Penetrating Trauma to the Parotid Gland.

Penetrating trauma to the parotid gland may present unique challenges especially when Stensen duct, neurovascular structures, and/or collateral organs are involved. Especially ballistic injuries caused by high-velocity projectiles or fragments of grenades and improvised explosive devices are often associated with massive tissue damage and a high risk of infections and other posttraumatic complications. Because penetrating parotid trauma is not very common, only limited information on the primary treatment of such injuries is available. This article gives a short overview about actual aspects on diagnosis and treatment strategies especially focusing on ballistic parotid injuries.

Efficacy and safety of AM-101 in the treatment of acute inner ear tinnitus--a double-blind, randomized, placebo-controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media. STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90. SETTING: Twenty-eight European sites (academic tertiary referral centers and private ENT practices). PATIENTS: 248 patients aged 16 to 65 years. INTERVENTIONS: Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days. MAIN OUTCOME MEASURES: Efficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events. RESULTS: The study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated. CONCLUSION: The study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests.

Nasal meatus plasty: a contribution to plastic reconstruction of the nasal valve during midfacial degloving.

Midfacial degloving is a proven method for easily accessing the midface, the nasal pyramid, the maxillary and ethmoidal sinuses, the orbits, as well as the anterior skull base. Indications for this method of access mainly include tumour resections in the area of the midface, the septum, the maxillary sinus, the paranasal to the sphenoidal sinus as well as the clivus. In addition, this method of access allows for the exposure of the bony structures of the midface in the event of extensive fractures. In general, this method of access combines an incision in the oral vestibule and circular incisions in the nasal vestibule area in order to release the nasal pyramid. After removing the facial wall of the maxillary sinus, extensive exposure of the surgical site is possible. One disadvantage of this method of access is the difficult reconstruction of the nasal valve area, which often leads to cicatricial stenoses and difficulties with breathing through the nose. Furthermore, wound healing problems and osteoradionecrosis in the area of the lateral margin of the anterior nasal aperture after replantation of the facial wall of the maxillary sinus have been described, because in this area sufficient soft tissue coverage cannot be ensured when a conventional technique is used. We describe a soft tissue flap pedicled in the cranial and caudal directions in the nasal valve area which makes both the reconstruction of the nasal vestibule and sufficient soft tissue coverage of the anterior nasal aperture possible.

Development and (pre-) clinical assessment of a novel surgical tool for primary and secondary tracheoesophageal puncture with immediate voice prosthesis insertion, the Provox Vega Puncture Set.

Development and (pre-) clinical assessment were performed of a novel surgical tool for primary and secondary tracheoesophageal puncture (TEP) with immediate voice prosthesis (VP) insertion in laryngectomized patients, the Provox Vega Puncture Set (PVPS). After preclinical assessment in fresh frozen cadavers, a multicenter prospective clinical feasibility study in two stages was performed. Stage-1 included 20 patients, and stage-2 had 27. Based on observations in stage-1, the PVPS was re-designed (decrease in diameter of the dilator from 23.5 to 18 Fr.) and further used in stage-2. Primary outcome measure was immediate VP insertion without requiring additional instruments. Secondary outcome measures for comparison of the new with the traditional TEP procedure were: appreciation, ease of use, time consumption, estimated surgical risks and overall preference. A mini-max two-stage study design was used to establish the required sample size. In stage-1, dilatation forces were considered too high in patients with a fibrotic TE wall. With the final thinner version of the PVPS, VPs were successfully inserted into the TEP in 'one-go' in 24/27 (89%) of TEPs: 20 primary and 7 secondary. Participating surgeons rated appreciation, ease of use, time consumption and estimated surgical risks as better. Related adverse events were few and minor. The new PVPS appeared to be the preferred device by all participating surgeons. This study shows that the novel, disposable PVPS is a useful TEP instrument allowing quick and easy insertion of the VP in the vast majority of cases without requiring additional instruments.

A modified false vocal fold flap for functional reconstruction after frontolateral partial laryngectomy: a comparison with conventional open resection and laser cordectomy.

OBJECTIVE: To describe a modified flap technique (MFT) involving the use of a false vocal fold flap for glottic reconstruction and the removal of arytenoid cartilage and to compare it with conventional frontolateral partial laryngectomy (FLPL) and laser cordectomy (LC). METHODS: Twenty-eight MFT, 13 FLPL and 12 LC patients completed a standardised questionnaire for assessing aspiration, respiration, quality of life, and subjective voice quality. We analysed vocal function in terms of roughness, breathiness and hoarseness, measured voice range profiles, and performed videoendoscopy. RESULTS: No patient reported respiratory problems. Aspiration occurred in 33.3% (MFT), 41.6% (FLPL) and 16.6% (LC). Voice quality was rated as good/satisfactory by 17 MFT patients (62%), satisfactory/sufficient by 69% of FLKT patients, and sufficient/poor by 75% of LC patients. CONCLUSIONS: The modified false vocal fold flap effectively covers defects and creates a neocord that ensures good phonatory rehabilitation and has positive effects on postoperative quality of life.

