Christian Freudlsperger

Universität Heidelberg, Heidelberg, Baden-Wuerttemberg, Germany

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Publications (30)46.07 Total impact

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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment. This study evaluated the prognostic value of the phosphorylation status of AKT on Ser473 and Thr308 for the clinical outcome of patients with advanced HNSCC upon radiotherapy. Furthermore, we investigated the impact of AKT(Ser473) phosphorylation [p-AKT(Ser473)] in the context of radioresistance using ex vivo tissue cultures that resemble the complex tissue architecture and paracrine interaction with the tumor microenvironment. In a cohort of 120 patients with advanced HNSCC, who were treated with primary or adjuvant radiotherapy, a significant association was found between relative p-AKT(Ser473) levels and overall survival (p=0.006) as well as progression-free survival (p=0.021), while no significant correlation was revealed for relative p-AKT(Thr308) levels. In ex vivo tissue cultures p-AKT(Ser473) levels were increased upon irradiation and treatment with the PI3K inhibitor LY294002 inhibited both basal and irradiation induced AKT(Ser473) phosphorylation. Strikingly, pretreatment with LY294002 sensitized tissue cultures derived from primary and recurrent tumors to radiotherapy as determined by impaired tumor cell proliferation and enhanced DNA damage. In conclusion, phosphorylation status of AKT(Ser473) in tumor specimens serves as a novel biomarker to identify patients with advanced HNSCC at high risk for treatment failure following radiotherapy, and our data from ex vivo tissue cultures support the assumption that pharmacological inhibition of AKT(Ser473) phosphorylation might circumvent radioresistance to improve efficiency and reduce toxicity of current treatment modalities. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 11/2014; · 6.20 Impact Factor
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    ABSTRACT: Orbital hypertelorism is defined as an increased distance between both medial and lateral sides of the orbits. Most common causes are frontonasal malformations, craniofacial fissures, encephalocele and a miscellaneous group of various syndromic or chromosomal disorders. Surgical correction of orbital hypertelorism is still challenging. The present report describes a case of severe orbital hypertelorism of an 11-year-old boy, where surgical correction was planned using three-dimensional printing modelling. This approach allowed reducing time of surgery, accurately planning the location of the osteotomies and precontouring the osteosynthesis material. Three-dimensional models are very helpful tools in planning complex craniofacial operative procedures.
    Oral and Maxillofacial Surgery 09/2014;
  • Christian Freudlsperger, Jens Philipp Bodem, Eva Engel, Jürgen Hoffmann
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    ABSTRACT: Because optimal reconstruction of maxillofacial defects requires functional rehabilitation, the current study demonstrates the successful secondary reconstruction of a large mandibular continuity defect using a fully digitally planned prefabricated free vascularized fibula with immediate implant-supported prosthodontic restoration.A 56-year-old man presented with a large mandibular continuity defect after resection of an enlarged squamous cell carcinoma arising from the floor of the mouth. For secondary reconstruction, the shape of the neomandible and implant position for support of the lower prosthesis were planned virtually. The combined cutting and drilling guide was printed in 3 dimensions.In a 2-step surgical approach, first, the implants were inserted into the fibula and covered with a split-thickness skin graft to form a neogingiva. In a second operation, the fibula was harvested, osteotomized, and fixed with the denture on the preinserted implants. The fibula was placed to its final position guided by the occlusion.Using three-dimensional virtual backward planning, it was feasible to perform a mandibular reconstruction with immediate prosthetic rehabilitation.
