
    10. Ribavirin
    11. Cidofovir (HPMPC)
    12. Mumps/MMR vaccine
    13. GERD Treatment/Proton Pump Inhibitors
    14. MMC (Mitomycin C)
    15. Celebrex
    16. Beta Mannan

       

     Surgery

    Surgery using Cold Steel

    Summary: Until the advent of the laser, surgeons used traditional surgical tools such as the forceps and scissors ("cold steel") to remove RRP from the vocal cord. Stripping the entire vocal cords of its mucosal layer, which went out of fashion in the late 70’s, is inappropriate for RRP, but use of cold steel is still favored by certain physicians today.
     
    Mechanism of Action: Mechanical (cutting, grasping, etc.).
     
    Considerations: (1) See "Laser” and “Surgical Microdebrider” below. (2) While scalpels and forceps generally cannot match the pinpoint accuracy of laser, such pinpoint concentration of energy can be very destructive in the hands of a surgeon who isn't sufficiently respectful of the laser's power. Unlike the laser, steel doesn't burn tissues, causing scarring and loss of vocal function. (3) Steel also does not create a vapor plume, which, if the surgery is not well managed, may (??) seed the trachea or lungs. On the other hand, there is more blood loss with steel, and there is a possibility that blood and fragments of infected tissue can get into the trachea and lungs and seed them with active HPV. (4) Steel gives a tactile feedback, whereas the laser doesn’t (5) Some physicians use cold steel to debulk papillomas prior to laser cauterization, thus mitigating the possibility of thermal trauma to deeper tissue. (6) Cold steel definitely has its place in the surgical treatment arsenal. It's a different tool from the laser. RRP surgeons should be skilled in using both tools. (7) The surgical "technique" is never any better than the individual using it.
     
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    Surgery using the laser

    Summary: Since the late 70's, the carbon dioxide laser has been used to treat Recurrent Respiratory Papillomatosis. The Pulsed Dye Laser is being used by a number of specialists on an outpatient basis.

    Mechanism of Action: The carbon dioxide (CO2) laser is most widely used laser in vocal cord surgery. Theoretically, it can be set to vaporize exposed tissues while minimizing the chances of burning underlying tissues. Theory and practice are very different, however, and the laser inevitably does cause some degree of subdermal burning of healthy tissue. The laser works by focusing a beam of concentrated light on the surgical target. Lasers can be set to continuous or pulsed wave. They can be set on power levels ranging from low to high. A great amount of experience and judgment are required in order to properly set up and use the laser. The laser beam is bounced off a mirror onto the surgical target. If this sounds like playing a game of billiards, you wouldn't be far off. Doing it right--and coordinating one's movements with the anesthesiologist--requires a great amount of experience and skill.

    The pulsed dye laser (PDL) doesn't vaporize tissues like the carbon dioxide laser does, but instead coagulates the blood vessels feeding the papilloma. There is reportedly (Zeitels) an even steeper learning curve for the PDL than for the carbon dioxide laser. It is not just an application of science, but also an art.

    Considerations: (1) See "Cold Steel” and “Surgical Microderider.” (2) A few anesthesiologists fear the possibility of the CO2 laser's burning a hole in the endotracheal tube and causing a fire. (3) RRP ISA has heard from some patients who have been very satisfied but it has also heard from an equal number whose healing took much longer (that may suggest more trauma) and who remained hoarse for quite some time. (4) The fact that it cuts off the blood supply to the lesions suggests the possibility that it might also reduce recurrence rate. Steve Zeitels, M.D., however, states the PDL doesn't reduce recurrence rate. (5) It is very easy for a physician to be over-aggressive with the laser, and this applies to the pulsed dye laser as well as the carbon dioxide laser. Many RRP patients have been inadvertently injured by physicians using the laser, and the results can be devastating. Because of mixed patient reports with the pulsed dye laser, we tend to regard this method of treating papilloma as still experimental. (6) In working at the anterior commissure--the point where the vocal cords come together in a V--it is important that the surgeon not try to simultaneously excise papilloma on both sides of the larynx. If this happens, there is a greater than average chance that a web (scar) will develop within the anterior commissure that will impair vocal function. (Most surgeons, whether using cold steel or laser, are likely to leave a small amount of papilloma on one cord and excise it only after the other side has healed.) (7) Many experienced laser surgeons warn against using more than 5 watts on the CO2 laser. Many physicians use as little as 2 watts on adults and 1-2 watts on children. (8) Many surgeons have moved away from the laser to the microdebrider, but they still use the laser for hard-to-access areas like the ventricles. Research has shown that papillomas tend to be particularly active in the ventricles, which is why some physicians continue to prefer the laser.

