Clinical Benefits of the Utrecht Questionnaire for Aesthetic Outcome Assessment in Rhinoplasty: An Update.

Presently, there is no consensus on which patient-reported outcome measurement (PROM) instrument is best suited to assess the aesthetic outcomes of rhinoplasty. In this regard, at least seven different validated PROMs are available from the literature, each one with advantages and disadvantages.In this article, we review the development, validation, international translation, and clinical application of the Utrecht Questionnaire (UQ). The UQ was developed in 2009 with the idea to be a short and practical tool for the rhinoplasty surgeon to assess the aesthetic outcomes of rhinoplasty. The questionnaire was then validated in 2013. Body image in relation to nasal appearance is quantified with five simple questions on a 5-point Likert scale and a Visual Analogue Scale score. We discuss how the UQ can easily be incorporated and become an important asset in a rhinoplasty practice. Practical benefits, such as its role in the shared decision-making process, patient expectations management, identification of unsuitable patients, avoiding revision surgery, and the evaluation of the surgeon's personal performance curve, are exemplified. Currently, the UQ has been translated and validated in four languages, providing scientific opportunities to generate and compare international data for advances in rhinoplasty. We describe some of the significant scientific contributions of leaders in the field of rhinoplasty that used the UQ.

Optimization of the Soft Tissue Envelope of the Nose in Rhinoplasty Utilizing Fat Transfer Combined with Platelet-Rich Fibrin.

A thin or damaged skin soft tissue envelope may cause concerns in primary and secondary rhinoplasty. During postoperative healing, unpredictable scarring and contraction may occur and lead to significant aesthetic and trophic sequelae. Besides a meticulous surgical technique, there are no reliable techniques to prevent long-term skin damage and shrinkage. Fat transfer with addition of platelet-rich fibrin (PRF) harbors the possibility of local soft tissue regeneration and skin rejuvenation through growth factors and mesenchymal stem cells. It may also facilitate the creation of a thin fat layer on the dorsum to prevent shrink-wrap forces and conceal small irregularities. The goal is to provide evidence for the feasibility, durability, and beneficial effect of diced macrofat transfer bonded with PRF on the nasal dorsum. We present the technique of fat transfer conjugated with PRF as a nasal dorsal graft. Clinical endpoints were the prevention of trophic disturbances and atrophy at a 1-year postoperative follow-up. We present the skin mobility test as a clinical indicator of a healthy soft tissue envelope. The presented case series consists of 107 rhinoplasties. Fat was harvested in the umbilical or costal region. PRF was created by centrifugation of autologous whole blood samples. Macrofat was diced, cleaned, and bonded with PRF. The compound transplants were transferred to the nasal dorsum. There were no perioperative complications or wound-healing issues. Mean follow-up was 14 months. Clinical inspection showed good skin quality and no signs of shrinkage, marked scarring, or color changes with positive skin mobility test in all patients. Survival of fat was confirmed by ultrasonography and magnetic resonance imaging. Diced macrofat transfer in conjunction with PRF to the nasal dorsum is a feasible and safe method. A beneficial effect on the soft tissue envelope is demonstrated as well as the prevention of shrink-wrap forces.

The Impact of the Philtrum on Facial Attractiveness, Perioral Proportions, and Perceptions of Facial Aging.

BACKGROUND: Lip enhancement continues to be one of the most popular facial procedures. State-of-the-art lip enhancement involves sculpting of perilabial soft tissue, in particular, the philtrum, but it is unclear how patients perceive their philtral contours. OBJECTIVES: The aim of this study was to test the impact of the philtrum on attractiveness, and on the perception of facial proportions and age. METHODS: Respondents (1100, including 50 aesthetic specialists) were presented with 2 sets of identical portraits, 1 set of a young Caucasian female and 1 set of an aged Caucasian female, with 1 portrait in each set having an upper lip lacking any philtral contours. The respondents were asked to choose which upper lip was more attractive, appeared longer, and looked older. Rankings were analyzed according to population demographics. RESULTS: Overall, most respondents considered the young face (84%) and the aged face (68%) with philtral contours to be more attractive. Moreover, the majority of respondents (81%) considered the upper lip of the young face without a philtrum to appear longer in a craniocaudal orientation (67% for the aged image), and 67% of respondents described the image of the young woman with no philtral definition as appearing older (55% for the aged face with no philtrum). CONCLUSIONS: This study confirms the authors' hypothesis that the existence of philtral contours exerts a significant impact on perioral attractiveness, and that its absence can be related to a longer appearance of the upper lip as well as an older facial appearance.

