Paul Nankivell

Refeeding syndrome--awareness, prevention and management.

BackgroundRefeeding syndrome is an important, yet commonly overlooked condition affecting patients. It occurs when feeding is commenced after a period of starvation. Head and neck cancer patients are at particular risk owing to prolonged periods of poor nutritional intake. This may be from general effects such as cancer anorexia or from more specific problems of dysphagia associated with this group of patients. Awareness of the condition is crucial in identifying patients at risk and taking measures to prevent its occurrence.ObjectivesThe aims of this review are to:1) Highlight the condition and stress the importance of its consideration when admitting head and neck cancer patients.2) Discuss the pathophysiology behind refeeding syndrome.3) Review the literature for the best available evidence and guidelines.4) Highlight the need for further high quality research.ConclusionRefeeding syndrome is potentially fatal, yet is preventable. Awareness and identification of at-risk patients is crucial to improving management.Refeeding syndrome is caused by rapid refeeding after a period of under-nutrition, characterised by hypophosphataemia, electrolyte shifts and has metabolic and clinical complications.High risk patients include the chronically under-nourished and those with little intake for greater than 10 days. Patients with dysphagia are at particular risk.Refeeding should commence at 10 kcal/kg per day in patients at risk, and increased slowly. Thiamine, vitamin B complex and multi-vitamin supplements should be started with refeeding.New NICE guidelines state that pre-feeding correction of electrolyte and fluid deficits is unnecessary, but should be done concurrently with re-feeding.More research in this field is needed as the evidence base is lacking.

The risk and interval to malignancy of patients with laryngeal dysplasia; a systematic review of case series and meta‐analysis

Clin. Otolaryngol. 2010, 35, 364–372

Tympanoplasty for Chronic Tympanic Membrane Perforation in Children: Systematic Review and Meta-analysis

Objective To study the effectiveness of Type 1 tympanoplasty for chronic tympanic membrane perforations in the pediatric age group and to investigate factors influencing its success. Data Sources Searches were conducted of the MEDLINE database and the Cochrane Database of Systematic Reviews using terms focused around tympanoplasty and children. Searches were performed on June 23, 2014 and limited to English language entries since January 1, 1997. Study Selection Studies reporting tympanoplasty closure rates in children 18 years and younger, with a minimum follow-up of 6 months, were included. Studies focusing on more advanced forms of tympanoplasty and revision surgery were excluded. Data Extraction Five hundred sixty-four articles were screened identifying 2,609 cases from 45 eligible studies. Data were collected by consensus of the first two authors with the third author arbitrating disparities of opinion. Success was taken as the closure rate at 12 months where possible. Data Synthesis Forest plots with Mantel-Haenszel analyses were used to compare closure rates with respect to perforation size, adenoidectomy, status of contralateral ear, Eustachian tube function, active infection, and graft position. Linear regression and Fisher’s exact were used to analyze closure rate with respect to age. Conclusion The mean weighted closure rate for pediatric tympanoplasty was 83.4%. Subgroup analysis found age not to be a significant factor affecting the closure rate. Tympanoplasties performed on larger perforations or in children with abnormal contralateral ear findings were more likely to fail. Surgery may be best delayed until contralateral otitis media with effusion has settled.

Oral Dysplasia: Biomarkers, Treatment, and Follow-up

Dysplasia affecting the oral mucosa has a malignant potential. The options for treatment of oral dysplasia are limited. Surgery remains the mainstay of management, with no strong evidence for medical treatments currently available. Histological grading alone does not accurately predict which dysplastic lesions will progress to cancer, which poses the clinician with difficult decisions regarding the most appropriate treatment and may lead to some patients being overtreated, with potentially unnecessary morbidity. The use of biomarkers may help to improve prediction of which cases are likely to transform. The efficacy of individual markers for prediction will be discussed in this paper. There is also a lack of consensus on the optimal frequency and duration of follow-up for patients with oral dysplasia.

The binary oral dysplasia grading system: validity testing and suggested improvement

OBJECTIVES A binary system is reputed to be superior to the World Health Organization (WHO) system in grading oral dysplasia. We aimed to validate its reproducibility and prognostic ability and examine whether it could be improved. STUDY DESIGN Three pathologists graded 141 oral epithelial dysplasia biopsies with the use of both systems. Observer variability and prognostic ability were assessed with the use of kappa and logistic regression models. RESULTS The binary system showed superior agreement to the WHO system (multirater kappa 0.59 vs. 0.49, respectively) but similar prognostic ability (odds ratio [OR] 4.59 [P = .014] vs. OR 2.25 [P = .02], respectively). Adding smoking and alcohol slightly improved the prognostic ability of both systems (OR 5.10 vs. OR 2.42, respectively). Our new binary system with a refined diagnostic threshold demonstrated a slightly greater prognostic ability and improved ability to differentiate between high- and low-risk moderate dysplasia cases. CONCLUSIONS The binary system has similar prognostic ability but superior reproducibility compared with the WHO system. Prognostication is improved still further by using a new threshold.