    RRP ISA has learned (2006) that Dr. Steve Zeitels, the physician who initially introduced PDL to the RRP community, is no longer using it. It is far more likely to cause subepithelial bleeding than the pulsed KTP laser. He reported this in the "2006 Annals of Otology, Rhinology and Laryngology,: 115(8):571-580." 

    In the few years in which it took him to say this, RRP ISA has heard from a number of PDL patients who had disappointing treatment outcomes.

    There are a couple of "new PDL studies," one that has been announced which is recruiting children.

    RRP ISA's own survey results (through 2007) show a very close split in nearly two dozen patients, half of whom rated the PDL excellent to good, and half of which rated it poor to fair. (Interestingly, cold steel got the lowest patient approval ratings.)


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    Surgery Using the Microdebrider

    Summary: This device first appeared began being used on RRP patients at the turn of the century. It is essentially a very precise rotary shaver with a suction device. As the papillomas are caught in the razor, they are suctioned out. Reports of very quick recovery time are frequent, and there is little scarring, although this depends on the patient’s underlying condition and the surgeon’s skill with the device.

    Mechanism of Action: A rotary razor blade mechanically severs the papillomas, at which point they are suctioned up and out.

    Considerations: (1)See “Cold Steel” and “Laser.” (2) The surgical microdebrider has an even steeper learning curve than the CO2 laser. This implies the need for rigorous training and experience. (3) Many physicians moved away from the laser when the surgical debrider came out. In the right hands and in appropriate circumstances, it can greatly shorten the amount of time for healing. But the microdebrider doesn’t do that well in certain areas like the ventricles, where papilloma grow. Many physicians these days are using a combination of the laser and the surgical microdebrider.

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    Adjunctive Treatments

    Gardasil and artemisinin

    Preliminary observations suggest that this is quite possibly one of the most exciting adjunctive modalities to be presented on this page. RRP ISA isn't definitively stating that "it works," because much more research is necessary in order to make any definitive statement. But it definitely deserves to be studied.


    A thorough discussion on this approach can be found here.

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    Indole-3-carbinol (I3C) and its derivatives [diindolylmethane (DIM)]


    Summary: Indole-3-carbinol (I3C) and its derivatives (DIM) were initially thought to work by affecting metabolites of estrogen.

    For more updated information, see this article.

    Those involved in its writing seem to have a fiduciary interest in promoting it, and not all the statements should be accepted uncritically. It was published in 2007, however, far later than Dr. Leon Bradlow's early work on estrogen metabolites.

    Considerations: (1) The National Cancer Institute (NCI) published a paper in 1997 entitled "Clinical Development Plan: Indole-3-Carbinol." In it, the NCI described a number of potential toxicity markers that needed further investigation. At high dosage levels, I3C changes into multiple condensation products. There is a lot we do not know about the toxicity and teratogenic effects of these compounds. I3C exhibits both anti-estrogenic and estrogenic effects, and data confirms that it promotes some cancers and suppresses other cancers. RRP ISA suggests that patients consider the option of using DIM instead of I3C since DIM does not seem to have the same toxicity markers as I3C and is allegedly more stable. If anything, DIM yields results that are at least as good or better than I3C, and it does this without all the potential toxicities that are associated with I3C. (2) There have been a few dramatic remissions that have occurred after starting I3C/DIM (e.g., children who required surgery every few weeks prior to starting DIM-therapy; and who haven't needed any surgery in many years since; adults who required surgery every 2-3 months, but who haven't required surgery in several years since starting DIM). (3) I3C and DIM do not work on everyone, but there is no RRP treatment that does. Data shows that dramatic positive response does occur in about 33-40% of people who have taken I3C/DIM. (4) There have been a few patient-reports of bone mineral density loss following use of I3C. There has, however, been no report suggesting that DIM results in bone mineral density loss. RRP ISA would be remiss not to strongly encourage patients taking either of these products to get a baseline bone mineral density scan and subsequent bone mineral density scans under the supervision of a specialist and preferably by the most reliable method available. (5) Refrigerate I3C. Although the manufacturer of Phytososb-DIM affirms that it is not light sensitive, etc. the stability of DIM has been called into question by other specialists. Store DIM a dark, cool place.

