Treatment of juvenile recurrent parotitis with irrigation therapy without anesthesia.

PURPOSE: No standardized treatment regimen exists for juvenile recurrent parotitis (JRP). The investigators hypothesized that irrigation with saline only without local anesthesia will be an effective and beneficial option. METHODS: Using a retrospective study design, a series of children with typical symptoms of JRP who were treated with at least one irrigation therapy were evaluated. This treatment consisted of irrigation of the affected gland with 3-10 ml saline solution without any type of anesthesia. The outcome variables were patient/parent satisfaction, frequency and duration of acute JRP episodes, and the need for antibiotics before and after irrigation therapy. RESULTS: The case series was composed of six boys aged 3.3-7.7 years who experienced one to eight sessions of irrigation therapy. The period of follow-up was 9-64 months. We observed a total resolution of symptoms in two children and an improvement in the other four. No relevant side effects were seen. CONCLUSION: Our results suggest that irrigation therapy is a reasonable, simple, and minimally invasive treatment alternative for JRP. In contrast to sialendoscopy or sialography, there is no need for general anesthesia or radiation exposure.

Trauma Can Induce Telangiectases in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease of the fibrovascular tissue resulting in visceral vascular malformations and (muco-) cutaneous telangiectases with recurrent bleedings. The mechanism behind the disease is not fully understood; however, observations from HHT mouse models suggest that mechanical trauma may induce the formation of abnormal vessels. To assess the influence of environmental trauma (mechanical or light induced) on the number of telangiectases in patients with HHT, the number of telangiectases on the hands, face, and lips were counted on 103 HHT patients possessing at least three out of four Curaçao criteria. They were then surveyed for information concerning their dominant hand, exposure to sunlight, and types of regular manual work. Patients developed more telangiectases on their dominant hand and lower lip (Wilcoxon rank sum test: p < 0.001). Mechanical stress induced by manual work led to an increased number of telangiectases on patients' hands (Mann-Whitney U test: p < 0.001). There was also a positive correlation between sun exposure and the number of telangiectases on the lips (Mann-Whitney U test: 0.027). This study shows that mechanical and UV-induced trauma strongly influence the formation of telangiectases in HHT patients. This result has potential implications in preventive measures and on therapeutic approaches for HHT.

Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas.

Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors. Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device. Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers. Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism.

Modeling the Test-Retest Statistics of a Localization Experiment in the Full Horizontal Plane.

HYPOTHESIS: Two approaches to model the test-retest statistics of a localization experiment basing on Gaussian distribution and on surrogate data are introduced. Their efficiency is investigated using different measures describing directional hearing ability. BACKGROUND: A localization experiment in the full horizontal plane is a challenging task for hearing impaired patients. In clinical routine, we use this experiment to evaluate the progress of our cochlear implant (CI) recipients. Listening and time effort limit the reproducibility. METHODS: The localization experiment consists of a 12 loudspeaker circle, placed in an anechoic room, a "camera silens". In darkness, HSM sentences are presented at 65 dB pseudo-erratically from all 12 directions with five repetitions. This experiment is modeled by a set of Gaussian distributions with different standard deviations added to a perfect estimator, as well as by surrogate data. Five repetitions per direction are used to produce surrogate data distributions for the sensation directions. To investigate the statistics, we retrospectively use the data of 33 CI patients with 92 pairs of test-retest-measurements from the same day. RESULTS: The first model does not take inversions into account, (i.e., permutations of the direction from back to front and vice versa are not considered), although they are common for hearing impaired persons particularly in the rear hemisphere. The second model considers these inversions but does not work with all measures. CONCLUSION: The introduced models successfully describe test-retest statistics of directional hearing. However, since their applications on the investigated measures perform differently no general recommendation can be provided. The presented test-retest statistics enable pair test comparisons for localization experiments.

The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma.

Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.

Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany.

The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.

[Cartilage vs. temporal fascia as graft material]. / Knorpel vs. temporale Faszie als Transplantatmaterial.

So far, comparative studies have shown no significant audiological difference between cartilage and fascia grafts. In this retrospective study, the Turkish scientists E E Callioglu et al. examined next audiological results and morphological results after surgical cartilage and fascial tympanoplasty in patients with comparable preoperative hearing and middle ear pathology.

Perioperative image-adapted brachytherapy for the treatment of paranasal sinus and nasal cavity malignancies.

