Paul Chatrath

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions

Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (ρ=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.

A review of the current management of infantile subglottic haemangioma, including a comparison of CO2 laser therapy versus tracheostomy

OBJECTIVES We reassessed the current practice and treatment options used in the management of subglottic haemangiomas (SGHs), including the place for open submucosal surgical excision, and have compared the results of different therapeutic modalities used for SGHs. METHODS The two studies were conducted as separate exercises; (1) a retrospective review of 36 patients collected over a recent 8-year period to assess the current practice and treatment options in use; (2) a retrospective comparative study of a previous cohort of 51 patients with SGHs treated in one of four groups: (a) tracheostomy alone, (b) tracheostomy and CO(2) laser, (c) systemic steroids and CO(2) laser (no tracheostomy) and (d) intralesional steroid injection, CO(2) laser therapy, or both, followed by intubation. RESULTS Systemic steroids were the most commonly used modality of treatment. Resolution of the SGH was achieved in 89% of cases at a mean follow up duration of 34 months. However, tracheostomy was required in 58% of cases, with a mean time from diagnosis to decannulation of 30 months. The time to resolution of SGHs does not appear to be reduced by laser therapy compared with treatment by tracheostomy alone. Intralesional steroid injection or laser therapy together with intubation was associated with avoidance of a tracheostomy in 66% of cases. Single-stage open surgical excision in two cases resulted in successful resolution of the SGH and discharge after a mean follow up period of 3 months. CONCLUSIONS Despite the more widespread use of steroids and other treatment modalities, the requirement for tracheostomy has remained unchanged over the last 20 years. The use of laser therapy does not appear to confer any additional therapeutic benefit over and above tracheostomy alone in bringing about resolution of SGHs. Systemic steroids may reduce the size of the haemangioma but are associated with multiple adverse effects. The decision to use the above techniques must, therefore, be made in the light of these observations. Our early experience of single-stage excision suggests that this technique represents an exciting and promising surgical alternative, and its more widespread adoption may be the only way of further improving the outcome of patients with SGHs.

Endonasal endoscopic approach to the petrous apex: an image-guided quantitative anatomical study.

Background:  The petrous apex is a relatively inaccessible region, deeply situated within the skull base. Removal of lesions from this area, traditionally accomplished via lateral approaches, can cause significant morbidity. We undertook an anatomical study to investigate the surgical anatomy of the petrous apex through an endonasal endoscopic approach, which has been sporadically described in the literature, to investigate its feasibility and to characterise clear and consistent surgical landmarks for access.

Screening patients with sensorineural hearing loss for vestibular schwannoma using a Bayesian classifier

Objectives:  Selecting patients with asymmetrical sensorineural hearing loss for further investigation continues to pose clinical and medicolegal challenges, given the disparity between the number of symptomatic patients, and the low incidence of vestibular schwannoma as the underlying cause. We developed and validated a diagnostic model using a generalisation of neural networks, for detecting vestibular schwannomas from clinical and audiological data, and compared its performance with six previously published clinical and audiological decision‐support screening protocols.

Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia

We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n=8), laryngeal dysplasia (n=10) and laryngeal squamous cell carcinoma (n=10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (ρ=0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P=0.001), Ki67 (P=0.0002), cyclin D1 (P=0.015), cyclin A (P=0.0001) and cyclin B1 (P=0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.

Deafness in Vogt-Koyanagi-Harada syndrome.

Sudden onset sensorineural hearing loss is a well recognized entity frequently encountered in otolaryngological practice. However, the combination of such deafness as part of a wider systemic disorder is fortunately rare. Almost 100 years after the syndrome was classified, we describe a case of Vogt-Koyanagi-Harada syndrome occurring unusually in a Caucasian woman and characterized by sudden hearing loss. A brief review of this rare condition is presented.

A multi-centre audit of epistaxis management in England: Is there a case for a national review of practice?

OBJECTIVE The ENT-UK Clinical Audit and Practice Advisory Group initiated a pilot audit to investigate variance in epistaxis management between six units nationwide. METHOD All patients with a diagnosis of epistaxis who were admitted for in-patient care at six ENT departments between November 2011 and February 2012 were prospectively enrolled. RESULTS A total of 166 patients were included in the study. Variance was demonstrated between the six units in a number of the key outcome areas. Twenty-eight per cent of patients were identified as eligible for operative intervention for epistaxis in one unit, compared with only 12.5 per cent in another. CONCLUSION There are measurable, patient-relevant outcomes to assess epistaxis management and these can highlight areas of potential improvement. This pilot audit gives a snapshot of modern practice, which shows variance between the six units assessed. A national audit may allow us to improve patient experience and maximise efficiency in delivering emergency care in our most common patient encounter.

Identification of predictors and development of a screening protocol for cerebello-pontine lesions in patients presenting with audio-vestibular dysfunction.

Objectives:  Magnetic resonance imaging (MRI) scanning in the investigation of cerebellopontine angle lesions represents a finite resource, the use of which needs to be carefully rationalised. Our aim was to identify predictive factors that can distinguish between patients with and without cerebellopontine angle lesions, and develop a screening protocol which could be useful in the clinical setting as an aid to clinical judgment.

Endoscopic Repair of Cerebrospinal Fluid Rhinorrhea Using Bone Pate

INTRODUCTION The endoscopic endonasal technique has become the modality of choice for the surgical management of cerebrospinal fluid (CSF) rhinorrhea in current rhinologic practice, a trend that reflects improvements in both perioperative morbidity and recurrence rates. The precise surgical strategy adopted depends in part on the etiology as well as the size and site of the leak. Several factors mitigate against successful endoscopic repair, including anterior frontal recess and far anterolateral sphenoid sites, elevated body mass index (BMI), massive skull base defect, and a spontaneous etiology.1 We report the application of a novel technique involving the use of autologous bone pate and fascia, which precisely replicates the layered in situ anatomic characteristics and which in our opinion facilitates the endoscopic repair of even the most challenging sinonasal CSF leaks.

Atypical keratosis obturans

Keratosis obturans is a rare condition characterized by the accumulation of desquamated keratin material in the bony portion of the external auditory canal. Classically, it is reported to present with severe otalgia, conductive deafness and global widening of the canal. A case of keratosis obturans is described in which the principal symptom was a metallic taste and the main finding was extensive erosion of the hypotympanum with exposure of the facial nerve and the annulus of the tympanic membrane. This presenting symptom and resorption pattern are atypical of keratosis obturans and have not been documented previously.