Bio


Dr. Pepper is a double-board certified surgeon who specializes in aesthetic and reconstructive surgery of the face, in particular surgery for the treatment of facial paralysis. He is the Director of the Stanford Facial Nerve Center since 2017. He has broad expertise in facial plastic and reconstructive surgery, including facial reanimation surgery, facelift surgery, rhinoplasty, and the reconstruction of the face after skin cancer resection. Dr. Pepper performed his undergraduate studies at Brown University, majoring in Neuroscience. He completed a one-year research fellowship at the National Institutes of Health in preparation for a career in academic medicine. He was awarded his M.D. at the University of California, Irvine, graduating with highest honors and Alpha Omega Alpha designation in 2007. He went to the University of Michigan for residency training in Otolaryngology – Head & Neck Surgery in 2012. He then completed fellowship training in Facial Plastic & Reconstructive Surgery in 2013, also at the University of Michigan. Dr. Pepper was honored to receive the highest board score in the nation on the American Board of Facial Plastic & Reconstructive Surgery examination in 2013. For this accomplishment, he was given the Jack R. Anderson Award for Scholastic Achievement. He also directs the scientific work of the Stanford Facial Nerve Center and his NIH-funded research explores regenerative strategies to improve nerve regeneration after injury.

Clinical Focus


  • Facial Paralysis Surgery
  • Facial Plastic Surgery
  • Rhinoplasty
  • Skin cancer reconstruction
  • Facelift Surgery
  • Facial Reconstructive Surgery
  • Aesthetic Surgery
  • Filler and Botox(tm)
  • Otolaryngology
  • Bell's Palsy
  • Ramsay Hunt Syndrome
  • Cranial Nerve Injuries
  • Facial Nerve Injuries
  • Facial Nerve
  • Nerve Regeneration

Academic Appointments


Administrative Appointments


  • Director, Stanford Facial Nerve Center (2017 - Present)

Honors & Awards


  • Faculty Scholar Award, Donald E. and Delia B. Baxter Foundation (2015)
  • Research Scholar Award, American Association of Facial Plastic & Reconstructive Surgeons (2015)
  • Research Scholar Award, American Association of Facial Plastic & Reconstructive Surgeons (2014)
  • Jack Anderson Award (Given for highest national board score), American Board of Facial Plastic & Reconstructive Surgery (2013)
  • Dr. Paul Holinger Resident Research Award, Triological Society (2010)
  • Zeta Chapter, Alpha Omega Alpha Honor Medical Society (2007)

Boards, Advisory Committees, Professional Organizations


  • Chair elect, Plastic and Reconstructive Surgery Committee, American Academy of Otolaryngology - Head and Neck Surgery (2020 - Present)
  • Member, Education Committee, American Academy of Otolaryngology - Head and Neck Surgery (2020 - Present)
  • Exam writer, American Board of Otolaryngology (2018 - Present)

Professional Education


  • Board Certification: American Board of Facial Plastic and Reconstructive Surgery, Facial Plastic Surgery (2016)
  • Board Certification: American Board of Otolaryngology, Otolaryngology (2013)
  • Fellowship: University of Michigan Health System Internal Medicine Residency (2013) MI
  • Residency: University of Michigan Health System (2012) MI
  • Medical Education: University of California, Irvine (2007) CA

Current Research and Scholarly Interests


Facial paralysis is a debilitating condition that affects thousands of people. Despite excellent surgical technique, we are currently limited by the regenerative capacity of the body. The mission of our research is to identify new treatments that improve current facial paralysis treatments. We do this by exploring the regenerative cues that the body uses to restore tissue after nerve injury, in particular through pathways of neurogenesis and nerve repair in small mammals.

Please visit our website at the URL below to see ongoing projects, open positions, publications, and more information about our research.

https://med.stanford.edu/ohns/research/labs/jon-paul-pepper-lab.html

2023-24 Courses


All Publications


  • Evidence Based Medicine for Facial Reanimation. Facial plastic surgery : FPS Kimura, K. S., Kfoury, P., Pepper, J. P. 2023

    Abstract

    This article provides a brief historical overview of the assessment instruments that have been developed to categorize the severity of disease in patients with facial palsy. Important advances in the quality of these instruments in discussed. The modern day instruments that are commonly required for evidenced-based patient assessment are then presented, with emphasis on the level of evidence of the studies that describe these instruments.

    View details for DOI 10.1055/a-2023-9051

    View details for PubMedID 36720255

  • Synkinesis and Communicative Participation. Facial plastic surgery & aesthetic medicine Okland, T. S., Willens, S. H., Pepper, J. 2022

    Abstract

    Background: Facial palsy (FP) impacts verbal and nonverbal communication, but the effect of synkinesis on communicative ability is unknown. Objective: Among patients with nonflaccid FP, or synkinesis, is there a correlation between disease-specific quality-of-life and communicative ability or dysfunction? Methods: Retrospective study of a series of adult patients with unilateral synkinesis. Subjects were evaluated using the Communicative Participation Item Bank (CPIB) Short Form, Facial Clinimetric Evaluation (FaCE) scale, and Synkinesis Assessment Questionnaire (SAQ). Associations between these scales were evaluated by computing Pearson correlation coefficients. Results: A total of 69 confirmed synkinesis patients were included. Synkinesis patient mean (standard deviation) CPIB score was 20.68 (±8.27; range of scale 0-30), indicative of communication restriction. A strong correlation was observed between total CPIB and FaCE scores (r=0.66), indicating patients with synkinesis who reported better facial function also reported greater communicative ability. There was a weak correlation between CPIB and SAQ scores (r=-0.27). Conclusion: Synkinesis is associated with significant deficits in communicative ability. Communication restrictions track strongly with the FaCE scale.