PURPOSE: Sinonasal malignancies are a rare group of cancers often associated with late presentation and poor prognosis. In the past, there was little progress regarding survival rate, and often, multimodal treatment regimens are required. The aim of this study was to evaluate the clinical outcome of perioperative image-adapted brachytherapy (IABT) as part of a multidisciplinary treatment regimen for the therapy of sinonasal cancer. METHODS AND MATERIALS: Since 2006, patients with sinonasal cancer at the University Hospital of Schleswig-Holstein Campus Luebeck, Germany, were offered a multimodal treatment concept including head and neck surgery, perioperative IABT with or without external beam radiation therapy, and chemotherapy. In a retrospective study, such patients were analyzed for survival rate, tumor control, and toxicity of the interdisciplinary treatment. RESULTS: Thirty-five consecutive patients were analyzed. The majority of patients (63%) were treated for a primary tumor and 62% presented with tumor Stages III-IV. The mean follow-up time with IABT was 28 months. Overall survival estimate was 72% after 3 years. Disease-specific survival, disease-free survival, and local control rates were 83%, 63%, and 67%, respectively. On univariate analysis, a significant better disease-free survival rate was found in patients treated for primary, but not recurrent, sinonasal cancer (p = 0.006). The overall treatment toxicities were mainly classified Grade I. CONCLUSIONS: Interdisciplinary perioperative IABT is associated with excellent locoregional control and survival rates. IABT is well tolerated and shows low toxicity. Furthermore, visual acuity can be preserved in advanced cases. The implementation of perioperative IABT into multimodal treatment regimens improves the oncologic outcome.

The Young's procedure for severe epistaxis from hereditary hemorrhagic telangiectasia.

BACKGROUND: Surgical treatment of epistaxis in hereditary hemorrhagic telangiectasia (HHT) has historically been managed with the laser procedure or the septodermoplasty procedure. For transfusion-dependent patients with severe epistaxis we have been performing the Young's procedure or surgical closure of the nostrils. The objective of this study was to report treatment of severe epistaxis related to HHT with the Young's procedure and assess patient outcome. METHODS: Patients with severe iron or blood transfusion-dependent epistaxis who underwent a Young's procedure in three otolaryngology HHT centers were reviewed. Patients were evaluated for postoperative epistaxis and subjective outcome. RESULTS: Forty-three patients underwent a Young's procedure for severe epistaxis and were observed for a mean of 34 months. The procedure was well tolerated by all patients and 30 of 36 patients (83%) experienced complete cessation of bleeding after the Young's procedure. Patients had a mean increase in hemoglobin of 4.68 g/dL after the procedure. The average Glasgow Benefit Inventory score after surgery was 43.56. No patients requested a reversal of the procedure. CONCLUSION: The Young's procedure is a safe and efficacious procedure with complete cessation of epistaxis in most patients with severe epistaxis and HHT.

Pathogenic Mechanisms and In Vitro Diagnosis of AERD.

Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis, nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in asthmatics following the exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway mucosa as well as blood cells. Genetic and functional metabolic studies on vital and non-vital cells pointed to the variability and the crucial role of lipid mediators in disease susceptibility and their response to medication. Eicosanoids, exemplified by prostaglandin E(2) (PGE(2)) and peptidoleukotrienes (pLT), are potential metabolic biomarkers contributing to the AERD phenotype. Also other mediators are implicated in the progress of AERD. Considering the various pathogenic mechanisms of AERD, a multitude of metabolic and genetic markers is suggested to be implicated and were introduced as potential biomarkers for in vitro diagnosis during the past decades. Deduced from an eicosanoid-related pathogenic mechanism, functional tests balancing PGE(2) and pLT as well as other eicosanoids from preferentially vital leukocytes demonstrated their applicability for in vitro diagnosis of AERD.

Ultrasound-guided mechanical fragmentation of sialoliths (sonoguide forceps).

BACKGROUND: Little data about the efficacy and limitations of ultrasound-guided mechanical intraductal stone fragmentation and removal of sialoliths (Sonoguide Forceps) exist. METHODS: This was a chart review of patients treated within the last 4 years at 2 tertiary care centers. RESULTS: Sonoguide Forceps were used as a second-line treatment in 22 patients with sialolithiasis. Ten patients were free of stones and symptoms afterwards (7 of 17 submandibular, 2 of 4 parotid, 1 of 1 sublingual). Six patients were primarily treated for parotid sialolithiasis, 4 with successful stone retrieval. The reasons for failure were a lack of accessibility to the stone by the forceps (n = 9), the impossibility of grasping the stone (n = 5), and/or the concomitant grabbing of soft tissue together with the stone (n = 3). CONCLUSION: The efficacy of Sonoguide Forceps as both a secondary and primary treatment modality makes it an interesting, simple, and inexpensive therapeutic alternative. Relevant parameters for treatment success include the size and position of the stones.

Endoscopic laser resection of laryngeal cancer: is it oncologically safe? Position statement from the American Broncho-Esophagological Association.

