Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. METHODS: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis. RESULTS: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21-0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL(high)=96%, HPV-positive/TIL(low)=59%). Survival of HPV-positive/TIL(low) patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a 'training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82). INTERPRETATION: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

Relationships between the history of thermal stress and the relative risk of diseases of Caribbean corals.

The putative increase in coral diseases in the Caribbean has led to extensive declines in coral populations. Coral diseases are a consequence of the complex interactions among the coral hosts, the pathogens, and the environment. Yet, the relative influence that each of these components has on the prevalence of coral diseases is unclear. Also unknown is the extent to which historical thermal-stress events have influenced the prevalence of contemporary coral diseases and the potential adjustment of coral populations to thermal stress. We used a Bayesian approach to test the hypothesis that in 2012 the relative risk of four signs of coral disease (white signs, dark spots, black bands, and yellow signs) differed at reef locations with different thermal histories. We undertook an extensive spatial study of coral diseases at four locations in the Caribbean region (10(3) km), two with and two without a history of frequent thermal anomalies (approximately 4-6 years) over the last 143 years (1870-2012). Locations that historically experienced frequent thermal anomalies had a significantly higher risk of corals displaying white signs, and had a lower risk of corals displaying dark spots, than locations that did not historically experience frequent thermal anomalies. By contrast, there was no relationship between the history of thermal stress and the relative risk of corals displaying black bands and yellow signs, at least at the spatial scale of our observations.

Coral-seeding devices with fish-exclusion features reduce mortality on the Great Barrier Reef.

Restoration methods that seed juvenile corals show promise as scalable interventions to promote population persistence through anthropogenic warming. However, challenges including predation by fishes can threaten coral survival. Coral-seeding devices with refugia from fishes offer potential solutions to limit predation-driven mortality. In an 8-month field study, we assessed the efficacy of such devices for increasing the survival of captive-reared Acropora digitifera (spat and microfragments) over control devices (featureless and caged). Devices with fish-exclusion features demonstrated a twofold increase in coral survival, while most corals seeded without protection suffered mortality within 48 h. Overall, spat faced more grazing and higher mortality compared to microfragments, and upward-facing corals were more vulnerable than side-facing corals. Grazing-induced mortality varied by site, with lower activity in locations abundant in mat-forming cyanobacteria or Scleractinian corals. Many scraping parrotfish were found feeding on or near the seeded corals; however, bites by Scarus globiceps explained the most site-related variation in grazing. Cyanobacteria may be preferred over corals as a nutritional resource for scraping parrotfish-advancing our understanding of their foraging ecology. Incorporating side-facing refugia in seeding devices and deploying to sites with nutrient-rich food sources for fish are potential strategies to enhance coral survival in restoration programs.

Hierarchical settlement behaviours of coral larvae to common coralline algae.

Natural regeneration of degraded reefs relies on the recruitment of larvae to restore populations. Intervention strategies are being developed to enhance this process through aquaculture production of coral larvae and their deployment as spat. Larval settlement relies on cues associated with crustose coralline algae (CCA) that are known to induce attachment and metamorphosis. To understand processes underpinning recruitment, we tested larval settlement responses of 15 coral species, to 15 species of CCA from the Great Barrier Reef (GBR). CCA in the family Lithophyllaceae were overall the best inducer across most coral species, with Titanoderma cf. tessellatum being the most effective species that induced at least 50% settlement in 14 of the coral species (mean 81%). Taxonomic level associations were found, with species of Porolithon inducing high settlement in the genus Acropora; while a previously understudied CCA, Sporolithon sp., was a strong inducer for the Lobophyllidae. Habitat-specific associations were detected, with CCA collected from similar light environment as the coral inducing higher levels of settlement. This study revealed the intimate relationships between coral larvae and CCA and provides optimal coral-algal species pairings that could be utilized to increase the success of larval settlement to generate healthy spat for reef restoration.

Assessing the role of historical temperature regime and algal symbionts on the heat tolerance of coral juveniles.