    For more, also see Michael's posting on the message board.

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    Interferon

    Summary: Interferon has been used in treating Recurrent Respiratory Papillomatosis in the United States since the early 80's. It’s taken a back seat to cidofovir in recent years, but when used judiciously, it can cool things down and move patients out of an acute phase and into a chronic phase. The key concept is “judiciously,” which is described below under "Considerations." Alpha interferon seems to be the type that is most biologically active in treating Recurrent Respiratory Papillomatosis. The Schering product (Intron-A) is approved for treating condyloma (genital warts). It is probably the most widely used interferon in treating Recurrent Respiratory Papillomatosis. Patients and physicians should also be aware of Alferon.

    Mechanism of Action:

    Interferon mechanism of action is quite complex (see below). The following was sent to the author by Interferon Sciences, Inc:

    1. Antiproliferative Action: [Slowing target cell growth by increasing the length of their multiplication cycle; depleting essential metabolites increasing cell lysis through a cytotoxic mechanism; inhibiting the expression of certain oncogenes.]

    2. Immunomodulatory Action: [Enhancing expression of cell surface antigens, resulting in increased recognition and killing of infected cells by cytotoxic leukocytes; enhancing induction of antibodies to improve cell lysis mediated by complement and by antibody-dependent, cell-mediated cytotoxic leukocytes; activating macrophages, regulating natural killer cells (NK), cytotoxic T-lymphocytes, and complement for enhanced toxicitiy of target cells; triggering the secondary release of potent cytokines such as interleukins, which themselves have profound immunostimulating effects throughout the entire immune system.]

    3.) Antiviral Action: [Reducing the translation of viral proteins by interfering with normal host cell translation mechanisms; enzymatically degrading the viral RNA, thus diminishing its usability as a template for assembly of viral proteins; inhibiting viral transcription; altering the cell membrane (e.g., increasing cell fluidity) which may influence virion maturation and release; and modifying glycosylation patterns of viral proteins which could influence virus packaging, release or virulence.]

    Risk/Benefit Factors: (1) Most interferons cause flu-like side-effects that diminish, but do not entirely vanish, over time. Interferon can also place stress on the liver in the process of detoxification, and it is known to lower white blood cell counts. (2) If it works, interferon can be a life-saver. Used wisely, it can really slow things down. (3) Sudden discontinuance of interferon has been known to result in a "rebound phenomenon," where the disease flares up even worse than before treatment started. The chance of this occurring seems to be significantly mitigated by reducing the dosage downwards in gradual increments over a period of several weeks, instead of suddenly discontinuing the drug. (4) There is some controversy over how much interferon one should take. Many physicians like to put their patients on 9 million or more units a week for months or years at a time. Infants have also been treated with this dose, and we believe that there is great danger in this. Although the researchers at Johns Hopkins (Kashima, Healy) used large doses of interferon, they didn’t have great success. There were breakthroughs and rebounds. Why? Because high doses rapidly elicit the production of neutralizing antibodies. Ironically, some patients report that the “best” dosing protocol is to start with 3 million units three times a week in adults (commensurately less in children) and maintain that dosing level for about 6 weeks, after which the dose is gradually reduced. They say that they’ve been able to reduce their need for surgery and keep it there with as little as 1.5 million units two times a week, titrating down to that level over a period of around 4 months. (5) A decision must be made as to which type of interferon to use. There is some evidence that some (Roferon has been implicated in this in the past) recombinant DNA products cause the body to produce more antibodies than other recombinant DNA products. One doesn't want the body to develop antibodies to interferon. This tendency to produce fewer neutralizing antibodies may be one of the reasons why Schering's Intron-A became the interferon of choice in treating Recurrent Respiratory Papillomatosis.

