V o l u m e 1 1 • N u m b e r 6 • J u l y - A u g u s t 2 0 0 6
`I n d e x e d b y t h e U S N a t i o n a l L i b r a r y o f M e d i c i n e a n d P u b M e d
`
`EDITOR-IN-CHIEF
`Stuart Maddin, MD
`University of British Columbia, Vancouver, Canada
`
`ASSOCIATE EDITORS
`Hugo Degreef, MD, PhD - Medical Dermatology
`Catholic University, Leuven, Belgium
`Jason Rivers, MD - Medical Dermatology
`University of British Columbia, Vancouver, Canada
`Jeffrey S. Dover, MD - Surgical Dermatology
`Yale University School of Medicine, New Haven, USA
`Dartmouth Medical School, Hanover, USA
`
`Vaccines for the Prevention of
`Human Papillomavirus Infections
`L.M. Speck1 and S.K. Tyring, MD, PhD, MBA2
`1University of Texas Medical Branch, Galveston, USA
`2University of Texas, Health Sciences Center, Houston, USA
`
`ASSISTANT ASSOCIATE EDITOR
`Murad Alam, MD - Surgical Dermatology
`Northwestern University Medical School, Chicago, USA
`
`EDITORIAL ADVISORY BOARD
`Kenneth A. Arndt, MD
`Beth Israel Hospital
`Harvard Medical School, Boston, USA
`Wilma Fowler Bergfeld, MD
`Cleveland Clinic, Cleveland, USA
`Jan D. Bos, MD
`University of Amsterdam, Amsterdam, Holland
`Alastair Carruthers, MD
`University of British Columbia, Vancouver, Canada
`Bryce Cowan, MD, PhD
`University of British Columbia, Vancouver, Canada
`Boni E. Elewski, MD
`University of Alabama, Birmingham, USA
`Barbara A. Gilchrest, MD
`Boston University School of Medicine, Boston, USA
`Christopher E.M. Griffiths, MD
`University of Manchester, Manchester, UK
`Aditya K. Gupta, MD, PhD, MBA/HCM
`University of Toronto, Toronto, Canada
`Mark Lebwohl, MD
`Mt. Sinai Medical Center, New York, USA
`James J. Leydon, MD
`University of Pennsylvania, Philadelphia, USA
`Harvey Lui, MD
`University of British Columbia, Vancouver, Canada
`Howard I. Maibach, MD
`University of California Hospital, San Francisco, USA
`Jose Mascaro, MD, MS
`University of Barcelona, Barcelona, Spain
`Larry E. Millikan, MD
`Tulane University Medical Center, New Orleans, USA
`Jean Paul Ortonne, MD
`Centre Hospitalier Universitaire de Nice, Nice, France
`Ted Rosen, MD
`Baylor College of Medicine, Houston, USA
`Alan R. Shalita, MD
`SUNY Health Sciences Center, Brooklyn, USA
`Wolfram Sterry, MD
`Humboldt University, Berlin, Germany
`Richard Thomas, MD
`University of British Columbia, Vancouver, Canada
`Stephen K. Tyring, MD, PhD, MBA
`University of Texas Health Science Center, Houston, USA
`John Voorhees, MD
`University of Michigan, Ann Arbor, USA
`Guy Webster, MD
`Jefferson Medical College, Philadelphia, USA
`Klaus Wolff, MD
`University of Vienna, Vienna, Austria
`
`MANAGING EDITOR
`Penelope Gray-Allan
`
`ABSTRACT
`
`
`Human papillomavirus (HPV) infection is the known cause of almost all cases of
`cervical cancer. An understanding of the HPV genome has allowed the development of
`two prophylactic vaccines capable of protecting against both persistent HPV infection
`and cervical intraepithelial neoplasia (CIN) with 100% efficacy in fully vaccinated
`women. The vaccines, manufactured by Merck (Gardasil®, which was approved by
`the US FDA in June, 2006) and GlaxoSmithKline (Cervarix®, which will be submitted
`for US FDA approval by the end of 2006), both target HPV types 16 and 18, which
`together account for 70% of cervical cancer. Merck’s vaccine also targets HPV 6 and
`11, covering ≥90% of genital warts. These vaccines are highly immunogenic and have
`an excellent safety profile. HPV vaccines promise to offer an exciting contribution to
`healthcare and cancer prevention. However, many questions remain concerning who
`to vaccinate, the duration of protection, cost, public acceptance, and the potential for
`worldwide distribution.