    The Journal of craniofacial surgery 03/2014; · 0.68 Impact Factor
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    ABSTRACT: Resorbable osteosynthesis is a widespread tool in craniofacial surgery, however only a limited number of studies have focused on ultrasound-assisted pinned resorbable systems in the treatment of craniosynostosis. Thirty-eight children with various types of craniosynostosis including scaphocephaly, trigonocephaly, anterior and posterior plagiocephaly were treated using the Sonic Welding resorbable osteosynthesis system. All patients were evaluated for operation time, stability of the surgical results, rate of local infections and visibility or palpability of the osteosynthesis material in the follow-up ranging from 15 to 21 month. Mean operation time was not significantly higher compared to conventional osteosynthesis material and all remodelled cranial vaults showed immediate stability. Only one patient showed signs of an inflammatory skin reaction, which recovered spontaneously. The number of palpable or visible plates, respectively, increased during the first months with a maximum at 12 months (34 (89%) plates palpable, 26 (68%) plates visible). After this time point, the number decreased continuously until the end of the follow-up period at 21 months when 3 (20%) plates were palpable, 0 (0%) plates were visible). Ultrasound-assisted pinned resorbable systems seem to be a promising tool in craniofacial surgery providing a timesaving and stable osteosynthesis. An initial swelling of the plates during the first 12 months before the complete degradation might result in a palpable and visible bulge.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 09/2013; · 1.25 Impact Factor
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    ABSTRACT: In the majority of the craniofacial literature, preservation of the supraorbital nerve during fronto-orbital advancement (FOA) is recommended. However, only a few studies have evaluated the incidence of sensory disturbance in the forehead after FOA during long-term follow-up. 57 children who underwent FOA in their first year of life because of isolated nonsyndromic craniosynostosis including trigonocephaly, anterior plagiocephaly or oxycephaly, were evaluated for sensory disturbance in the frontal region with a minimum follow-up of 27 months. An objective and repeatable measurement using the Semmes-Weinstein test was possible in 36 children older than 5 years at last follow-up. We revealed no sensory deficits in all patients, even in 3 patients, where one of the supraorbital nerves was transected during FOA. As previous reports have suggested a full recovery of sensation after transection of the supraorbital nerve during FOA I seen, the need to preserve the nerve has to be evaluated. However, as release of the nerve from the supraorbital rim is possible, we generally recommend preserving this structure, to minimize the risk of sensory deficits in the forehead region.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 08/2013; · 1.25 Impact Factor
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    ABSTRACT: Despite numerous studies, specific guidelines for cervical lymph node surgery in cutaneous malignant melanoma of the head and neck are still missing.In a retrospective study, the modalities of neck dissection (ND), the histologic results, and the outcome in 59 patients with cutaneous malignant melanoma of the head and neck were evaluated to verify the benefit of this therapy.Patients with proven lymph node metastasis often benefit from complete ND because about 50% of the patients showed more metastases in their ND specimen than before surgery. In addition, suspicious but not surely malignant lymph nodes often proved to be benign.This study reveals that patients with proven lymph node metastasis often benefit from complete ND because the number of infiltrated nodes is often higher than suspected; nevertheless, when planning the surgical therapy, the overall prognosis has to be kept in mind.
    The Journal of craniofacial surgery 03/2013; 24(2):483-7. · 0.68 Impact Factor
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    ABSTRACT: Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. X-linked dominant hypophosphatemic rickets (XLHR) is the most prevalent genetic type of hypophosphatemic rickets and is caused by germ line mutations in the PHEX-gene. In XLHR, only few case reports of craniosynostosis were described. Here, we present a clinical report of an 18 months old child with XLHR and bilateral coronal and sagittal synostosis who was treated by subtotal cranial vault remodelling with fronto-orbital advancement and right-angled Z-osteotomies. As a consequence of the child's diminished bone regeneration capacity, surgery that is performed after the age of 1 year requires more extensive craniectomy, multiple osteotomies and rigid fixation for calvarial vault remodelling to prevent extensive bone defects.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 02/2013; · 1.25 Impact Factor
