Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM: To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS: Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS: Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION: In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.

Cervicofacial Surgical Emphysema following Tonsillectomy.

We report the case of a patient who developed cervicofacial subcutaneous emphysema following a routine tonsillectomy. An 18-year-old male with swallowing difficulties underwent a tonsillectomy and developed swelling of the right side of his neck and face 36 hours after surgery. A neck X-ray revealed subcutaneous emphysema. Unlike similar previously published cases, there were no postoperative issues of coughing, straining, or use of positive pressure ventilation. The complication also occurred after a considerable length of time. Further complications may include pneumothorax and pneumomediastinum and these should be excluded.

Hearing benefit in allograft tympanoplasty using tutoplast processed malleus.

Objectives. Tutoplast processed human cadaveric ossicular allografts are a safe alternative for ossicular reconstruction where there is insufficient material suitable for autograft ossiculoplasty. We present a series of 7 consecutive cases showing excellent air-bone gap closure following canal-wall-down mastoidectomy for cholesteatoma and reconstruction of the middle ear using Tutoplast processed malleus. Patients and Methods. Tympanoplasty with Tutoplast processed malleus was performed in seven patients to reconstruct the middle ear following canal-wall-down mastoidectomy in a tertiary ENT centre. Main Outcome Measures. Hearing improvement and recurrence-free period were assessed. Pre-and postoperative audiograms were performed. Results. The average pre operative hearing loss was 50 ± 13 dB, with an air-bone gap of 33 ± 7 dB. Post operative audiograms at 25 months demonstrated hearing thresholds of 29 ± 10 dB, with an air-bone gap of 14 ± 6 dB. No prosthesis extrusion was observed, which compares favourably to other commercially available prostheses. Conclusions. Tutoplast processed allografts restore conductive hearing loss in patients undergoing mastoidectomy and provide an excellent alternative when there is insufficient material suitable for autograft ossiculoplasty.

Plasma cell mucositis of Oro- and hypopharynx: a case report.

Objective. To raise awareness of plasma cell mucositis as a rare differential diagnosis for oral mucosal ulceration and its macroscopic similarity to malignancy. Method. We report a patient who presented with oral features suggestive of malignancy. A biopsy revealed plasma cell mucositis. Results. The patient successfully had a full excision of one lesion and a spontaneous resolution of the other. Conclusion. With the increasing incidence of oral mucosal pathology, physicians should be aware of this differential diagnosis.

Kikuchi-fujimoto disease: a case report and literature review.

Case. 38-year-old lady was referred to the ENT clinic with history of right-sided facial pain, otalgia, and odynophagia. Clinical examination revealed enlarged right-sided lymph nodes in the neck. Further radiological scans showed a mass near the carotid and enlarged level V lymph nodes. Lymphoma was initially suspected. Fine-needle aspiration and excision biopsy were undertaken. Histological analysis later suggested Kikuchi-Fujimoto disease, also known as histiocytic necrotising lymphadenitis. Literature Review. Kikuchi-Fujimoto disease (KFD) was described in 1972 as lymphadenitis with focal proliferation of reticular cells accompanied by numerous histiocytes and extensive nuclear debris. KFD, frequently found in East Asian countries, is rare in the UK. No definite aetiology of KFD is known despite autoimmune and infection factors being suggested. The diagnostic hallmark is histological findings from lymph nodes. Malignancy should be excluded. This condition is mainly self-limiting; hence, management is limited to supportive care. Steroid therapy could be used in severe cases. KFD is relatively unknown in the UK and this case report aims to highlight its occurrence in our population.

Sandwich technique in nasal dorsal augmentation.

Tutoplast fascia lata (TFL) has been used as an onlay graft for nasal dorsal augmentation in open approach rhinoplasty; however, insertion of layers of moist TFL in the closed approach is technically challenging. We have presented a "sandwich" technique which facilitates graft insertion in a closed approach rhinoplasty. The available autologous graft (cartilage or perpendicular plate of ethmoid) is sandwiched and secured between layers of TFL (sandwich technique) prior to insertion of the graft for nasal dorsal augmentation in a closed rhinoplasty approach. All our cases of nasal dorsal augmentation were reviewed in a 2 year period. Eight cases of nasal dorsal augmentation in secondary rhinoplasty through a closed approach were reviewed. The ease of insertion and the subsequent manipulation of the graft were noted in all the cases. Good aesthetic results have been noticed in all the cases after an average of 14 months follow-up. The sandwich technique ensures ease of the graft insertion and the subsequent manipulation in a closed approach secondary rhinoplasty for dorsal augmentation.

