Clinical research, national studies and grant applications: United Kingdom National Multidisciplinary Guidelines.

Head and neck cancer clinical research is thriving. Infrastructure for clinical research is supported through the National Institute for Health Research Clinical Research Network with operates through 15 local clinical research networks for studies within the UK Clinical Research Network Portfolio. The National Clinical Research Institute is a partnership of UK cancer research funders that support high-quality cancer research, although the National Institute for Health Research also has funding streams that will fund cancer-related research. Their websites provide up-to-date information regarding ongoing research projects. Other specialty organisations such as the British Association of Head and Neck Oncologists play important subsidiary roles in supporting research.

Purpose and effectiveness of psychoeducation in patients with bipolar disorder in a bipolar clinic setting.

OBJECTIVE: This article reviews psychological therapies in the treatment of bipolar disorder, in particular psychoeducation, and how the inclusion of four fundamental principles - patient/therapist communication, flow of information, patient involvement and a trusting relationship - can improve patient outcomes. METHOD: The content of this article is based on the proceedings of a 1-day standalone symposium in November 2011 exploring how to establish a bipolar clinic within the context of existing services in the UK's National Health Service. RESULTS: Certain psychological interventions have emerged as beneficial add-on treatments to pharmacotherapy in bipolar disorder and are associated with greater stabilisation of symptoms, fewer relapses and longer time to relapse. Psychoeducation is a simple approach to support prevention of future episodes by delivering behavioural training to improve illness insight, early symptom identification and development of coping strategies. Empowering patients to actively participate in their treatment provides independence, counteracts the current disconnect of therapist and patient, and increases awareness and understanding of the challenges of living with and treating bipolar disorder. CONCLUSION: Psychoeducation enables patients to understand bipolar disorder, get actively involved in therapy planning, and be aware of methods for episode prevention, therefore effectively contributing to improved treatment outcomes and patient quality of life.

Post radiation myofibrosarcoma of hypopharynx.

Malignant tumours of myofibroblasts are rare lesions. Post radiation sarcoma is a rare potential late sequel of ionizing radiation. We present the first case of myofibrosarcoma of the hypopharynx in a 67-year-old man, occurring 16 years after radiotherapy for laryngeal carcinoma.

Do-it-yourself grommets.

In the absence of a healthcare budget enabling the import of ready-made aural grommets, Myanmar ENT surgeons have devised an ingenious 'home-grown' solution. We describe how grommets are made from raw materials bought from the local market.

Resting behaviour of Anopheles gambiae s.l. and its implication on malaria transmission in Uyui District, western Tanzania.

An entomological survey to determine resting behaviour and species composition of malaria vectors was carried out in Uyui District in western Tanzania in May 2009. Mosquitoes were collected using indoor resting catch, window exit trap and outdoor "bed-net" techniques. The mosquitoes were identified using morphological key and polymerase chain reaction (PCR). A total of 672 Anopheles gambiae sensu lato were collected. Of these, 661 (98.4%) were collected outdoor whereas few (1.6%) were collected indoor. The exit trap catch: mechanical aspirator catch ratio was 1:1.75. The overall indoor resting density of An. gambiae s.l. as determined by mechanical aspirator and exit trap was 0.7 and 0.5 mosquitoes per room, respectively. The overall density of the host-seeking as determined by bed net trap outdoor was 44.1 mosquitoes per person. A sample of 44 specimens taken randomly from morphologically identified An.gambiae s.l. population was further analyzed to species level using PCR techniques. Of these 44 specimens 26 (59%) and 18 (41%) were Anopheles arabiensis and Anopheles gambiae sensu stricto respectively. This study contributes to the understanding of the distribution of malaria vectors with respect to species composition and their resting behaviour that could contribute to vector control operations in western Tanzania. A longitudinal study considering dry and wet seasons is recommended to provide more information on the seasonal distribution, abundance and biting behaviour of malaria vectors in the study area.

Quantifying the burden of rhodesiense sleeping sickness in Urambo District, Tanzania.