The purpose of this report is to summarize the salient points made during a panel discussion at the 88th Annual Meeting of the American Broncho-Esophagological Association about the efficacy and oncological safety of endoscopic laser treatment of laryngeal cancer. Guidelines for endoscopic laser management of early glottic and supraglottic cancer, including contraindications for this treatment modality, are presented. On the basis of all currently available data, the panel, which critically considered the question of oncological safety, is of the opinion that endoscopic laser resections are oncologically safe when applied judiciously and by a skilled oncological surgeon. Relative contraindications for endoscopic laser resection of laryngeal cancer include instances in which the whole tumor cannot be visualized; large tumors that require removing too much of the functional laryngeal unit, severely decreasing airway protection and leading to aspiration; and cartilage invasion. Specific contraindications for supraglottic cancer include bilateral arytenoid involvement and direct extension into the neck.

Overexpression of p68 mRNA in head and neck squamous cell carcinoma cells.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are aggressively growing tumors with only marginal improvement in outcome despite ongoing developments in treatment protocols. This problem has been associated with a lack of therapy individualization on tumor biological properties. MATERIALS AND METHODS: mRNA expression profiles of HNSCC and normal epithelial cells were compared in order to identify genes associated with cancer formation. Differential display was used to trace gene fragments showing differential expression in HNSCC cells, which were than isolated, re-amplified, cloned and sequenced. RESULTS: A 131-bp-long fragment was identified to be overexpressed in HNSCC cells that revealed a 99.3% homology with p68 mRNA. The differential expression was confirmed by Northern hybridization. CONCLUSION: The data presented suggest an involvement of p68 in the process of malignant transformation or progression of HNSCC.

Nasal RANTES and eotaxin production pattern in response to rhinovirus infection.

Tissue eosinophilia is a hallmark of nasal polyposis and its pathogenesis is an area of high interest. RANTES and eotaxin are both known to recruit eosinophils, however, the mechanisms triggering their induction are still uncertain, and viral infections have been suggested to be involved in this process. Therefore, we investigated whether rhinovirus infection is a stimulus for RANTES and eotaxin expression and production. Fibroblasts were cultured from healthy nasal mucosa obtained during endonasal surgery. Cultured cells were infected with human rhinovirus-16 for one to 72 hours. Following total RNA isolation and reverse transcription, RANTES- and eotaxin-mRNA levels were analyzed. In addition, RANTES and eotaxin secretion was measured in culture supernatants by means of an ELISA. Rhinovirus infection induces RANTES-mRNA expression as early as one hour after infection, persisting for up to 72 hours. Eotaxin-mRNA profiles did not alter significantly from control. Protein production was confirmatory for both chemokines, indicating distinct translational latency. Our data suggest that RANTES functions as a host defence mechanism responding to rhinovirus infection, thus supporting a linkage between rhinovirus infections and the pathogenesis of nasal polyposis.

Comparison of the glottic closure reflex in traditional "open" versus endoscopic laser supraglottic laryngectomy.

OBJECTIVES: Cancer of the supraglottic larynx may be surgically treated with either traditional "open" supraglottic laryngectomy (OSL) or endoscopic laser supraglottic laryngectomy (ELSL). Pharyngeal dysphagia is a well-documented consequence of traditional OSL from which near-normal swallowing characteristically recovers 14 to 40 days after surgery. Conversely, ELSL results in the resumption of serviceable swallowing within 2 to 7 days after surgery. METHODS: A prospective assessment of the glottic closure reflex in 6 consecutive patients who had ELSL was performed by fiberoptic endoscopic evaluation of swallowing with sensory testing. RESULTS: All 6 patients with ELSL demonstrated an intact glottic closure reflex both before surgery and 48 to 72 hours after surgery. In contrast, 7 of 8 historical control patients who had OSL demonstrated a persistent absence of the glottic closure reflex 3 weeks to 12 years later. CONCLUSIONS: Although a number of clinical factors influence swallowing recovery, one important factor separating our patient groups was the preservation of the glottic closure reflex in patients who underwent endoscopic laser resection. Because the loss of the glottic closure response persists for years after traditional OSL, it is concluded that the sensory field deficit caused by superior laryngeal nerve section is largely not recoverable; however, compensatory mechanisms remain important in serviceable recovery, even if delayed after operation. Indeed, preservation of the glottic closure response appears to enhance swallowing recovery when equivalent compensatory mechanisms are used.

Association between human beta defensin expression and cholesteatoma formation.