Orbital cellulitis: a rare presentation of metastatic bronchial carcinoma.

Objective. We report a rare and unusual case of bronchial carcinoma presenting with symptoms of complications of sinonasal disease. Case Report. A 66-year-old lady was referred with a 1-week history of progressive ocular pain, chemosis, and visual disturbance. Computed tomography of the paranasal sinuses revealed frontal and ethmoidal sinus opacification with orbital involvement consistent with a diagnosis of orbital cellulitis secondary to sinusitis. Surgical exploration revealed that the sinuses and right orbit were filled with soft tissue and subsequent histopathological examination of the biopsies indicating metastases from an adenosquamous bronchial carcinoma. Further imaging revealed a large, asymptomatic, bronchial primary with deposits in the brain and liver. The advanced presentation of the disease limited treatment to best supportive care. Conclusion. Orbital cellulitis and sinonasal malignancies have a similar pattern of clinical presentation, posing a potential diagnostic pitfall. There are only two previously reported cases of metastatic lung carcinoma in the frontal sinus with 15 cases of sinonasal tract involvement reported overall. There are no reported cases of adenosquamous carcinoma in the sinonasal tract.

Tobacco abuse relates to significantly reduced survival of patients with oropharyngeal carcinomas.

This study represents an in-depth evaluation of the impact of smoking and alcohol consumption on patients' outcome in 809 cases of oropharyngeal carcinoma. Prognostic parameters and additional information such as smoking and drinking habits were evaluated referring to the patients' case notes at the time point of first diagnosis. The overall 10-year survival rate was 45.5%, whereas 33.4% of the patients remained relapse-free. The great majority (92%) of patients had a history of smoking or were current smokers, whereas only 8% of the collective never smoked in their lifetime. Interestingly, we found a significant reduction of 10-year survival rates for smokers (28.8%) in comparison with nonsmokers (43.1%) and ex-smokers (P=0.0007). This study presents data from a large cohort of patients with oropharyngeal carcinoma providing evidence for a relationship between alcohol and tobacco consumption, and significantly worse prognosis.

Double-blind, placebo-controlled trial with esomeprazole for symptoms and signs associated with laryngopharyngeal reflux.

OBJECTIVE: To determine the efficacy of proton pump inhibitor (PPI) therapy with esomeprazole on symptoms and signs associated with laryngopharyngeal reflux (LPR). STUDY DESIGN AND METHODS: Prospective, double-blind, randomized, placebo-controlled study. Sixty-two patients with a reflux finding score (RFS)>7 and a reflux symptom index (RSI)>13 were enrolled and received either esomeprazole 20 mg twice daily or placebo for three months. RSI and RFS were assessed at baseline, after six weeks, and after three months. RESULTS: Reductions of total RSI and RFS as well as of several subscores were significantly higher in the treatment group compared to placebo after three months (P<0.05 each). The difference between study groups was most pronounced for posterior commissure hypertrophy (P<0.01). CONCLUSION: In the treatment of LPR-related symptoms a high placebo effect can be observed. However, compared to control, twice-daily PPI treatment for three months demonstrated a significantly greater improvement in laryngeal appearance and LPR symptoms.

HER3 expression in cutaneous tumors.

BACKGROUND: In order to elucidate the role of the receptor tyrosine kinase HER3, the expression characteristics in different tissues of cutaneous malignancies and in normal skin were compared. MATERIALS AND METHODS: In this study HER3 expression was evaluated by RT-PCR analysis and immunohistochemistry from different tissue specimens of cutaneous tumors like nevi, primary malignant melanomas, basal cell carcinoma, squamous cell carcinoma and malignant melanoma metastases and normal skin samples and graded into weak, moderate and strong expression. Associations of tumor thickness in these specimens with HER3 expressions were also analyzed. RESULTS: HER3 expression was found in 63% (10/16) of the basal cell carcinomas, in 4/5 of squamous cell carcinomas and in one Merkel cell carcinoma. Within the group of different malignant melanomas, HER3 expression was detected in 35% of the nodular malignant melanomas (6/17) and in 9/19 of the superficial spreading melanomas, including 2 lentigo malignant melanomas. The majority of melanomas with a higher tumor thickness expressed HER3, and 85% of melanoma metastasis were HER3-positive. CONCLUSION: HER3 expression was associated with hyperproliferate tumor stages and suggested that HER3 expression could reflect an increased malignant potential in cutaneous lesions.

