Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: a systematic review of local control outcomes.

BACKGROUND: Systematic reviews comparing treatment of early glottic cancer with transoral surgery or radiotherapy demonstrate similar oncological outcomes. Most studies of 'early-stage' laryngeal cancer include Tis, T1a, T1b and T2 cases. The data are dominated by patients with T1 and Tis tumours, although extrapolating these results and applying them for T2 cases may be inappropriate. No previous systematic reviews have focused on T2 cancers as a separate group. OBJECTIVE OF REVIEW: This review compares local control outcomes for T2 glottic squamous cell carcinoma, treated with transoral microsurgery or external beam radiotherapy. TYPE OF REVIEW: This is a systematic review of case series and comparison studies, focusing on oncological outcomes. SEARCH STRATEGY: Independent searches of MEDLINE, EMBASE and the Cochrane Database were conducted by two authors, using the search terms: laryngeal/glottic/vocal cord combined with carcinoma/cancer/tumour and laser/microsurgery or radiotherapy. Studies of adult patients treated for primary T2N0 glottic squamous cell carcinoma (SCC) with laser surgery or curative radiotherapy were included. EVALUATION METHOD: Full text of studies satisfying the inclusion criteria were reviewed with extraction of local control and survival data and laryngeal preservation rates. The primary endpoint is local control at 5 years. RESULTS: Initial searches identified 3252 studies. Following full-text review of 183 papers, 59 studies met the inclusion criteria, all level IV evidence. A total of 48 studies specified 5-year local control for 1156 patients treated with transoral laser surgery and 3191 patients treated with radiotherapy. Weighted averages of local control at 5 years demonstrated similar results: 75.81% for radiotherapy versus 77.26% for transoral laser surgery. CONCLUSIONS: The results of this review indicate no difference in 5-year local control between radiotherapy and transoral surgery for T2 glottic SCC. The data demonstrated higher rates of local failure for T2b compared with T2a cases, although outcomes were similar between laser excision and radiotherapy for each substage. Further research focusing upon functional outcomes for T2 glottic tumours is imperative to guide decision-making, ideally with subgroup analysis of T2a and T2b cases.

Autonomy and identity: the role of two developmental tasks on adolescent's wellbeing.

Developmental tasks theory suggests that the wellbeing of adolescents can be better understood by considering their developmental tasks, rather than just viewing it as a specific age. This concept has significantly influenced contemporary studies on the transition to adulthood. Study explains that psychosocial developmental tasks involve shifts in an individual's psychological state and social relationships, potentially disrupting their previous equilibrium. Authors stress the importance of forming personal identity and fostering a healthy sense of independence, especially concerning identity and autonomy tasks, as crucial elements for adolescent wellbeing analysis. In line with this, the study focuses on the concurrent and predictive relationship between identity process of commitment, emotional autonomy, and psychological wellbeing among adolescents. Four hundred fifty-four (454) participants with an age ranged from 15 to 19 years (m = 17.96) completed surveys measuring emotional autonomy, identity commitment, and psychological wellbeing. The findings revealed that both emotional autonomy and identity commitment predicted psychological wellbeing, but in different ways. The study revealed that emotional autonomy is inversely associated with psychological wellbeing in middle and late adolescents, indicating that their ability to establish independence from their parents or relinquish unrealistic parental expectations may be linked to a decline in their mental health. The results also indicated that identity commitment is moderately and positively related to psychological wellbeing, suggesting that when adolescents have a clear sense of their identity, they may experience greater wellbeing. This finding underscores the importance of encouraging adolescents to explore their values, interests, and goals, as well as providing them with support and guidance throughout the process. Additionally, the findings of the study revealed that emotional autonomy has a negative influence on psychological wellbeing when identity commitment is low or average. Specifically, when individuals have a low level of identity commitment, emotional autonomy significantly predicts lower psychological wellbeing. Similarly, when identity commitment is at an average level, emotional autonomy also has a detrimental effect on psychological wellbeing. Lastly, the study revealed that when individuals have a high level of identity commitment, emotional autonomy does not have a significant impact on psychological wellbeing. In simpler terms, when individuals possess a strong sense of commitment to their identity, their level of emotional autonomy does not play a significant role in influencing their psychological wellbeing.

Modulation of presynaptic Ca(2+) currents in frog motor nerve terminals by high pressure.

