Joanne Rimmer

Olfactory neuroblastoma: A 35‐year experience and suggested follow‐up protocol

Objectives/Hypothesis To validate a follow-up protocol based on the long-term outcomes and recurrence rates in patients who have undergone surgical treatment for olfactory neuroblastoma. Methods A prospective review of all patients treated for olfactory neuroblastoma at our institution over a 35-year period. Results Ninety-five patients were treated from 1978 to 2013, with craniofacial (65 patients) or endoscopic resection (30 patients). Duration of follow-up ranged from 1 to 309 months (mean, 88.66 months). Fifty-six patients were alive and well, and 13 were alive with recurrent disease. Twenty-one patients had died of disease, and three had died of intercurrent disease. Overall survival was 83.4% at 5 years and 76.1% at 10 years. Disease-free survival at 5 years was 80% and at 10 years was 62.8%. A Cox regression analysis showed orbital extension and intracranial involvement to be significant independent factors affecting outcome. Local and regional recurrence occurred after an average of 49 months but with a range of 3 to 233 months. Conclusions In our series, olfactory neuroblastoma most commonly recurred within the first 4 years but can recur very late, after 19.4 years in one case. There is currently no universally accepted follow-up regime, but even late recurrence is eminently treatable. We therefore propose a protocol for lifelong follow-up with both clinical examination and serial imaging, including the neck and entire intracranial compartment. Level of Evidence 4 Laryngoscope, 124:1542–1549, 2014To validate a follow‐up protocol based on the long‐term outcomes and recurrence rates in patients who have undergone surgical treatment for olfactory neuroblastoma.

IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa.

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown. Objective We sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP. Methods Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Control nasal biopsy specimens and blood were obtained from healthy volunteers. Tissue was cultured in a short-term explant model. T-cell surface phenotype/intracellular cytokines were assessed by means of flow cytometry. T-cell receptor variable β-chain analysis was performed with the immunoSEQ assay. Microarrays were performed for gene expression analysis. Results IL-25 receptor (IL-17RB)–expressing TH2 effector cells were identified in nasal polyp tissue but not the healthy nasal mucosa or periphery. IL-17RB+CD4+ polyp–derived TH2 cells coexpressed ST2 (IL-33 receptor) and responded to IL-25 and IL-33 with enhanced IL-5 and IL-13 production. Within IL-17RB+CD4+ T cells, several identical T-cell receptor variable β-chain complementarity-determining region 3 sequences were identified in different subjects, suggesting clonal expansion driven by a common antigen. Abundant IL-17–producing T cells were observed in both healthy nasal mucosal and polyp populations, with TH17-related genes the most overexpressed compared with peripheral blood T cells. Conclusion IL-25 and IL-33 can interact locally with IL-17RB+ST2+ polyp T cells to augment TH2 responses in patients with CRSwNP. A local TH17 response might be important in healthy nasal mucosal immune homeostasis.

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps

Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin‐exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti‐SAEs. Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity‐determining regions (CDRs) or framework regions. Methods: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE‐specific B cells from the nasal polyps of 3 patients with aspirin‐exacerbated respiratory disease by using fluorescence‐activated cell sorting. Recombinant antibodies with “matched” heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen‐binding fragments. IgE activities were tested in basophil degranulation assays. Results: Thirty‐seven SAE‐specific, IgG‐ or IgA‐expressing B cells were isolated and yielded 6 anti‐SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti‐SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti‐SEE mediated SEE‐induced basophil degranulation, and IgG1 or antigen‐binding fragments of each anti‐SEE enhanced degranulation by the other anti‐SEE. Conclusions: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti‐SEE IgE in anti‐SEE IgE‐Fc&egr;RI complexes. Anti‐SEE IgG1s can enhance the activity of anti‐SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as “superantibodies” through CDRs and framework regions to SEEs in SEE–anti‐SEE IgE‐Fc&egr;RI complexes.

Eosinophilic angiocentric fibrosis of the nose and sinuses

BACKGROUND Eosinophilic angiocentric fibrosis is a rare benign disorder of the upper respiratory tract. It is slow growing and progressive, with characteristic histological appearances. METHODS We report the largest single-institution case series of sinonasal eosinophilic angiocentric fibrosis to date, comprising nine patients. The current literature is reviewed, showing emerging evidence that this condition may belong to the immunoglobulin G4-related disease spectrum. RESULTS The series comprised five female and four male patients, with a mean age at presentation of 53 years. All were treated surgically. Six patients had no signs of recurrent disease after an average of 8.5 years. One patient went on to develop granulomatosis with polyangiitis (Wegeners granulomatosis), which required immunosuppressive therapy. CONCLUSION The first-line management of this rare condition is complete surgical excision. Chronic granulomatous conditions, including granulomatosis with polyangiitis, should be excluded before a diagnosis is made, and patients should be carefully followed.

