Olfaction in Juvenile Nasopharyngeal Angiofibroma: The first study.

BACKGROUND: To study the pattern of olfactory dysfunction/recovery in juvenile nasopharyngeal angiofibroma (JNA). METHODS: Olfactory assessment was undertaken in 30 patients (category1) both pre- & post-operatively and in another 18 (category 2) only postoperative. All patients underwent transpalatal excision and variables of interest included age, radiological stage/parameters & tumor size. RESULTS: Objective olfactory dysfunction was seen in 60% while involvement of olfactory strip was suggested in 50%. Despite some marginal trends only noted between size/age with change of olfaction, Pearson's correlation test did not reveal any significance amongst multiple variables. However a better recovery of olfaction following surgery was evident in Category-2 where Chi-Square test (p < 0.05) significantly revealed this to be a function of postoperative duration. This regenerative course in JNA suggests an optimum period of 4 years for full recovery after surgery. CONCLUSION: In this first study of olfaction in JNA many new trends have been appreciated. In general, deteriorations of olfaction were seen due to 'vascular-concussion' effect in early postoperative phase where post-surgical clearance of airway showed minimal effect in terms of improvement. The hypervascularity of olfactory epithelium with possible hormonal effects may be responsible for the unique pattern of olfactory function and recovery in JNA.

Cellular Angiofibroma of the Nasopharynx.

Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

[The transperygoid approach to the removal of a recurrent juvenile angiofibroma at the base of the skull without preoperative embolization]. / Transkrylovidnoe udalenie retsidiviruiushchei iuvenil'noi angiofibromy osnovaniia cherepa bez predoperatsionnoi émbolizatsii.

The authors report a clinical case of successful elimination of a recurrent juvenile angiofibroma at the base of the skull (JAFBS) with the application of the optical navigation system and a cold plasma scalpel in the absence of preoperative embolization. It has been demonstrated using the proposed transperygoid approach to the extirpation of the tumour that a recurrent juvenile angiofibroma at the base of the skull can be efficiently removed by means of a modern minimally invasive and at the same time radical surgical method.

The ominous sequence in patients with tuberous sclerosis complex.

BACKGROUND: The clinical phenotypes and their severity in patients with tuberous sclerosis complex can be quite variable and are sometimes never determined simply by the primary mutation. These make clinically selecting appropriate treatments and predicting disease outcome difficult. In this report, the prognostic ominous sequence was evaluated in association with clinical manifestations and gene mutations. METHODS: The patients were classified by each renal lesion of angiomyolipomas and polycystic disease. The other clinical manifestations and outcomes of epilepsy, mental retardation, facial angiofibromas, subependymal giant cell astrocytoma, cortical tubers were reviewed and each gene mutations were analyzed in seven unrelated patients. RESULTS: Two patients with multiple and large proliferative renal angiomyolipoma showed poor clinical outcome than the patients with other renal lesions. These patients presented with progressively proliferative facial angiofibroma, West syndrome, Lennox-Gastaut syndrome, severe mental retardation, subependymal giant cell astrocytoma and they were affected by TSC2 gene mutations. CONCLUSION: The sequence of progressively proliferative renal angiomyolipoma, facial angiofibroma, West syndrome and TSC2 gene mutations might be prognostic ominous factors.

Endoscopic surgery for juvenile angiofibroma: a critical review of indications after 46 cases.

BACKGROUND: At present, transnasal endoscopic surgery is considered a viable option in the management of small-intermediate size juvenile angiofibromas (JAs). The authors critically review their 14-year experience in the management of this lesion to refine selection criteria for an endoscopic approach. METHODS: From January 1994 to May 2008, 46 patients were treated by a pure endoscopic resection after vascular embolization (87%). The lesions were classified according to Andrews (Andrews JC, et al., The surgical management of extensive nasopharyngeal angiofibromas with the infratemporal fossa approach, Laryngoscope 99:429-437, 1989) and Onerci (Onerci M, et al. Juvenile nasopharyngeal angiofibroma: A revised staging system, Rhinology 44:39-45, 2006) staging systems. All patients were followed by regular endoscopic and magnetic resonance imaging (MRI) examinations. RESULTS: Lesions were classified as follows: stage I, n = 5; stage II, n = 24; stage IIIa, n = 14; stage IIIb, n = 3 according to Andrews classification system; stage 1, n = 9; stage II, n = 12; stage III, n = 26 according to Onerci's system. Unilateral blood supply was detected in 39 (85%) cases. Feeding vessels from the internal carotid artery (ICA) were also reported in 14 (30%) patients. Intraoperative blood loss ranged from 250 to 1300 mL (mean, 580 mL). In four (8.7%) cases, suspicious residual disease was detected by MRI. In one patient, a 1-cm persistent lesion was endoscopically removed because septoplasty was required and a slight increase in size was noticed. The other three lesions, all located in the root of the pterygoid plate, are nearly stable in size and are currently under MRI follow-up. CONCLUSION: The improvement of surgical instrumentation and the experience acquired during a 14-year period have contributed to expanding the indications for endoscopic surgery in the management of JAs. Even stage III lesions may be successfully managed, unless the ICA is encased or if it provides an extensive blood supply. An external approach may be required when critical structures such as the ICA, cavernous sinus, or optic nerve are involved by lesions that are persistent after previous treatment; such a situation may prevent safe and radical dissection with a pure endoscopic approach. Better understanding of the factors influencing the growth of residual lesions is needed to differentiate those requiring re-treatment from those which can be simply observed.