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

BACKGROUND: There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. METHODS: A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. RESULTS: Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). CONCLUSIONS: Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Role of reflux in tracheoesophageal fistula problems after laryngectomy.

OBJECTIVES: The purpose of this 2-year prospective nonrandomized study was to investigate the relationship between pathological supraesophageal reflux and the occurrence of speech fistula complications, especially severe fistula enlargement, in patients who underwent total laryngectomy and prosthetic voice restoration. METHODS: We objectively assessed the presence of reflux disease using 24-hour dual-probe pH monitoring in 60 laryngectomized patients, correlated the incidence of tracheoesophageal fistula complications with the severity of reflux, and assessed the risk of problems by determining the absolute number of reflux events at the level of the speech fistula, the reflux area index score, and the DeMeester score. RESULTS: All patients with fistula enlargement showed highly pathological results in the diagnostic tests for reflux disease. Depending on reflux severity, the relative risk of developing fistula complications was up to 10 times higher for these patients. CONCLUSIONS: We found a significant correlation between the occurrence of tracheoesophageal fistula complications and the severity of supraesophageal reflux. Potential chronic irritation of the esophageal and tracheal mucosa can possibly contribute to the development of these problems. If the presence of reflux disease has been confirmed by 24-hour dual-probe pH monitoring, patients with fistula complications should be treated with proton pump inhibitors.

One-stage reconstruction of the entire upper lip and the columella with a modified bilateral nasolabial flap.

The functional and cosmetic reconstruction of the upper lip after a subtotal defect is a highly demanding challenge, especially when the columella is involved. In the majority of cases, the surgical techniques described in the literature are suitable only for restoring the function and appearance of the upper lip but not for reconstructing adjacent areas. In this article, we present the case of an 85-year-old female patient with an extensive, aggressive and highly invasive basal cell carcinoma of the upper lip and the columella. We describe a modification of the nasolabial flap technique using cheek tissue for the reconstruction of the defect. The modified flap is used for both the full-thickness reconstruction of the subtotal upper-lip defect and the restoration of the function and appearance of the columella. This technique allows excellent cosmetic and functional results to be obtained in a single-stage procedure.

Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients.

Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin and mucosa. After the injection of a photosensitizing agent, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy tumour cells. From November 2003 to July 2007, a total of 35 patients with recurrent squamous cell carcinoma or secondary tumours of the head and neck region were treated with PDT at the German Armed Forces Hospital in Ulm. These patients had failed or found unsuitable for other treatments. Meta-tetrahydroxyphenylchlorin (mTHPC), known under the trade name of Foscan, was used as the photosensitizing agent. Local control was achieved in 21 patients (60%) and partial remission in 10 patients (28.5%). Four patients (11.5%) did not respond to PDT treatment. The mean duration of overall survival was 401.45 (+/-321.2) days, median was 356 after the completion of treatment. The mean duration of recurrence-free survival was 327.7 (+/-131.1) days, median was 181 for patients with complete remission. None of the patient developed serious complications. Photodynamic therapy is an important treatment option for patients who present with recurrent carcinoma or secondary tumours of the upper aerodigestive tract and who have failed or unsuitable for other treatments. Due to the excellent treatment results that have been achieved so far, PDT may in the future also play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx.

Genotoxic effects of pentachlorophenol, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae.

