B cell zone reticular cell microenvironments shape CXCL13 gradient formation.

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.

Otitis media with effusion.

Otitis media with effusion (OME) is a common problem facing general practitioners, pediatricians and otolaryngologists. This article reviews the etiopathogenesis, epidemiology, presentation, natural history and management of OME. The literature was reviewed by using the PubMed search engine and entering a combination of terms including 'otitis media with effusion', 'epidemiology' and 'management'. Relevant articles were identified and examined for content. What is the take home message? While OME is a very common entity in the pediatric population, the majority of cases will resolve spontaneously. Surgery in the form of grommet insertion, with or without adenoidectomy is the most effective treatment in persistent symptomatic cases.

Acute otitis media.

Acute otitis media (AOM) is a common problem facing general practitioners, paediatricians and otolaryngologists. This article reviews the aetiopathogenesis, epidemiology, presentation, natural history, complications and management of AOM. The literature was reviewed by using the PubMed search engine and entering a combination of terms including 'AOM', 'epidemiology' and 'management'. Relevant articles were identified and examined for content. What is the take-home message? AOM is a very common problem affecting the majority of children at least once and places a large burden on health care systems throughout the world. Although symptomatic relief is often enough for most children, more severe and protracted cases require treatment with antibiotics, especially in younger children.

Chronic otitis media.

Chronic otitis media (COM) is a common problem facing general practitioners, pediatricians and otolaryngologists. This article reviews the aetiopathogenesis, epidemiology, presentation, natural history, complications and management of COM. The literature was reviewed by using the PubMed search engine and entering a combination of terms including "COM", "diagnosis", "incidence", "complications" and "management". Relevant articles were identified and examined for content. What is the "take-home" message for the clinician? COM is a common problem with various sub-categories according to the disease state. It most commonly presents with painless otorrhoea and hearing loss. Treatment options vary according to the activity and type of disease encountered. COM carries significant patient morbidity.

Interventions for adult Eustachian tube dysfunction: a systematic review.

BACKGROUND: Eustachian tube dysfunction (ETD) is the inability of the Eustachian tube (ET) to adequately perform at least one of its functions: to protect the middle ear from sources of disease, to ventilate the middle ear, and to help drain secretions away from the middle ear. There are a number of treatment options for ETD, but there is little consensus about management. OBJECTIVES: To determine the clinical effectiveness of interventions for adult ETD and to identify gaps in the evidence to inform future research. DATA SOURCES: Twelve databases were searched up to October 2012 for published and unpublished studies in English (e.g. MEDLINE from 1946, EMBASE from 1974, Biosis Previews from 1969 and Cumulative Index to Nursing and Allied Health Literature from inception). References of included studies, relevant systematic reviews and regulatory agency websites were checked. REVIEW METHODS: A systematic review was undertaken. Controlled studies evaluating prespecified treatments for adult patients diagnosed with ETD were eligible. Uncontrolled studies with at least 10 participants were included for interventions where no controlled studies were found. Outcomes included change in symptoms severity/frequency (primary outcome), quality of life, middle ear function, hearing, clearance of middle ear effusion, early ventilation tube extrusion, additional treatment, adverse events and complications. All aspects of the review process were performed using methods to reduce reviewer error and bias. Owing to heterogeneous data, a quantitative synthesis could not be performed, and results were reported in a narrative synthesis. RESULTS: Nineteen studies were included: three randomised controlled trials (RCTs) and two non-RCTs evaluating pharmacological interventions or mechanical devices for middle ear pressure equalisation; and 13 case series and one retrospective controlled before-and-after study evaluating surgical interventions. None was conducted in the UK. All studies were small (11 to 108 participants). Most non-surgical studies reported including mixed populations of adults and children. All except two studies were at high risk of bias, and subject to multiple limitations. Based on a single RCT, nasal steroids showed no improvement in symptoms or middle ear function for patients with otitis media with effusion and/or negative middle ear pressure. Very short-term improvements in middle ear function were observed in patients receiving directly applied topical decongestants or a combination of antihistamine and ephedrine. Single trials found two pressure equalisation devices were each associated with significant short-term improvements in symptoms, middle ear function and/or hearing. Eustachian tuboplasty (seven case series) and balloon dilatation (three case series) were associated with improved outcomes. Positive results were also reported for myringotomy (two case series), directly applied topical steroids (one case series) and laser point coagulation (one controlled before-and-after study). High rates of co-interventions were documented. Minor complications of surgery and pharmacological treatments but no serious adverse effects were reported. LIMITATIONS: The evidence was limited in quantity and overall was of poor quality. No data were identified on several interventions despite extensive searches. CONCLUSIONS: It is not possible to draw conclusions regarding the effectiveness of any of the interventions for the treatment of adults with an ETD diagnosis, and there is insufficient evidence to recommend a trial of any particular intervention. Further research is needed to address lack of consensus on several issues, including the definition of ETD in adults, its relation to broader middle ear ventilation problems and clear diagnostic criteria. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003035. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24.