    View details for DOI 10.1089/fpsam.2022.0094

    View details for PubMedID 36260346

  • Facial Paralysis and Communicative Participation: The Importance of Facial Symmetry at Rest. The Annals of otology, rhinology, and laryngology Ayoub, N. F., Abdelwahab, M. n., Zhang, M. n., Ma, Y. n., Stranberg, S. n., Okland, T. S., Pepper, J. P. 2020: 3489420912446

    Abstract

    There is a paucity of research devoted to understanding the communication restrictions encountered by facial paralysis patients. We aim to explore the relationship between patient-reported restrictions in communicative participation and objective facial paralysis severity using validated scales of facial movement.We performed a pilot retrospective study using a consecutive series of adult patients with a diagnosis of unilateral facial paralysis. In addition to baseline demographics, subjects were evaluated using the Communicative Item Participation Bank Short Form (CPIB), Electronic Facial Assessment by Computer Evaluation (eFACE), and Sunnybrook Facial Grading System (SFGS).Twenty patients were included, 10 (50%) of whom were female with a mean age of 61 ± 13 years and mean duration of facial paralysis of 53 ± 82 months. The mean CPIB score was 14.6 ± 10.0 (range 0-29) and was comparable to scores of patients with conditions known to cause significant communicative disability. The mean eFACE scores were 67.4 ± 29.2, 44.2 ± 30.1, and 73.8 ± 30.0 for the static, dynamic, and synkinesis domains, respectively, with a composite smile score of 58.5 ± 16.9. After adjusting for age, gender, and duration of facial paralysis, significant moderate correlations were observed between the CPIB and the static eFACE domain (r = -0.51, P = .03) and smile composite score (r = 0.48, P = 0.0049), in addition to between the CPIB and SFGS synkinesis domain (r = 0.48, P = 0.04).Patients with unilateral facial paralysis experience significant limitations in communicative participation. These restrictions demonstrate moderate to strong correlations with objective assessments of facial paralysis and quality of life measures. Communicative participation may be a helpful means of tracking response to treatment.IV.

    View details for DOI 10.1177/0003489420912446

    View details for PubMedID 32192355

  • Dual Nerve Transfer for Facial Reanimation JAMA FACIAL PLASTIC SURGERY Pepper, J. 2019; 21 (3): 260–61
  • Speech and Communicative Participation in Patients With Facial Paralysis. JAMA otolaryngology-- head & neck surgery Kim, J. H., Fisher, L. M., Reder, L., Hapner, E. R., Pepper, J. 2018; 144 (8): 686–93

    Abstract

    Importance: Problems with speech in patients with facial paralysis are frequently noted by both clinicians and the patients themselves, but limited research exists describing how facial paralysis affects verbal communication.Objective: To assess the influence of facial paralysis on communicative participation.Design, Setting, and Participants: A nationwide online survey of 160 adults with unilateral facial paralysis was conducted from March 1 to June 1, 2017. To assess communicative participation, respondents completed the Communicative Participation Item Bank (CPIB) Short Form questionnaire and the Facial Clinimetric Evaluation (FaCE) Scale.Main Outcomes and Measures: The CPIB Short Form and the correlation between the CPIB Short Form and FaCE Scale. In the CPIB, the level of interference in communication is rated on a 4-point Likert scale (where not at all=3, a little=2, quite a bit=1, and very much=0). Total scores for the 10 items range from 0 (worst) to 30 (best). The FaCE Scale is a 15-item instrument that produces an overall score ranging from 0 (worst) to 100 (best), with higher scores representing better function and higher quality of life.Results: Of the 160 respondents, 145 (90.6%) were women and 15 were men (mean [SD] age, 45.1 [12.6] years). Most respondents reported having facial paralysis for more than 3 years. Causes of facial paralysis included Bell palsy (86 [53.8%]), tumor (41 [25.6%]), and other causes (33 [20.6%]), including infection, trauma, congenital defects, and surgical complications. The mean (SD) score on the CPIB Short Form was 0.16 (0.88) logits (range, -2.58 to 2.10 logits). The mean (SD) score of the FaCE Scale was 40.92 (16.05) (range, 0-83.3). Significant correlations were observed between the CPIB Short Form and overall FaCE Scale scores, as well as the Social Function, Oral Function, Facial Comfort, and Eye Comfort subdomains of the FaCE Scale, but not with the Facial Movement subdomain.Conclusions and Relevance: Patients with facial paralysis in this study sample reported restrictions in communicative participation that were comparable with restrictions experienced by patients with other known communicative disorders, such as laryngectomy and head and neck cancer. We believe that communicative participation represents a unique domain of dysfunction and can help quantify the outcome of facial paralysis and provide an additional frame of reference when assessing treatment outcomes.

    View details for PubMedID 29955841

  • The role of Hedgehog-responsive fibroblasts in facial nerve regeneration EXPERIMENTAL NEUROLOGY Dogaru, G., Juneja, S. C., Shokrani, A., Hui, R. Y., Chai, Y., Pepper, J. 2018; 303: 72–79

    Abstract

    Facial nerve paralysis is a significant cause of morbidity, affecting facial appearance, emotional expression, speech, oral competence, and vision. A more complete understanding of the complex cellular events required for successful nerve regeneration may reveal new therapeutic targets. The role of fibroblasts in regeneration, and the process by which the nerve reforms its three-dimensional structure after a transection injury, are not fully understood. The Hedgehog signaling pathway has been shown to mediate nerve sheath formation during development. We therefore sought to characterize the role of Hedgehog-responsive cells following transection of the facial nerve.Two transgenic mouse lines with reporters for the downstream effector of Hedgehog signaling, Gli1, were used. The animals underwent a unilateral facial nerve transection injury, and the contralateral side served as a control. Facial nerves were analyzed via immunohistochemistry and immunofluorescence at predetermined time points as the facial nerve regenerated after the transection injury.There was a statistically significant increase in Gli1+ cells both at the site of injury and within the distal nerve segment over time. Gli1+ cells are fibroblasts within the nerve and appear to contribute to the reformation of the nerve sheath after injury.These findings describe a key signaling pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts that reside within the nerve respond to injury and may represent a novel therapeutic target in the context of facial nerve regeneration after transection injury.