Complications of acute frontal sinusitis: a retrospective study.

Even though being a rare condition in the era of antibiotic treatment, complications of acute frontal sinusitis still pose a potentially life-threatening problem. We present a clinical case series using a combined surgical approach. Within a 7 year period, all patients with a suppurative complication of an acute frontal sinusitis were included into this retrospective study and evaluated concerning histories, diagnostic and therapeutic procedures and achieved outcomes. Twelve patients (11-74 years) were identified; this corresponds to 0.3% of all patients that have undergone paranasal sinus surgery and 15.4% of all patients with infectious complications of sinusitis. The cases could be subdivided as follows: intracranial complications (4/12), osteomyelitis of the frontal bone (4/12), frontal/orbital soft tissue involvement (3/12) and endoluminal empyema (1/12). These were all correctly diagnosed by CT and (especially in the cases of intracranial complications) MRI. The microbiological spectrum comprised mostly non-multiresistant Staphylococci and Streptococci. All patients received aggressive antibiotic and combined surgical treatment. Within a mean follow up period of 32 months, the disease-related mortality and the rate of severe long-term ailment was 0%. If detected and treated early, both long-term morbidity and mortality can be minimised. A close cooperation with the related specialties (neurosurgery, ophthalmology, radiology) is thereby of utmost importance.

Fibrous dysplasia of the frontal bone.

Fibrous dysplasia typically occurs in patients between the ages of 5 and 15 years. We report the case of a middle-aged woman with longstanding monostotic fibrous dysplasia who responded well to conservative treatment. She had presented with a very long (15 yr) history of frontal headache and pressure over the frontal sinus. On examination, a protuberance was noted in the region of the right frontal sinus. No other symptoms were evident, and findings on the ENT examination were normal. Computed tomography (CT) detected a widening of the frontal bone with osteolytic changes of the cancellous bone of the diploe. Partial multiphase skeletal scintigraphy and single-photon emission CT of the cranium showed increased bone metabolism in the area of the right frontal bone. No other hot spots were seen. In view of the absence of any complications, no tissue biopsy was performed. The patient was prescribed bisphosphonates for symptom relief. Follow-up CT 1 year later revealed no progression of the lesion. Overtreatment of fibrous dysplasia should be avoided because most patients respond to conservative management. In those cases that are refractory to medical treatment, surgery--in experienced hands--can result in a good functional and cosmetic outcome.

Genomic approach of AIDS pathogenesis: exhaustive genotyping of the TNFR1 gene in a French AIDS cohort.

Large-scale genomic studies in cohorts have been made possible for the last few years thanks to the progress of molecular biology and bioinformatics. This systematic approach allows a better understanding of the molecular mechanisms of disease development and as a consequence can contribute to the rational design of new diagnostic and therapeutic tools. We present here the exhaustive genotyping of a candidate gene, tumor necrosis factor receptor 1 (TNFR1), in the genetic of resistance to immunodeficiency virus (GRIV) AIDS cohort. This gene was chosen because it is likely to be involved in the apoptosis pathways of CD4+ and CD8+ T-cells during human immunodeficiency virus 1 (HIV-1) infection. Seven frequent polymorphisms were characterized in 319 HIV-1 seropositive patients from the GRIV cohort with extreme disease progression phenotypes, slow progression or rapid progression, and in 427 healthy controls. The TNFR1 gene locus does not appear to be part of any haploblock and contains only a small haploblock of two successive SNPs. One promoter SNP (TNFR1_17444594, position -581) and one intronic SNP (TNFR1_27223241, position +11511) gave weak positive signals of association (resp. P=0.03 and P=0.04) as well as two haplotypes. To our knowledge, this is the first genetic association study dealing with the TNFR1 gene in AIDS and the putative associations identified will need to be validated through other AIDS cohort analyses or by further biological experimentation.