Five single nucleotide polymorphisms (SNPs) associated with thyroid cancer (TC) risk have been reported: rs2910164 (5q24); rs6983267 (8q24); rs965513 and rs1867277 (9q22); and rs944289 (14q13). Most of these associations have not been replicated in independent populations and the combined effects of the SNPs on risk have not been examined. This study genotyped the five TC SNPs in 781 patients recruited through the TCUKIN study. Genotype data from 6122 controls were obtained from the CORGI and Wellcome Trust Case-Control Consortium studies. Significant associations were detected between TC and rs965513A (p=6.35×10(-34)), rs1867277A (p=5.90×10(-24)), rs944289T (p=6.95×10(-7)), and rs6983267G (p=0.016). rs6983267 was most strongly associated under a recessive model (P(GG vs GT + TT)=0.004), in contrast to the association of this SNP with other cancer types. However, no evidence was found of an association between rs2910164 and disease under any risk model (p>0.7). The rs1867277 association remained significant (p=0.008) after accounting for genotypes at the nearby rs965513 (p=2.3×10(-13)) and these SNPs did not tag a single high risk haplotype. The four validated TC SNPs accounted for a relatively large proportion (∼11%) of the sibling relative risk of TC, principally owing to the large effect size of rs965513 (OR 1.74).

Inferior turbinate surgery for nasal obstruction in allergic rhinitis after failed medical treatment.

BACKGROUND: Allergic rhinitis is a highly prevalent disease that results from an IgE-mediated hypersensitivity reaction of the nasal mucosa to inhaled allergens. It is primarily treated by allergen avoidance and medical treatment, but when these measures fail to control symptoms then surgery to the inferior turbinates of nose is often performed. It is unclear whether these procedures are beneficial in the long term or indeed whether the risks outweigh the benefits. OBJECTIVES: To assess the effectiveness of inferior turbinate surgery on unrelieved or partially relieved nasal obstruction in patients after maximal medical treatment of proven allergic rhinitis, to compare the results using different surgical techniques and to measure short and long-term results. SEARCH STRATEGY: We searched the following databases from their inception for published, unpublished and ongoing trials: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; CNKI; mRCT (Current Controlled Trials); ClinicalTrials.gov; ISRCTN; ICTRP (International Clinical Trials Registry Platform); Cambridge Scientific Abstracts; Google and additional sources for published and unpublished trials. We modelled subject strategies for databases on the search strategy designed for CENTRAL. The date of the most recent search was 6 July 2010. SELECTION CRITERIA: Randomised controlled trials of inferior turbinate surgery versus continued medical treatment for proven allergic rhinitis, or comparisons between one technique of inferior turbinate surgery versus another technique, after maximal medical treatment. DATA COLLECTION AND ANALYSIS: Both authors independently screened the search results and assessed the full text of potentially relevant studies. We attempted to contact trial authors for additional information. MAIN RESULTS: There were no studies that fulfilled the inclusion criteria of the review. AUTHORS' CONCLUSIONS: This review highlights the need for randomised controlled trials to evaluate the role of inferior turbinate surgery for nasal obstruction in allergic rhinitis after failed medical treatment. Future trials needs to be rigorous in design and delivery, separate adults from paediatric patients, not combine allergic with non-allergic patients and last long enough to determine long-term results and complications.

Evaluation of patient benefit from nasal septal surgery for nasal obstruction.