Presynaptic Ca(2+) -dependent mechanisms have already been implicated in depression of evoked synaptic transmission by high pressure (HP). Therefore, pressure effects on terminal Ca(2+) currents were studied in Rana pipiens peripheral motor nerves. The terminal currents, evoked by nerve or direct stimulation, were recorded under the nerve perineurial sheath with a loose macropatch clamp technique. The combined use of Na(+) and K(+) channel blockers, [Ca(2+) ]o changes, voltage-dependent Ca(2+) channel (VDCC) blocker treatments and HP perturbations revealed two components of presynaptic Ca(2+) currents: an early fast Ca(2+) current (ICaF ), possibly carried by N-type (CaV 2.2) Ca(2+) channels, and a late slow Ca(2+) current (ICaS ), possibly mediated by L-type (CaV 1) Ca(2+) channels. HP reduced the amplitude and decreased the maximum (saturation level) of the Ca(2+) currents, ICaF being more sensitive to pressure, and may have slightly shifted the voltage dependence. HP also moderately diminished the Na(+) action current, which contributed to the depression of VDCC currents. Computer-based modeling was used to verify the interpretation of the currents and investigate the influence of HP on the presynaptic currents. The direct HP reduction of the VDCC currents and the indirect effect of the action potential decrease are probably the major cause of pressure depression of synaptic release.

The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis.

BACKGROUND: To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer. METHODS: Four snoRNAs, commonly used for normalisation, RNU44, RNU48, RNU43 and RNU6B, and miRNA known to be associated with pathological factors, were measured by real-time polymerase chain reaction in two patient series: 219 breast cancer and 46 head and neck squamous cell carcinoma (HNSCC). SnoRNA and miRNA were then correlated with clinicopathological features and prognosis. RESULTS: Small-nucleolar RNA expression was as variable as miRNA expression (miR-21, miR-210, miR-10b). Normalising miRNA PCR expression data to these recommended snoRNAs introduced bias in associations between miRNA and pathology or outcome. Low snoRNA expression correlated with markers of aggressive pathology. Low levels of RNU44 were associated with a poor prognosis. RNU44 is an intronic gene in a cluster of highly conserved snoRNAs in the growth arrest specific 5 (GAS5) transcript, which is normally upregulated to arrest cell growth under stress. Low-tumour GAS5 expression was associated with a poor prognosis. RNU48 and RNU43 were also identified as intronic snoRNAs within genes that are dysregulated in cancer. CONCLUSION: Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias when determining miRNA expression.

Improved survival prediction for oropharyngeal cancer beyond TNMv8.

PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ±â€¯SE = 0.72 ±â€¯0.02 vs 0.53 ±â€¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ±â€¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.

Physically restraining children for induction of general anesthesia: survey of consultant pediatric anesthetists.

OBJECTIVES: To discover whether any consensus exists among the Association of Paediatric Anaesthetists of Great Britain and Ireland (APA) members regarding the use and acceptability (or otherwise) of physical restraint. BACKGROUND: Despite growing recognition of children's right to be consulted regarding their healthcare, the issue of how to proceed when faced with a child unwilling to undergo induction of general anesthesia remains relatively unaddressed. METHODS: APA members were surveyed regarding their use or avoidance of physical restraint and alternate techniques to facilitate induction; factors affecting choice of technique; and extent of preoperative discussion. The anonymous online survey used both structured and free text responses. RESULTS: Of 596 surveys, 310 were returned, a 52% response rate. Use of physical restraint and extent of restraint employed declines with increasing child age. Distraction techniques are frequently employed for children under 6 years, with the use of sedative premedication increasing as child age increases. Urgency of procedure, developmental delay, and preoperative discussion all have an effect. Comments demonstrated a wide range of views and lack of consensus on what constitutes physical restraint, and what degree of restraint, if any, is acceptable. CONCLUSION: Our results are similar to the US Society of Pediatric Anesthesia members, suggesting this remains an issue internationally. Consideration of practices in other specialties gives some guidance. Our survey shows a range of views as to what physical restraint is or involves, and what constitutes acceptable practice regarding the use or avoidance of physical restraint. We were unable to demonstrate consensus.

The role of nervus intermedius in side specific nasal responses.