    Neutralizing Antibody Considerations: Neutralizing antibodies have been found to decrease both the antiviral and the antiproliferative activity of interferon. Research by Von Wussow et al (J Interferon Res, 1994;14:217-219) concluded that binding antibodies appeared in 31% of Roferon-A patients and neutralizing antibodies in 25%, compared to 9% and 3% respectively when treated with Intron-A. Of 18 patients followed, 15 developed secondary resistance to Roferon, 3 to Intron. Antonelli et all (JID, 1992;165:593-594 and 1993;163:882-885) tested 296 hepatitis patients treated with the two drugs. Roferon-A showed a 20.2% and Intron-A a 6.9% incidence of neutralizing antibodies. Oberg et al (Biotherapy, 1997;10:1-5) reported the comparative incidence of neutralizing antibodies to be 38% (Roferon) vs 17% (Intron). Grander et al (Lancet, 1990;336:337-340) reported 50% of patients developing neutralizing antibodies with Roferon and 0% with Intron. These figures are dose-related, but commensurate dosages of drugs were given in these studies. There are *MANY* other published studies, all showing the same trend.

    The presence of antibodies not only reduces the effectiveness of the drug over time but, we are told, could conceivably produce a kind of "allergic reaction" to the drug. For no good reason that we can discern or that they were able to explicate, certain physicians and teaching institutions, reportedly including the prestigious Johns Hopkins, decided (ca. 1997-9) to use a form of alpha interferon (Roferon-A) that not only wasn't approved by the FDA for treatment of condyloma (HPV-disease) but which seems more likely to produce more neutralizing antibodies than its chief competitor (Intron-A), which was approved for condyloma by the FDA.

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    Photo-Dynamic Therapy (PDT)

    Summary: Photodynamic therapy involves giving a patient a light sensitive dye and bringing them into the operating room so that their papillomas, which have absorbed the dye, may be exposed to laser light of a certain wavelength.

    Mechanism of Action: PDT requires an initial IV-infusion of a light sensitive dye into the patient's bloodstream. The dye travels throughout the body. The photosensitizing dye is absorbed by rapidly growing epithelial cells. After a period of hours, it is supposed to "wash out" of healthy tissue. (It took over two months to do this in the early research.) When the dye that has been absorbed is exposed to red laser light, a singlet oxygen reaction takes place. PDT is supposed to kill the capillary structure feeding the papillomas (it exhibits an angiogenesis inhibiting effect).

    Considerations: (1) Attempts to effect a statistically significant number of extended remissions using PDT have been very disappointing. (2) Moreover, the manufacturer stopped making Foscan, the preferred light sensitive dye. (3) The side-effect profile of PDT should be noted in case it is ever used again. Side-effects included occasional vocal cord and tracheal burning, and extended periods of extreme photosensitivity. (4) After nearly 15 years of research on the use of PDT in treating RRP, Long Island Jewish Medical Center (LIJ), under Alan Abramson, M.D., has moved on. The PDT project is finished. LIJ is now researching the effects of the COX-2 inhibitor, Celebrex. assuredly probably for the best.

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    13-cis retinoic acid and other retinoids

    Summary: 13-cis retinoic acid (Accutane is the trade name, isotretinointhe generic name) is a powerful retinoid, an analogue of vitamin A. Taking this drug is not like taking a beta carotene supplement. The drug is very toxic. Some researchers have alleged that the drug has a clinical effect on Recurrent Respiratory Papillomatosis.

    Mechanism of Action: It affects the process of cellular maturation. There may be other effects on RRP which are as yet not well-understood. Considerations: (1) 13-cis retinoic acid is so toxic that the side-effects of interferon pale by comparison. It is also highly teratogenic, and it stays in the body for many months. (The package insert warns expectant mothers run great risks if they have taken the drug within six months of becoming pregnant.) (2) RRP ISA knows of no reliable data which shows that the hypothetical benefits of this drug outweigh its very real dangers, even in cases where Recurrent Respiratory Papillomatosis has been difficult to manage. (3) Researchers do not always tell the truth. In 1982, the executive director of RRP ISA entered a protocol using this drug. He was clearly identified in the published report, and, in contrast to the authors' representations, there were severe side-effects even with the lowered dosage. Nor did this patient go into any lasting remission. Data published in the abstract of an article by another set of researchers in 1994 also seems overly sanguine. One has to read several pages into the article to learn that the patient who was called “responsive” actually DIED in the operating room of florid respiratory papillomatosis. (4) Several other recognized retinoid experts (Hong, et al) concluded that this drug has no place in the treatment of RRP due to its toxicity and ineffectiveness. Curiously, Wiatrak reported in 2002 that he found the drug effective against RRP.