The aim of this study was to determine the usefulness of Glasgow Benefit Inventory (GBI) to assess the patient's perception of benefit derived from nasal septal surgery for nasal obstruction. Seventy-five patients undergoing septal surgery +/- inferior turbinate reduction for nasal obstruction were included in the study. A cross-sectional questionnaire survey was performed. The patients completed the Glasgow Benefit Inventory, indicated their pre-operative and post-operative nasal symptoms and subjective improvement in nasal obstruction. There was a highly significant correlation (P<0.001) between the GBI total score, subjective post-operative nasal obstruction, post-operative nasal symptoms score and change in nasal symptoms score. The mean standardised GBI score was 2.96 (S.D.=0.28, S.E.M.=0.03) and 3.26 (S.D.=0.18, S.E.M.=0.03) in patients with and without post-operative nasal obstruction, respectively. The mean difference was 0.29 (S.E.D.=0.06, 95% CI=0.16 to 0.42, P<0.001). Thus the GBI discriminates between above and below criteria in this group of patients. Multiple regression analysis showed that subscale scores of GBI explain about 40% of the variance in the outcome, which is highly significant (R2=0.39, F=15, d.f.=3.70, P<0.001). We conclude that GBI is a valuable tool for the assessment of benefit from nasal septal surgery for nasal obstruction and may be applicable in clinical practice.

A comparison of patient satisfaction with conventional and nurse led outpatient follow-up after grommet insertion.

OBJECTIVE: The need to reduce costs while providing a first class service has led to the expansion in the role of nurses in otolaryngology practice in the National Health Service (NHS) in recent years. The aim of this study was to compare patient satisfaction with conventional and nurse led follow-up after grommet insertion. The hypothesis was that patient satisfaction is much greater with doctor led conventional follow-up as compared with nurse led out-patient follow-up. METHODS: The study was performed using a questionnaire survey using a validated patient satisfaction questionnaire. RESULTS: Our results indicate that there is no statistically significant difference in the mean factorial scores for interpersonal skills and technical competence, physical surroundings, and convenience between the conventional and nurse led follow-up clinic. The overall patient satisfaction was higher with nurse led grommet follow-up clinic than with conventional doctor led out-patient follow-up. This was statistically significant (Mann-Whitney U = 1357.50, Z = 02.39, P = 0.01). The waiting time in out-patients was also significantly less in the nurse led grommet clinic. CONCLUSIONS: We conclude that nurses provide a high quality service resulting in high patient satisfaction. Nurse led grommet follow-up clinic has the potential for substantial reduction in outpatient access times in the NHS.

Upper aerodigestive tract squamous cell carcinoma: distribution of extracapsular spread and soft tissue deposits in the neck.

OBJECTIVE: Extracapsular spread (ECS) and soft tissue deposits (STD) of squamous cell carcinoma (SCC) in the neck of patients with metastatic SCC of the upper aerodigestive tract have been shown to adversely affect actuarial and disease-free survival. No studies to date have detailed the distribution of ECS and STD within the neck. MATERIAL AND METHODS: A total of 215 neck dissections from 155 patients were prospectively collected and analysed for the presence of both STD and ECS. As no classification for STD exists, their distribution was classified according to the nodal levels used for classification of cervical lymph nodes as described by the Memorial Sloan-Kettering Cancer Center. RESULTS: A total of 81 neck dissections from 59 patients were found to have either metastatic lymph nodes with ECS, STD or both. The distribution of lymph node metastasis, ECS and STD was very similar. Level II was most frequently affected, with Levels III and IV being affected less frequently. There were very few lymph node metastases to Level V, and this level contained no evidence of either ECS or STD. CONCLUSION: The method of pathological assessment of neck dissection specimens and reporting on the presence of ECS and STD has not been formalized. By analysing neck dissection specimens in the manner described we can report on the presence or absence of ECS and STD with increased accuracy. This has considerable implications for patient management.

Soft tissue deposits in neck dissections of patients with head and neck squamous cell carcinoma: prospective analysis of prevalence, survival, and its implications.