BACKGROUND: Nervus intermedius (NI) dysfunction is common in patients who have had vestibular schwannoma (VS) surgery. Such patients have a unilateral parasympathetic-denervated nasal cavity. A number of side-specific nasal reflexes have been demonstrated in normal individuals, including hand cold-water immersion. It is not understood whether these reflexes have parasympathetic or sympathic efferent pathways. We aimed to evaluate the side specific nasal reflex to cold-water immersion in post-operative VS patients with NI dysfunction, in order to determine the nature of the efferent pathway of these reflexes. METHOD: Side specific responses to cold-water immersion were tested by acoustic rhinometry in 10 normal individuals and 18 patients with NI dysfunction (proven by Schirmer s test) after VS surgery. RESULTS: A consistent pattern of ipsilateral congestion and contralateral decongestion after the cold-water immersion was seen in normal individuals (p smaller than 0.001). We found no consistent response in VS patients both ipsilateral and contralateral to the side of NI dysfunction. CONCLUSIONS: We confirm the consistent side-specific nasal reflexes to cold-water hand immersion in normal individuals. This is disturbed in patients with NI dysfunction. We have also shown unexpectantly that the contralateral side-specific reflex is disturbed in these patients. These data suggest that the reflex is parasympathetic and crosses the midline.

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer.

BACKGROUND: Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract. METHODS: Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment. RESULTS: In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P=0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P=0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation. CONCLUSION: We conclude that the CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour's biological aggression.

Scientific and clinical aspects of the use of cidofovir in recurrent respiratory papillomatosis.

OBJECTIVE: Cidofovir is the most contemporary adjuvant treatment for recurrent respiratory papillomatosis (RRP) and its use is increasing. Cidofovir is potentially harmful. Otolaryngologists should understand the science of cidofovir and review the current published data on the effects of this therapy. METHOD: Pubmed was searched using the terms cidofovir and papillomatosis. Comparisons were made between published articles. RESULTS: Thirteen articles were identified between 1998 and 2006, representing the treatment of 142 patients. Cidofovir did result in a significant improvement of papillomatous lesions in the majority (60%) of patients despite the use of different regimes of cidofovir administration. There was no unifying protocol in use. A partial response was demonstrated in 29% of patients. 7.5% had no response however, an additional 3.5% patients were lost to follow-up. No malignant change was reported. CONCLUSION: Cidofovir does appear to be effective in improving the outcome of patients with RRP. There are no reports of malignant transformation despite concerns raised by toxicology studies.

Surgery in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Surgery is one of the key modalities used in head and neck cancer treatment. Recent advances and a greater awareness of the short- and long-term toxicities associated with non-surgical modalities and newer technologies that permit minimal access resections have led to a resurgence in surgery. This paper provides an overview of the role of surgery in head and neck cancer practice.

Subcranial craniofacial resection for advanced sinonasal malignant tumours involving the anterior skull base.

BACKGROUND: The subcranial approach is a modification of traditional craniofacial resection. It provides similar broad access to the anterior skull base, but with lower mortality and morbidity. It has been the surgical technique of choice at our institution since 2006 for treating advanced stage sinonasal tumours (American Joint Committee on Cancer stage III or above). This paper reports our experience and outcomes. METHOD AND RESULTS: Eighteen patients underwent subcranial craniofacial resection over a seven-year period, this being combined with a second adjunctive procedure in 89 per cent of cases. Forty per cent of patients required reconstruction of the primary defect. No peri-operative deaths occurred. One patient had a transient cerebrospinal fluid leak. The major complication rate was 33 per cent, of which 67 per cent were directly related to soft tissue reconstruction. Tumour recurrence rate was 17 per cent and the five-year disease-free survival estimate was 40 per cent. CONCLUSION: The subcranial approach is a safe and effective technique that may be used to successfully treat advanced sinonasal malignancies with anterior skull base extension.

Management of lateral skull base cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • All patients with more than one of: chronic otalgia, bloody otorrhoea, bleeding, mass, facial swelling or palsy should be biopsied. (R) • Magnetic resonance and computed tomography imaging should be performed. (R) • Patients should undergo audiological assessment. (R) • Carotid angiography is recommended in select patients. (G) • The modified Pittsburg T-staging system is recommended. (G) • The minimum operation for cancer involving the temporal bone is a lateral temporal bone resection. (R) • Facial nerve rehabilitation should be initiated at primary surgery. (G) • Anterolateral thigh free flap is the workhorse flap for lateral skull base defect reconstruction. (G) • For patients undergoing surgery for squamous cell carcinoma, at least a superficial parotidectomy and selective neck dissection should be carried out. (R).