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    Acyclovir

    Summary: In the early 90’s, there was a flurry of interest and anecdotes on how Acyclovir might help Recurrent Respiratory Papillomatosis. A treatment research protocol was started at the University of Iowa.

    Mechanism of Action: Acyclovir works on the herpes virus. Recurrent Respiratory Papillomatosis is caused by the HPV virus, not herpes. No hypothesis has been advanced that purports to explain how Acyclovir could possibly affect RRP unless it was exacerbated by a coexisting herpetic disease. The latter condition doesn’t seem to apply, based on patient survey responses in the RRP ISA database.

    Considerations: The research findings showed that Acyclovir isn’t effective in treating Recurrent Respiratory Papillomatosis.

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    Ribavirin

    Summary: This drug was one of the first drugs used on AIDS. It wasn’t very effective. It was studied in a clinical trial against RRP at the University of Minn.

    Mechanism of Action: There is no hypothesis that has been advanced on a mechanism of action relative to RRP. The point is moot because it does not work on RRP.

    Considerations: (1) The outcome data on this drug does not suggest that Ribavirin is effective in treating RRP. (2) Ribavirin is toxic. The treatment protocol at the University of Minn. required the patient to live there so that blood toxicity could be routinely monitored.

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    Cidofovir (Vistide, HPMPC)

    Summary: Cidofovir (Vistide) is injected interlesionally during surgery or during office visits in transdermal injections that do not require general anesthesia.

    Mechanism of action: Theories have been advanced but it is still somewhat unclear how cidofovir works.

    Considerations: (1) Cidofovir does not work in every patient. It does not appear to cure RRP, but the drug has demonstrated biological activity against RRP. There are still questions to be answered, however, regarding Cidofovir's long-term efficacy and its long and short-term effects. (2) Concern was expressed in the 2005 RRP Taskforce that cidofovir was over-prescribed. The Taskforce published its recommendation that—because of questions about its oncogenic potential over time (could it cause cancer?)—treatment be reserved only for patients with severe RRP, not mild RRP. (3) A very number of patients have said that their voices got worse rather than better as a result of treatment. (4) Seth Pransky, MD, reported on the drug at the RRP Focus Group in conjunction with the 2002 American Academy of Otolaryngology convention in San Diego. He said that if injections are given every two weeks (not every 3 or 4 weeks, but every 2 weeks) and if they are given for a minimum of at least 8 injections, then his data confirms that long-lasting remission appears possible in many cases. Dr. Pransky recently reported, however, that he has pretty much stopped using cidofovir except in desperately ill cases. This suggests that he has had to revise his view of cidofovir's efficacy as compared to risks of long term side-effects. (5) Clark Rosen, MD, also reported very positive results at this Focus Session, but he noted that cidofovir can cause scarring in some patients. Dr. Rosen reiterated this point about scarring in the 2003 AAO mini-symposium on RRP.

    Also, you may wish to see:


    1. McMurray J, Connor  N, Ford  C. Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled study.  Ann Otol Rhinol Laryngo. 2008;117(7):477-83.

    2.. Naiman AN, Froehlich P, Gagnieu MC, et al. Cidofovir plasma assays after local injection in respiratory papillomatosis. Laryngoscope. 2004;114(7):1151-6. 

    3. MA Soma, Albert D. Cidofovir: to use or not to use? . Current Opinion Otolaryngol Head Neck Surgery. 2008;16(1):86-90.

    There is yet more literature cited in Professionals and Researchers>Library.

    Also, please be sure and see the cautionary notes by the RRP Taskforce.  These notes are summarized below:

    1) Given the promising results reported in pediatric and adult patients, cidofovir should be routinely presented as a treatment option in moderate to severely afflicted RRP patients. i.e.; those patients whose disease is not improving on surgical therapy alone or in conjunction with less potentially morbid adjuvant measures and/or requiring surgical intervention greater than 3 times a year. With appropriate consent, cidofovir therapy should be a viable option in patents whose disease severity is resulting in a need for frequent surgery, worsening airway compromise or severely impaired communication or those who otherwise may be considered candidates for tracheostomy.