    View details for PubMedID 29337143

  • Human Induced Pluripotent Stem Cell-Derived Motor Neuron Transplant for Neuromuscular Atrophy in a Mouse Model of Sciatic Nerve Injury. JAMA facial plastic surgery Pepper, J., Wang, T. V., Hennes, V., Sun, S. Y., Ichida, J. K. 2017; 19 (3): 197-205

    Abstract

    Human motor neurons may be reliably derived from induced pluripotent stem cells (iPSCs). In vivo transplant studies of human iPSCs and their cellular derivatives are essential to gauging their clinical utility.To determine whether human iPSC-derived motor neurons can engraft in an immunodeficient mouse model of sciatic nerve injury.This nonblinded interventional study with negative controls was performed at a biomedical research institute using an immunodeficient, transgenic mouse model. Induced pluripotent stem cell-derived motor neurons were cultured and differentiated. Cells were transplanted into 32 immunodeficient mice with sciatic nerve injury aged 6 to 15 weeks. Tissue analysis was performed at predetermined points after the mice were killed humanely. Animal experiments were performed from February 24, 2015, to May 2, 2016, and data were analyzed from April 7, 2015, to May 27, 2016.Human iPSCs were used to derive motor neurons in vitro before transplant.Evidence of engraftment based on immunohistochemical analysis (primary outcome measure); evidence of neurite outgrowth and neuromuscular junction formation (secondary outcome measure); therapeutic effect based on wet muscle mass preservation and/or electrophysiological evidence of nerve and muscle function (exploratory end point).In 13 of the 32 mice undergoing the experiment, human iPSC-derived motor neurons successfully engrafted and extended neurites to target denervated muscle. Human iPSC-derived motor neurons reduced denervation-induced muscular atrophy (mean [SD] muscle mass preservation, 54.2% [4.0%]) compared with negative controls (mean [SD] muscle mass preservation, 33.4% [2.3%]) (P = .04). No electrophysiological evidence of muscle recovery was found.Human iPSC-derived motor neurons may have future use in the treatment of peripheral motor nerve injury, including facial paralysis.NA.

    View details for DOI 10.1001/jamafacial.2016.1544

    View details for PubMedID 27978547

  • Current state of stem cell-mediated therapies for facial nerve injury CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY Wang, T. V., Delaney, S., Pepper, J. 2016; 24 (4): 285-293

    Abstract

    Interest in the application of stem cell therapy to nerve injury has grown exponentially in recent years, as the armamentarium of potential stem cell sources has increased. This article reviews literature on the recent developments in the application of stem cell therapy for facial nerve injury.Current stem cell therapy for the treatment of peripheral nerve injury can be generalized into those that either enhance native neural regeneration via an anti-inflammatory effect or growth factor secretion, replace Schwann cells, or replace motor neurons. Animal studies have shown that nerve conduits seeded with stem cells (either undifferentiated or differentiated into Schwann-like cells) in sciatic and facial nerve injury models can promote nerve regeneration with similar efficacy to autologous nerve autografts. In-vivo studies have also shown that induced pluripotent stem cell-derived motor neurons, when transplanted into transected mouse tibial nerves, can form functional neuromuscular junctions with the denervated mouse triceps surae.The authors believe that induced pluripotent stem cells have significant therapeutic potential. This source of human stem cells can be harvested with little morbidity, is isogenic to the donor, and has fewer ethical concerns compared with embryonic cellular sources. Further research is required to determine stem cell efficacy and safety. Questions of stem cell fate unpredictability and possible tumorigenesis must be addressed prior to human trials.

    View details for DOI 10.1097/MOO.0000000000000292

    View details for Web of Science ID 000379665900004

    View details for PubMedID 27379549

  • Transcutaneous Lower Blepharopllasty with Fat Transposition CLINICS IN PLASTIC SURGERY Pepper, J., Baker, S. R. 2015; 42 (1): 57-?

    Abstract

    Fat preservation lower lid blepharoplasty is the authors’ preferred technique for surgical rejuvenation of the aging lower lid. Key technical refinements are overlaid on a conceptual framework developed over the past 2 decades by several investigators. The use of the orbicularis oculi muscle suspension flap is a useful adjunct to the transcutaneous approach to lower lid blepharoplasty.

    View details for DOI 10.1016/j.cps.2014.09.002

    View details for Web of Science ID 000346754200006

    View details for PubMedID 25440741

  • Local Flaps: Cheek and Lip Reconstruction JAMA FACIAL PLASTIC SURGERY Pepper, J., Baker, S. R. 2013; 15 (5): 374-382

    Abstract

    The reconstruction of cutaneous defects of the cheek and lip is a foundational topic for facial plastic and reconstructive surgeons. Facial defects have a significant impact on patient quality of life that has been well demonstrated.To review new findings that have an impact on the planning and understanding of local flaps for the reconstruction of cutaneous defects of the cheek and upper lip; recent research in facial soft-tissue anatomy and vascular anatomy is integrated into a discussion of local flap reconstruction.A Medline search of scientific literature was conducted, with an emphasis on 1980 to the present. Search terms included cheek; lip; reconstruction; vascular anatomy, soft-tissue anatomy, aging face, outcomes, and perforator flap. Cadaveric studies were specifically sought for anatomic review, and comparison group outcome studies are preferentially cited over clinical case series.Reconstruction of large medial defects of the cheek and upper lip is particularly challenging, and the V-Y subcutaneous tissue pedicle island advancement flap is valuable for repair of these defects. Outcomes analyses for local flap reconstruction are in high demand. Pedicled perforator flaps will likely see increased application for facial reconstruction in the near future.Detailed knowledge of the soft-tissue anatomy of the cheek and lip is critical to accurate surgical planning in local flap reconstruction.