`Key Words: human papillomavirus, HPV infection, cervical intraepithelial neoplasia,
`HPV vaccine
`
`HPV and Cervical Cancer
`Cervical cancer is the second most common cause of death from cancer,
`after breast cancer, among women worldwide. The American Cancer Society
`estimates that over 9,700 women will be diagnosed with cervical cancer in 2006
`and approximately 3,700 will die from it. Worldwide >500,000 develop cervical
`cancer resulting in 290,000 deaths annually. Persistent infection with high-risk
`HPV genotypes is the main cause of most, if not all, cervical carcinogenesis.
`HPV infects the stratified squamous epithelia of skin and mucous membranes,
`potentially causing a range of epithelial proliferative lesions ranging from
`warts to cancer. About 30–40 of the 100 known genotypes of HPV are sexually
`transmitted and cause genital infection. While there is no routine screening for
`HPV infection, it is thought to be the most common sexually transmitted disease
`in the United States. Approximately 6.2 million new cases of genital HPV occur
`each year, with an estimated prevalence of about 20%–40% among sexually
`active young women. The lifetime risk for women is thought to be at least 75%
`for one or more genital HPV infections.1-4
`HPVs are small, nonenveloped viruses whose 8-kb circular genome is comprised
`of three regions: the long control region (LCR), the early region (E), and
`the late region (L). The early region consists of genes E1–E8 which encode
`
`Exhibit 1076
`Prollenium v. Allergan
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`nonstructural proteins responsible for transcription,
`plasmid replication, and transformation. The late
`region codes for the major (L1) and minor (L2)
`proteins that form the viral capsid. The development
`of a prophylactic HPV vaccine stemmed from findings
`that L1, the major capsid protein, self-assembles into
`empty capsids, called virus-like particles (VLPs),
`when it is expressed from eukaryotic vectors such
`as recombinant vaccinia, baculovirus, and yeast.5,6
`VLPs are free of viral DNA and are noninfectious.
`Their morphologic similarity to virions provides a
`source of neutralizing epitope that elicits an antibody
`response.
`
`Prophylactic Vaccine Development
`Two pharmaceutical companies, Merck and
`GlaxoSmithKline (GSK) have each developed an
`L1 VLP vaccine. Merck’s vaccine, Gardasil®, is
`quadrivalent and targets HPV types 16/18/6/11. HPV
`16 and 18 account for about 70% of cervical cancer
`(50% and 20%, respectively)4, while types 6 and 11
`account for ≥90% of genital warts. Gardasil® received
`a unanimous 13–0 vote on May 19, 2006 from a US
`FDA Advisory Committee endorsing the vaccine, and
`on June 8th it received full US FDA approval for use
`in women 9–26 years of age. It will be marketed as
`a prevention of cervical cancer, precancerous genital
`lesions, and genital warts due to HPV types 6, 11,
`16, and 18. The Centers for Disease Control’s (CDC)
`Advisory Committee on Immunization Practices
`(ACIP) will draft recommendations and schedules
`for the administration of the vaccine in the US. Merck
`Executive Director of Medical Affairs, Rick Haupt,
`said the company is prepared to make Gardasil®
`available “within weeks” of the FDA’s decision.7
`The catalog price for Gardasil® is $120 for each of
`the three doses, a possible impediment to worldwide
`vaccination campaigns.
`GlaxoSmithKline’s vaccine, Cervarix®, is a bivalent
`HPV 16/18 vaccine that is currently in Phase III
`clinical trials. GSK submitted a marketing application
`for Cervarix® in March of this year to the European
`Agency for the Evaluation of Medicinal Products
`(EMEA). Filings will follow in Australia, parts of
`Asia, and Latin America, with submission to the US
`FDA anticipated by the end of 2006.