    2) Patients with more mild disease, particularly children, should be discouraged from seeking treatment with cidofovir, until a better understanding of the long-term implications of the use of this drug have been established. With appropriate informed consent, cidofovir could still be utilized on a case-by-case basis, at the discretion of the prescribing physician, for the more mildly affected patient.

    3) As with all surgical procedures, informed consent should be obtained and documented in the patient's record. At a minimum, this should include a frank discussion of the nephrotoxic and carcinogenic potential of this drug.

    4) Adverse responses, particularly evidence of dysplasia or malignant transformation to squamous cell carcinoma, either locally or remotely, should be reported simultaneously to the FDA (form 3500 or 3500A) and to the RRP Task Force through email communication with its Chairman, Craig Derkay, MD. (derkaycs@chkd.com)"

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    Mumps/MMR vaccine

    Summary: Live mumps or MMR (mumps, measles and rubella) vaccine is injected into the larynx. Some patients with highly aggressive disease appear to have benefited, while others have not.

    Mechanism of Action: (1) Mumps/MMR vaccine appears to induce an inflammatory local response where it is injected. Reportedly, it hits the immune system like a Mac Truck. It may cause this area to “light up” so the immune system can see it. More studies need to be conducted to determine whether it stimulates, say, NK cell activity. Or perhaps it works through some other antigenic or bystander mechanism of action affecting cell-mediated immunity. There is much about cell-mediated immunity that we do not understand.

    Considerations:

    (1) Nigel Pashley, M.D. said he presented the first paper on the use of mumps vaccine with RRP. "Can Mumps Vaccine Induce Remission in Recurrent Respiratory Papillomatosis" was presented at the ASPO meeting in Scottsdale, Arizona on May 10, 2001. It was submitted for publication in the Archives of Otolaryngol Head and Neck Surgery.

    (2) In ca. 1984-85, Dr. Pashley claimed to have injected more than 50 patients with the mumps or MMR vaccine, with a remission rate of around 85%.

    (3) These figures are at significant variance with RRP ISA’s patient survey data. As of July 2006, about 50% of patients who reported in rated their satisfaction with Dr. Pashley's protocol in the POOR to FAIR range.

    (4) In 2005, Dr. Pashley stated that an adult can receive up to 15 ampules of MMR vaccine in one surgical procedure. RRP ISA has interviewed patients who were not in remission after 20 treatments using this method. In 2007, Dr. Pashley reported treating adults with up to 29 ampules at a single session with MMR. Does this show that treating with lower amounts worked very well? We think not.

    (5) As for 29 ampules? In even 10 procedures that could be 290 ampules. Is that safe? We think not.

    (6) When two health care professionals presented as patients to this physician, they were told the protocol was safe and there were no adverse side-effects. The informed consent also showed it as safe, listing none of the potential side-effects shown in the links immediately below. So were there any side-effects? After receiving 15 ampules of MMR vaccine, one of these patients—the writer of this website section, it turns out—woke up from the surgery with severe pain and barely able to breathe. When he urgently caught the attention of the recovery room nurse, she gratuitously declared that Dr. Pashley was “the best RRP doctor in the world.” This may have been good PR, but it didn’t help the patient's acute breathing problem. For some time after discharge, this patient experienced significant joint swelling and pain. The physician showed little or no interest in this, indicating that he didn’t believe it was related to the MMR injections. The second health care professional reported that he felt coerced and bullied into taking MMR vaccine. He also reported that he was told that only one person had ever reported side-effects and that was a gentleman who claimed to have arthritic symptoms. Dr. Pashley reportedly told him, with preternatural confidence, that the arthritic symptoms were unrelated to MMR. We can testify to the fact that Dr. Pashley initiated no test and reviewed no medical reports that would have reasonably allowed him to make this determination. Since the mumps and MMR protocols operate outside the purview of an IRB, it is more important than ever that systematic procedures are put in place for monitoring and evaluating reported side-effects. Treating them dismissively is neither professional nor ethical.

    (7) See the statements relating to protocol safety and informed consent that were written by Bettie Steinberg, Ph.D. and Vincent Bonagura, M.D.