OBJECTIVE: To investigate an association between human beta defensin (hBD) expression and cholesteatoma formation. METHODS: hBD-2 mRNA expressions were assessed in healthy external acoustic meatus skin organ cultures before and after stimulation with Pseudomonas aeruginosa. In addition, hBD-1 and hBD-2 protein production of stimulated and non-stimulated external acoustic meatus skin was visualized by immunohistochemistry. Furthermore, hBD-1 and hBD-2 mRNA expression was analyzed in 25 external acoustic meatus skin, 29 cholesteatoma, and 18 non-cholesteatoma control samples. Non-stimulated meatal tissue preparation did not express hBD-2, whereas incubation with P. aeruginosa demonstrated hBD-2 induction. RESULTS: The hBD-1 mRNA expression was detected in cholesteatoma (14/17), meatal skin, and middle ear mucosa (11/18). hBD-2 mRNA expression was shown in eight cholesteatoma (28.5%) and in three middle ear mucosa tissue samples (37.5%). CONCLUSION: Our data suggest constitutional hBD-1 and inducible hBD-2 expression in chronic middle ear infection and cholesteatoma. Failure of hBD-1 and hBD-2 expression might dispose to exacerbation of cholesteatoma disease. The organ culture model of the external acoustic meatus skin is effective in order to evaluate germ stimulation experiments.

Defensin and chemokine expression patterns in the palatine tonsil: a model of their local interaction.

Defensins and chemokines are an essential part of the immune response mechanisms in the head and neck mucosa. This work investigates their correlation and their expression pattern in tonsillar disease. Forty-four tonsil tissue samples were obtained from patients who underwent tonsillectomy between 1998 and 1999 for chronic tonsillitis with (n =9) and without (n =25) inflammatory infiltrates and hyperplasia of the tonsil (n =10). Defensin (hBD-1, hBD-2, HNP-1 and HNP-4) and chemokine (RANTES, eotaxin, eotaxin-2, MCP-3, MCP-4 and IL-8) mRNA expressions were analyzed by SQRT-PCR. HNP-4 and eotaxin-2 expressions were positively correlated (P <0.05) in the acute tonsillitis group. HBD-2 and MCP-3 expressions were positively correlated in the hyperplastic tonsils group. Within all groups together, HNP-4 and RANTES expressions were highly positively correlated (P <0.01), and HNP-1 and hBD-2 were positively correlated with IL-8 expressions. Immunohistochemistry demonstrated eotaxin-1 as well as IL-8 production to be predominantly located within the lymphoid follicles and submucosa. RANTES production was shown in the epithelial lining and perivascular tissue. The expression of hBD-1 and hBD-2 was limited to the epithelial lining. Our data support an association between the innate and acquired immune systems on the defensin-chemokine level. The finding of positively correlated hBD-2 and IL-8 expression is biologically relevant because of the proximity of hBD-2 (epithelium) and IL-8 (submucosa) release, as well as the synergistic support of the Th1 system. In addition, our data suggest RANTES as a first-line mediator of perivascular leukocyte recruitment.

Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas.

BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC). METHODS: Of 48 laryngeal squamous cell carcinoma (LSCC) biopsies and 10 HNSCC cell lines, mRNA was isolated, reversely transcribed, and subjected to polymerase chain reaction (PCR) amplifying MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, and TIMP-2. Silver nitrate-stained gel electrophoresis demonstrated MMP and TIMP expression status. Exemplary immunohistochemistry and zymography confirmed translation and enzyme activity. RESULTS: Densitometric analysis revealed MMP-2 expression and lymph node metastases to be positively and TIMP-1 and TIMP-2 to be negatively correlated with lymph node metastases. TIMP-2 expression and tumor size were negatively correlated. MMP-1, MMP-9, and MMP-10 expression were not correlated to metastasis formation or tumor size. CONCLUSIONS: Our results suggest that MMP-2 expression enhances, whereas TIMP-1 and TIMP-2 both suppress, cancer spread in LSCC.

Quality of life assessment in otorhinolaryngology. History, measures and methods.

The term "quality of life" was first mentioned in 1920 in economic journals and became an issue in the early 1960s in North America. Initially it became accepted in social sciences and later in medicine. The development of generic measures began in the early 1970s and continues today. Disease-specific measures were introduced in the 80th and 90th. During that time methodological studies were implemented and additional emphasis was put on analytic approaches, interpretation of scale scores and cultural including language issues. In ENT study groups began slowly with research in the 1980s and expanded during the 1990s. Today Quality of Life is an accepted part of medical research and covers a broad field of issues. Study groups in ENT work on allergy treatment, oncology and economic aspects of Quality of Life research as well as patient's perception of hearing devices. Future challenges include conceptualization and testing of theoretical models, further refinement of individualized measures for use in routine clinical practice and the inclusion of Quality of Life information in health databases. This article describes the methodological concept, the history of Quality of Life assessment in ENT and gives a detailed overview on current measures.