Juvenile nasopharyngeal angiofibroma recurrence associated with exogenous testosterone therapy.

BACKGROUND: Juvenile nasopharyngeal angiofibromas (JNAs) are rare benign lesions that express hormonal receptors. This report describes a recurrence of a JNA 20 years after excision associated with exogenous testosterone therapy. METHODS: A 36-year-old man developed a sphenoid mass 20 years following resection of a JNA, shortly after initiating exogenous testosterone therapy for symptomatic low endogenous testosterone. RESULTS: The mass was subsequently excised and was histologically consistent with a JNA. The patient resumed his testosterone therapy postoperatively. Repeated imaging has demonstrated no recurrence after 3 years. CONCLUSION: This unique case adds further evidence to the role of testosterone in the pathogenesis of JNAs. Exogenous testosterone can cause tumor regrowth at any time, even decades following treatment. The patients with a history of JNA, even those without recurrence for years, should weigh the risk of recurrence before the use of exogenous testosterone.

GNAS haploinsufficiency leads to subcutaneous tumor formation with collagen and elastin deposition and calcification.

INTRODUCTION: The heterotrimeric G protein alpha-subunit G(s)alpha links receptors to stimulation of cAMP/protein kinase A signaling, which inhibits skin fibroblast proliferation and collagen synthesis. We now describe the development of fibrous tumors in mice with heterozygous disruption of the Gnas gene, which encodes G(s)alpha and other gene products. METHODS AND RESULTS: Disruption of Gnas exon 2 on either the maternal or paternal allele (Gnas(E2-/+)) results in fibromas or angiofibromas on the ears, paws and tail beginning at 4 months of age. The tumors were composed of fibroblastic cell proliferation with collagen and elastin deposition and calcification, and seemed to be associated with mechanical skin damage. The presence of calcification was associated with greater amounts of matrix metalloproteinase-2, suggesting an association between calcium deposition and extracellular matrix degradation. Osteoblast-specific markers were absent, consistent with the calcification not being secondary to ossification. Molecular studies showed that the tumors were not associated with deletion of the wild-type allele, making it unlikely that these tumors resulted from homozygous loss of G(s)alpha. CONCLUSIONS: These findings provide in vivo evidence that G(s)alpha pathways inhibit fibroblast and endothelial proliferation and matrix deposition.

Juvenile nasopharyngeal angiofibroma in a tertiary centre: ten-year experience.

INTRODUCTION: This is a retrospective study that aimed to examine the outcomes of patients presenting with juvenile nasopharyngeal angiofibroma (JNA) at a tertiary centre in Malaysia. METHODS: The demographical data, clinical presentation, investigations as well as treatment of 13 JNA patients were reviewed and collected from the medical record office at our centre from 1995 to 2005. RESULTS: All JNA patients were male and the average age at diagnosis was 17 (range 14-28) years. They presented with recurrent painless spontaneous epistaxis, nasal obstruction, nasal discharge, a reduced sense of smell, snoring, headache and facial swelling. One patient was at stage I, eight were at stage II, three at stage III and one patient was at stage IV, based on the Fisch classification. Angiography showed that nine tumours were supplied by both internal maxillary arteries of the external carotid system, and only four tumours received blood supply from the ipsilateral internal maxillary artery. All 13 patients underwent primary surgical resection. The overall recurrence rate was 38.5 percent for the first procedure and 60 percent for the second procedure. No major complications occurred in this group of patients as a consequence of treatment, neither for the primary tumours nor for the recurrences. CONCLUSION: JNA is a rare vascular benign tumour with highly exclusive persistence and recurrence, and typically affects adolescent boys. The management of JNA presents a challenge to ENT surgeons. Preoperative angiography and embolisation minimise intraoperative blood loss and the current shift in the treatment to endoscopic excision in selected lesions reduces perioperative morbidity.

Common genodermatoses: what the pediatrician needs to know.