BACKGROUND: Human African trypanosomiasis is a severely neglected vector-borne disease that is always fatal if untreated. In Tanzania it is highly focalised and of major socio-economic and public health importance in affected communities. OBJECTIVES: This study aimed to estimate the public health burden of rhodesiense HAT in terms of DALYs and financial costs in a highly disease endemic area of Tanzania using hospital records. MATERIALS AND METHODS: Data was obtained from 143 patients admitted in 2004 for treatment for HAT at Kaliua Health Centre, Urambo District. The direct medical and other indirect costs incurred by individual patients and by the health services were calculated. DALYs were estimated using methods recommended by the Global Burden of Disease Project as well as those used in previous rhodesiense HAT estimates assuming HAT under reporting of 45%, a figure specific for Tanzania. RESULTS: The DALY estimate for HAT in Urambo District with and without age-weighting were 215.7 (95% CI: 155.3-287.5) and 281.6 (95% CI: 209.1-362.6) respectively. When 45% under-reporting was included, the results were 622.5 (95% CI: 155.3-1098.9) and 978.9 (95% CI: 201.1-1870.8) respectively. The costs of treating 143 patients in terms of admission costs, diagnosis, hospitalization and sleeping sickness drugs were estimated at US$ 15,514, of which patients themselves paid US$ 3,673 and the health services US$ 11,841. The burden in terms of indirect non-medical costs for the 143 patients was estimated at US$ 9,781. CONCLUSIONS: This study shows that HAT imposes a considerable burden on affected rural communities in Tanzania and stresses the urgent need for location- and disease-specific burden estimates tailored to particular rural settings in countries like Tanzania where a considerable number of infectious diseases are prevalent and, due to their focal nature, are often concentrated in certain locations where they impose an especially high burden.

Recurrent familial malignant carotid body tumour presenting with lymph node metastasis: case report, and review of diagnosis and management of familial carotid body tumours.

OBJECTIVE: We report the case of a recurrent familial malignant carotid body tumour presenting with metastasis to local ipsilateral lymph nodes; the rarity of both recurrence combined with nodal spread is emphasised in this article. METHOD: We present a case report, and a review of the world literature concerning the diagnosis and management of carotid body tumours in the familial setting. CASE REPORT: A woman with a family history of succinate dehydrogenase complex subunit B gene mutation presented with right vocal fold palsy. A causative carotid body tumour was excised. Fifteen years later, the patient developed a right-sided swelling in the jugulo-digastric region, together with shooting pains towards her right ear. Imaging revealed right posterior triangle lymphadenopathy. Fine needle aspiration cytology of the node was equivocal. Computed tomography of her neck revealed, in addition, a mass within the right side of the larynx. Excision biopsy of the lymph node demonstrated metastatic paraganglioma. A carotid angiogram revealed a right-sided carotid body tumour. This was embolised prior to neck exploration and excision of the carotid body tumour with en bloc resection of adjacent nodes. Histological analysis confirmed the presence of lymph nodes containing metastatic paraganglioma. CONCLUSION: This case report demonstrates the need for extra vigilance to enable early disease detection in the familial setting of carotid body tumour, in order to reduce the surgical morbidity associated with disease progression. In addition, our report highlights the atypical aspects of presentation in the familial setting, together with the difficulty and lack of standardisation regarding monitoring of the disease.

Oral voriconazole for invasive fungal skull base infection.

BACKGROUND: Intravenous amphotericin or intravenous voriconazole, both followed by oral voriconazole, have previously been given to treat invasive aspergillosis of the skull base. CASE REPORT: Exclusively oral voriconazole was used in an immunocompetent patient with biopsy-proven, invasive aspergillosis. She had a large, erosive lesion extending from the central skull base to the right orbit and ethmoid sinus, and displacing the right internal carotid artery. After four months of oral treatment as an out-patient, a repeated computed tomography scan showed a fully treated infection with post-infectious changes only, and treatment was terminated. Two years later, there had been no recurrence. CONCLUSION: Substantial cost savings were made by using exclusively oral treatment, compared with the use of intravenous voriconazole or amphotericin, or a switch strategy.

Immunotherapy in head and neck cancer: current practice and future possibilities.

The survival of patients with head and neck squamous cell carcinoma has changed little over the last 30 years. However, with recent advances in the fields of cellular and molecular immunology, there is renewed optimism with regards to the development of novel methods of early diagnosis, prognosis estimation and treatment improvement for patients with head and neck squamous cell carcinoma. Here, we present a critical review of the recent advances in tumour immunology, and of the current efforts to apply new immunotherapeutic techniques in the treatment of head and neck squamous cell carcinoma.

Head and neck tumour immunology: basic concepts and new clinical implications.

An understanding of the immune system and its modes of action is fundamental to understanding the causes, natural history, management and treatment of many diseases. As such, a grasp of the principles of immunology is essential for every physician.This paper represents a succinct overview of the immune system, discussing the major components in turn, in respect of structure, function and integrated organisation, in relation to head and neck cancer.

Genetic profile of head and neck squamous cell carcinoma: clinical implications.

The outcome for patients with head and neck squamous cell carcinoma remains poor, despite improvements in diagnosis and treatment over the past three decades. This has triggered great interest in the genetic events that underpin the aetiology and clinical behaviour of this group of cancers. As a result, the genetic profile for head and neck squamous cell carcinomas at different sub-sites has been relatively well characterised at the chromosomal level. Various studies have shown links between specific aberrations in head and neck squamous cell carcinoma and clinical outcome, e.g. loss of heterozygosity at 2q and 18q is commonly associated with poor prognosis, and loss of heterozygosity at 9p21 is associated with recurrence. However, there is as yet no significant clinical application of this genetic knowledge as regards the screening, diagnosis or treatment of head and neck squamous cell carcinoma. Here, we summarise the current state of knowledge, and highlight the most promising areas of research that may facilitate the translation of genetic data into clinical benefit.