Systematic Review of Quality-of-Life Measurement After Aesthetic Rhinoplasty.

INTRODUCTION: The assessment of outcomes in aesthetic rhinoplasty is highly relevant because patient satisfaction and improved health-related quality of life (QoL) are the predominant factors in determining success. The patient-reported outcome measures (PROMs) employed in rhinoplasty research studies are remarkably diverse, thus yielding difficulties with data analysis. The aim of this article is to provide a comprehensive review of the literature to reveal the relevance of the QoL assessment for rhinosurgeons. METHODS: A systematic literature search with the terms "Rhinoplasty" and "Quality of Life" was conducted using PubMed/MEDLINE, Google Scholar and Cochrane databases. Primarily, all publications related to QoL following aesthetic rhinoplasty between 2002 and 2017 were identified. As a secondary selection, we focused on articles with a prospective study design, a significant cohort size (at least 50 patients) and a follow-up period of at least 6 months after aesthetic rhinoplasty. RESULTS: A total of 62 PROM studies assessing QoL following aesthetic rhinoplasties were obtained. We ascertained an increasing publication rate of QoL articles over the last 15 years. Only 17 studies satisfied comprehensive inclusion criteria of a high qualitative study selection. The Rhinoplasty Outcome Evaluation was the most frequently used QoL questionnaire of the secondary selection (70.6%). The total number of 16 various questionnaires exhibit high heterogeneity. CONCLUSION: Our data strengthen the increasing importance of the assessment of QoL after rhinoplasty. Despite a lack of reliable publications with considerable heterogeneity and large variability in outcomes, functional-aesthetic rhinoplasty leads to a significant improvement of patient's health-related QoL. LEVEL OF EVIDENCE II: 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 www.springer.com/00266 .

Cartilage Scales Embedded in Fibrin Gel.

Multiple techniques have been described for dorsal nasal augmentation in rhinoplasty. In this article, we review common surgical techniques for raising the dorsum or eliminating dorsal irregularities, by highlighting inherent advantages and disadvantages of each method. Within the past few years, the use of diced cartilage grafts has become the workhorse in this field of interest. To overcome drawbacks of methods based on diced cartilage, we present a new concept for autologous augmentation, using regenerative medicine protocols. A mix of cartilage scales with cartilage pâté was embedded in platelet-rich fibrin (PRF). Since December 2015, a total of 48 patients were treated with this technique. Based on our preliminary results, cartilage scales in PRF appear to be a promising and reliable alternative to existing procedures for dorsal nasal augmentation.

Dorsal Onlay with Diced Homologous Processed Rib Cartilage Grafts.

BACKGROUND: Diced cartilage wrapped in fascia or modeled with tissue sealant has successfully been used as dorsal onlay grafts in rhinoplasty. The use of autologous material introduces the risk of donor site morbidity, and sometimes availability is limited. METHODS: We present a series of nine cases that were performed using diced irradiated homologous rib cartilage as an onlay graft. RESULTS: Good functional and cosmetic outcomes were achieved in all nine patients, and no significant resorption was seen after a mean follow-up of 20 months. CONCLUSION: Homologous diced cartilage grafts are an attractive and well-tolerated alternative. The use of diced homologous material does not seem to lead to significant resorption. These results must be reproduced in larger series. LEVEL OF EVIDENCE IV: 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 www.springer.com/00266 .

Dome Reconstruction in a Rare Case of Alar Cartilage Agenesis of the Middle and Lateral Crura.

UNLABELLED: Congenital deformities of the nasal cartilage are extremely rare. Often, they remain undiscovered until an open approach is completed during rhinoplasty. We present a case of unilateral congenital agenesis of the middle and lateral crura of the alar cartilage. A new concept for dome reconstruction using conchal cartilage is introduced. Additionally, current concepts of embryology are summarized, which will help understanding the pathophysiology of such rare deformities. LEVEL OF EVIDENCE V: 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 www.springer.com/00266 .

Selective neurolysis in post-paralytic facial nerve syndrome (PFS).