Biomarkers in laryngeal dysplasia: a systematic review.

Prediction of which laryngeal dysplasia cases will progress to cancer is poorly achieved. The differential expression of biomarkers in dysplastic and cancerous lesions may help to improve this.

Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia.

Background:Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort.Methods:One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed.Results:Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability.Conclusion:This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition.

Validation of tissue microarrays in oral epithelial dysplasia using a novel virtual-array technique

Background Malignant transformation risk in oral epithelial dysplasia (OED) is currently determined by histological assessment. The subjectivity of this approach has led to interest in identifying prognostic biomarkers. Tissue microarrays (TMA) can reduce the utilization of the finite resources of a pathological archive. However, the selectivity involved in TMA construction necessitates the need to ensure that individual cores are representative of the overall features of the donor specimen. We aimed to validate, for the first time, the use of the TMA technique in OED by using a novel virtual array technique. Methods Sections from 38 cases of OED were stained with H&E and 6 immunohistochemical (IHC) biomarkers. All were then digitally scanned. Virtual cores were generated by image capturing a 0.6mm2 area of the IHC slide that corresponded to the same dysplastic area marked on the H&E slide. Two trained blinded observers scored both whole slides and virtual cores independently. The degree of reliability in scores between the individual raters and between virtual TMA cores and slides was assessed using both interclass correlation coefficient (ICCC) and weighted κ statistics. Results Excellent inter-observer reliability was demonstrated with all the immunohistochemical markers. ICCC ranged from 0.67−1.0 and κ scores >0.8. There was also a high reliability in the scores between whole slides and virtual TMAs, with ICCC of between 0.66 and 0.89 for the 6 markers. Conclusions This study validates the use of TMAs in OED using a variety of biomarkers. We also report a novel method for achieving this using a novel virtual-array technique.

Feasibility of recruitment to an oral dysplasia trial in the United Kingdom

BackgroundOral epithelial dysplasia (OED) has a malignant potential. Therapeutic options for OED remain both limited and without good evidence. Despite surgery being the most common method of treating OED, recurrence and potentially significant morbidity remain problematic. Consequently, there has been much interest in non-surgical treatments for OED. Cyclo-oxygenase (COX) up-regulation is known to occur in the dysplasia-carcinoma sequence and evidence now exists that COX-2 is a prognostic marker of malignant transformation in OED. COX-inhibitors are therefore considered a potential therapeutic strategy for treating this condition. We aimed to provide both proof of principal evidence supporting the effect of topical COX inhibition, and determine the feasibility of recruitment to an OED chemoprevention trial in the UK.MethodsRecruitment of 40 patients with oral leukoplakia to 4 study arms was planned. The total daily dose of Aspirin would increase in each group and be used in the period between initial diagnostic and follow-up biopsies.ResultsDuring the 15-month recruitment period, 15/50 screened patients were eligible for recruitment, and 13 (87%) consented. Only 1 had OED diagnosed on biopsy. 16 patients were intolerant of, or already taking Aspirin and 16 patients required no biopsy. Initial recruitment was slow, as detection relied on clinicians identifying potentially eligible patients. Pre-screening new patient letters and directly contacting patients listed for biopsies improved screening of potentially eligible patients. However, as the incidence of OED was so low, it had little impact on trial recruitment. The trial was terminated, as recruitment was unlikely to be achieved in a single centre.ConclusionThis feasibility trial has demonstrated the low incidence of OED in the UK and the difficulties in conducting a study because of this. With an incidence of around 1.5/100,000/year and a high proportion of those patients already taking or intolerant of Aspirin, a large multi-centred trial would be required to fulfil the recruitment for this study. The ability of topical non-steroidal anti-inflammatory drugs to modify COX and prostaglandin expression remains an important but unanswered question. Collaboration with centres in other parts of the world with higher incidences of the disease may be required to ensure adequate recruitment.ISRCTN31503555.

Do corticosteroids improve outcomes in peritonsillar abscess

BACKGROUND Peritonsillar abscess (PTA), also known as quinsy, is the collection of pus in the peritonsillar space. It is one of the most common emergency presentations to otolaryngologists, with an incidence of around 30 cases per 100,000 population. The use of systemic corticosteroids in PTA can reduce pain and trismus, resulting in an earlier return to normal diet and activities. Their use is widespread but inconsistent, perhaps due to concerns about the immediate immunosuppressive effects and long-term side effects associated with these drugs.