Liam Masterson

De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma

BACKGROUNDnHuman papillomavirus-associated oropharyngeal squamous cell carcinomas are a distinct subgroup of tumours that may have a better prognosis than traditional tobacco/alcohol-related disease. Iatrogenic complications, associated with conventional practice, are estimated to cause mortality of approximately 2% and high morbidity. As a result, clinicians are actively investigating the de-escalation of treatment protocols for disease with a proven viral aetiology.nnnOBJECTIVESnTo summarise the available evidence regarding de-escalation treatment protocols for human papillomavirus-associated, locally advanced oropharyngeal squamous cell carcinoma.nnnSEARCH METHODSnWe searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 25 June 2013.nnnSELECTION CRITERIAnRandomised controlled trials investigating de-escalation treatment protocols for human papillomavirus-associated, locally advanced oropharyngeal carcinoma. Specific de-escalation categories were: 1) bioradiotherapy (experimental) versus chemoradiotherapy (control); 2) radiotherapy (experimental) versus chemoradiotherapy (control); and 3) low-dose (experimental) versus standard-dose radiotherapy (control). The outcomes of interest were overall and disease-specific survival, treatment-related morbidity, quality of life and cost.nnnDATA COLLECTION AND ANALYSISnThree authors independently selected studies from the search results and extracted data. We planned to use the Cochrane Risk of bias tool to assess study quality.nnnMAIN RESULTSnWe did not identify any completed randomised controlled trials that could be included in the current version of this systematic review. We did, however, identify seven ongoing trials that will meet our inclusion criteria. These studies will report from 2014 onwards. We excluded 30 studies on methodological grounds (seven randomised trials with post hoc analysis by human papillomavirus status, 11 prospective trials and 12 ongoing studies).nnnAUTHORS CONCLUSIONSnThere is currently insufficient high-quality evidence for, or against, de-escalation of treatment for human papillomavirus-associated oropharyngeal carcinoma. Future trials should be multicentre to ensure adequate power. Adverse events, morbidity associated with treatment, quality of life outcomes and cost analyses should be reported in a standard format to facilitate comparison with other studies.

Minimally invasive surgery versus radiotherapy/chemoradiotherapy for small-volume primary oropharyngeal carcinoma

BACKGROUNDnMore than 400,000 cases of oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed each year worldwide and the incidence is rising, partly as a result of human papillomavirus. Human papillomavirus-associated OPSCC affects younger patients and often presents at a higher stage; however, it is associated with a better prognosis.Until recently, first-line management of OPSCC involved chemoradiotherapy, as research had demonstrated comparable survival outcomes when compared with open surgery, with significantly decreased morbidity. However, interventions have now evolved with computerised planning and intensity-modulated radiotherapy, and the advent of endoscopic head and neck surgery, which provide the potential for decreased treatment-associated morbidity.The oropharynx plays an essential role in swallowing, speech and protecting the airway as it is situated at the bifurcation of the respiratory and digestive tracts. Treatment modality recommendations are based on survival outcomes. Given the younger patient demographic, establishing the safety of modalities that potentially have better functional outcome is becoming increasingly important.nnnOBJECTIVESnTo assess the efficacy of endoscopic head and neck surgery (transoral robotic surgery or transoral laser microsurgery) for small-volume, primary (T1-2, N0-2) oropharyngeal squamous cell carcinoma (OPSCC) in comparison to radiotherapy/chemoradiotherapy.nnnSEARCH METHODSnThe Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 10); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 8 November 2016.nnnSELECTION CRITERIAnRandomised controlled trials in patients with carcinoma in the oropharynx subsite (as defined by the World Health Organization classification C09, C10). Cancers included were primary squamous cell carcinomas arising from the oropharyngeal mucosa. The tumours were classified as T1-T2 with or without nodal disease and with no evidence of distant metastatic spread. The intervention was transoral, minimally invasive surgery with or without adjuvant radiotherapy or adjuvant chemoradiotherapy. The comparator was primary radiotherapy with or without induction or concurrent chemotherapy for the tumour. The treatments received and compared were of curative intent and patients had not undergone prior intervention, other than diagnostic biopsy.nnnDATA COLLECTION AND ANALYSISnWe used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related mortality was to be studied where possible), locoregional control, disease-free survival and progression-free survival or time to recurrence. All outcomes were to be measured at two, three and five years after diagnosis. Our secondary outcomes included quality of life, harms associated with treatment, patient satisfaction and xerostomia score.nnnMAIN RESULTSnNo completed studies met the inclusion criteria for the review. Two ongoing trials fulfilled the selection criteria, however neither are complete.Early-stage squamous cell carcinoma of the oropharynx: radiotherapy versus trans-oral robotic surgery (ORATOR) is a phase II randomised controlled trial comparing primary radiation therapy with primary transoral robotic surgery for small-volume primary (T1-2, N0-2) OPSCC. It is currently in progress with an estimated completion date of June 2021.European Organisation for Research and Treatment of Cancer 1420 (EORTC 1420-HNCG-ROG) is a phase III, randomised study assessing the best of radiotherapy compared to transoral robotic surgery/transoral laser microsurgery in patients with T1-T2, N0 squamous cell carcinoma of the oropharynx and base of tongue. It was due to start accrual mid-2016.nnnAUTHORS CONCLUSIONSnThe role of endoscopic head and neck surgery in the management of OPSCC is clearly expanding as evidenced by its more overt incorporation into the current National Comprehensive Cancer Network guidelines. Data are mounting regarding its outcomes both in terms of survival and lower morbidity. As confidence increases, it is being used in the management of more advanced OPSCC.Based on this review, there is currently no high-quality evidence from randomised controlled trials regarding clinical outcomes for patients with oropharyngeal cancer receiving endoscopic head and neck surgery compared with primary chemoradiotherapy.