UNLABELLED: Post-paralytic facial nerve syndrome (PFS) summarizes specific symptoms that result from an incomplete or poor recovery of the facial nerve after peripheral facial palsy. Selective chemodenervation using botulinum toxin A (Btx A) and mime therapy represent the therapeutic standard for treating PFS. We report on a 35-year-old male who was suffering greatly from unilateral PFS-specific movement disorders, including periorbital contractions and oculofacial synkinesis that did not respond to Btx A administration. We present a surgical alternative to overcome periorbital movement disorders by selective neurolysis and review therapeutic options for this rare syndrome. In conclusion, selective neurolysis appears to be an efficient alternative treatment method of PFS in which the quality of life is severely impacted due to movement disorders and there was no therapeutic benefit from Btx A. LEVEL OF EVIDENCE V: 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 http://www.springer.com/00266 .

Effect of endoscopic brow lift on contractures and synkinesis of the facial muscles in patients with a regenerated postparalytic facial nerve syndrome.

BACKGROUND: Delayed recovery after facial palsy results in aberrant nerve regeneration with symptomatic movement disorders, summarized as the postparalytic facial nerve syndrome. The authors present an alternative surgical approach for improvement of periocular movement disorders in patients with postparalytic facial nerve syndrome. The authors proposed that endoscopic brow lift leads to an improvement of periocular movement disorders by reducing pathologically raised levels of afferent input. METHODS: Eleven patients (seven women and four men) with a mean age of 54 years (range, 33 to 85 years) and with postparalytic facial nerve syndrome underwent endoscopic brow lift under general anesthesia. Patients' preoperative condition was compared with their postoperative condition using a retrospective questionnaire. Subjects were also asked to compare the therapeutic effectiveness of endoscopic brow lift and botulinum toxin type A. RESULTS: Mean follow-up was 52 months (range, 22 to 83 months). No intraoperative or postoperative complications occurred. During follow-up, patients and physicians observed an improvement of periorbital contractures and oculofacial synkinesis. Scores on quality of life improved significantly after endoscopic brow lift. Best results were obtained when botulinum toxin type A was adjoined after the endoscopic brow lift. Patients described a cumulative therapeutic effect. CONCLUSIONS: These findings suggest endoscopic brow lift as a promising additional treatment modality for the treatment of periocular postparalytic facial nerve syndrome-related symptoms, leading to an improved quality of life. Even though further prospective investigation is needed, a combination of endoscopic brow lift and postsurgical botulinum toxin type A administration could become a new therapeutic standard.

Bipolar radiofrequency volumetric tissue reduction of the inferior turbinates: evaluation of short-term efficacy in a prospective, randomized, single-blinded, placebo-controlled crossover trial.

The objective of the study was to assess the short-term efficacy of radiofrequency volumetric tissue reduction (RFVTR) of the inferior turbinates in patients with nasal obstruction caused by turbinate hypertrophy. The study is a prospective, randomized, single-blinded, placebo-controlled, crossover trial. A total of 22 patients (age range 21-72 years; median age 41 years) were randomized into two treatment arms. Using a bipolar radiofrequency system, the first group (VP-group) received RFVTR (verum = V) first (at t1) followed by a placebo treatment (P) 6-8 weeks later (at t2). The PV-group was treated with placebo first at t1 and received RFVTR at t2. Subjects in both groups underwent identical procedures in an office-based setting. Delivery of radiofrequency energy was the only difference between the two groups. The outcome measures assessed were rhinomanometry, physician's evaluation of the degree of hypertrophy of the inferior turbinates and patients' estimation of nasal obstruction. Physician and patient evaluations were documented using a score ranging from 0 = none to 4 = severe. Evaluation was performed 6-8 weeks after every intervention. No intraoperative or postoperative complications occurred. Inferior turbinate hypertrophy improved significantly in both groups after RFVTR was performed (VP-group: p < 0.001; PV-group: p = 0.002). Nasal obstruction also decreased only after RFVTR (VP-group: p = 0.004, PV-group: p = 0.002). This study confirmed the safety of bipolar RFVTR as an office-based treatment of nasal obstruction due to inferior turbinate hypertrophy. We could prove that RFVTR is superior to placebo for reduction in turbinate hypertrophy and subjective improvement in nasal obstruction. To our knowledge, this is the first level I study proving the short-term efficacy of a bipolar radiofrequency system.

Split hump technique for reduction of the overprojected nasal dorsum: a statistical analysis on subjective body image in relation to nasal appearance and nasal patency in 97 patients undergoing aesthetic rhinoplasty.