    (8) Dr. Pashley first said he began using the trivalent MMR vaccine in March 2002, reporting that it seemed to work better (~85% success claimed) than the earlier mumps vaccine. (~75% success claimed.)  Question: Is a 10% advantage a good reason for using trivalent MMR over monovalent mumps vaccine? As of the date of this writing, RRP ISA knows of no well-developed scientific studies into the side-effect profiles of any RRP patients who have received multiple interlesional injections of mumps or MMR. On more than one occasion in 2005 and again in 2006, RRP ISA proposed the possibility of donating some serious grant money to test patients for antibody levels and to take baseline data in order to test for evidence of auto-immune disorders (e.g., autoimmune disorders like arthritis) following repeated courses of MMR injections. Dr. Pashley refused.

    (9) Mumps vaccine was reintroduced in an announcement by Merck at the 2004 RRP Focus Session in New York. Dr. Pashley himself was a featured speaker and has long been aware that it is available. Since that time, a number of patients have reported that that they were told that the mumps vaccine was unavailable. Dr. Pashley told the writer of this website section that it was unavailable, forgetting that he and Dr. Pashley were both in the same room when Merck told them that Mumpsvax is indeed available.

    (9) RRP ISA isn’t interested in closing down Dr. Pashley’s MMR practice. MMR appears to have benefited some people. We do insist, however, that side-effects be properly monitored, that accurate information be reported, and that Dr. Pashley should cease and desist in the telling of fibs. Furthermore, patients should be properly apprised of safety concerns, and these concerns need to appear on the surgical release and on informed consent documents.  We urge all RRP surgeons contemplating the use of mumps or MMR vaccine to work under an institutional review board (IRB). It will protect patients by ensuring that they are fully informed about safety issues and will ensure that such issues are systematically addressed in the future.

    For a list of MMR’s potential side-effects:

    http://www.rxlist.com/cgi/generic3/mmr_ad.htm
    http://pediatrics.about.com/cs/immunizations/a/mmr_vis_2.htm

    For the 2007 report on MMR, which several other physicians have used without much success, see the Dr. Pashley piece in the 2007 Focus Session.

    Also see "Informed Consent," written by Dr. Bettie Steinberg, for what we consider to be a strong critique of "procedures" used by Dr.Pashley's in his MMR approach (ed: no baseline immunological data, no IRB, arguable deceit regarding disclosure of side-effects, no substantive or accurate informed consent, etc.).

    Another strong cautionary statement from Dr. Vincent Bonagura, a respected immunologist working on a cure for RRP/HPV under a substantial NIH grant, can be found here,

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    GERD Treatment/Proton Pump Inhibitors

    Summary: GERD (gastric esophageal reflux disease) and laryngeal acid-reflux disease are challenging to definitively diagnosis without elaborate testing. If you have GERD, you may very well have heartburn, but not necessarily. Because GERD has the potential to cause RRP to flare even when no heartburn exists —the larynx is still being bathed in stomach acid on a routine basis—many otolaryngologists are routinely prescribing anti-GERD medication for RRP patients.

    Mechanism of Action: Anti-reflux medication is taken which lowers the acid content in the stomach. With a lowered acid level, there is less risk of irritating the larynx.

    This is an abstract on the effect of acid-reflux on RRP. We hope you find it of interest.

    Laryngoscope. 2002 Nov; 112(11):1926-9.

    Laryngopharyngeal reflux and laryngeal web formation in patients with pediatric recurrent respiratory papillomas. Holland BW, Koufman JA, Postma GN, McGuirt WF Jr. Department of Otolaryngology-Head and Neck Surgery, Wake Forest University School of Medicine, Brenner Children's Hospital, Winston-Salem, North Carolina 27157-1034, USA.