BACKGROUND: Animal experiments and epidemiological studies suggest that pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (lindane) should be classified as possible human carcinogens. In the past, both have had a variety of applications in the civilian and military sectors and in forestry. They have, e.g., been used to impregnate and treat uniforms and other fabrics and to control human lice. Animal experiments indicate that PCP in particular causes mutations and chromosome aberrations and thus DNA damage. Studies on whether or not this also applies to newer substances and especially to natural type I and type II pyrethroids still are not available. What is particularly lacking are data on the genotoxic effects of these substances on human target cells. Our study describes the genotoxic effects of PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum on human mucosal cells of the inferior and middle nasal conchae. METHODS: Epithelial cells were isolated from nasal mucosa, which was removed in the surgical treatment of chronic sinusitis and nasal concha hyperplasia. After the cells had been tested for vitality using the trypan blue exclusion test, the short-term culture method was used. The material was incubated with PCP (0.3, 0.75, and 1.2 mmol), lindane (0.5, 0.75, and 1.0 mmol), transfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), cyfluthrin (0.05, 0.1, 0.5, 0.75, and 1.0 mmol), natural pyrethrum (0.001, 0.005, 0.01, 0.05, and 0.1 mmol), and N-methyl-N'-nitro-N-nitrosoguanidine for 60 minutes. Substance-induced DNA damage (single-strand and double-strand breaks) were determined using single-cell microgel electrophoresis. A fluorescence microscope was used together with an image processing system to analyze the results obtained. RESULTS: After exposure to all tested substances, a high percentage of the cells of the middle nasal concha in particular were found to have severely fragmented DNA as a result of strong genotoxic effects. Although the reaction of the cells of the inferior nasal concha was significantly less strong (p < 0.001), the tested substances were nevertheless found to have a notable genotoxic effect on these cells too. CONCLUSION: Our study strongly suggests that exposure to PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum has a genotoxic effect on the epithelial cells of human nasal mucosa. In addition, we have shown that nasal structures differ in susceptibility to the various pesticides used in the tests. Thus, the study provides new evidence supporting the biological plausibility of PCP- and lindane-induced effects, thereby helping evaluate potential PCP- and lindane-induced mucous membrane carcinomas of these parts of the nose. In addition, our study shows that other substances that today are widely used for controlling pests have a considerable genotoxic effect on human target cells. The results obtained indicate the need for additional studies on the genotoxicity of these substances and their adverse effects on human health.

Flow cytometric DNA ploidy in salivary gland tumours.

This study on 279 tumours of the salivary glands was conducted to analyse whether the assessment of DNA ploidy by flow cytometry may assist histopathology in discriminating benign from malignant types of tumours. The group of benign tumours included 164 pleomorphic adenomas, 51 Warthin's tumours, 7 basal cell adenomas, 2 lipomas as well as 5 other different tumours. All of the 229 benign tumours were diploid. The malignant tumours consisted of 18 adenoid cystic adenomas, 10 mucoepidermoid carcinomas, 5 acinic cell carcinomas, 5 carcinoma in pleomorphic adenoma as well as of 12 other malignancies belonging to 7 different tumour entities. Twelve of 50 malignant salivary gland tumours were aneuploid. There was no significant relationship between the DNA ploidy status and histopathological grading, lymph node metastasis and local recurrence development, respectively. In three cases which initially were taken for pleomorphic adenomas by routine histological examination, aneuploid cell populations exposed by DNA flow cytometric analysis gave rise to a closer inspection of the suspect lesions. Examination of consecutive slides actually revealed small assemblies of carcinoma cells that required a final diagnosis as non-invasive carcinoma in pleomorphic adenoma. The most obvious value of DNA flow cytometry in salivary gland tumours is thus its contribution to assist histopathology in identifying potentially malignant lesions.

p53-positive tumor-distant squamous epithelia of the head and neck reveal selective loss of chromosome 17.

OBJECTIVES/HYPOTHESIS: The progression of clinically manifest premalignant lesions in the head and neck region to primary or second primary cancer is characterized by numerical and structural chromosomal aberrations. However, many tumors arise from histologically inconspicuous mucosal sites. The objective was to investigate whether chromosomal aberrations can be detected in tumor-distant mucosa and whether they can help predict the risk of second primary malignancy. STUDY DESIGN: A retrospective series of 72 clinically healthy, arbitrarily taken mucosal samples from 53 patients with squamous cell carcinoma of the head and neck was studied. A previous analysis of the p53 protein status had revealed both p53-positive and p53-negative samples. METHODS: The samples were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes specific for the chromosomes 1, 10, 17, and 18. RESULTS: Tumor-distant mucosa generally showed increased numerical chromosomal aberrations, which consisted mainly of monosomies. In the group of patients with p53-positive epithelia, all aberrations including gains of chromosomes (trisomies, tetrasomies) were more frequent. Monosomy for chromosome 17 was most significantly and selectively enhanced in this group (Wilcoxon Scores [rank sum] test, P =.0002). CONCLUSION: Detectable chromosomal aberrations occur in clinically healthy epithelia in patients at risk for secondary head and neck cancer. Specifically, unbalanced chromosome 17 monosomy in conjunction with p53 protein overexpression may constitute a valuable biomarker for progressive "field cancerization."

Follicular dendritic cell sarcoma of the tonsil: report of a rare case.