`
`Safety, Efficacy, and Duration of Protection
`Clinical
`trials by both companies have been
`randomized, double-blinded, placebo-controlled,
`multicenter trials conducted in HPV-negative young
`women ranging from 15–25 years of age. The safety
`profile is excellent, with the most common side-effect
`being brief soreness at the injection site.
`
`To evaluate vaccine efficacy, the end points used were
`a reduction in the incidence of moderate (CIN2) and
`high-grade (CIN3) dysplasia. In Merck’s FUTURE
`II trial, more than 12,167 women ages 16–23 were
`randomly assigned to receive three doses of Gardasil®
`or placebo over 6 months. Women were followed for
`an average of 2 years after enrollment, and no one in
`the Gardasil® group developed persistent infection
`with HPV strains 16 or 18. Gardasil® prevented
`100% (n=5,301) of cases of CIN 2/3 associated with
`HPV types 16 and 18 compared with 21 cases in the
`placebo group (n=5,258). Efficacy was found to be
`97% when analyzing a broader group, which included
`the women who did not receive all of the Gardasil®
`doses or did not follow the study protocol. All
`participants experienced 100% antibody responses to
`the HPV strains 6, 11, and 16, and 99.1% developed
`strain 18 antibodies. Merck has studied the vaccine in
`males, who also displayed ≥99% antibody response.
`However, vaccine efficacy in males is difficult to
`evaluate considering that HPV-related anogenital
`cancer is very rare in the US, with the exception of
`HIV-positive homosexuals. In an effort to find out
`how long the vaccine will be protective, Merck will
`be following participants of the FUTURE II study for
`several years.8-9
`GSK’s Cervarix® vaccine has also been shown to be
`100% effective in preventing infection with HPV
`strains 16 and 18. A follow-up study looked at 776 of
`the 1,113 women aged 15–25 years in the US, Canada,
`and Brazil enrolled in the 2004 study in which women
`were given three doses of Cervarix® or a placebo.
`This study reported high levels of antibodies for up to
`4.5 years after receiving the vaccine, providing useful
`information regarding duration of protection.6
`
`Type Specificity and Therapeutic Potential
`Cross-protection and
`therapeutic potential are
`important issues under continued investigation by
`both companies. GSK’s Cervarix® has been associated
`with some cross-protection against HPV45 and
`HPV31, although this protection was less complete
`than that offered against types 16 and 18.6 Merck has
`noted a potential therapeutic benefit of the vaccine for
`women who already have an HPV infection. In one
`study a subcohort of women who were HPV16 DNA-
`positive at enrollment but anti-HPV16-seronegative
`were found to be less likely to develop subsequent
`HPV16-related CIN2–3 than those who received
`placebo injections. A therapeutic vaccine could be
`used to halt the progression or prevent the recurrence
`of established disease.
`
`2
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`Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 11 No. 6 • July-August 2006
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`8. Harper DM, Franco EL, Wheeler CM. Sustained
`efficacy up to 4.5 years of a bivalent L1 virus-like
`particle vaccine against human papillomavirus
`types 16 and 18: follow-up from a randomized
`control trial. Lancet 367:1247-55 (2006).
`9. Graham J. FDA panel backs key STD vaccine.
`The Chicago Tribune (2006 May 18).
`10. Stanley MA. Human papillomavirus vaccines.
`Rev Med Virol 16:139-49. (2006).
`11. Lowy DR, Schiller JT. Prophylactic human
`papillomavirus vaccines. J Clin Invest 116:1167-
`73 (2006).
`12. Zhou J, Sun XY, Stenzel DJ. Expression of vaccinia
`recombinant HPV 16 L1 and L2 ORF proteins in
`epithelial cells is sufficient for assembly of HPV
`virion like particles. Virology 185:251-7 (1991).
`
`Implementation Issues
`the
`There are many questions surrounding
`implementation of
`the HPV vaccine. Debate
`concerning who should be vaccinated will soon be
`revealed by the CDC, but the public’s recognition,
`understanding, and acceptability of the vaccine is
`yet to be determined. Critics are also concerned that
`women will consider the vaccine a replacement for
`routine Pap smears; however, vaccinated women will
`still be vulnerable to other types of HPV, accounting
`for 30% of all cases of cervical cancer, and will need
`to continue to be screened. The challenge remains
`for feasible distribution in developing countries,
`where 80% of cervical cancers occur. Despite these
`concerns, the potential for a vaccine that protects
`against HPV-related cervical cancer is a tremendous
`advancement in public health. It will have a powerful
`impact on healthcare costs, the future of cancer
`prevention, and the overall well-being of women
`worldwide.