A Modified Technique for Septodermoplasty in Hereditary Hemorrhagic Telangiectasia

INTRODUCTION Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant vascular disease with an incidence of approximately 1:5000. Diagnosis is based on the international consensus clinical Curacao criteria. It is characterized by mucocutaneous telangiectasia and visceral arteriovenous malformations, with recurrent epistaxis being the predominant symptom for most patients. The genetic abnormality, of which there are various, leads to inappropriate maturation of blood vessels in response to angiogenic stimuli. Fragile vessel walls make the nasal lesions prone to hemorrhage, even in response to minor trauma such as nasal airflow, and a lack of elastic fibers in vessel walls leads to prolonged bleeding as they are unable to undergo vasoconstriction. Epistaxis varies in severity and frequency but is often moderate to severe and significantly affects patients’ quality of life. Treatment is therefore aimed at reducing the frequency and severity of bleeding. Medical treatments are available, from topical barrier ointments to hormonal agents such as tamoxifen, which has been shown to significantly reduce the frequency and severity of bleeding in many patients. Surgical treatment in the form of laser coagulation of individual telangiectasia is often helpful, but if the lesions are more than approximately 2 mm in diameter they often bleed profusely in response to the laser. In such cases, septodermoplasty (SDP) is often the next step, perhaps prior to considering a more definitive treatment in the form of nasal closure. First described by Saunders in 1964, the principle of SDP is to replace the anterior nasal epithelium with a split-thickness skin graft (STSG). It is our practice to remove septal mucosa under endoscopic control, extending onto the floor of the nose as required, although Saunders also excised lateral nasal wall tissue. Our previous technique, employed in 75 cases, used a scalpel blade to define the mucosal area to be excised, prior to sharp dissection in the submucosal/supraperichondrial plane. Despite making the posterior incision first, bleeding can be profuse with this technique, often requiring a second operator to provide suction to allow the primary surgeon to visualize the surgical field. Although the bleeding slows significantly as soon as the mucosa is resected, it can be significant enough to compromise the plane of dissection or the area of mucosa removed, simply by obscuring the field of view. The aim of this report was to describe a modified technique for SDP that we believe provides improved visualization, and a review of our results.

Endoscopic sinus surgery and musculoskeletal symptoms.

BACKGROUND Endoscopic sinus surgery is a common surgical procedure, with low morbidity for patients. Studies have shown that endoscopic and laparoscopic surgeons have a significant risk of developing musculoskeletal symptoms, with potential adverse effects on their careers as well as patient care. We aimed to identify the prevalence of such symptoms, and any associated risk factors relating to surgical technique, in European rhinologists. METHODOLOGY An online survey was distributed to all members of the European Rhinologic Society and data collected for statistical analysis. The relevant literature was reviewed, and ergonomic recommendations made. RESULTS There were 250 responses, with nearly 80% of surgeons experiencing musculoskeletal symptoms. The neck and back were the most common site of symptoms, in approximately 60% of cases. There were significant correlations between musculoskeletal symptoms and the number of procedures performed each year, operating in a standing position, and operating without a monitor. CONCLUSIONS There is a high prevalence of musculoskeletal symptoms in endoscopic sinus surgeons, which appears to be particularly related to posture during surgery. Surgeons need to be more aware of the risk factors, and good ergonomic habits should be encouraged to try and reduce the development of such symptoms.

Visual loss in patients with sphenoethmoidal cells.

BACKGROUND A sphenoethmoidal cell is a posterior ethmoid cell that pneumatises superiorly and/or laterally to the sphenoid sinus. Disease within such a cell may cause visual symptoms because of the close relationship of the optic nerve. CASE REPORTS This paper reports four cases of chronic rhinosinusitis involving a sphenoethmoidal cell, two with visual loss. The management of such cases is discussed and the current literature is reviewed. CONCLUSION Pathology within a sphenoethmoidal cell must be considered in cases of optic neuropathy. The presence of these cells may be relevant even in cases of seemingly uncomplicated rhinosinusitis as they are associated with a higher rate of optic nerve protrusion and dehiscence.

Immunisations and antibiotics in patients with anterior skull base cerebrospinal fluid leaks.