The homeopathic preparation Vertigoheel versus Ginkgo biloba in the treatment of vertigo in an elderly population: a double-blinded, randomized, controlled clinical trial.

OBJECTIVE: Alternative medical practices are common in the treatment of vertigo. This study compared the effects of Ginkgo biloba treatment with the homeopathic remedy Vertigoheel (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany). DESIGN: Randomized, double-blinded, parallel group study. SUBJECTS: One hundred and seventy (170) patients, ages 60-80 years, with atherosclerosis-related vertigo. INTERVENTIONS: Patients were randomly allocated to receive treatment with either Vertigoheel (n = 87) or G. biloba (n = 83). OUTCOME MEASURES: The results were analyzed for the non-inferiority of Vertigoheel to G. biloba on the combined endpoint of changes from baseline to week 6 in dizziness score (assessed by questionnaire), frequency, duration, and intensity of vertigo episodes (recorded in patient diaries). RESULTS: Both treatments improved vertigo status. From a baseline mean value of 26.1 +/- 5.2 (on a 50-point scale) in the Vertigoheel group, the dizziness questionnaire score improved by -10.6 +/- 10.0, and by -10.7 +/- 9.0 from 25.8 - 4.7 in the G. biloba group. Statistical analysis of this endpoint showed that Vertigoheel was not inferior to G. biloba. The 95% confidence interval for the difference between treatment did not reach the inferiority threshold of 0.36 at any of the time points tested. The results were supported by the results of a line walking test, Unterberger's stepping test, and patient and physician global assessments of therapeutic effect. Both treatments were well tolerated. CONCLUSIONS: Vertigoheel is an appealing alternative to established G. biloba therapy for atherosclerosis-related vertigo.

Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma.

Fibroblast growth factor receptors (FGFRs) have been implicated in various forms of human hyperproliferative disorders such as cancers of the cervix and bladder. We investigated the expression pattern of FGFR4 and the clinical significance of the recently identified Gly/Arg polymorphism (388) in head and neck squamous cell carcinomas (HNSCCs) of the oral cavity and the oropharynx. Sections from 104 paraffin-embedded tumors were analyzed by a restriction fragment length polymorphism-based method to determine the FGFR4 genotypes. Protein expression was investigated immunohistochemically and graded into a low, intermediate, or high degree of staining. FGFR4 expression was scored as high in 17, as intermediate in 59 and as low in 28 cases. The FGFR4 Arg388 allele was found in 59 tumors, 46 of them having heterozygous and 13 homozygous genotypes. High expression of the FGFR4 Arg388 allele was significantly associated with reduced overall survival (p = 0.032) and with an advanced tumor stage (p = 0.023), whereas expression of the FGFR4 Gly388 had no impact on disease progression. Our findings indicate that high expression of FGFR4 in connection with the Arg388 allele is associated with poor clinical outcome and support the significance of FGFR4 as a diagnostic marker and a target for therapeutic intervention in human HNSCC.

Cervical metastases of microcystic adnexal carcinoma in an otherwise healthy woman.

Microcystic adnexal carcinoma is a rare cutaneous neoplasm characterized by slow but locally aggressive growth, which normally does not lead to systemic metastasis. Frequent local recurrences are reported, which are most likely due to insufficient operative technique. We present the fourth case of cervical ipsilateral metastatic microcystic adnexal carcinoma in an otherwise healthy woman. The patient presented with a previously diagnosed but not completely resected microcystic adnexal carcinoma in the area of the right posterior scalp and two palpable ipsilateral lymph nodes. The tumor was resected using intraoperative snap frozen histological evaluation of the resection borders. In the same procedure two lymph nodes were resected from the right neck. The lymph nodes were histologically assessed and showed infiltration by small strains of tumor cells. After exclusion of a second primary tumor, e.g., mammary carcinoma, as the cause for cervical lymph node metastases, we performed a modified radical neck dissection with resection of the sternocleidomastoid muscle and the accessory nerve, which was histologically proven to be perineurally infiltrated by tumor cells. In this second procedure the histological evaluation of the specimen showed no sign of remaining tumor infiltration. After exclusion of distant metastasis the patient was irradiated with 60 Gy. The patient is well 1 year after the initial treatment without signs of recurrence.