    OBJECTIVE: To determine whether treatment of laryngopharyngeal reflux reduces the laryngeal soft tissue complications encountered in surgery for recurrent respiratory papillomas. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective chart review of all pediatric patients treated for laryngeal recurrent respiratory papillomas between 1984 and 1999 was performed. Thirty-one such patients were identified. Twenty-four were at "high risk" for developing complications based on the number of operating suite visits and the presence of disease at the anterior commissure. Twelve patients underwent 24-hour double pH probe testing. RESULTS: Overall, 13 of 31 patients (42%) developed laryngeal webs. No other soft tissue complications were encountered. Of the patients who had pH probe testing, 12 of 12 (100%) had at least one pharyngeal episode of acid exposure. Of the "high-risk" patients, 10 were treated for reflux and only 2 of 10 (20%) developed webs. Eleven of 14 (79%) of the "high-risk" patients who were not treated for reflux developed webs. The difference in rate of web formation between patients treated for reflux and those not treated for reflux was statistically significant (P =.011). CONCLUSIONS: Antireflux treatments for patients undergoing surgery for laryngeal recurrent respiratory papillomas may reduce the soft tissue complications, especially scarring and web formation. Prophylactic antireflux therapy may be warranted in any patient undergoing surgery during which laryngeal mucosal disruption is anticipated.


    Considerations: (1) Anti-GERD medication has proven to be helpful for a number of patients. Proton pump inhibitors work splendidly, and if there are no overt symptoms of GERD or laryngeal acid reflux disease, smaller doses may be appropriate. (2) Some people have GERD during the day but not at night, and other patients have it only at night. Some are affected by GERD on a 24/7 basis. If possible, get tested. Then your physician will know your pattern and will be better able to prescribe. (2) In treating GERD and laryngeal acid reflux disease, patients are discouraged from using Cimetidine/Tagamet since it has been reported that this drug causes an INCREASE in 16 hydroxyestrone levels, which is what you are trying to reduce when taking DIM.

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    MMC (Mitomycin C)

    Summary: Mitomycin C (MMC) is a powerful systemic DNA inhibiting anticancer agent that has been around for years. Topical and highly diluted applications have been used in ophthalmic surgery as well. Ophthalmic use shows Mitomycin C to be "safe," and on that basis, there was some speculation that it may be safe for use in trying to prevent stenosis (webbing) in managing RRP.

    Mechanism of Action: DNA inhibition.

    Considerations: (1) We do not know enough about how this drug's topical application affects RRP patients over the long haul. Several RRP patients have used Mitomycin C—they were seen by different surgeons—with extremely negative results. Significant and persistent voice problems followed from the use of MMC, and laryngeal motility was adversely affected. (2) For a very strong admonitory statement about MMC and RRP patients, see “Steven Gray, MD Talks about Laryngeal Scarring, Mitomycin C and Cidofovir."

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    Celebrex

    Summary: The Department of Otolaryngology at Long Island Jewish Medical Center is conducting a research study on Celebrex and RRP.

    Mechanism of Action: When the Epidermal Growth Factor EGF) receptor is expressed at high levels, as it is in RRP and some cancers, it stimulates cells to make an enzyme called COX-2. Lots of things can stimulate cells to make COX-2, including infections, inflammation from arthritis, etc. It is made in many different cancers and also some pre-cancers like colon polyps. COX-2 is also made in papillomas but it is not made in most normal tissues including the tissues of the larynx and trachea and lung. Celebrex is an inhibitor of COX-2, and has been used to treat rheumatoid arthritis, colon polyps, etc. and is currently being studied to treat breast and bladder and lung cancers. [Steinberg]

    Considerations: (1) This Celebrex protocol requires surgery to remove the papillomas, after which patients are given Celebrex (celecoxib) for one year and a placebo for 6 months. Patients must be at least 18 years old and must have had at least 3 surgeries in the past year to remove papillomas. If you are interested, you can contact Ginny Mullooly at gmulool@lij.edu. (2) Patients are urged not to take Celebrex on their own for RRP; it should be used as part of a study with appropriate monitoring and evaluation. (3) Patients are also discouraged from assuming that herbal COX-2 inhibitors have anti-RRP effects or that they are safe to use. (4) Serious cardiovascular events have been reported with Cox2 inhibitors, though LIJ has decreased its dose to 400 mg/day to try and reduce those side-effects. Patients considering this class of drugs should be evaluated for cardiovascular issues.

    See more on Celebrex (and safety issues) in the 2007 RRP Focus Session report.

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    Beta Mannan

    This is in no way a "treatment" for RRP, but if people use it properly (not expecting remissions, for example), they may notice that it's a great help after surgery, in that it tones the laryngeal mucosa. I was very skeptical of the advertisements for Beta Mannan on the Alotek site, but several people reported that it seemed to help. 

    See the Resource page for sourcing and directions.

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