The rate of coral reef degradation from climate change is accelerating and, as a consequence, a number of interventions to increase coral resilience and accelerate recovery are under consideration. Acropora spathulata coral colonies that survived mass bleaching in 2016 and 2017 were sourced from a bleaching-impacted and warmer northern reef on the Great Barrier Reef (GBR). These individuals were reproductively crossed with colonies collected from a recently bleached but historically cooler central GBR reef to produce pure and crossbred offspring groups (warm-warm, warm-cool and cool-warm). We tested whether corals from the warmer reef produced more thermally tolerant hybrid and purebred offspring compared with crosses produced with colonies sourced from the cooler reef and whether different symbiont taxa affect heat tolerance. Juveniles were infected with Symbiodinium tridacnidorum, Cladocopium goreaui and Durusdinium trenchii and survival, bleaching and growth were assessed at 27.5°C and 31°C. The contribution of host genetic background and symbiont identity varied across fitness traits. Offspring with either both or one parent from the northern population exhibited a 13- to 26-fold increase in survival odds relative to all other treatments where survival probability was significantly influenced by familial cross identity at 31°C but not 27.5°C (Kaplan-Meier P=0.001 versus 0.2). If in symbiosis with D. trenchii, a warm sire and cool dam provided the best odds of juvenile survival. Bleaching was predominantly driven by Symbiodiniaceae treatment, where juveniles hosting D. trenchii bleached significantly less than the other treatments at 31°C. The greatest overall fold-benefits in growth and survival at 31°C occurred in having at least one warm dam and in symbiosis with D. trenchii Juveniles associated with D. trenchii grew the most at 31°C, but at 27.5°C, growth was fastest in juveniles associated with C. goreaui In conclusion, selective breeding with warmer GBR corals in combination with algal symbiont manipulation can assist in increasing thermal tolerance on cooler but warming reefs. Such interventions have the potential to improve coral fitness in warming oceans.This article has an associated First Person interview with the first author of the paper.

Author Correction: Some coral diseases track climate oscillations in the Caribbean.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP.

Stimulation with extracellular ATP causes a rapid initial transient rise followed by asynchronous periodic oscillations in cytosolic calcium ion activity ([Ca2+]i) in individual aortic smooth muscle cells in either HEPES-buffered or HCO3(-)-buffered saline. The dose at which one-half of the cells display an initial rise in cytosolic calcium is 0.11 microM ATP in the presence of external Ca2+ and 0.88 microM ATP in the absence of external Ca2+; the corresponding value for oscillations in the presence of external Ca2+ is 2.6 microM ATP. While the initial transient displays rapid desensitization, the oscillations persist for greater than 30 min in the continuous presence of ATP. The presence of the agonist ATP is also absolutely required for the maintenance of the oscillations, presumably to provide continuous activation of P2 purinoceptors. The average frequency of oscillation is approximately 0.9 min-1. The frequency depends only slightly on the concentration of ATP, and oscillations do not collapse into a prolonged elevated [Ca2+]i at high concentrations of ATP. Both Ca2+ influx and release from internal stores participate in the initial transient. Oscillations are not produced in the absence of external Ca2+ but are initiated upon the addition of external Ca2+ in the continued presence of ATP. Oscillations in progress are abolished by the removal of extracellular Ca2+ with one additional peak occurring after the Ca2+ removal. These data suggest that extracellular Ca2+ influx is required for the maintenance of the posttransient oscillations, presumably to provide the Ca2+ necessary for refilling intracellular Ca2+ pools that are the source of the oscillating [Ca2+]i. The Ca2+ influx is not regulated by voltage-gated Ca2+ channels. The data in this report are consistent with the view that the initial transient has contributions from two receptor-mediated pathways, and the oscillations are controlled either by a mechanism separate from the ones that control the initial transient or by steps whose control diverges before the point of desensitization.

Some coral diseases track climate oscillations in the Caribbean.

