2002 (San Diego)
RRP Focus Session
Bill Stern from the RRPF opened the meeting and spoke on that organization's work, summarizing its data.
Michael Green from the International RRP ISA Center also presented, described the work of that organization, highlighting some of the unique obstacles and challenges faced by RRP patients and their families.
Five RRP physicians/researchers then presented:
(1) Craig Derkay, M.D. (pediatric otolarynology, Eastern Virginia Medical School, Chair of RRP Task Force.
Uniform staging and severity study software is available to physicians for "scoring" RRP severity.
Summary of PDT results using latest Foscan protocol [ed. note, for more recent developments not reported in this session, click here. MG]
Cidofovir results (Data exists on 200 patients who have used Cidofovir.]
Data shows that 12 out of 103 patients (~12 had pulmonary spread, and all 12 had jet ventilation anesthesia.
Phytosorb-DIM update on dosage recommended dosage level. (This organization has received recommendation for a higher dose than reported by Dr. Derkey, viz., 7-8 mg/kg on a sustained basis (not limited to 3 mos. for moderate to severe cases of RRP. For more, click here.
The drug 5ALA can make latent papilloma visible in the OR under fluorescence. This will be published in Laryngoscope in near future.
The CDC's RRP Task Force has prepared a registry of juvenile-onset RRP and issued clinical practice guidelines for children. The Centers for Disease Control recently decided to withdraw funding for the Taskforce, however. It will be moving Task Force funding to study West Nile and bio-terrorism. This is a very serious blow to the RRP community.
A proposed gene mapping multi-center study is being considered. (See Dr. Farrell Buchinsky's presentation below.
(2) Clark Rosen, M.D. (otolaryngology, Univ. of Pittsburgh Voice Clinic
Dr. Rosen addressed the question of vocal scarring. He opened by explaining the mechanism of vocal fold vibration (800 times a second. The lamina propria is especially vulnerable to surgical trauma. It loses elasticity, gets rigid, and can no longer maintain its stability as it vibrates (analogy to a rigid rubber band on a paddle board. Phonation therefore becomes effortful and sporadic (voice breaks.
Dr. Rosen is opposed to using the laser on the vocal folds themselves (it inflicts sub-dermal burning, is not able to provide tactile feedback, causes scarring. He prefers very precise phono-microsurgery.
Dr. Rosen does not endeavor to repair vocal cord scarring unless a minimum of one year has elapsed with no recurrence of RRP.
There are non-surgical treatments that can help restor the voice such as voice therapy and therapy that requires the patient to sing. Anti-GERD medication (e.g., Prevacid might also help.
In trying to repair damage to the vocal cords, a physician can use lipoinjection thyroplasty or collagen injection; patioent's own fat is injected. Collagen works OK if the problem isn't very severe. The future lies in tissue engineering, gene therapy, study of growth factors, etc.
Dr. Rosen reported excellent RRP treatment results using Cidofovir before/after the reconstruction procedure. However, he also reported that Cidofivir seemed to cause vocal cord scarring in some patients.
(3) Farrell Buchinsky, M.D. (pediatric otolaryngology, Allegheny General Hospital, Pittsburgh, PA.; also at Center for Genomic Sciences
Dr. Buchingsky is interested in the science of asking questions regarding RRP genetics. He reports that there is evidence in favor of there being a genetic component.
There is HLA evidence (proteins on the cell surface-is a tag that can modulate immune response. Certain types are disproportionately frequent in RRP patients.
DQA evidence (rabbit model.
Transmission disequilibrium (TDT is a relatively new test.
Dr. Buchinsky will be needing subjects in the future. Needs blood and papilloma samples from mother, father and infected child. Can also take blood from infected siblings if mother/father not available. Is coordinating with RRP Taskforce. Still going through human subjects approval reviews, etc., prior to actual subject recruitment.
(4) Seth Pransky, M.D. (pediatric otolaryngology, San Diego Children's Hospital
Dr. Pransky did not provide us with a copy of his PowerPoint presentation, but we do have notes and some screen shots of that presentation.
Screenshots of PowerPoint Photo
Dr. Pransky confirmed that a tracheostomy changes the cell lining of the trachea to facilitate seeding and papilloma growth.
Dr. Pransky talked about the pros and cons of CO2 laser use. He conceded that it is the standard of care currently and controls for bleeding, but it also causes scarring, there is concern about the laser plume and sometimes about fire, it is difficult to use for bulky lesions, extra OR staff are needed, etc.
He described the Xomed microdebrider (see screen shots as having many advantages, but it does require experience and has a steep learning curve. The surgeon needs to learn how to control bleeding, suctioning, speed settings, etc. The blade rotates at 600-6000 RPM.
Dr. Pransky described his research with cidofovir in some detail. Dr. Pransky's data on Cidofovir was described as "hot off the press." He just presented it in Engand. In the 1999 research, 5 children with severe RRP were treated. They needed surgery every month, 8-13 injections were given, and all 5 improved markedly. In 2000, 5 children received shorter courses of treatment (4 injections every two weeks. All had initially marked response, but the RRP tended to break-through and recur. The screen shot photographs show the dramatic initial improvement. Dr. Pransky believes that 4 injections were simply not enough.
Post-session and in private conversation, Dr. Pransky explained that it looked as if dosing in an every other week schedule for at least 8 injections was optimal. He said that if this schedule were followed, there is a *much* greater probability of sustained remission than if there are less than 8 injections or if the injection intervals were longer than 2 weeks. [Ed. note: Physicians thinking of using cidofovir are encouraged to contact Dr. Pransky for themselves directly to obtain his recommendations. MG]
Outpatient transdermal injections of cidofovir may be done in a physician's office without the use of general anesthesia.
Dr. Pransky reported that his cidofovir subjects were tested regularly and that no liver or renal pathologies have been detected, nor has there been any evidence of malignant transformation.
(5) Brian Wiatrak, M.D. (pediatric otolaryngology, Children's Hospital of Alabama
Dr. Wiatrak did not provide us with a copy of his PowerPoint presentation, but we do have notes and some screen shots of that presentation. Click here to see these screen shots.
Screenshots of PowerPoint Photo
Dr. Wiatrak confirmed that HPV Type 11 *can* express as skin warts. This was news to most of us. He presented research history, as shown in the screen shots.
Dr. Wiatrak presented on his research on the advantages of using the Xomed microdebrider, also reflected in the screen shots. Click here for conclusions.
His research on Cidofovir did not yield the same positive results as those of Dr. Pransky's. (Ed. note: It is unclear, however, whether his protocol entailed a commensurate number of injections; see the screenshots for more. MG
Dr. Wiatrak reported that in a research protocol involving 13-cis retinoic acid (Accutane, several of his RRP patients (specifically, HPV type 6 patients, but not HPV type 11 responded (see screen shots. Dosing was @ 1-2 mg/kg, and it was not protracted beyond a few months. [Ed. note: Dr. Wiatrak's research contributions with this drug definitely deserve positive acknowledgement--the observation that response seems to depend on HPV type is itself quite significant--but patients should note that these results need to be replicated, and moreover, there has been a lot of prior controversy about this teratogenic and extremely toxic drug and its effects on RRP. It can cause severe deformities in newborns, severe depression, spinal bone spurs, encephalitis, to name of the side-effects.]
Immunological studies appear to suggest that there is definitely a deficiency in the immune (local? system of RRP patients.