Recognizing the patterns of the skin findings and establishing the correct diagnosis can also help avoid subjecting patients to unnecessary tests, such as lumbar punctures to rule out herpes simplex virus in neonates with a Blaschkoid distribution of vesicles in incontinentia pigmenti. The cutaneous features of genetic disorders provide important clues to the underlying diagnoses for conditions such as tuberous sclerosis, neurofibromatosis, incontinentia pigmenti, and help direct the diagnostic evaluation and health supervision in those individuals.

Case studies in the surgical management of pediatric nasal airway obstruction.

The authors present two case studies on pediatric nasal obstruction that highlight the consequences of a delayed diagnosis and the complexities of managing obstructed lesions in children.

Tuberous sclerosis complex: advances in diagnosis, genetics, and management

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem neurocutaneous syndrome characterized by the development of multiple hamartomas distributed throughout the body, skin, brain, heart, kidneys, liver, and lungs. Two-thirds of patients represent sporadic mutations. The classic triad is seizures, mental retardation, and cutaneous angiofibromas. However, the full triad occurs in only 29 por cento of patients; 6por cento of them lack all three of them. Two tumor suppressor genes responsible for TSC have been identified: TSC1 gene on chromosome 9 and TSC2 on chromosome 16. This article highlights the most recent significant advances in the diagnosis and genetics of TSC, along with a discussion on the limitations and the usefulness of the revised 1998 clinical criteria for the tuberous sclerosis complex. The [quot ]ash leaf[quot ] macule often comes in other shapes, such as round; most are polygonal, usually 0.5 cm to 2.0 cm in diameter, resembling a thumbprint. Since the death of its describer, Thomas Fitzpatrick, we call each a [quot ]Fitzpatrick patch.[quot ] Special attention is paid in this work to TSC treatment options, including therapeutic trials with rapamycin, also known as sirolimus. LEARNING OBJECTIVE: After completing this learning activity, participants should familiar with tuberous sclerosis complex, its cutaneous signs and systemic findings stratified by patient age, its genetics, and the potential for meaningful therapeutic intervention.

p53 and Her-2/neu in juvenile angiofibromas.

The pathogenesis of juvenile angiofibroma (JA) remains unsolved. Further, it is unknown whether this fibrovascular tumour arises from the endothelial or stromal cells. Comparative genomic hybridisation analysis of these tumours revealed deletions of chromosome 17, including regions for the tumour suppressor gene p53 as well as the Her-2/neu oncogene, which are altered in many human tumours. In order to analyse if they are also important for progression of JA, the p53 gene and Her-2/neu gene were evaluated in 7 tumours by two-colour in situ hybridisation analysis using probes for the centromer of chromosome 17 either with a specific probe against p53 or Her-2/neu. In 5 out of 7 JAs, gene losses were detected for both genes ranging from 10.5 to 31.5%, respectively. Gene amplifications were not observed. Semi-quantitative RT-PCR analysis from laser microdissected single endothelial cells and fibroblasts showed up-regulated p53 mRNA levels in 4 out of the 7 JAs analysed in both investigated cell types and in one case in only endothelial cells. Her-2/neu mRNA was noted to be up-regulated in 2 JAs and down-regulated in 1 JA for both cell types. Western blot analysis as well as immunohistochemistry detected no p53 protein in the 5 investigated JAs, indicating absence of mutated p53. Our findings indicate that chromosomal losses on chromosome 17 imply p53 gene and Her-2/neu gene losses in JAs. However, comparison of p53 and Her-2/neu mRNA levels in laser microdissected endothelial and stromal cells were not conclusive to answer the question of the tumour cell of origin in JA.

Anesthetic management of juvenile nasopharyngeal angiofibroma resection.

OBJECTIVE: To evaluate the anesthetic implications of the surgical resection of juvenile nasopharyngeal angiofibroma (JNA). DESIGN: Retrospective study. SETTING: University-affiliated community hospital. PARTICIPANTS: Ten patients undergoing resection of JNA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from the records of 10 patients undergoing resection of JNA were reviewed and analyzed with regard to demographics, history of the disease, characteristics of the tumor, surgical resection techniques, and anesthetic management. Patients were age 11 to 29 years. All had nasal obstruction as presenting symptom. There was no intracranial invasion. Eight tumors were resected via a lateral rhinotomy and 2 endoscopically (after embolization of the tumor's feeding vessels). Duration of surgery was 6 +/- 1 hours for rhinotomy and 6 and 6.5 hours for the 2 endoscopic resections. Anesthesia was induced in a rapid-sequence manner. Arterial and central venous catheters were placed in all patients. Mean arterial pressure was targeted to 55 to 65 mmHg by using increasing concentrations of isoflurane. The estimated blood loss was 4,800 +/- 1,600 mL and blood replacement was 3,200 +/- 1,400 mL in the first group. The 2 other patients lost 600 mL and 1,500 mL. Blood replacement in this group was 0 and 700 mL respectively. No mortality or major morbidity occurred. CONCLUSION: Resection of JNA should be considered a major procedure with many anesthetic challenges. Isoflurane may be employed to provide deliberate hypotension.