`
`References
`1. Gerberding JL. Report to Congress: Prevention
`of Human Papillomavirus Infection. Centers for
`Disease Control and Prevention. (2004 Jan).
`2. Weinstock H, Berman S, Cates W. Sexually
`Transmitted Infections
`in American Youth:
`Incidence and Prevalence Estimates. Perspect Sex
`Reprod Health 36(1):6210 (2004 Jan-Feb).
`3. Lowy DR, Howley PH. Papillomaviruses. In:
`Knipe DM, Howley PH, editors. Fields Virology
`Philadelphia: Lippincott, William & Wilkins p. 2231-
`64 (2001).
`4. Zur Hausen H. Papillomaviruses and cancer:
`from basic studies to clinical application. Nat Rev
`Cancer 2:342-50 (2002).
`5. Kirnbauer R, Booy F, Cheng N, et al. Papillomavirus
`L1 major capsid protein self-assembles into virus-
`like particles that are highly immunogenic. Proc
`Nat Acad Sci USA 89:12180-4 (1992).
`6. Neeper MP, Hofmann KJ, Jansen KU. Expression
`of the major capsid protein of human papillomavirus
`type 11 in Saccharomyces cerevisae. Gene 180:1-
`6 (1996).
`7. Stanley MA. The end for genital human
`papillomavirus infections? Lancet Oncol 6:256-7
`(2005).
`
`Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 11 No. 6 • July-August 2006
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`ADVANCES IN DERMATOLOGIC SURGERY
`Editors: Jeffrey S. Dover, MD and Murad Alam, MD
`
`Novel Flaps for Lip Reconstruction
`A. J. Kaufman, MD1 and T. E. Rohrer, MD2
`1David Geffen School of Medicine at UCLA, Los Angeles, USA and
`Private Practice, Center for Dermatology Care, Thousand Oaks and Santa Barbara, USA
`2 Boston University School of Medicine, Boston, USA and
`Private Practice, Skin Care Physicians, Chestnut Hill, USA
`
`
`ABSTRACT
`Reconstruction of the lips requires careful attention to aesthetic and functional goals. We describe our approach to lip
`repair and present novel methods to maintain symmetry and function, and optimize cosmetic results.
`Key Words: Lip repair, vermillion
`
`Reconstruction of the lips is a challenging task for the
`dermatologic surgeon. From a functional standpoint,
`the lips serve a critical role in speech, eating, and
`demonstrative emotions. Aesthetically, there are
`numerous subtle, but very important, variations in
`contour, color, and texture. With no underlying bony or
`cartilaginous framework, they are extremely sensitive
`to distortion. The lips are a focus of facial beauty, and
`their central location does not permit concealment of
`unsightly scars or asymmetrical results.
`As with most repairs on the face, repair along relaxed
`skin tension lines and within cosmetic subunits
`optimizes cosmetic outcome. Cosmetic subunits of
`the upper lip include two lateral segments and one
`central or philtral unit. While the lower lip is a single
`unit, it is helpful to consider whether the defect is
`more central or lateral. Another cosmetic subunit to
`consider is the vermillion, and defects involving only
`the vermillion should be reconstructed within that
`cosmetic subunit whenever possible.
`Categorization into partial or full-thickness defects
`also identifies ideal reconstructive methods. Defects
`that involve a full-thickness portion of the lip (i.e.,
`skin, muscle, and mucosa) require full-thickness
`repair. The size of the surgical defect also impacts
`alternatives for repair. The dermatologic surgeon
`should strive to keep incision lines within or parallel
`to relaxed skin tension lines and place incisions at
`the boundaries between cosmetic units or subunits
`whenever possible.
`We will describe our approach to reconstruction of the
`lips and some novel methods of repair. As mentioned,
`the first step is to consider the location of the defect
`and what tissue has been lost.