    View details for DOI 10.1001/jamafacial.2013.1608

    View details for Web of Science ID 000325179000010

    View details for PubMedID 24051684

  • Upper Blepharoplasty The Aesthetic Ideal CLINICS IN PLASTIC SURGERY Pepper, J., Moyer, J. S. 2013; 40 (1): 133-?

    Abstract

    Upper lid blepharoplasty is a procedure associated with a high level of patient and surgeon satisfaction. New insights into the anatomic underpinnings of the periorbital aging process have enabled more successful and reproducible surgical results. The authors provide a detailed discussion of the relevant anatomy and integrate this into their surgical philosophy for upper lid blepharoplasty. Special focus is given to presurgical planning.

    View details for DOI 10.1016/j.cps.2012.07.001

    View details for Web of Science ID 000313146200016

    View details for PubMedID 23186763

  • Patient Assessment of Psychosocial Dysfunction following Nasal Reconstruction PLASTIC AND RECONSTRUCTIVE SURGERY Pepper, J., Asaria, J., Kim, J. C., Baker, S. R., Moyer, J. S. 2012; 129 (2): 430-437

    Abstract

    Postoperative psychosocial distress is a critical aspect of surgery, particularly in aesthetically sensitive areas. In this study, the authors assess the level of psychosocial distress associated with nasal reconstruction. The authors also compare postoperative distress levels associated with different reconstructive techniques throughout the healing process.The authors conducted a prospective study of patients undergoing nasal reconstruction following excision of cutaneous malignancy. The main outcome measure was the Derriford Appearance Scale 24, a measure of psychosocial distress. The Derriford Appearance Scale was administered at preoperative assessment, 1 < x < 4 weeks, 4 ≤ x < 12 weeks, and x ≥ 12 weeks. The entire cohort was analyzed with respect to distress levels before and after surgery. Reconstructions were categorized as interpolated, local tissue, or full-thickness skin graft. Analyses were performed for reconstruction type, patient, and defect data.Fifty-nine patients were enrolled. Reconstructions included 14 interpolated flaps, 17 local tissue flaps, and 28 full-thickness skin grafts. For the entire cohort, distress levels were significantly higher at the first postoperative visit (p < 0.05), with normalization at subsequent follow-up evaluations. At the first assessment, the interpolated flap group had significantly higher levels of distress in comparison with the full-thickness skin graft group (p < 0.05). At late follow-up, levels of distress were equivalent.Nasal reconstruction is associated with short-term increases in psychosocial distress that corrects by approximately 12 weeks after surgery. Interpolated flaps cause significantly higher distress at early assessment. Distress levels at late follow-up appear to be equivalent to those following a full-thickness skin graft despite larger and deeper initial defects.Therapeutic, II.

    View details for DOI 10.1097/PRS.0b013e31823aeb0a

    View details for Web of Science ID 000300240000077

    View details for PubMedID 22286425

  • Steps Forward: Contemporary Treatment of Facial Paralysis. Facial plastic surgery clinics of North America Pepper, J., Tollefson, T. T. 2021; 29 (3): xv-xvi

    View details for DOI 10.1016/j.fsc.2021.04.001

    View details for PubMedID 34217452

  • Dual Nerve Transfer for Facial Reanimation. Facial plastic surgery clinics of North America Okland, T. S., Pepper, J. 2021; 29 (3): 397-403

    Abstract

    This article describes a method of performing a dual nerve transfer procedure and provides illustrative cases for analysis and discussion. Clinical indications, technical pearls, and pitfalls are discussed. Dual nerve transfer for facial reanimation efficiently combines the strengths of the hypoglossal and masseteric nerve transfers and builds on existing nerve transfer techniques.

    View details for DOI 10.1016/j.fsc.2021.03.004

    View details for PubMedID 34217442

  • Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature. The Annals of otology, rhinology, and laryngology Feng, A. Y., Jin, M. C., Wong, S., Pepper, J., Jackler, R., Vaisbuch, Y. 2020: 3489420966611

    Abstract

    OBJECTIVE: We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature.PATIENT: 61 F with right facial palsy.INTERVENTION: Following a single intravenous dexamethasone injection with oral steroids over 2months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation.OUTCOME AND RESULTS: The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8months, facial function has improved substantially (HB 2/6).CONCLUSION: Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3months.

    View details for DOI 10.1177/0003489420966611

    View details for PubMedID 33135423

  • How do we teach surgical residents in the COVID-19 era? Journal of surgical education Okland, T. S., Pepper, J., Valdez, T. A. 2020

    Abstract

    OBJECTIVE: In response to ongoing concerns regarding transmission of the novel coronavirus (COVID-19), surgical practice has changed for the foreseeable future. Practice guidelines recommend only urgent or emergent surgical procedures be performed to minimize viral transmission. This effectively limits standard training and practice for surgical residents. The purpose of this article is to describe opportunities in surgical simulation, and highlights the challenges associated with training in the COVID-19 era.DESIGN: This is a perspective summarizing the potential role of surgical simulation to target training gaps caused by decreased surgical caseloads.CONCLUSIONS: This manuscript concisely discusses simulation options available to training programs, including the novel concept of "surgical kits." These kits include all instruments necessary to simulate a procedure at home, effectively pairing safety and utility.