Long-term effects of Le Fort I osteotomy for resection of juvenile nasopharyngeal angiofibroma on maxillary growth and dental sensation.

OBJECTIVE: To analyze the long-term effects of the Le Fort I osteotomy approach for the resection of juvenile nasopharyngeal angiofibroma (JNA) on maxillary growth and dental sensation. DESIGN: Prospective collection of structured data. SETTING: Tertiary care academic teaching hospital. PATIENTS: Between 1993 and 1998, 5 adolescents (aged 10-14 years) constituted the evaluable cohort among 14 patients who underwent Le Fort I osteotomy for JNA resection. Mean follow-up was 47.2 months. INTERVENTIONS: The Le Fort I osteotomy approach was used to resect JNA. Cephalometric x-ray films were taken at various postoperative intervals to assess maxillary growth. The results were matched against age-correlated predictions from Dentofacial Planner software. MAIN OUTCOME MEASURES: Horizontal and vertical maxillary growth were each measured anteriorly and posteriorly by comparing interval postoperative cephalometric x-ray films. Dental sensation was longitudinally evaluated by performing interval pulp testing postoperatively. RESULTS: (1) Average vertical growth of the maxilla achieved 30% of predicted growth anteriorly (P =.02). (2) Average horizontal growth matched predicted growth in all patients. (3) All patients demonstrated long-term maxillary dental denervation. CONCLUSIONS: Le Fort I osteotomy provides excellent surgical exposure for resection of JNA in the growing facial skeleton. Although it significantly affects vertical but not horizontal growth, its cosmetic effect is negligible. It also causes long-term dental denervation, which in most cases is undetected by patients.

Manejo quirúrgico del angiofibroma nasofaríngeo juvenil / Surgical management of the juvenile nasopharyngeal angiofibroma

Objetivo. Presentamos nuestra experiencia en el tratamiento quirúrgico del angiofibroma nasofaríngeo juvenil (ANJ) en los últimos años, realizando a continuación una recopilación de las distintas posibilidades terapéuticas. Diseño. Han sido intervenidos tres pacientes diagnosticados a través de imagen y confirmados mediante estudio histopatológico. Resultados. Los pacientes tratados se encuentran actualmente asintomáticos, habiéndose extirpado a través del tratamiento quirúrgico en su totalidad excepto en un caso en el que persisten mínimos restos tumorales. Conclusiones. Las posibilidades terapéuticas del ANJ son muy variadas (tratamiento quirúrgico a cielo abierto o mediante endoscopia), radioterapia, quimioterapia, hormonoterapia y cirugía estereotáxica, debiendo individualizar cada caso a la hora de determinar el tratamiento a seguir. El tratamiento quirúrgico a cielo abierto es de elección en los tumores con estadio de Fisher superior a II (AU)

[The specific features of the functional status of the pituitary- adrenal and sympatho-adrenal system in children with angiofibromas of the skull base]. / Osobennosti funktsional'nogo sostoianiia gipofizarno-nadpochechnikovoi i simpatiko-adrenalovoi sistem pri angiofibromakh osnovaniia cherepa u detei.

Analyzing the results of examination of 14 boys aged 6 to 13 years who had angiofibromas of the skull base has led to the conclusion that the disease runs in the presence of the markedly activated sympathoadrenal and pituitary-adrenal systems and lipid oxidation products. While choosing a therapy, it is necessary to take into account hormonally metabolic and antioxidative imbalance and to prescribe metabolic and membrane-stabilizing drugs.

Angiofibromas juveniles nasofaríngeos / Youthful rhinofaringeal angiofibromas

Los angiofibromas juveniles nasofaríngeos son los tumores nasofaríngeos benignos más frecuentes. Se presentan predominantemente en varones púberes. Los síntomas más frecuentes son obstrucción nasal y epistaxis recurrentes. A pesar de que su comportamiento biológico es benigno, tiende a crecer destruyendo las estructuras óseas vecinas a la nasofaringe hasta extenderse a la base del cráneo. Recurren con una frecuencia que va del 35 al 57 por ciento después de la extirpación quirúrgica incompleta. El diagnóstico diferencial debe hacerse con hemangiopericitoma, tumor fibroso solitario, hemangiomas, schwannoma e histiocitoma fibroso