Water precautions for prevention of infection in children with ventilation tubes (grommets).

BACKGROUNDnFollowing middle ear ventilation tube (tympanostomy tube or grommet) insertion, most surgeons advise that a childs ears should be kept dry during the immediate postoperative period. Following the initial period some surgeons will permit swimming or bathing, whereas other surgeons will recommend ongoing water precautions. A large number of studies have been conducted to explore the association between water exposure and ear infections in children with ventilation tubes, however a range of differing conclusions exist regarding the need for water precautions and there is wide variation in clinical practice.nnnOBJECTIVESnTo assess the effectiveness of water precautions for the prevention of ear infections in children with ventilation tubes (grommets), at any time while the tubes are in place.nnnSEARCH METHODSnThe Cochrane ENT Trials Search Co-ordinator searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 September 2015.nnnSELECTION CRITERIAnRandomised controlled trials recruiting children (0 to 17 years) with ventilation tubes and assessing the effect of water precautions while the tubes are in place. We considered all forms of water precautions, including behavioural (i.e. avoidance or swimming/bathing restrictions) and mechanical (ear plugs/moulds or hats/bands).nnnDATA COLLECTION AND ANALYSISnWe used the standard methodological procedures expected by Cochrane. Our primary outcome measures were episodes of otorrhoea and adverse effects; secondary outcomes were antimicrobial prescriptions for ear infections, ventilation tube extrusion, surgical intervention to remove ventilation tubes and hearing outcomes.nnnMAIN RESULTSnTwo randomised controlled trials recruiting a total of 413 patients met the criteria for inclusion in our review; one study had a low risk of bias and the other study had a high risk of bias. Ear plugs versus control One study recruited 201 children (aged six months to six years) who underwent myringotomy and ventilation tube insertion. The study compared an intervention group who were instructed to swim and bathe with ear plugs with a control group; the participants were followed up at one-month intervals for one year. This study, with low risk of bias, showed that the use of ear plugs results in a small but statistically significant reduction in the rate of otorrhoea from 1.2 episodes to 0.84 episodes in the year of follow-up (mean difference (MD) -0.36 episodes per year, 95% confidence interval (CI) -0.45 to -0.27). There was no significant difference in ventilation tube extrusion or hearing outcomes between the two study arms. No child required surgical intervention to remove ventilation tubes and no adverse events were reported. Water avoidance versus control Another study recruited 212 children (aged three months to 12 years) who underwent myringotomy and ventilation tube insertion. The study compared an intervention group who were instructed not to swim or submerge their heads while bathing with a control group; the participants were followed up at three-month intervals for one year. This study, with high risk of bias, did not show any evidence of a reduction or increase in the rate of otorrhoea (1.17 episodes per year in both groups; MD 0 episodes, 95% CI -0.14 to 0.14). No other outcomes were reported for this study and no adverse events were reported. Quality of evidence The overall quality (GRADE) of the body of evidence for the effect of ear plugs on the rate of otorrhoea and the effect of water avoidance on the rate of otorrhoea are low and very low respectively.nnnAUTHORS CONCLUSIONSnThe baseline rate of ventilation tube otorrhoea and the morbidity associated with it is usually low and therefore careful prior consideration must be given to the efficacy, costs and burdens of any intervention aimed at reducing this rate.While there is some evidence to suggest that wearing ear plugs reduces the rate of otorrhoea in children with ventilation tubes, clinicians and parents should understand that the absolute reduction in the number of episodes of otorrhoea appears to be very small and is unlikely to be clinically significant. Based on the data available, an average child would have to wear ear plugs for 2.8 years to prevent one episode of otorrhoea.Some evidence suggests that advising children to avoid swimming or head immersion during bathing does not affect rates of otorrhoea, although good quality data are lacking in this area. Currently, consensus guidelines therefore recommend against the routine use of water precautions on the basis that the limited clinical benefit is outweighed by the associated cost, inconvenience and anxiety.Future high-quality studies could be undertaken but may not be thought necessary. It is uncertain whether further trials in this area would change the findings of this review or have an impact on practice. Any future high-quality research should focus on determining whether particular groups of children benefit more from water precautions than others, as well as on developing clinical guidelines and their implementation.