    View details for DOI 10.1016/j.jsurg.2020.05.030

    View details for PubMedID 32773336

  • Commentary on "Deep Dive into Denervation: Institutional Experience with Selective Denervation in Nonflaccid Facial Palsy" by Miller and Hadlock. Facial plastic surgery & aesthetic medicine Pepper, J. P. 2020

    View details for DOI 10.1089/fpsam.2020.0497

    View details for PubMedID 33121275

  • Contrast-Enhanced Ultrasound With Perflubutane for Sentinel Lymph Node Mapping in Cutaneous Melanoma: A Pilot Study LARYNGOSCOPE Bertelsen, C., King, K. G., Swanson, M., Duddalwar, V., Pepper, J. 2019; 129 (5): 1117–22

    View details for DOI 10.1002/lary.27397

    View details for Web of Science ID 000467083900032

  • Health Outcome Studies in Skin Cancer Surgery. Facial plastic surgery clinics of North America Olds, C. E., Pepper, J. 2019; 27 (1): 163–70

    Abstract

    As cutaneous cancers are the most common malignancies affecting US citizens, they represent a significant public health problem and health care cost burden. There are a variety of treatment options available to manage cutaneous malignancies, but limited data are available regarding outcomes, including quality of life, recurrence, and mortality. Here, we examine outcomes of skin cancer surgery as they relate to sociodemographic data and treatment factors.

    View details for PubMedID 30420070

  • Contrast-Enhanced Ultrasound With Perflubutane for Sentinel Lymph Node Mapping in Cutaneous Melanoma: A Pilot Study. The Laryngoscope Bertelsen, C., King, K. G., Swanson, M., Duddalwar, V., Pepper, J. 2018

    Abstract

    OBJECTIVE: To study the feasibility of contrast-enhanced ultrasound (CEUS) for identification of SLN associated with cutaneous melanoma.STUDY DESIGN: Single arm pilot study in a swine animal model.METHODS: One milliliter of perflubutane (Sonazoid, GE Healthcare, Milwaukee, WI) was injected into the peritumoral dermis in five swine with cutaneous melanoma. Ultrasonography was used to follow enhancing lymphatic channels to lymph nodes (LN). Intradermal injection of vital blue (VB) dye was used as a positive control. LN identified by either method were excised and examined histologically.RESULTS: There were five primary cutaneous melanomas with mean area of 4.36±4.75cm2 and Breslow depth of 3.6±1.5mm. Six possible sentinel lymph node (SLN)s were identified with CEUS, and nine were identified with VB. SLN averaged 12.44±6.15cm from the primary tumor. Four of six (67%) SLNs identified by CEUS and four of nine (44%) candidate SLNs identified by VB contained histologically confirmed metastatic melanoma. All six CEUS-identified SLNs were also identified with VB. Two LNs not containing melanoma were identified by CEUS; three were identified with VB. In all SLN with metastases, metastatic cells were scattered throughout the LN and not clustered in a discrete mass.CONCLUSION: CEUS with perflubutane feasibly identifies SLN associated with cutaneous melanoma and may be a useful adjunct technology in facilitating precise SLN dissection. Our work supports a clinical trial investigating the use of CEUS for this application.LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

    View details for PubMedID 30284307

  • Cisplatin and Cetuximab Treatment for Metastatic Cutaneous Squamous Cell Carcinoma: A Systematic Review DERMATOLOGIC SURGERY Trodello, C., Pepper, J., Wong, M., Wysong, A. 2017; 43 (1): 40-49

    Abstract

    Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and metastasizes in 2% to 5% of cases.Systematic evaluation of published cases of metastatic cSCC (mSCC) treated with cisplatin or cetuximab from 1989 to 2014.A literature search was performed to identify cases of mSCC treated with cisplatin or cetuximab. Patient demographics, tumor characteristics, response rates, and disease-free survivals were extracted.A total of 60 cases of mSCC treated with cisplatin and 9 cases treated with cetuximab reported in the literature from 1989 to 2014 were included in the analysis. Patients treated with cetuximab obtained a complete response of 67%, an overall response of 78%, and a median disease-free survival of 25 (range 3-48) months. Patients treated with cisplatin obtained a complete response of 22%, an overall response of 45%, and a median disease-free survival of 14.6 (range 3-112) months.Head-to-head prospective clinical studies between cetuximab and cisplatin are needed to determine which is more efficacious. In addition, prospective tumor registries and randomized controlled trials should be developed in order to establish the ideal systemic regimen in cSCC.

    View details for DOI 10.1097/DSS.0000000000000799

    View details for Web of Science ID 000393668000007

    View details for PubMedID 27618393

  • Nasopharyngeal airway to prevent tension pneumocephalus after open resection of anterior skull base tumors. Ear, nose, & throat journal Spector, M. E., Pepper, J., Sullivan, S., Marentette, L., McKean, E. 2016; 95 (12): E32-E35

    Abstract

    We conducted a retrospective study to assess the efficacy of using a nasopharyngeal airway in lieu of a tracheotomy or prolonged intubation for the diversion of airflow to prevent tension pneumocephalus after an open resection of anterior skull base tumors. Our study population was made up of 120 patients-74 males and 46 females, aged 12 to 84 years (mean: 48.7)-who had undergone an anterior skull base resection with documented nasopharyngeal airway placement from 1996 through 2009. Our main outcome measure was the presence of tension pneumocephalus while controlling for the placement of a lumbar drain, the development of a cerebrospinal fluid (CSF) leak, and the type of reconstruction. All patients had been extubated on the day of surgery, and their nasopharyngeal airway had remained in place for 3 days. No documented complications of nasopharyngeal airway placement (e.g., nasal septum pressure necrosis or the displacement of tubes) had been documented. Tension pneumocephalus occurred in 3 patients (2.5%). A total of 33 patients (27.5%) received a lumbar drain, 14 (11.7%) experienced a CSF leak, and 5 (4.2%) had both. There was a statistically significant difference in the rate of tension pneumocephalus between patients who did and did not receive a lumbar drain placement (p = 0.02), between those who did and did not experience a CSF leak (p = 0.04), and between those who did and did not meet both criteria (p = 0.004). We conclude that resection of anterior skull base tumors does not necessitate a prophylactic tracheotomy or prolonged intubation and that the use of a nasopharyngeal airway to divert airflow is well tolerated and highly successful. Lumbar drainage, the development of a CSF leak, or both may increase the risk of tension pneumocephalus.