Follow-up after treatment for head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. In the absence of high-level evidence base for follow-up practices, the duration and frequency are often at the discretion of local centres. By reviewing the existing literature and collating experience from varying practices across the UK, this paper provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition. Recommendations • Patients should be followed up to a minimum of five years with a prolonged follow-up for selected patients. (G) • Patients should be followed up at least two monthly in the first two years and three to six monthly in the subsequent years. (G) • Patients should be seen in dedicated multidisciplinary head and neck oncology clinics. (G) • Patients should be followed up by dedicated multidisciplinary clinical teams. (G) • The multidisciplinary follow-up team should include clinical nurse specialists, speech and language therapists, dietitians and other allied health professionals in the role of key workers. (G) • Clinical assessment should include adequate clinical examination including fibre-optic rigid or flexible nasopharyngolaryngoscopy. (R) • Magnetic resonance imaging and positron emission tomography combined with computed tomography imaging should be used when recurrence is suspected. (R) • Narrow band imaging can be used in the follow-up in selected sites. (R) • Second primary tumours should be part of rationale of follow-up and therefore adequate screening strategies should be used to detect them. (G) • Patients should be educated with regard to the appearance and detection of recurrences. (G) • Patients with persistent pain should be investigated to exclude recurrent disease. (R) • Patients should be offered support with tobacco and alcohol cessation services. (R).

Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care. Recommendations • Cross-sectional imaging is required in all cases to complete assessment and staging. (R) • Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and chest. (R) • Positron emission tomography combined with computed tomography scanning is recommended for the assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R) • Examination under anaesthetic is strongly recommended, but not mandatory. (R) • Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative intent. (R) • Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of Pathologists Guidelines. (G) • Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as recommended in The Royal College of Pathologists Guidelines. (R) • Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where the laboratory procedures and reporting standards are quality assured. (G) • Treatment options for T1-T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse pathological features on histological examination). (R) • Transoral surgery is preferable to open techniques and is associated with good functional outcomes in retrospective series. (R) • If treated surgically, neck dissection should include levels II-IV and possibly level I. Level IIb can be omitted if there is no disease in level IIa. (R) • If treated with radiotherapy, levels II-IV should be included, and possibly level Ib in selected cases. (R) • Altering the modalities of treatment according to HPV status is currently controversial and should be undertaken only in clinical trials. (R) • Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G).

Persistent hiccups after attempted interscalene brachial plexus block.

OBJECTIVE: We describe a case of persistent hiccups after attempted interscalene brachial plexus block. CASE REPORT: A 38-year-old man was admitted for arthroscopic repair of a right shoulder injury. An interscalene block was attempted in the preoperative area and combined with general anesthesia for surgery. The procedure lasted 5(1/4) hours. After transfer to the recovery room, the patient complained of severe right shoulder pain and had no discernible sensory or motor block. He was noted to be hiccuping. The patient was discharged home the following morning but returned 2 days later complaining of persistent hiccups since surgery, with associated insomnia and nausea. He was readmitted and given chlorpromazine 50 mg intravenously every 8 hours and metoclopramide 10 mg intravenously every 6 hours. The patient was discharged 4 days later on chlorpromazine 25 mg by mouth every 8 hours and baclofen 5 mg by mouth every 12 hours, with hiccups greatly reduced in both intensity and frequency. Hiccups ceased 1 day after discharge. Eighteen days after surgery, he was off all medication with no return of his hiccups; 1 month later he remains hiccup free. CONCLUSIONS: Persistent hiccups have many postulated causes, including several that are common in the perioperative period, but this is the first time to our knowledge that persistent hiccups have been described in association with attempted interscalene brachial plexus block.

Nodular fasciitis of the head and neck.

Nodular fasciitis is an unusual benign reactive process affecting superficial and deep fascia. Its rapid growth, rich cellularity, high mitotic activity and poorly circumscribed nature result in it being easily misdiagnosed as a sarcomatous lesion. Three cases of nodular fasciitis presenting as neck lumps are reported. They were successfully treated with local excision, with no signs of recurrence following two years of follow up. This paper describes the clinical presentation and microscopic features of this rare benign lesion and it emphasizes the need for accurate histopathology and clinical suspicion, if inappropriate aggressive management is to be avoided.

SINNMR studies of acoustically induced rotation of suspended particles.

Experiments and data analyses are reported on the 20 kHz acoustic manipulation of samples of trisodium phosphate dodecahydrate, of varying particle size, suspended in suitable support media. Data are obtained to expand the understanding and optimisation of the SINNMR (sonically induced narrowing of the nuclear magnetic resonance spectra of solids) technique, and use this to determine acoustically induced particle rotational correlation times. It is concluded that the average particle rotational correlation time decreases with increasing particle size and decreasing viscosity/density of the support media. Acoustic cavitation and accompanying interparticle collisions are shown to be important in the observation of SINNMR spectra.