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    ABSTRACT: Children with unilateral isolated coronal suture synostosis suffer from frontal plagiocephaly. In this retrospective study we analyzed 21 patients who were treated with an identical and standardized surgical technique of fronto-orbital advancement with hypercorrection with an average follow-up of 57.5 months. The median age at surgery was 12.1 months. The median average amount of blood loss during the operation was less than 188 ml. Not a single major complication was observed. According to the classification of Whitaker, 15 patients had a Class 1 outcome, with excellent surgical results. Three patients were defined as Class 2 outcome. One of our patients was Class 3 and two patients were Class 4 because of severe forehead retrusion and temporal hollowing. Re-operation rate was 14.3%. 67% of our patients showed a correction or an improvement of the typical C-shaped deformity in their follow-up examination. Aesthetic outcomes were excellent in 13, good in 5, and poor in 3 of cases, as judged by their families and the craniofacial team. Unilateral coronal synostosis can be successfully treated by fronto-orbital advancement with a low complication rate and an excellent clinical outcome. To minimize the need of re-operations, fronto-orbital advancement should be performed with an overcorrection on the affected side.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 02/2013; · 1.25 Impact Factor
  • Dr. J. Bodem, C. Freudlsperger, S. Rohde, J. Hoffmann
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    ABSTRACT: Die Behandlung ausgedehnter vaskulärer Anomalien macht ein differenziertes interdisziplinäres Vorgehen notwendig. Hierfür ist die Kenntnis der Einteilung der Gefäßveränderungen nach der International Society for the Study of Vascular Anomalies (ISSVA) essenziell. Diese unterscheidet zwischen vaskulären Malformationen und vaskulären Tumoren. Die vaskulären Malformationen werden wiederum nach ihren hämodynamischen Eigenschaften in „Low-flow“- und „High-flow“-Malformationen unterschieden. Für diese Diagnosestellung spielt die Schichtbildgebung mittels Magnetresonanztomographie (MRT) eine Schlüsselrolle. Ergänzend hierzu ist in ausgewählten Fällen eine Magnetresonanzangiographie (MRA) sinnvoll. Die Therapieindikation ist primär vom klinischen Verhalten der vaskulären Malformation abhängig, die Behandlung sollte interdisziplinär geplant werden. Die interventionelle Radiologie mit der perkutanen Sklerosierung und transarteriellen Embolisation als Monotherapie oder in Kombination mit einem chirurgischen Vorgehen ist wesentlicher Bestandteil des interdisziplinären therapeutischen Konzepts.
    Der MKG-Chirurg 02/2013; 6(1).
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    ABSTRACT: Tailoring the most suitable reconstructive approach to each patient remains challenging especially in the head and neck region. To compare the applicability of the latissimus dorsi (LD) and anterolateral thigh (ALT) flap, we retrospectively analyzed patients who had had reconstruction of extensive and/ or bulky composite tissue defects in the head and neck area. We performed 85 free tissue transfers (44 LD and 41 ALT flaps). LD mean flap surface was 115.8 cm2. ALT mean flap surface was 67.0 cm2. Pedicle length ranged from 8-16 cm in LD and 11-16 cm in ALT flaps. The survival rate was 93% in ALT and 91% in LD flaps. Donor-site morbidity occurred in 5% (ALT) and 7% (LD). A Two-team-approach was possible in 24% of the LD group, whereas all ALT flaps were raised in a Two-team-approach. Both flaps present excellent opportunities for the reconstruction of extensive and/ or bulky defects. They largely meet the requirements of an ideal soft tissue flap in terms of versatility, skin texture and tissue stock. Both flaps can be raised with a double skin paddle. The advantages and disadvantages of each flap have to be weighed up against each other and both flaps should be in the repertoire of every microvascular surgeon.
    Journal of Cranio-Maxillofacial Surgery 01/2013; · 2.60 Impact Factor
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    ABSTRACT: The reconstruction in case of large nasal defects, especially affecting the cartilaginous portion, is a surgical and aesthetic challenge. The result has to fulfill functional and aesthetic aspects concerning shape, texture, and nasal breathing, which requires accurate reproduction of nasal lining, support, and coverage. Here, we describe nasal reconstruction in a 36-year-old woman after near-total nasal resection due to a malignant peripheral nerve sheath tumor in the glabellar and nasal regions. After tumor resection, the cartilaginous and bone structures were reconstructed using a dynamic titanium mesh, which was precontoured on a three-dimensional-print model of the preoperative situation. Soft tissue defects were covered as a 2-stage procedure using a Converse scalp flap. We achieved an adequate long-term functional and aesthetic and oncological result. Titanium mesh in combination with Converse flap proved to be an alternative in extensive composite midfacial defects.