BACKGROUND: Soft tissue deposits of squamous cell carcinoma in the necks of patients with squamous cell carcinoma of the upper aerodigestive tract may represent either total effacement of a lymph node by carcinoma or extralymphatic deposits of carcinoma. There are few reports of their clinical or prognostic significance. METHODS: Data from 215 neck dissections from 155 patients with squamous cell carcinoma of the upper aerodigestive tract were studied prospectively to assess the prevalence of soft tissue deposits within the neck. The case notes of these patients were subsequently reviewed to analyze the effect on both the overall survival and recurrence-free survival. RESULTS: The prevalence rate for soft tissue deposits occurring alone was 10.3%; the prevalence rate for soft tissue deposits occurring with extracapsular spread was 13.5%. The overall prevalence rate for soft tissue deposits was 23.9%. There was a statistically significant reduction in actuarial and recurrence-free survival in patients with soft tissue deposits compared with patients with pathologically node-negative necks (P=.001), and in patients with soft tissue deposits compared with those with pathologically node-positive necks without extracapsular spread (P=.001). No statistically significant differences were found between patients with soft tissue deposits and patients with pathologically node-positive necks with extracapsular spread, for actuarial survival or recurrence-free survival. CONCLUSIONS: In this series, soft tissue deposits were associated with an aggressive clinical course and poor survival. It is therefore important that histopathologists agree on a uniform terminology when reporting soft tissue deposits and actively look for their presence when examining neck dissection specimens.

Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits.

BACKGROUND: Literature regarding the prognostic significance of extracapsular spread and soft tissue deposits in cervical lymph node metastases of squamous cell carcinoma of the upper aerodigestive tract shows variable results. METHODS: We analyzed 215 prospectively collected neck dissections from 155 patients with upper aerodigestive tract squamous cell carcinoma to assess the prevalence of extracapsular spread and soft tissue deposits and to assess their effect on survival. RESULTS: Both extracapsular spread and soft tissue deposits significantly reduced survival (actuarial and recurrence free) compared with pN0 necks (p <.001) and pN+ve necks without extracapsular spread (p <.0025). There was no statistically significant difference between pN+ve necks without soft tissue deposits or extracapsular spread compared with those with pN0 necks (p =.24). Multivariate analysis revealed comparable results. CONCLUSIONS: Microscopic and macroscopic extracapsular spread and soft tissue deposits are of prognostic significance for survival and recurrence-free survival in patients with upper aerodigestive tract squamous cell carcinoma.

Cervical metastases in upper aerodigestive tract squamous cell carcinoma: histopathologic analysis and reporting.

BACKGROUND: Accurate histopathologic assessment of neck dissections is of paramount importance. Retrospective analyses of the distribution of lymph node metastases have formed the rationale for elective neck dissection. However, standard techniques for examination of neck dissection specimens may have difficulty in correctly recognizing node levels and may also miss micrometastases, microscopic extracapsular spread, and soft tissue deposits. METHODS: Two hundred thirty-seven neck dissections were performed in 173 patients with squamous cell carcinoma of the upper aerodigestive tract between August 1995 and November 2000. The neck dissections were separated into node levels peroperatively, sectioned at 6 microm thickness, and stained with hematoxylin and eosin. RESULTS: Eleven thousand three hundred forty-nine lymph nodes were identified and examined. The mean yield per neck dissection was 50.4 (range, 12-131); 21.4% had extracapsular spread, 11.0% had soft tissue deposits, and 13.3% had both. A third of the metastatic nodes were 3 mm or less in diameter. CONCLUSIONS: The accurate pathologic staging of the neck in patients with upper aerodigestive tract squamous cell cancer is important for providing prognostic information and optimizing the treatment plan for the patient. Accurate staging also allows the changing patterns of disease to be monitored and allows equitable comparison of patients in clinical trials and among surgical units.

Cervical node metastases in oropharyngeal squamous cell carcinoma: prospective analysis of prevalence and distribution.

The treatment of cervical lymph node metastases is an important part of the management of oropharyngeal squamous cell cancer. Metastases are already clinically present in 61 per cent (+ or -2.6 per cent) of patients at presentation. Previous studies concerning the prevalence and distribution of neck node metastases in oropharyngeal carcinoma have been retrospective, and little or no information is available about the histopathological methods used. This study has prospectively analysed 85 neck dissection specimens in 72 consecutive patients with squamous cell carcinoma of the oropharynx, both with clinically N(0) and N+ve necks, to identify the prevalence and distribution of cervical metastases. We have used a technique to separate the neck dissection into nodal levels per-operatively, and then embedded the entire specimen for histological examination to avoid missing metastatic disease in small lymph nodes (<3mm diameter).