    View details for PubMedID 27929605

  • Esthesioneuroblastoma: Updating Histologic Grading as It Relates to Prognosis ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Gallagher, K. K., Spector, M. E., Pepper, J., McKean, E. L., Marentette, L. J., McHugh, J. B. 2014; 123 (5): 353-358

    Abstract

    The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/- adjuvant chemoradiation.A retrospective review of 27 patients with ENB was performed.The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome.There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohort's mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis.An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.

    View details for DOI 10.1177/0003489414526368

    View details for Web of Science ID 000335494400009

    View details for PubMedID 24668054

  • Synchronous ipsilateral sebaceous lymphadenoma and membranous basal cell adenoma of the parotid ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY Scheller, E. L., Pritchett, C. V., Shukla, A., Pepper, J. P., Marentette, L. J., McHugh, J. B. 2013; 115 (4): E41-E46

    Abstract

    A 46-year-old man presented with persistent right otalgia and hearing loss. Exam was significant for a mildly tender retromandibular mass with intact nonerythematous overlying skin. Computerized tomography with intravenous contrast of the neck revealed 2 relatively well circumscribed masses in the right parotid gland. Although 1 lesion was suspected to be a necrotic lymph node, histologic analysis after superficial parotidectomy demonstrated 2 unique salivary gland tumors. Diagnoses of both sebaceous lymphadenoma and membranous basal cell adenoma were rendered. The occurrence of unique, synchronous, ipsilateral salivary gland tumors is distinctly unusual and this combination of parotid gland neoplasms has not previously been documented. In this report, we present the case with its management, followed by a discussion of the histopathologic nature of each tumor including the possible overlap between these two entities.

    View details for DOI 10.1016/j.oooo.2012.10.014

    View details for Web of Science ID 000316666700009

    View details for PubMedID 23312537

  • The Persian Woman's Face: A Photogrammetric Analysis AESTHETIC PLASTIC SURGERY Sepehr, A., Mathew, P. J., Pepper, J., Karimi, K., Devcic, Z., Karam, A. M. 2012; 36 (3): 687-691

    Abstract

    The aim of this study was to establish normative quantitative anthropometric measurements of the Persian woman's face and assess differences from established North American White women's measurements.Standard photographs (frontal, left lateral, and base views) of 107 Persian women volunteers (both parents of Persian ancestry) between the ages of 18 and 40 were digitally acquired. Twenty-six standard anthropometric measurements were obtained using Adobe Photoshop. The results were compared with those previously published for North American White women using an unpaired t test with differences being considered significant if p<0.05.A statistically significant difference was found between Persian women and North American White women in 18 of 26 anthropometric measurements.The anthropometric differences between Persian women and North American White women reflect fundamental differences in the osseochondrous scaffold and soft tissue covering of the face. These differences partially account for the disharmony and loss of ethnic identity that occurs when surgery is planned using classical canons. For patients wishing to maintain their ethnic features following aesthetic surgery, access to ethnicity-specific normative anthropometric data will help guide the surgeon to achieve this goal.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

    View details for DOI 10.1007/s00266-012-9870-9

    View details for Web of Science ID 000304203800031

    View details for PubMedID 22350308

  • Olfactory Groove Meningioma: Discussion of Clinical Presentation and Surgical Outcomes Following Excision Via the Subcranial Approach LARYNGOSCOPE Pepper, J., Hecht, S. L., Gebarski, S. S., Lin, E. M., Sullivan, S. E., Marentette, L. J. 2011; 121 (11): 2282-2289

    Abstract

    To describe surgical outcomes and radiographic features of olfactory groove meningiomas treated by excision through the subcranial approach. Special emphasis is placed on paranasal sinus and orbit involvement.Retrospective review of a series of patients.Nineteen patients underwent excision of olfactory groove meningioma (OGM) via the transglabellar/subcranial approach between December 1995 and November 2009. Nine patients had previously undergone prior resection at outside institutions, and four had prior radiotherapy in addition to a prior excision. Transglabellar/subcranial surgical approach to the anterior skull base was performed.Tumor histology included three World Health Organization (WHO) grade III lesions, one WHO grade II lesion, and 15 WHO grade I lesions. Fourteen patients had evidence of extension into the paranasal sinuses, with the ethmoid sinus being most commonly involved. Kaplan-Meier estimates of mean overall and disease-free survival were 121.45 months and 93.03 months, respectively. The mean follow-up interval was 41.0 months, and at the time of data analysis three patients had recurrent tumors. Seven (36.8%) patients experienced a major complication in the perioperative period; there were no perioperative mortalities. Orbit invasion was observed in four patients, with optic nerve impingement in 11 patients. Of these, three patients had long-term diplopia. No patients experienced worsening of preoperative visual acuity.Olfactory groove meningiomas demonstrate a propensity to spread into the paranasal sinuses, particularly in recurrent cases. Given a tendency for infiltrative recurrence along the skull base, this disease represents an important area of collaboration between neurosurgery and otolaryngology. The subcranial approach offers excellent surgical access for excision, particularly for recurrences that involve the paranasal sinuses and optic apparatus.