    The Journal of craniofacial surgery 09/2012; 23(5):e410-2. · 0.68 Impact Factor
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    ABSTRACT: This is a survey of the long-term result after various surgical treatments in a child with microcephalic osteodysplastic primordial dwarfism type II (MOPD II) and craniosynostosis. We report a 17-year-old patient with MOPD II but some unusual clinical signs including bilateral knee dislocation, a misplaced upper lobe bronchus, and hypoplasia of the anterior corpus callosum. Because of premature fusion of several cranial sutures, the child developed signs of increased intracranial pressure with somnolence and papilledema.Cranial vault remodeling with fronto-orbital advancement was performed twice at the age of 16 and 21 months to open the abnormally closed suture, increase the intracranial volume, and relieve the elevated intracranial pressure. Following this procedure, the child's neurologic situation recovered significantly.Surgical procedure of fronto-orbital advancement and the performed reoperation in our patient were safe with no major complications intraoperatively and postoperatively with good functional and satisfying aesthetic outcomes in the long-term follow-up, expressed by the patient, his parents, and the surgeons.
    The Journal of craniofacial surgery 08/2012; 23(5):1407-9. · 0.68 Impact Factor
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    ABSTRACT: The significance of Chiari malformation in nonsyndromal-isolated craniosynostosis is still not well documented. Hence, in the present study we investigated the incidence of Chiari malformation in a larger series of patients with nonsyndromic-isolated single-suture craniosynostosis over a 9-year period using preoperative magnetic resonance imaging (MRI). Of 215 children who had undergone surgery for nonsyndromic-isolated craniosynostosis, 89 cases (41.4 %) had MRI prior to surgery. All MRIs were screened for Chiari malformation. Only one patient (1.1 %) with isolated lambdoid synostosis showed Chiari malformation preoperatively, which was defined as a cerebellar tonsillar descent greater than 5 mm below the foramen magnum. However, no clinical symptoms were associated with Chiari malformation in this patient. As Chiari malformation is more likely to be associated with syndromic craniosynostosis, nonsyndromic bilateral coronal synostosis, or synostosis of the lambdoid suture, a general use of MRI as a screening tool for Chiari malformation should not be recommended for patients with nonsyndromic-isolated craniosynostosis who lack clinical symptoms.
    Acta Neurochirurgica 07/2012; 154(10):1803-7. · 1.79 Impact Factor
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    ABSTRACT: Isolated fusion of the sagittal suture is the most prevalent form of craniosynostosis. Although the typical clinical appearance usually points the way to the right diagnosis, computed tomographic (CT) scans are still recommended as necessary tools for both the diagnosis of scaphocephaly and the preoperative planning. Because CT scans are accompanied by the biological effects of ionizing radiation, some authors have already postulated the use of magnetic resonance imaging (MRI) especially because MRI seems to be valuable for detecting intracranial anomalies compared with CT scans. Hence, we investigated the preoperative MRIs of 42 children with isolated sagittal synostosis to evaluate the frequency of brain anomalies and their therapeutic consequences.In our study, 10 patients (23.8%) showed pathologic MRI findings such as ventricular dilatation and hypoplastic corpus callosum, whereas 32 patients (76.2%) had an unremarkable MRI except a pathognomonic secondary deformation of the brain caused by the abnormally shaped skull, which was present in all patients. Seven patients showed clinically significant symptoms including papilledema or psychomotoric developmental delay; however, the clinical appearance was not predictive for pathologic MRI findings and vice versa.As the detection of brain anomalies had no influence on the surgical procedure or led to any additive therapy in our patients, we conclude that evaluation of possible pathologic brain findings does not legitimate the general use of MRI in clinically normal children with isolated sagittal synostosis.