`
`Partial Thickness Surgical Defects
`Vermillion
`Small superficial defects limited to the vermillion may
`be allowed to heal by secondary intention with good
`results;1 however, larger or deeper defects or wounds
`near the vermillion border risk distortion if allowed
`to heal in this manner. Full-thickness grafts from the
`labial or buccal mucosa may be used, but often develop
`trapdoor deformity or mismatch color, texture, and
`thickness with the surrounding vermillion.
`For defects approaching 50% of the vermillion width
`or greater, a complete vermillionectomy and mucosal
`advancement flap repair may be performed (Figures
`1A–C). By removing the entire vermillion the risk of
`subsequent malignancy from adjacent actinic cheilitis
`is lessened, and the uniform repair and scarring help
`maintain symmetry of the lip. Like other repairs of the
`perioral area, mucosal advancement flaps should be
`marked out prior to the injection of local anesthesia.
`Mucosal advancement flaps are undermined below
`the level of the minor salivary glands, but above the
`orbicularis muscle. They are dissected back to a point
`where there is minimal closure tension at the vermillion
`border, and then closed by the rule of halves with
`absorbable and nonabsorbable sutures. While useful for
`large defects, mucosal advancement flaps have potential
`disadvantages. Advancement of mucosa to reconstruct
`vermillion often decreases the anterior-posterior
`dimension of the lip and can give a more rounded and
`reddish color to the reconstructed vermillion. Patients
`also frequently complain of persistent hypoesthesia, and
`men may note redirection of beard hair upward, causing
`irritation to the upper lip.
`Another approach to vermillion repair for defects
`that are <40% of the vermillion width is a bilateral
`vermillion rotation flap (Figures 2A–C).2 This
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`Figure 1A: Vermillion defect prior to reconstruction.
`
`Figure 2A: Medium-size vermillion defect prior to repair.
`
`Figure 1B: Residual dry vermillion is removed
`(vermillionectomy), and defect repaired with mucosal
`advancement flap.
`
`Figure 2B: Bilateral vermillion rotation flap completed
`by incision along vermillion border bilaterally to
`oral commissures with backcuts to permit rotation.
`Undermine widely deep to salivary glands on the
`labial mucosa and rotate and secure flaps centrally.
`Central tricone excised at end.
`
`Figure 1C: Healed result.
`
`Figure 2C: Short-term healed result.
`
`Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 11 No. 6 • July-August 2006
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`flap utilizes adjacent vermillion to rotate centrally.
`The arcs of the rotation flap are drawn along the
`vermillion border with the redundant triangle of
`skin (dog ear) removed posteriorly. Back cuts are
`made at the oral commissures to permit rotation of
`the flaps and minimize pivotal restraint. Like the
`mucosal advancement flap, the bilateral vermillion
`rotation flap is undermined in a plane between the
`minor salivary glands and orbicularis muscle. This
`flap maintains the anterior-posterior dimension of the
`lip, avoids redirection of beard hairs, and decreases
`the risk of persistent hypoesthesia. This flap is
`an excellent alternative for repair of medium-sized
`defects in patients with less actinic damage to the
`adjacent vermillion.
`
`Cutaneous Lip, Lateral
`In many instances, surgical defects in the lateral
`cutaneous lip may be closed in a simple, linear
`fashion along the relaxed skin tension lines radiating
`from the lip. Although M-plasties can be performed to
`shorten the length and keep the repair from crossing
`the vermillion border, violating the vermillion border
`with a linear closure is generally not an aesthetic
`problem at all, as long as the vermillion border is
`properly aligned during closure. It is certainly better
`to violate the border than leave an elliptical closure
`too short and create a protrusion of tissue or tricone on
`the lip. Also, remember that elliptical excisions may
`push tissue at the poles outward. This force on the lip
`can create a displeasing downward displacement of
`the lip and should be watched for and avoided during
`closure. To reduce motion and tension on the wound
`during healing, a novel trick is to use a small amount
`of botulinum toxin injected around the perioral area
`(i.e., place 0.5–1 unit in four sites circumferentially
`around the vermillion border) during the immediate
`postoperative period.3
`For defects
`too
`large for side-to-side repair,
`advancement flaps are the most useful repair for
`partial-thickness defects of the lateral cutaneous lip.