Follicular dendritic cell tumors are extremely rare. Only 17 cases have been previously described in the literature, and only three of them involved primary tumours of the oral cavity. We describe a new case of the latter, which occurred in a 51-year-old man who sought evaluation for a painless enlargement of his left palatine tonsil. The tonsil was excised, and histologic examination revealed that the tumor was a primary sarcoma that had arisen from the dendritic reticulum cells of the palatine tonsil. Postoperatively, the tumor site was treated with percutaneous irradiation (total dose: 70 Gy). After more than 5 years of follow-up, the patient showed no evidence of recurrence. We also discuss the salient features of the immunohistochemical examination.

Endoreduplication in conjunction with tumor progression in an aneuploid laryngeal squamous cell carcinoma.

We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied DNA flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM DNA index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a DNA index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation.

Cell proliferation and p27Kip1 expression in endophytic schneiderian papillomas.

OBJECTIVE: To clarify epithelial cell proliferation and p27Kip1 expression along the stepwise histological changes from endophytic schneiderian papillomas to associated carcinomas. STUDY DESIGN: Retrospective investigation involved surgical specimens from 58 patients. METHODS: Immunohistochemical assessment involved the nuclear Ki67 antigen expressed in proliferating cells. Further, the cyclin-dependent kinase (cdk) inhibitor p27Kip1 was assessed. Binding of p27Kip1 to the cyclin E-cdk2 complex inhibits this kinase, which results in cell cycle arrest. The expression rates of both proteins were compared between nonpapillomatous nasal mucosa, endophytic schneiderian papillomas, carcinoma in situ, and invasive squamous cell carcinomas. Statistics involved the Wilcoxon and Mann-Whitney u tests. Significance was set at P <.05. RESULTS: Comparable cell proliferation rates were observed between non-papillomatous nasal mucosa and cylindrical cell papillomas. Significant increases in cell proliferation were found along the stepwise series of histological changes involving non-papillomatous nasal mucosa, columnar epithelium in inverted papillomas, transitional and squamous metaplasia in inverted papillomas, and dysplastic inverted papillomas (P <.05, respectively). A tendency toward increased cell proliferation in carcinoma in situ compared with dysplastic inverted papillomas was present; however, this was not statistically significant. The expression rates of p27Kip1 were comparable between non-papillomatous nasal mucosa and all histological subtypes within nondysplastic endophytic schneiderian papillomas. Significantly reduced p27Kip1 expression was found in surface cells in dysplastic compared with non-dysplastic inverted papillomas, as well as in the total number of cells in carcinoma in situ compared with dysplastic inverted papillomas (P <.05, respectively). CONCLUSIONS: Inverted papillomas but not cylindrical cell papillomas show increased cell proliferation compared with nonpapillomatous nasal mucosa. Stepwise increases in cell proliferation accompany the consecutive histological changes within inverted papillomas. Among them, increased cell proliferation along with the development of dysplasia and carcinoma in situ is associated with reduced p27Kip1 expression.

Genotoxicity studies on permethrin, DEET and diazinon in primary human nasal mucosal cells.

Possible genotoxic effects exerted by three widely used pesticides, permethrin, N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells were investigated. Primary nasal mucosa cells were prepared from tissue biopsies taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0 mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects were detected by the alkaline microgel electrophoresis assay ("comet assay"). Within the concentration range, no significant cytotoxic effects were observed, but all three tested pesticides showed a significant genotoxic response that was concentration dependent. More pronounced genotoxic effects were observed in mucosal cells from the middle turbinate than in the inferior turbinate. The results provide some evidence for the potential carcinogenicity of these agents to human nasal mucosal cells. This should be further investigated.

A New Strategy for the Prevention of Noise-induced Hearing Loss(NIHL) / 解放军医学杂志

Noise induced hearing loss(NIHL) is an enormous social and economic cost to the country and represents a vital unmet medical need,for which there is now a solution.Currently there are no FDA-approved products for the prevention of NIHL.The protective device market,consisting of earplugs and earmuffs,is $243 million(in US),with 75% of sales coming from earplugs.While physical hearing protection can reduce sound pressure levels,they do not adequately prevent NIHL in very noisy environments.In addition,these barrier technologies compromise operation/activity requiring speech communication and hearing for personal safety.The past decade has witnessed a remarkable increase in our understanding of the molecular and biochemical mechanisms that determine cell survival and cell death with stress,pathology and aging.We have begun to define the apoptotic and necrotic pathways that lead to cell death,their external environmental and endogenous hereditary initiating factors,the genes and transduction factors that regulate these pathways and with that we have begun to define new interventions that attenuate or prevent cell death and cause cell survival.With this new understanding,now for the first time,we have an opportunity to prevent or treat diseases and disorders previously not possible.One of these disorders that now can be prevented is hearing loss.