OBJECTIVE There are no UK guidelines for the use of antibiotics and/or immunisations in patients with an active anterior skull base cerebrospinal fluid leak. This study aimed to define current UK practice in this area and inform appropriate guidelines for ENT surgeons. METHOD A web-based survey of all members of the British Rhinological Society was carried out and the literature in this area was reviewed. RESULTS Of those who responded to the survey, 14 per cent routinely give prophylactic antibiotics to patients with cerebrospinal fluid leaks, and 34.9 per cent recommend immunisation against at least one organism, most commonly Streptococcus pneumoniae (86.7 per cent). CONCLUSION There is no evidence to support the use of antibiotic prophylaxis in patients with a cerebrospinal fluid leak. We propose that all such patients are advised to seek immunisation against pneumococcus, meningococcus and haemophilus.

Re: Inferior turbinate mucosal graft combined with radiofrequency for the treatment of nasal hereditary haemorrhagic telangiectasia: our experience in sixteen patients.

Sir, We read with interest the article regarding the use of an inferior turbinate graft in the treatment of hereditary haemorrhagic telangiectasia (HHT) in a series of 16 cases where reduction in bleeding was achieved when inferior turbinate mucosa was used to replace septal mucosa in a modification of septodermoplasty. Septodermoplasty in the treatment of hereditary haemorrhagic telangiectasia was first described by Saunders, whose principle was ‘to replace the fragile epithelium in the anterior nose by a split-thickness skin graft from the thigh’. Hereditary haemorrhagic telangiectasia is an end-organ disease characterised by telangiectasia throughout the nose that bleedmore frequently when exposed to higher airflow in the anterior nasal cavities. Traditionally, skin has been the graft of choice as keratinised squamous epithelium is more resistant to trauma and therefore less likely to bleed. In 131 of our cohort of over 350 patients with hereditary haemorrhagic telangiectasia who were treated surgically over a fiveyear period at our institution, septodermoplasty using a split skin graft led to a 57% reduction in the need for subsequent laser treatment. It seems counter-intuitive to replace septal mucosa with mucosa from elsewhere in the nasal cavity which also is likely to be affected by telangiectasia. We are therefore intrigued that this did not prove to be the case during their reasonable period of follow-up. We are also surprised that the authors suggest that one turbinate could be sufficient for grafting both sides given that a conventional SDP usually covers the anterior half of the septum, an area which would be too great for an inferior turbinate to adequately cover bilaterally. In our experience, harvesting a ‘healthy’ piece of nasal mucosa of sufficient size in this patient group would be exceptionally difficult as the ‘normal’ grafted area would be in excess of 4 cm 9 2.5 cm. In addition, the postoperative bleeding risk associated with partial inferior turbinectomy has been reported as up to 20%. Packing the nose is traditionally avoided in patients with hereditary haemorrhagic telangiectasia as the trauma of inserting and removing packs can itself precipitate major haemorrhage; a procedure with a high postoperative bleeding rate should perhaps be avoided. Furthermore, undertaking simultaneous bilateral SDP considerably increases the risk of septal perforation, even though Abdelghany et al. have not as yet experienced this in their small cohort. The author reports that ‘no method (of treatment) has resulted in a complete cessation of epistaxis’. We disagree with this statement as complete closure of the nose in over 50 severe hereditary haemorrhagic telangiectasia patients at our institution has achieved exactly that using a technique previously described. We therefore do not support the premise that septodermoplasty is ‘the only definitive treatment’ for hereditary haemorrhagic telangiectasia. We commend innovative techniques in the management of hereditary haemorrhagic telangiectasia but would urge caution in using nasal mucosa instead of skin when performing septodermoplasty, a procedure which is best suited to patients with moderate but not severe epistaxis.

Frontal Sinus Malignancies

Frontal sinus malignancies are very rare, and tumour extension from adjacent structures is more common than primary frontal sinus tumours. Tumours are often very advanced at presentation due to vague early symptoms, and a high index of suspicion should be maintained for patients with unilateral, persistent or worsening symptoms despite medical therapy. Depending on the site and extension of the tumour, patients may complain of pain, nasal obstruction, swelling, bleeding, numbness, epiphora or diplopia. Frontal sinus malignancies can be divided into four groups according to their site of origin: primary tumours of frontal sinus mucosa; tumours that extend into the frontal sinus from adjacent regions; tumour deposits within the frontal sinus; and tumours arising in the bony walls of the frontal sinus. Prognosis is generally poor, but treatment is usually with surgery. Postoperative radiotherapy may improve local control and survival in some cases.