Disease outbreaks continue to reduce coral populations worldwide. Understanding coral diseases and their relationships with environmental drivers is necessary to forecast disease outbreaks, and to predict future changes in coral populations. Yet, the temporal dynamics of coral diseases are rarely reported. Here we evaluate trends and periodicities in the records of three common coral diseases (white-band disease, yellow-band disease, and dark-spot syndrome) that were surveyed between 1997 and 2014 at 2082 sites throughout the Caribbean. The relationship between the periodicities of disease prevalence and El Niño Southern Oscillation (ENSO) cycles was examined using cross-wavelet analyses and convergent cross mapping (CCM). The prevalence of the diseases peaked every two to four years, and matched periodicities in ENSO conditions. CCM models suggested that environmental conditions associated with recent ENSO cycles may have influenced the patterns in disease prevalence. We also found no increasing trends in disease prevalence through time. Instead, our work suggests that the prevalence of coral diseases is dynamic and complex. The gradual increase in sea-surface temperature, a consequence of increasing greenhouse gas emissions, progressively raises the modal temperature threshold of each ENSO cycle. These dynamic cycles and the increasing modal temperatures appear to influence the dynamics of coral diseases.

Is the binding of the lectin Helix pomatia agglutinin (HPA) of prognostic relevance in tumours of the upper aerodigestive tract?

The lectin Helix pomatia agglutinin (HPA) has been used as a prognostic indicator in a number of clinical studies including those of breast, colorectal and gastric cancer. Binding of HPA to tissue sections was associated with a bad prognosis indicating that the carbohydrate residue recognized by this lectin is linked to metastasis. In order to investigate whether HPA binding is also of prognostic relevance in squamous cell carcinomas of the upper aerodigestive tract, 53 tumours of this region were stained with HPA. Almost all tumours (95%) bound HPA to various degrees and hence HPA binding is of no prognostic relevance in this group of tumours. These findings indicate a fundamental difference in the role of carbohydrate residues in metastasis between squamous cell carcinoma (as in our study) and in tumours derived from glandular tissues such as breast, colon and stomach.

Dysphagia after fast neutron therapy to the head and neck.

Nine patients presenting with dysphagia following successful treatment for head and neck cancer with neutron radiotherapy are reviewed. Combined clinical and videofluoroscopic investigation is used to analyse their deficits and provide indications for management. All patients show impairment of both the oral and pharyngeal phases of the swallow, with the exception of one subject who shows signs of focal neurological damage. It is suggested that fibrosis is the underlying cause of dysphagia in the remainder.

Observations on femoral head abnormalities in broilers.

Detachment of the proximal femoral cartilaginous epiphysis was observed in broilers that were being down-graded at slaughter as a result of haemorrhage into thigh musculature. A traumatic aetiology is proposed with injury occurring at catching. Examination of field case material, and birds culled from a commercial flock of the same strain, revealed that physeal lesions are not infrequent in proximal femora. Clefts and areas of matrix necrosis occurred in normal and dyschondroplastic physeal cartilage. Clefts were thought to result from repetitive minor trauma insufficient to cause total detachment of the cartilaginous epiphysis. Total detachment may result from an acute traumatic episode or be a consequence of pre-existing physeal lesions. A traumatic aetiology suggests that in such cases the terms fracture separation or traumatic epiphyseolysis of the cartilaginous epiphysis are more appropriate than femoral head necrosis or degeneration.

Tendon lesions in broiler fowls.

Tendon lesions have been studied in 35 broiler or broiler breeder fowls. Tendon rupture most commonly affected the gastrocnemius and flexor muscles but was also seen in cranial tibial muscles (four cases) and the patellar tendon (one case). In nine birds tenosynovitis, characterised by a marked inflammatory response, was identified. In others, however, rupture occurred without appreciable inflammation and these cases were concluded to be comparable to spontaneous tendon rupture in other species. A traumatic aetiology is suggested in these cases, as other pelvic limb tendons or ligament rupture was a frequent concomitant finding. Degenerative tendon lesions were present but it is uncertain whether such changes are primary or secondary to rupture.