    The Journal of craniofacial surgery 07/2012; 23(4):e366-9. · 0.68 Impact Factor
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    ABSTRACT: Isolated fusion of the sagittal suture is usually treated before 1 year of age, but some patients present at a later age. The aim of this study was to evaluate the impact of children's age on the surgical outcome. The authors investigated 46 patients with isolated nonsyndromic sagittal craniosynostosis limited to the anterior two-thirds of the cranial vault. All patients underwent subtotal cranial vault remodelling, 36 patients (78.3%) before the age of 12 months (mean 8.92 months) and 10 patients after the age of 12 months (mean 15.77 months). Perioperative parameters and measurements of the cephalic index, preoperatively and postoperatively, were evaluated. All 46 patients showed improved head shape independent of their age. In patients younger than 12 months, mean cephalic indices improved from 65.99 to 74.49 (p<0.0001) and in patients older than 12 months from 66.38 to 74.38 (p<0.0004). There were no statistical differences in perioperative parameters including length of surgery, intraoperative blood loss and duration of hospital stay. In this study, patients showed no significant differences in surgical outcome that could have been related to the age at surgery. Surgical treatment should be performed early enough to benefit from the remodelling potential of the skull.
    International Journal of Oral and Maxillofacial Surgery 06/2012; 41(10):1232-7. · 1.52 Impact Factor
  • C Freudlsperger, K Freier, J Hoffmann, M Engel
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    ABSTRACT: The prognostic relevance of Ki-67 expression in oral squamous cell carcinoma (OSCC) is still controversial. As proliferating cells are more susceptible to ionizing radiation, the authors investigated if a high proliferation rate reflected by Ki-67 expression, predicts radiosensitivity in OSCC patients. In 52 patients with OSCC who received primary surgery followed by radiation therapy, the proliferation rate was assessed by Ki-67 immunhistochemistry and correlated to recurrent free survival and overall survival. Low proliferative carcinomas showed a significantly shorter mean time to recurrence of 27.5 months compared to 49.5 months of high proliferative tumours (p=0.048). The 5-year survival rate of low proliferative tumours was 49% compared to 80% for high proliferative tumours (p=0.042). This study indicates that tumours with high proliferative activity are more susceptible to radiation therapy. Ki-67 might be used as a marker to predict the response to radiation therapy in patients with OSCC.
    International Journal of Oral and Maxillofacial Surgery 05/2012; 41(8):965-9. · 1.52 Impact Factor
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    ABSTRACT: Radiographic evaluation including plain radiographies and computed tomographic (CT) scans are considered as a necessary tool for diagnosis of craniosynostosis. As recently concerns about harmful effects of ionising radiation in children have been raised, some authors have suggested the use of magnetic resonance imaging (MRI) as a helpful alternative in preoperative imaging of patients with isolated metopic synostosis. Besides confirming the diagnosis of trigonocephaly, MRI is the superior technique for the evaluation of underlying brain anomalies. However, if the benefit of preoperative imaging justifies possible side effects is still discussed controversially. Hence, this study investigated the value of preoperative imaging for the diagnosis of isolated synostosis of the metopic suture compared to a sole clinical examination. In a series of 63 cases with isolated metopic craniosynostosis operated at the Department of Oral and Maxillofacial Surgery, 48 (76.2%) patients received additional radiography or MRI investigation, while in 15 (23.8%) patients the diagnosis was based on clinical examinations only. In all patients, diagnosis was confirmed intra-operatively by a fused metopic suture. CT scans with three-dimensional reconstruction (12.5%) or plain radiographs (39.6%) did not provide any additional benefit for the diagnosis or the surgical treatment. In 23 patients (47.9%), MRI showed the typical soft-tissue alterations like triangular brain deformation in the frontal area. Besides these findings, no brain or other underlying anomalies were diagnosed which had required any additional treatment. The incidence of underlying brain abnormalities in isolated metopic synostosis seemed not to be different from that of the general population. As the characteristic clinical manifestations were sufficient for an accurate diagnosis of isolated metopic synostosis, and with respect to the biological effects of ionising radiation and risks of sedation especially in infants, preoperative imaging should be reduced to a minimum.