    View details for DOI 10.1002/lary.22174

    View details for Web of Science ID 000296714800002

    View details for PubMedID 21994142

  • Histopathologic Findings and Clinical Manifestations in a Patient With Dysphonia and Vocal Fold Involvement by Systemic Sclerosis ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Pepper, J., Kupfer, R. A., McHugh, J. B., Hogikyan, N. D. 2011; 137 (8): 816-819

    View details for Web of Science ID 000293857000013

    View details for PubMedID 21844416

  • Perioperative Outcomes in Patients Undergoing the Transglabellar/Subcranial Approach to the Anterior Skull Base SKULL BASE-AN INTERDISCIPLINARY APPROACH Pepper, J., Ward, P. D., Lin, E. M., Sullivan, S. E., Hecht, S. L., Marentette, L. J. 2011; 21 (4): 215-222

    Abstract

    We analyzed the effect of predefined patient demographic, disease, and perioperative variables on the rate of complications in the perioperative period following subcranial surgery for anterior skull base lesion. A secondary goal of this study was to provide a benchmark rate of perioperative mortality and morbidity through comprehensive analysis of complications. Retrospective review of a consecutive series of patients (n = 164) who underwent the transglabellar/subcranial approach to lesions of the anterior skull base between December 1995 and November 2009 in a tertiary referral center. Main outcome measures were perioperative morbidity and mortality. No perioperative mortalities were observed over the period of consecutive review. The overall complication rate was 28.7%, with 30 (18%) patients experiencing major complication. Multivariate analysis revealed that the following variables were independent predictors of perioperative complication of any type: positive margins on final pathology, perioperative lumbar drain placement, and dural invasion. The subcranial approach provides excellent access to the anterior skull base with zero mortality and acceptable morbidity in comparison with other contemporary open surgical approaches. It should be considered a procedure with distinct advantages in terms of perioperative morbidity and mortality when selecting a therapeutic approach for patients with anterior skull base lesions.

    View details for DOI 10.1055/s-0031-1277261

    View details for Web of Science ID 000292876600002

    View details for PubMedID 22470264

    View details for PubMedCentralID PMC3312117

  • The autospreader flap in reduction rhinoplasty. Archives of facial plastic surgery Pepper, J., Baker, S. R. 2011; 13 (3): 172-?

    View details for DOI 10.1001/archfacial.2011.34

    View details for PubMedID 21576664

  • The cephalic tuck procedure. Archives of facial plastic surgery Pepper, J., Baker, S. R. 2011; 13 (3): 213-?

    View details for DOI 10.1001/archfacial.2011.35

    View details for PubMedID 21576670

  • Perioperative Lumbar Drain Placement: An Independent Predictor of Tension Pneumocephalus and Intracranial Complications Following Anterior Skull Base Surgery LARYNGOSCOPE Pepper, J., Lin, E. M., Sullivan, S. E., Marentette, L. J. 2011; 121 (3): 468-473

    Abstract

    To measure the effect of routine perioperative lumbar drain placement during anterior skull base surgery on the frequency of: 1) tension pneumocephalus and 2) total intracranial complications.Retrospective review of a series of patients (n = 161) who underwent the transglabellar/subcranial approach to lesions of the anterior skull base between December 1995 and November 2009. A retrospective cohort (n = 45) underwent routine lumbar drain placement at the time of skull base surgery. The remainder of the series did not undergo routine perioperative lumbar drain placement.Transglabellar/subcranial surgical approach to the anterior skull base, with or without routine perioperative lumbar drain placement.Routine placement of perioperative lumbar drains was an independent predictor of tension pneumocephalus (P =.022, odds ratio = 11.22 [1.218-103.3]). In addition, this practice was also associated with an increased risk of intracranial complications overall (P =.025, odds ratio = 2.623 [1.104-6.233]).Routine placement of perioperative lumbar drain may be associated with an increased risk of tension pneumocephalus and intracranial complications during surgery of the anterior cranial base.

    View details for DOI 10.1002/lary.21409

    View details for Web of Science ID 000287789400004

    View details for PubMedID 21298642

  • Osteomyelitis of the hard palate secondary to actinomycosis: a case report. Ear, nose, & throat journal Garg, R., Schalch, P., Pepper, J., Nguyen, Q. A. 2011; 90 (3): E11-2

    Abstract

    Osteomyelitis of the hard palate is a rare and difficult-to-eradicate sequela of actinomycosis. In this case report, we illustrate the necessity of aggressive surgical management of actinomycotic infection of the hard palate. The patient was initially treated with multiple local debridements supplemented with oral and then parenteral antibiotics, but his disease progressively worsened. His condition eventually resolved only after a partial palatectomy was performed to remove all the necrotic bone, followed by a prolonged course of intravenous and oral antibiotic treatment.

    View details for PubMedID 21412725

  • SMAS flap rhytidectomy. Archives of facial plastic surgery Pepper, J., Baker, S. R. 2011; 13 (2): 108-?

    View details for DOI 10.1001/archfacial.2011.11

    View details for PubMedID 21422445

  • Angioleiomyoma of the Internal Auditory Canal: Clinical and Radiographic Features OTOLOGY & NEUROTOLOGY Pepper, J., McKeever, P., Gebarski, S., Spector, M., Thompson, B. G., Arts, H. A. 2010; 31 (9): 1451-1454

    Abstract

    Discussion of a rare case of angioleiomyoma of the internal auditory canal.Thirteen-year-old female patient with a 1-year history of progressive hearing loss.Middle cranial fossa approach providing complete surgical extirpation.Surgical pathology.Radiography and history suggestive of vestibular schwannoma; pathology revealed angioleiomyoma.Angioleiomyoma is a rare lesion of the internal auditory canal that has many similar clinical and radiographic features of a vestibular schwannoma. There are no previous reports of this tumor occurring within the internal auditory canal in this age group.

    View details for DOI 10.1097/MAO.0b013e3181f1ce20

    View details for Web of Science ID 000284111700018

    View details for PubMedID 20838354

  • Key issues in nasal reconstruction CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY Asaria, J., Pepper, J. P., Baker, S. R. 2010; 18 (4): 278-282

    Abstract

    To review recent research and advances in nasal reconstruction over the last 12 months.Although the major principles of replacing surgically ablated tissues with like tissue and respecting the nasal aesthetic subunits have not changed, recent advances in nasal reconstruction have focused on producing superior aesthetic and functional results, while minimizing deformity and morbidity. Future directions may also include the application of allotransplantation and tissue engineering.A large variety of sophisticated techniques continue to emerge with the goal of producing increasingly natural results for patients undergoing nasal reconstruction.