Oropharyngeal metastasis of a Merkel cell carcinoma of the skin.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin characterized by frequent local and regional recurrence, a high incidence of distant metastases and therefore a high mortality. Here, we report a case of an oropharyngeal metastasis of a Merkel cell carcinoma of the skin localized at the left base of the tongue causing dysphagia and the sensation of globus pharyngeus. The unusual metastatic site is presented, and diagnosis and treatment are discussed.

Diagnosis and management of carcinoma of unknown primary in the head and neck.

Carcinoma of unknown primary is defined as the histological diagnosis of metastasis without the detection of a primary tumor. In the literature, the incidence of CUP in all patients with a malignant disease is said to be between 3% and 15%. The most frequent histopathological results of CUP metastases are adenocarcinoma, followed by undifferentiated carcinoma and squamous cell carcinoma. In this retrospective investigation the clinical records of 167 patients were studied. All patients had been admitted and treated for cervical CUP at the Department of Otorhinolaryngology of the Grosshadern Clinic from 1979 to 1998. Cervical swelling was the first noted symptom in all cases, followed by pain and dysphagia. The study group comprised 134 men and 33 women with an average age of 55 years at admission. Squamous cell carcinoma (n=123) was the predominant histopathological finding of the cervical lymph nodes. During the 10-year follow-up, a primary tumor was detected in 36 (21.5%) of the 167 initially diagnosed CUP patients. In over 90% of these cases the tumor was localized in the head and neck region. The most frequent origin of the tumor was the tonsilla palatina (n=7). Neck dissection and additional postoperative radiotherapy was performed in 118 (70.7%) of the 167 CUP patients. Primary radiotherapy was the treatment of choice in 28 patients; eight patients received combined radio-chemotherapy as the primary treatment and seven patients were treated with chemotherapy alone. Six patients had no treatment. Comparison of different treatment protocols revealed a significant difference in patient survival: in comparison with primary radiotherapy alone or neck dissection and postoperative radiotherapy, the survival rate improved significantly in patients that received a bilateral tonsillectomy in addition to neck dissection and postoperative radiotherapy. The treatment of choice in patients with cervical CUP should be a surgical procedure including (radical) neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage. Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the entire pharyngeal and laryngeal mucosa should also be considered in order to treat a possible small primary tumor in this region.

Association of laryngopharyngeal symptoms with gastroesophageal reflux disease.

OBJECTIVES: The prevalence of gastroesophageal reflux disease (GERD) in patients with laryngopharyngeal disorders is probably greater than realized. STUDY DESIGN: Prospective study. METHODS: To investigate the incidence of gastroenterological diseases including GERD in patients complaining of nonspecific laryngopharyngeal symptoms, laryngological examinations and gastroenterological evaluation with esophagogastroduodenoscopy were performed in 30 patients who refused to undergo 24-hour pH monitoring. Therapeutic intervention by behavioural and dietary modifications, antireflux medication, and eradication of Helicobacter pylori were assessed for changes in laryngeal findings and relief of symptoms. RESULTS: Posterior laryngitis was present in 26 patients and in 19 of them was accompanied by erythema and edema of the interarytenoid region. Gastroenterological diseases such as GERD (43%), hiatal hernia (43%), and Helicobacter pylori-positive antrum gastritis (23%) were confirmed in 22 (73%) cases by esophagogastroduodenoscopy and histological examination of biopsy specimens. Medical antireflux treatment and eradication of Helicobacter pylori resulted in a remarkably therapeutic success rate of 90% because there was resolution of laryngopharyngeal symptoms and laryngeal findings in 20 of 22 patients with gastroenterological diseases for the mean follow-up period of 8 months. CONCLUSIONS: Laryngopharyngeal symptoms can be predictors of gastroesophageal diseases and GERD because the most frequent underlying cause is supposed to be associated with posterior laryngitis. Medical antireflux treatment is effective for relief of symptoms and mucosal healing of posterior laryngitis.