OBJECTIVES: To describe the split hump technique (SHT) and to examine its effectiveness for correction of an overprojected nasal dorsum in patients undergoing aesthetic rhinoplasty. METHODS: This prospective study included 97 patients. Objective assessment was performed using a short, practical questionnaire. Investigation focused on nasal patency and the patient perception of body image in relation to nasal appearance using 5-point Likert scale questions and visual analog scales. RESULTS: Use of the SHT resulted in a significant improvement in nasal patency and aesthetic nasal perception. Sum functional question scores decreased from 9.154 to 6.351 and aesthetic question scores from 13.897 to 6.825 (P < .001 for both). Mean aesthetic visual analog scale scores improved in all patients, from 3.346 to 7.782 (P < .001). Graphic illustration of this improvement revealed a gaussian curve of normal distribution around a mean (SD) improvement of 4.48 (1.93). CONCLUSIONS: Traditional en bloc humpectomy maneuvers are frequently combined with spreader graft use to avoid postoperative inferomedial repositioning of the upper lateral cartilages and inverted-V deformity. The SHT for correction of the overprojected dorsum creates a paradigm change in this patient group. The transverse segments of the upper lateral cartilages are saved and repositioned instead of being resected as a part of an en bloc osseocartilaginous composite hump resection in a transverse plane. Several modifications of the SHT enable the surgeon to deproject the nose while keeping sufficient strength in the keystone area and augmenting dorsal width. Using statistical analysis of subjective patient data, we could prove a broad acceptance and appreciation for the SHT.

Auricular keloids: combined therapy with a new pressure device.

OBJECTIVE: To develop a new, custom-made pressure device that can be used with established designs as an adjuvant therapy for optimized treatment of auricular keloids. METHODS: Seven patients (4 males, 3 females; mean [SD] age, 22.6 [8.3] years) were treated with surgical excision and corticosteroid injection followed by application of our new auricular pressure device. RESULTS: All patients tolerated the adjuvant therapy and wore the device overnight for 5 nights per week. Usage was not interrupted or cancelled. No recurrence was observed during the follow-up period (mean [SD] duration of follow-up, 24 [6] months). All patients were satisfied with the results; none described pruritus, pain, or dysesthesia. CONCLUSION: Overnight usage of the new pressure device seems to be a safe and effective extension of established auricular keloid therapy with the potential for prophylaxis of recurrence.

IL-6 antisense-mediated growth inhibition in a head and neck squamous cell carcinoma cell line.

The growth of tumor cells can be regulated by a variety of cytokines. To investigate the pathogenesis of head and neck cancer and explore a new therapeutic approach for the carcinoma, the role of interleukin-6 (IL-6) in the growth of a human head and neck squamous cell carcinoma (HNSCC) cell line was examined. Whether or not IL-6 is increased in HNSCC and whether or not IL-6 antisense oligonucleotide treatment could decrease proliferation and angiogenic activity of HNSCC cell lines, was determined. Established human HNSCC cell lines were screened for IL-6 expression at both mRNA and protein levels. By using a 15-mer antisense phosphorothioate oligonucleotide targeting a sequence in the second exon of the IL-6 gene, modulation of IL-6 and vascular endothelial growth factor (VEGF) expression was examined in UMSCC IIA in cell supernatants by capture enzyme-linked immunosorbent assay (ELISA), and in cell lysates by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, cell growth was determined by cell count. Endothelial cell migration was measured using a modified Boyden chamber. IL-6 was identified in the supernatant of the cell culture medium, indicating that these cells secreted IL-6, and the mRNAs of IL-6 were shown to be present in the cell lysates. IL-6 antisense oligonucleotide treatment resulted in a significant reduction of IL-6 protein expression compared to the sense control. The antisense oligonucleotides targeting IL-6 mRNA, also, inhibited cell growth and IL-6 production as well as VEGF expression. The addition of conditioned medium from IL-6 antisense-treated tumor cells resulted in decreased endothelial cell migration and tubule formation. Taken together, these findings indicate that endogenous IL-6 plays an important role in the growth of HNSCC and exerts its action by an autocrine growth mechanism, and that therapeutic trials with antisense oligonucleotides targeted to IL-6 mRNA may have some value for the treatment of HNSCC due to a decrease of neovascularization.

TGF-ß1 antisense impacts the SMAD signalling system in fibroblasts from keloid scars.