`The procedure works well for the upper and lower
`lip due to the abundant reservoir of cheek and jowl
`tissue. Advancement flaps are generally drawn along
`the vermillion border with redundant tissue or tricone
`excised (superiorly on the upper lip and inferiorly on
`the lower lip) along relaxed skin tension lines radiating
`from the lip. Since a pure advancement flap has
`unequal lengths being drawn together (X vs. X + the
`length of the defect), there is significant potential for
`tissue distortion if this is not accounted for. Burrow’s
`triangles or crescents should be taken to minimize
`this difference and the risk of vermillion distortion.
`Advancement flaps are generally undermined in the
`
`deep subcutaneous fat above the orbicularis muscle.
`When defects are located in the superior aspect of
`the upper cutaneous lip, the flap may be drawn,
`extending along the nasal sill with a crescent taken
`lateral to the ala and the redundancy taken inferiorly
`along a relaxed skin tension line radiating from the
`lip. When designing and executing advancement flaps
`in the upper lip, care should be taken not to flatten
`or pull the philtral crests asymmetrically. Pulling the
`philtrum too far to one side creates an aesthetically
`unpleasing effect.
`Another option for lateral defects of the upper or lower
`lip is the inferior-based rotation flap (Figure 3A–C).
`One of the benefits of this repair in this location is that
`the arc of the incision is kept at the junction between
`cosmetic units, the melolabial fold on the upper lip
`and the labiomental crease on the lower lip. One of
`the basic tenets of reconstructive surgery, keeping an
`incision line at the junction between cosmetic units
`or subunits, helps to hide some of the incision lines
`in this repair.
`In a similar fashion the island pedicle flap is useful
`for defects of the lower lip and the upper lip. This is
`another example where at least half of the incision
`from the flap is hidden along the melolabial fold and
`more along the nasal sill. Great care must be taken to
`adequately undermine and dissect this flap to assure
`minimal tension on the mobile vermillion border.
`Transposition flaps may be useful for partial thickness
`defects of the lateral upper or lower lip, especially in
`instances where an advancement flap does not provide
`adequate tissue or mobility. One of the advantages of
`this flap is that part of the incision can be hidden
`along the melolabial or labiomental folds. However,
`a distinct disadvantage is the tendency to trapdoor,
`especially on the more mobile upper lip.
`
`Cutaneous Lip, Medial
`Defects in the central area of the lower lip and defects
`of the upper lip too large for repair with a unilateral
`procedure can be reconstructed using a bilateral
`advancement flap (Figures 4A–C). Large amounts
`of tissue can be recruited from the cheeks for repair,
`especially in elderly individuals. However, in men
`the reconstructed upper lip may lack beard hair. The
`key to successful aesthetic repair is to keep incision
`lines at cosmetic unit/subunit boundaries and avoid
`deviation of the lip (eclabium). Undermining in these
`large random flaps should be carried out in a plane
`that is superficial to the underlying facial musculature.
`Avoid trauma to neurovascular structures.
`For defects of the philtrum, several options are
`available. For defects <50% of the philtral width, a
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`Figure 3A: Partial-thickness defect of lateral upper
`cutaneous lip.
`
`Figure 4A: Partial-thickness defect of central upper
`cutaneous lip.
`
`Figure 3B: Rotation flap completed keeping incision
`line in melolabial fold and tricone excised in same
`direction as perioral rhytides.
`
`Figure 4B: Bilateral rotation flap to reconstruct
`defect. Incision lines are kept at junctions of cosmetic
`subunits (vermillion inferiorly, alar sill superiorly)
`and tissue superior to defect is sacrificed to better hide
`surgical scars.
`
`Figure 3C: Healed result.
`
`Figure 4C: Healed result.
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`complex repair works well. Defects 50%–100% of
`the philtral width can be reconstructed using an island
`pedicle flap, keeping the incisions along the philtral
`ridges, intersecting to a point at the base, or extending
`far up the nasal columella if necessary (Figures 5A–C).