    View details for DOI 10.1097/MOO.0b013e32833af8f8

    View details for Web of Science ID 000279889100010

    View details for PubMedID 20485171

  • Cavernous carotid injury during functional endoscopic sinus surgery: Case presentations and guidelines for optimal management AMERICAN JOURNAL OF RHINOLOGY Pepper, J., Wadhwa, A. K., Tsai, F., Shibuya, T., Wong, B. J. 2007; 21 (1): 105-109

    Abstract

    Surgery in the parasellar and paranasal regions is technically challenging because of the complex anatomic relationships between the sphenoid sinus, cavernous sinus, optic nerve, and internal carotid artery. Normal anatomic variations and pathological changes can lead to disastrous outcomes including carotid artery injury.We present two cases of carotid injury managed at our institution. The first case involves an elective endoscopic biopsy of a clival tumor encasing a friable carotid artery. The second case features a patient transferred emergently to our medical center when brisk bleeding was encountered during functional endoscopic sinus surgery (FESS). Both carotid injuries were managed via balloon embolization with close interaction between otolaryngology and interventional radiology. We review pertinent anatomic and surgical considerations as a backdrop to a treatment algorithm for cavernous carotid hemorrhage secondary to FESS complication.The treatment algorithm prevented mortality and minimized morbidity in the two cases considered.Through rare, injury to the cavernous carotid during FESS can be managed successfully given efficient hemostasis and seamless cooperation among emergency room physicians, otolaryngologists, and interventional radiologists.

    View details for DOI 10.2500/ajr.2007.21.2901

    View details for Web of Science ID 000243856100020

    View details for PubMedID 17283571

  • Design of a low-cost, USB-compatible, otoscope image-capture system LARYNGOSCOPE Pepper, J., Jackson, R. P., Crumley, R. L., Wong, B. J. 2006; 116 (12): 2224-2226
  • Molecular and functional dissection of TGF-beta 1-induced cerebrovascular abnormalities in transgenic mice 3rd World Congress on Vascular Factors in Alzheimers Disease Buckwalter, M., Pepper, J. P., Gaertner, R. F., Von Euw, D., Lacombe, P., Wyss-Coray, T. NEW YORK ACAD SCIENCES. 2002: 87–95

    Abstract

    Cerebrovascular abnormalities, such as reduced blood flow, microvascular fibrosis, and cerebrovascular amyloid angiopathy, are prominent in Alzheimer's disease (AD). However, their etiology is poorly understood and it is unclear whether cerebrovascular changes contribute to functional impairments in the absence of neurodegeneration. In humans with AD, transforming growth factor-beta1 (TGF-beta1) mRNA levels in the midfrontal gyrus correlate positively with the relative degree of cerebrovascular amyloid deposition in that brain region, suggesting a possible role for TGF-beta1 in human cerebrovascular abnormalities. Transgenic mice overexpressing TGF-beta1 in astrocytes develop AD-like cerebrovascular abnormalities, including perivascular astrocytosis, microvascular basement membrane thickening, and accumulation of thioflavin S-positive amyloid in the absence of parenchymal degeneration. Mice overexpressing TGF-beta1 alone or in addition to human amyloid precursor protein (hAPP) show selective accumulation of human beta-amyloid (Abeta) in blood vessels and develop cerebral hemorrhages in old age. In 9-month-old TGF-beta1 transgenic mice, cerebral blood flow (CBF) in the limbic system was significantly less than in nontransgenic littermate controls. Aged TGF-beta1 mice also showed overall reduced cerebral glucose uptake (CGU) as a measure of brain activity. Thus, chronic overproduction of TGF-beta1 in the brain results in structural and functional impairments reminiscent of those in AD cases with amyloid angiopathy.

    View details for Web of Science ID 000179767000009

    View details for PubMedID 12480736

  • Inhibition of MAO-A fails to alter cocaine-induced increases in extracellular dopamine and norepinephrine in rat nucleus accumbens MOLECULAR BRAIN RESEARCH Pepper, J. P., Baumann, M. H., Ayestas, M., Rothman, R. B. 2001; 87 (2): 184-189

    Abstract

    Monoamine oxidase (MAO) inhibitors are being investigated as possible medications for cocaine dependence, but there are potential problems with this approach. In the present study, we tested the hypothesis that inhibition of catecholamine metabolism with the MAO-A inhibitor, clorgyline, might enhance cocaine-induced increases in extracellular dopamine and norepinephrine in rat nucleus accumbens. Male rats were pretreated with clorgyline (1 mg/kg, s.c.) or its saline vehicle (1 ml/kg, s.c.), and microdialysis probes were inserted into previously implanted guide cannulae. After overnight perfusion of the probes in situ, rats received an acute challenge injection of either cocaine (1 mg/kg, i.v.) or its saline vehicle (1 ml/kg, i.v.). Clorgyline pretreatment alone caused significant elevations in basal levels of dialysate norepinephrine but not dopamine. Cocaine administration elicited significant increases in extracellular dopamine and norepinephrine in all groups of rats, and this effect was not altered by clorgyline pretreatment. The 1 mg/kg dose of clorgyline decreased dopamine metabolites in postmortem brain tissue by more than 80%. Our data are consistent with clinical studies that demonstrate pretreatment with the MAO-B selective inhibitor, selegeline, fails to alter cocaine-induced subjective effects in human drug users. Moreover, these findings suggest that adverse consequences related to altered catecholamine transmission would not occur if patients taking phenelzine, a non-selective MAO inhibitor, relapsed and used cocaine.

    View details for Web of Science ID 000167526800005

    View details for PubMedID 11245920