Malignant tumours of the tongue in young adults. Experience of a secondary referral centre.

Twenty-three cases of malignant tongue tumours in patients aged 15 to 30 are reported. Treatment and prognosis in the 18 for which follow-up information is available are discussed. The disease appears to be very similar to that in older subjects except for a greater incidence of neck node metastases. Close follow-up after primary treatment is essential since there is a high possibility of recurrent disease but which may respond well to salvage surgery if identified early. A greater awareness of the occurrence of tongue cancer in young adults is also necessary.

A survey to determine the extent of previous symptoms and surgery on patients presenting with nasal polyps.

The aim of our study was to investigate the prevalence of surgery on the nose prior to first time diagnosis of nasal polyps. We interviewed 60 patients who presented to the ENT Department at the Royal South Hants Hospital Southampton and were diagnosed as suffering from nasal polyps for the first time. Patients who suffered from cystic fibrosis or known primary ciliary dyskinesia were excluded. The average length of time of nasal blockage as the main symptom prior to the diagnosis of nasal polyps was less than two years. Out of the 60 patients six (10 per cent) had had previous nasal surgery. Out of these six patients, only four patients had a previous procedure on the nose that could be considered to be related to the later diagnosis of nasal polyps. Only one patient had had radiological investigation of his sinuses in the past. We conclude that polypoid nasal disease is a de novo diagnosis with a relatively short history in the majority of patients and not preceded by a long history of ENT investigations nor surgery on the nose.

Quinsy following tonsillectomy (five case reports).

Five cases of post-tonsillectomy quinsy are presented, usually associated with tonsillar remnants. Four of these had no pus and one did, but the clinical picture was the same. Hence, if tonsillectomy is performed to prevent further quinsies, it must be careful and complete.

Adult floppy epiglottis: a simple surgical remedy.

Epiglottic prolapse during inspiration is an unusual cause of upper airway obstruction. We present a case of a previously fit, 73-year-old, male with upper airway obstruction secondary to a floppy epiglottis. We describe a simple method of treatment without the need for partial or total excision of the epiglottis or tracheostomy.

Nasal septal chondrosarcoma (a long-term follow-up report).

A case of nasal septal chondrosarcoma is presented which, after radical surgery, recurred after seven and a half years. The post-mortem findings showed gross local spread and dural seedlings. The clinical implications are discussed and the literature reviewed.

Marginal mandibulectomy for malignant disease: indications, rationale, and results.

The theoretical basis for performing marginal mandibular resection, as opposed to segmental resection, is discussed; and criteria are suggested. Results are presented that suggest that, in the treatment of malignant disease around the jaw, although the mortality from other tobacco- and alcohol-related diseases remains high, good functional and cosmetic results can be achieved with no loss of local control.

Advanced laryngeal cancer: a management perspective.

A retrospective study of 197 T3 and T4 squamous cell carcinomas of the larynx presenting between 1969 and 1978 has been undertaken. These patients have in the main been treated by primary radiotherapy with back-up salvage surgery. The aim of the study was to examine survival, and to try to identify reasons for failure of control. Various prognostic factors have been analysed and are discussed. Overall 5-year survival was 53 per cent but patients with nodal disease responded poorly. Subglottic tumours have a better survival than usually reported. Failure to pick up recurrence was the main problem, and in particular a persistently fixed cord carried a very poor prognosis if laryngectomy was delayed.

A rare case of dysphagia: hypopharyngeal amyloidosis masquerading as a post-cricoid tumour.

Amyloidoses are a group of disorders in which deposition of abnormal amounts of protein complexes (amyloid) occurs in a variety of tissues. The upper aerodigestive tract may be affected, particularly the larynx, but hypopharyngeal involvement is rarely reported. We present a unique case of amyloidosis of the post-cricoid region causing dysphagia. This case report highlights the need for otolaryngologists to consider the possibility of submucosal amyloid deposition, in the absence of mucosal lesions, in patients who present with dysphagia secondary to an obstructive lesion of the post cricoid region.