`In this regard, the incision lines are kept at the junction
`of cosmetic subunits (philtral ridges) and similar
`vascularized tissue is utilized in the repair. If the defect
`extends to involve the vermillion, the defects should be
`repaired separately, using a mucosal advancement flap
`for the vermillion portion. Another option for defects
`involving most of the philtrum is to enlarge the defect
`to the full size of the philtrum and use a full-thickness
`skin graft. The obvious disadvantage to this option is
`the difference in skin characteristics, most obvious
`in men due to the lack of beard hair. In some rare
`instances, bilateral rhombic transposition flaps may be
`used to close philtral defects. The secondary defects
`of the rhombic flaps are taken along the philtral crests
`on each side of the philtrum and transposed into the
`defect.
`An excellent flap for closure of small defects on or
`just above the vermillion border involving both the
`cutaneous lip and vermillion lip is the Cupid’s bow
`repair as described by Mellette.4 The flap is drawn
`similar to a mucosal advancement flap, but incorporates
`a bow shape, mimicking the patient’s Cupid’s bow in
`the upper cutaneous lip. A disadvantage of this flap is
`the upward pull of the vermillion lip. If it is a relatively
`small defect, the slight pull can give a pleasant increase
`in upper lip fullness. Unfortunately, there is a limit to
`the amount of pull that is aesthetically acceptable and
`the flap is thereby limited to small defects in patients
`that would like a more full upper lip.
`
`Full-Thickness Surgical Defects
`Full-thickness surgical defects involve loss of various
`degrees of cutaneous, muscular, and mucosal lip.
`Defects up to 25% of the upper lip and one-third of the
`lower lip can be closed in a wedge-excision fashion.
`The key to success with this and other full-thickness
`repairs is careful and complete repair of the mucosa,
`orbicularis, and skin, and accurate approximation of
`the vermillion border.
`Larger defects necessitate repair with a “lip switch”
`staged procedure or a repair that moves tissue around
`the oral commissures. Fortunately, with the growth
`of Mohs micrographic surgery and its resultant tissue
`preservation and higher cure rates, the need for these
`larger repairs is less for the dermatologic surgeon. The
`original “lip switch” flap was described by Sabatinni,
`and later by Abbe, as a staged procedure where donor
`tissue is transposed from the unaffected lip across the
`oral aperture to the surgical defect, maintaining an
`
`Figure 5A: Partial-thickness philtral defect involving
`cutaneous lip and vermillion.
`
`Figure 5B: Repair with island pedicle flap for
`cutaneous lip and mucosal advancement flap for
`vermillion. Remember to consider repair of separate
`subunit defects separately.
`
`Figure 4C: Healed result.
`
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`intact vascular pedicle.5 The transposed flap should
`approximate one-half the size of the defect and
`should not exceed one-third of the donor lip width.
`After vascular ingrowth has developed within the
`flap from the recipient site, the pedicle is severed and
`inset. This flap may be used for defects up to 50% of
`the lip width, but disadvantages include prolonged
`denervation with incomplete recovery, risk of the
`trapdoor phenomenon, inconvenience of a transoral
`pedicle, and the need for two or more procedures.
`Other alternatives are available that avoid some of
`the disadvantages of a “lip switch” procedure. The
`Estlander flap moves tissue around the commissure
`in a single-stage procedure, though blunting of the
`oral commissure, necessitating revision surgery, is
`not uncommon. A circumferential incision permits the
`Karapandzic flap or Gillie’s flap to move donor tissue
`around the oral commissures, and is able to repair
`defects up to two-thirds of the lip.6 By maintaining
`an innervated and vascularized pedicle, there is good
`potential to maintain motor and sensory function.
`On the downside, there is frequent distortion of the
`oral commissures, requiring commissuroplasty, and
`the circumferential incision gives some patients a
`“clown-like” appearance.
`
`Conclusion
`The perioral area is a focal point of both spoken
`and nonspoken communication and an area of
`great aesthetic importance. Its mobile nature and
`varied contours make it a reconstructive challenge.