AIM: To identify the effect of a TGF-ß1 antisense treatment of keloid fibroblasts on the SMAD signalling system. MATERIAL AND METHODS: In this cross-sectional study, keloid and adjacent healthy tissue was harvested from 9 patients with keloid scars after otoplasty. Keloid fibroblasts were placed in monolayer cultures. Expression of SMAD2, -3, -4, -6, and SMURF2 were analysed by immunohistochemistry. Analysis of treatment with antisense oligonucleotides was conducted by immunohistochemistry, and RT-PCR. RESULTS: Immunohistochemical investigation demonstrated increased expression of SMAD2, -3 and -4, and decreased expression of SMURF2. TGF-ß1 antisense therapy significantly down-regulated SMAD2 and SMAD4, up-regulated SMURF2 and showed no effect on SMAD3 and SMAD6. CONCLUSION: TGF-ß1 led to elevated levels of the SMAD signalling cascade, indicating an abnormal sensitivity of keloid-derived fibroblasts to this cytokine. Abrogation correlated with potential suppression of the fibro-proliferative progress. There is growing evidence for an abnormal response to this cytokine in the intracellular signal transduction in keloid-derived fibroblasts.

Effect of transforming growth factor-beta1 antisense oligonucleotides on matrix metalloproteinases and their inhibitors in keloid fibroblasts.

OBJECTIVE: To identify changes in the expression of matrixmetalloproteinases (MMPs) and their specific inhibitors tissue inhibitors of metalloproteinases (TIMPs) after targeting of transforming growth factor-beta1 (TGF-beta1) with antisense oligonucleotides. STUDY DESIGN: Cross-sectional study. SETTING: The study was performed on tissue samples from nine patients with keloid scars after otoplasty presenting to the Otolaryngology-Head and Neck Surgery Department of the University Hospital in Mannheim, Germany. SUBJECTS AND METHODS: Keloid fibroblasts and normal fibroblasts were harvested from auricular keloid scars and healthy skin regions of the same patients during resection procedure of the keloid. Cells were placed in monolayer cultures. Expression of MMPs and TIMPs were analyzed by immunohistochemistry. The effect of TGF-beta1 targeting using antisense oligonucleotides on the expression of both protein groups in keloid-derived fibroblasts was analyzed by enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction. RESULTS: Immunohistochemical investigation demonstrated increased expression of MMP-2, -3, -9, and -13 and TIMP-1 and -2. TGF-beta1 antisense therapy significantly down-regulated MMP secretion in vitro. CONCLUSION: Usage of TGF-beta1 antisense oligodeoxynucleotides (ODNs) may show a potential chemopreventive or therapeutic option for keloids by blocking the effect of TGF-beta1. Furthermore, antisense ODNs can be used as an investigative approach toward a better understanding of molecular mechanisms in keloid pathophysiology.

In vitro analysis of radiation-induced dermal wounds.

OBJECTIVE: To investigate the pathophysiology of radiation-induced wounds of the head and neck at a molecular level. STUDY DESIGN: Basic science, prospective study. SETTING: The study was conducted at the Department of Otolaryngology-Head and Neck Surgery, Ruprecht Karls-University Heidelberg, Faculty of Medicine Mannheim, Mannheim, Germany. SUBJECTS AND METHODS: Keratinocytes from chronic nonhealing ulcers in irradiated areas as well as from healthy skin areas in the same patients (n = 3) were harvested during surgical procedures and isolated in cell culture. First, a proliferation assay was performed. Gene expression was analyzed by microarray, protein expression by immunohistochemistry. RESULTS: Keratinocytes from radiogenic wounds showed a shift from the high molecular keratins 1 and 10 to the low molecular keratins 5 and 14 compared to normal control skin. Keratinocytes from nonhealing wounds showed a decreased expression of transforming growth factor alpha and beta 1, fibroblast growth factor 1 and 2, keratinocyte growth factor, vascular endothelial growth factor, and hepatocyte growth factor. The matrix metalloproteinases 2, 12, and 13 showed increased expression in irradiated keratinocytes and fibroblasts. CONCLUSION: Our data showed a change of keratinocytes to a less differentiated state due to radiation. Additionally, it seems that radiation-induced dermal injuries often fail to heal because of decreased proliferation, impaired angiogenesis, and persistently high concentrations of matrix metalloproteinases.

Effect of the abrogation of TGF-beta1 by antisense oligonucleotides on the expression of TGF-beta-isoforms and their receptors I and II in isolated fibroblasts from keloid scars.