    Journal of Plastic Reconstructive & Aesthetic Surgery 04/2012; 65(9):1246-51. · 1.47 Impact Factor
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    ABSTRACT: Fusion of the sagittal suture is the most prevalent form of craniosynostosis. Due to the variety of deformities of scaphocephaly depending on the location of the fused sagittal suture, the surgical procedure has to be adjusted to the individual case. In this study, 38 patients with a predominantly posterior sagittal suture closure were treated with a modified technique of the pi-procedure and the surgical outcome has been evaluated with respect to complications, morphological and aesthetic outcome. The improvement of the cephalic index in our series in the follow-up examination (mean 60.1 months) after surgery was significant (p<0.0001). According to the classification of Whitaker, 31 patients had a Class 1 outcome, with excellent surgical results. Aesthetic outcomes were excellent in 29, good in 5, and poor in 4 of cases, as judged by both the families and the craniofacial team. No severe complications have been observed. Posterior sagittal suture with marked occipital bulging can be successfully treated with this modified posterior procedure with a low complication rate, significant improvement of the cephalic index and a good aesthetic outcome. In all cases of sagittal synostosis, the operative procedure should be tailored to the nature and severity of the deformity.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 03/2012; · 1.25 Impact Factor
  • Christian Freudlsperger, Timo Deiss, Jens Bodem, Michael Engel, Juergen Hoffmann
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    ABSTRACT: Postoperative inflammatory conditions, including alveolar osteitis, surgical site infections, and abscess, are frequent complications after surgical removal of impacted mandibular third molars and multiple associated risk factors have been identified. However, few studies have evaluated the influence of extraction difficulty according to anatomic variables on postoperative inflammatory complications. A retrospective study was performed of 585 surgically removed lower third molars. All molars were classified by a difficulty score (range 3 to 10) according to the anatomic parameters. For 109 third molars (19%), the extraction difficulty was rated noncomplex (score 3 to 4); for 341 (58%), moderate (score 5 to 7); and for 135 (23%), difficult (score 8 to 10). Molars rated as moderate or difficult for extraction were more often accompanied by postoperative infection than molars rated noncomplex (odds ratio 5.3 and 3.9, respectively, P < .0001). The results from the present study revealed a highly significant correlation between the level of difficulty for surgical removal of lower third molars (predicted by the anatomic variables) and postoperative inflammatory complications.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 02/2012; 70(6):1280-5. · 1.58 Impact Factor
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    ABSTRACT: Infantile myofibromatosis is a proliferative disorder characterized by the development of single or multiple nodular lesions in the soft tissue, skeleton, and internal organs. These tumors can occur at any anatomic site, but in one third of the cases, the head and neck region is involved. Here, we report a case of an infantile myofibroma occurring in a 7-year-old girl presented as a solitary lesion in the head and neck area. The clinical heterogeneity and the misleading histopathologic appearances may render the diagnosis difficult. Usually, treatment of choice is surgical removal of the tumor; however, the low rate of recurrence and the possibility of spontaneous regression may lead to conservative surgery or therapeutic abstention.
    The Journal of craniofacial surgery 11/2011; 22(6):e66-8. · 0.68 Impact Factor

Publication Stats

87 Citations
46.07 Total Impact Points

Institutions

  • 2012–2013
    • Universität Heidelberg
      • Oral and Maxillo-Facial surgery
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2008–2013
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 2008–2010
    • University Medical Center Hamburg - Eppendorf
      • Department Anatomy and Experimental Morphology
      Hamburg, Hamburg, Germany
  • 2006–2010
    • University of Hamburg
      • Department of Anatomy and Experimental Morphology
      Hamburg, Hamburg, Germany