`However, as in reconstruction in any area of the
`
`face, by understanding the anatomy (superficial and
`deep), keeping tension off the free margin (the
`vermillion lip), and placing incision lines in cosmetic
`unit junctions and/or along relaxed skin tension
`lines, aesthetically pleasing reconstruction can be
`consistently achieved. Given its place as a central
`focus of facial beauty, successful reconstruction of
`the perioral area is immensely rewarding.
`
`References
`1. Gloster HM. The use of second-intention healing
`for partial-thickness Mohs defects involving the
`vermillion and/or mucosal surfaces of the lip. J
`Am Acad Dermatol 47(6):893-7 (2002 Dec).
`2. Kaufman AJ. Bilateral vermillion rotation flap.
`Dermatol Surg 32(5):721-5 (2006 May).
`3. Bansal C, Omlin KJ, Hayes CM, Rohrer TE.
`Novel cutaneous uses for Botulinum toxin type A.
`Cosmet Dermatol (in press 2006).
`4. Paniker PU, Mellette JR. A simple technique for
`repair of Cupid’s bow. Dermatol Surg 29(6):636-
`40 (2003 Jun).
`5. Clarkson P. Use of the Abbe flap in the primary
`repair of the double cleft lip. Br J Plast Surg
`7(2):175-8 (1954 Jul).
`6. Karapandzic M. Reconstruction of lip defects by
`local arterial flaps. Br J Plast Surg 27(1):93-7
`(1974 Jan).
`
`Get more clinical information at
`www.SkinTherapyLetter.ca
`A Physician's site for:
`• A-Details™: Online Drug Presentations
`• Skin Therapy Letter© Articles
`• Meeting Abstracts and Proceedings
`• Refer your patients for self-help to www.SkinCareGuide.ca
` or any of the following sites:
`HerpesGuide.ca
`FungalGuide.ca
` AcneGuide.ca
`EczemaGuide.ca
`PsoriaticArthritisGuide.ca
`PsoriasisGuide.ca
`
`RosaceaGuide.ca SkinCancerGuide.ca
`MohsSurgery.ca
`MildCleanser.ca
`
`BotoxFacts.ca
`Lice.ca
`
`DermatologyCare.ca
`Sweating.ca
`
` Dermatologists.ca ColdSores.ca
`
`
`
`SkinPharmacies.ca
`SkinTherapyLetter.ca UnwantedFacialHair.ca
` We welcome your comments and suggestions. Please e-mail us at physicians@skincareguide.com
`
`Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 11 No. 6 • July-August 2006
`
`9
`
`

`

` Class
`
`Update on Drugs
`Name/Company
`Approval Dates and Comments
`
`Antiviral Agent
`
`Rosacea
`
`Antiaging Agent
`
`Zoster Vaccine Live
`Zostavax®
`Merck
`Doxycycline, 40mg
`Oracea®
`CollaGenex
`Pharmaceuticals
`Hyaluronic Acid
`Dermal Filler
`Juvéderm® Gel
`Allergan
`Mycophenolate
`Mofetil
`CellCept®
`Aspreva
`Pharmaceuticals/Roche
`Suberoylanilide
`Hydroxamic Acid
`(SAHA)
`Zolinza®
`Merck
`Quadrivalent Human
`Papillomavirus
`Recombinant Vaccine
`Gardasil®
`Merck
`TNF-blocking Agent Adalimumab
`Humira®
`Abbott
`
`Immunomodulatory
`Agent
`
`Oncologic Agent
`
`Vaccine
`
`The US FDA approved this new vaccine in May 2006 for the
`prevention of herpes zoster (shingles) in individuals 60 years of age
`and older. It is given as a single dose by injection.
`
`The US FDA approved this product in May 2006 for the
`treatment of inflammatory lesions (papules and pustules) of
`rosacea in adult patients.
`
`The US FDA approved this dermal filler in June 2005 for the
`treatment of facial wrinkles and folds. Juvéderm® should only
`be administered by a trained and qualified health care provider.
`
`The US FDA granted orphan drug designation for this
`immunosuppressive agent in June 2006 for the treatment of
`pemphigus vulgaris.
`
`The US FDA accepted a New Drug Application for this
`investigational histone deacetylase inhibitor in June 2006 for the
`treatment of advanced cutaneous T-cell lymphoma. This NDA
`has been granted priority review.
`
`The