Thyroid surgery for Graves’ disease and Graves’ ophthalmopathy

BACKGROUNDnGraves disease is an autoimmune disease caused by the production of auto-antibodies against the thyroid-stimulating hormone receptor, which stimulates follicular cell production of thyroid hormone. It is the commonest cause of hyperthyroidism and may cause considerable morbidity with increased risk of cardiovascular and respiratory adverse events. Five per cent of people with Graves disease develop moderate to severe Graves ophthalmopathy. Thyroid surgery for Graves disease commonly falls into one of three categories: 1) total thyroidectomy, which aims to achieve complete macroscopic removal of thyroid tissue; 2) bilateral subtotal thyroidectomy, in which bilateral thyroid remnants are left; and 3) unilateral total and contralateral subtotal thyroidectomy, or the Dunhill procedure. Recent American Thyroid Association guidelines on treatment of Graves hyperthyroidism emphasised the role of surgery as one of the first-line treatments. Total thyroidectomy removes target tissue for the thyroid-stimulating hormone receptor antibody. It controls hyperthyroidism at the cost of lifelong thyroxine replacement. Subtotal thyroidectomy leaves a thyroid remnant and may be less likely to lead to complications, however a higher rate of recurrent hyperthyroidism is expected and revision surgery would be challenging. The choice of the thyroidectomy technique is currently largely a matter of surgeon preference, and a systematic review of the evidence base is required to determine which option offers the best outcomes for patients.nnnOBJECTIVESnTo assess the optimal surgical technique for Graves disease and Graves ophthalmopathy.nnnSEARCH METHODSnWe searched the Cochrane Library, MEDLINE and PubMed, EMBASE, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the last search was June 2015 for all databases. We did not apply any language restrictions.nnnSELECTION CRITERIAnOnly randomised controlled trials (RCTs) involving participants with a diagnosis of Graves disease based on clinical features and biochemical findings of hyperthyroidism were eligible for inclusion. Trials had to directly compare at least two surgical techniques of thyroidectomy. There was no age limit to study inclusion.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently extracted and cross-checked the data for analysis, evaluation of risk of bias and establishment of Summary of findings tables using the GRADE instrument. The senior review authors reviewed the data and reconciled disagreements.nnnMAIN RESULTSnWe included five RCTs with a total of 886 participants; 172 were randomised to total thyroidectomy, 383 were randomised to bilateral subtotal thyroidectomy, 309 were randomised to the Dunhill procedure and 22 were randomised to either bilateral subtotal thyroidectomy or the Dunhill procedure. Follow-up ranged between six months and six years. One trial had three comparison arms. All five trials were conducted in university hospitals or tertiary referral centres for thyroid disease. All thyroidectomies were performed by experienced surgeons. The overall quality of the evidence ranged from low to moderate. In all trials, blinding procedures were insufficiently described. Outcome assessment for objective outcomes was blinded in one trial. Surgeons were not blinded in any of the trials. One trial blinded participants. Attrition bias was a substantial problem in one trial, with 35% losses to follow-up. In one trial the analysis was not carried out on an intention-to-treat basis.Total thyroidectomy was more effective than subtotal thyroidectomy techniques (both bilateral subtotal thyroidectomy and the Dunhill procedure) at preventing recurrent hyperthyroidism in 0/150 versus 11/200 participants (OR 0.14 (95% CI 0.04 to 0.46); P = 0.001; 2 trials; moderate quality evidence). Total thyroidectomy was also more effective than bilateral subtotal thyroidectomy at preventing recurrent hyperthyroidism in 0/150 versus 10/150 participants (odds ratio (OR) 0.13 (95% confidence interval (CI) 0.04 to 0.44); P = 0.001; 2 trials; moderate quality evidence). Compared to bilateral subtotal thyroidectomy, the Dunhill procedure was more likely to prevent recurrent hyperthyroidism in 20/283 versus 8/309 participants (OR 2.73 (95% CI 1.28 to 5.85); P = 0.01; 3 trials; low quality evidence). Total thyroidectomy compared with subtotal thyroidectomy conferred a greater risk of permanent hypocalcaemia/hypoparathyroidism in 8/172 versus 3/221 participants (OR 4.79 (95% CI 1.36 to 16.83); P = 0.01; 3 trials; low quality evidence). Effects of the various surgical techniques on permanent recurrent laryngeal nerve palsy and regression of Graves ophthalmopathy were neutral. One death was reported in one study in year three of follow-up. No study investigated health-related quality of life or socioeconomic effects.nnnAUTHORS CONCLUSIONSnTotal thyroidectomy is more effective than subtotal thyroidectomy (both bilateral subtotal thyroidectomy and the Dunhill procedure) at preventing recurrent hyperthyroidism in Graves disease. The type of surgery performed does not affect regression of Graves ophthalmopathy. There was some evidence that total thyroidectomy compared with subtotal thyroidectomy conferred a greater risk of permanent hypocalcaemia/hypoparathyroidism, which however, was not seen in comparison with bilateral subtotal thyroidectomy. Permanent recurrent laryngeal nerve palsy did not seem to be affected by type of thyroidectomy. Health-related quality of life as a patient-important outcome measure should form a core determinant of any future trial on the effects of thyroid surgery for Graves disease.

Management and outcomes in children with sinogenic intracranial abscesses

OBJECTIVEnTo report our experience of sinogenic intracranial abscesses in the paediatric population and to guide medical and surgical management.nnnMETHODSnAll children with sinogenic intracranial abscesses presenting to a large university teaching hospital over a five-year period were included in the study. Data on clinical presentation, radiological findings, microbiology, medical and surgical management and follow-up were recorded and analysed.nnnRESULTSnWe identified 27 children aged 12.9 ± 3.4 years of which 56% were male. Fourteen (52%) children had extradural abscesses, nine (33%) subdural abscesses and four (15%) parenchymal abscesses. Early sinus drainage procedures were performed on 24 (89%) patients, and the same number required neurosurgical drainage. Streptococcus milleri was isolated in 18 (67%) cases. An initial conservative neurosurgical approach failed in 50% of cases where trialled, and was associated with longer length of stay (p = 0.025). In comparison to extradural abscesses, subdural abscesses were more likely to present with neurological deficits (p < 0.001) and reduced consciousness (p = 0.018), and required multiple neurosurgical procedures (p < 0.001), longer stays (p = 0.017), and had greater morbidity at six months (p = 0.017). A third of children had significant morbidity at six months, which included cognitive and behavioural problems (25%), residual hemiparesis (19%) and expressive dysphasia (7%). There were no mortalities.nnnCONCLUSIONnSinusitis complicated by intracranial abscess remains a contemporary problem. We demonstrate good outcomes with an early combined rhinological and neurosurgical approach. S. milleri is identified as the causative organism in the majority of cases, and empirical antimicrobial treatments should reflect this.