Disequilibrium of dermal wound repair can result in continued accumulation of ECM and excessive scar formation. In susceptible genetically predisposed individuals, keloid formation can be observed. Keloid disease represents a benign dermal fibroproliferative tumor that is unique to humans. TGF-beta is known to play a key role in the pathogenesis of this disease which is still not fully understood. The isoforms TGF-beta1 and TGF-beta2 have profibrotic properties, whereas TGF-beta3 may have antifibrotic functions. TGF-beta exerts its influence by binding to type I and type II TGF-beta receptors, thereby forming a complex and activating specific downstream effector molecules. The aim of this study was to investigate the effect of TGF-beta1 targeting by antisense oligonucleotides on the RNA synthesis and protein expression of TGF-beta isoforms and their receptors in keloid-derived fibroblasts. In tissue samples with normal fibroblasts (NFs) serving as control samples, expression of TGF-beta1 and -beta2 was decreased when compared to keloid fibroblasts (KFs), while expression of TGF-beta3 and of TGF-betaRII was significantly higher in NFs. In the ELISA assay, abrogation of TGF-beta1 led to a significant decrease in TGF-beta1 and -beta2 (p<0.05). Expression of TGF-beta2 mRNA was reduced. Expression of TGF-beta3 mRNA revealed contrary patterns in KFs from different patients while expression of TGF-betaRI was found to be equal during the measurement period. TGF-betaRII mRNA expression was increased after 48 and 72 h respectively. There is growing evidence for a regulatory mechanism between TGF-beta1 and its receptors. Our findings support this theory by suggesting interrelations between the different TGF-beta isoforms and their receptors. Abnormal response of KFs to TGF-betamight reflect a modification in the regulatory pathway that occurs at the receptor level or during intracellular trans-duction. Improving the understanding of TGF-beta in keloid disease could lead to the development of clinically useful therapeutic modalities for treatment of keloid disease or even allow identification of preventive strategies.

Keloids: current concepts of pathogenesis (review).

Excess scar formation occurs after dermal injury as a result of abnormal wound healing. Hypertrophic scars and keloids both represent fibrotic skin conditions which can be very difficult, even frustrating, to treat. Identification of differences between hypertrophic scars, keloids and normal scars are a prerequisite for finding the correct therapeutical concept. Despite the relatively high prevalence of keloids in the general population, the mechanisms underlying keloid formation are only partially understood. This fact is reflected in the multiple treatment modalities, of which no single treatment has proven to be widely effective. Advances in our understanding of the wound healing process reveal new pathophysiological concepts for keloid formation. Our article presents an overview on physiological wound healing and the pathogenesis of scar formation, differentiates keloids from hypertrophic scars and reviews current hypotheses for keloid formation. This information might assist in deciphering the complexity of keloid pathogenesis and help in the development of an efficacious therapeutical strategy.

The platelet-derived growth factor receptor as a target for vascular endothelial growth factor-mediated anti-angiogenetic therapy in head and neck cancer.

Inhibition of angiogenesis by blocking angiogenic cytokines or their pathways has become a major target in experimental cancer therapies. This therapeutical approach requires a profound knowledge of growth factor profiles that contribute to tumor growth and progression. The respective knowledge is presently rather incomplete for head and neck squamous cell carcinomas (HNSCC). Therefore we studied the serum levels and expression of platelet-derived growth factor (PDGF) in HNSCC patients and in cell culture as well as the effect of a PDGF-receptor (PDGF-R) inhibition by Imatinib (Gleevec, STI571) on the secretion and expression activity of PDGF and vascular endothelial growth factor (VEGF) by postulating there is a correlation between the PDGF and VEGF networks. PDGF levels in patients with HNSCC, PDGF and VEGF secretion by HNSCC cells, were measured by ELISA, expression of PDGF and VEGF by RT-PCR. We found significantly increased PDGF levels in HNSCC patients' sera as well as in HNSCC cell lines. Treatment of the cell lines with Imatinib, a partially selective PDGF-R inhibitor, resulted in reduced secretion of PDGF and VEGF. This inhibiting effect was also reflected on the expression level of VEGF. In conclusion, the present study confirms the crucial role of PDGF in HNSCC growth and strongly suggests a correlation between the PDGF/PDGF-R and VEGF/VEGF-R pathway networks in HNSCC. Although further studies must be performed for a more complete understanding of this interaction, a targeting therapy for the inhibition of PDGF-R tyrosine phosphorylation by Imatinib may be a promising strategy for future tumor therapy by autocrine and paracrine inhibition of tumor growth and angiogenesis, presumably through simultaneous down-regulation of PDGF and VEGF.