Adult laryngeal rhabdomyosarcoma: report of a case and literature review.

Rhabdomyosarcoma is relatively seen in the pediatric age group with the head and neck region as the commonest site. To the best of our knowledge, few cases of laryngeal involvement in adult have been described in the literature. Biologically, rhabdomyosarcoma is different from squamous cell carcinoma, which is the commonest tumor of the larynx. A previously healthy non-smoker 77-year-old lady presented to the ENT outpatient with a six weeks history of intermittent alteration of voice quality. She had no history of sore throat, or any symptoms suggesting laryngo-pharyngeal reflux. Examination showed asymmetry of the left arytenoid cartilage and aryepiglottic fold. She subsequently had a direct laryngoscopy and biopsy. Histology and immunohistochemistry examination suggested the diagnosis of mesenchymal neoplasm. Following discussion at MDT she subsequently had a total laryngectomy. Histology confirmed a completely excised laryngeal rhabdomyosarcoma. Rhabdomyosarcoma of larynx in adult is a rare disease. Surgical treatment with or without adjuvant radiotherapy is currently the treatment of choice for this disease.

Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response. The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined. Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml, 37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169). These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.

Percutaneous endoscopic, radiological and surgical gastrostomy tubes: a comparison study in head and neck cancer patients.

A gastrostomy feeding tube has become the most acceptable method for long-term feeding support in patients with head and neck cancer. The aim of this study was to compare the complications of percutaneous endoscopically inserted gastrostomy (PEG) tubes, radiologically inserted gastrostomy (RIG) tubes and surgically inserted gastrostomy (open/laparoscopic) (SUR) tubes in head and neck cancer patients and also to compare the mortality rates of these patients. Seventy-eight head and neck cancer patients underwent gastrostomy tube insertion (40 PEG, 28 RIG and 10 SUR) during the period February 2002 to February 2005. There were no significant demographic differences between the three groups. Thirty-six patients (46 per cent) developed complications, 32 minor and four major. All three groups were similar in their rate of minor complications, with the dislodgement and blockage rate being lowest in the PEG group (p > 0.05). The mortality rate was 4 per cent within 30 days of gastrostomy tube insertion. There were no deaths in the PEG group, two deaths in the RIG group and one in the SUR group. The PEG tube was considered superior to the RIG and SUR gastrostomy tubes, had fewer complications and was safer. Thus, PEG tube insertion is our first choice for head and neck cancer patients.

Bcl-2 expression predicts radiotherapy failure in laryngeal cancer.

Early stage laryngeal cancer can be effectively cured by radiotherapy or conservative laryngeal surgery. In the UK, radiotherapy is the preferred first line treatment. However, up to 25% of patients with T2 tumours will demonstrate locally persistent or recurrent disease at the original site, requiring salvage surgery to achieve a definitive cure. Patients experiencing treatment failure have a relatively poor prognosis. A retrospective analysis was conducted consisting of 124 patients with early stage (T1-T2, N0) laryngeal squamous cell carcinoma. In total, 62 patients who failed radiotherapy were matched for T stage, laryngeal subsite and smoking history to a group of 62 patients successfully cured by radiotherapy. Using immunohistochemistry the groups were compared for expression of apoptotic proteins: bcl-2, bcl-X(L), bax, bak and survivin. Radioresistant laryngeal cancer was associated with bcl-2 (P < 0.001) and bcl-X(L) (P = 0.005) expression and loss of bax expression (P = 0.012) in pretreatment biopsies. Bcl-2 has an accuracy of 71% in predicting radiotherapy outcome. The association between expression of bcl-2, bcl-X(L) and bax with radioresistant cancer suggests a potential mechanism by which cancer cells avoid the destructive effects of radiotherapy. Predicting radioresistance, using bcl-2, would allow the clinician to recommend conservative laryngeal surgery as an alternative first line treatment to radiotherapy.

Assessment of dendritic cell number and radiosensitivity in laryngeal tumours.

OBJECTIVES: Radiotherapy is one of the principal treatment modalities for many types of head and neck tumour; what effects the dendritic cell (DC) population may have on treatment outcome have not been critically evaluated in laryngeal cancer. DESIGN: Retrospective, case-controlled study using immunohistochemistry to investigate the presence of S-100 positive DC in pre-treatment, archival biopsy tissue of early stage laryngeal cancers. SETTING: Patients with laryngeal cancer treated with radiotherapy in Head and Neck Departments in England. PARTICIPANTS: Patients diagnosed with early stage laryngeal cancer, treated with single modality radiotherapy with curative intent. Radioresistant tumours (n = 22), defined as recurrent tumours within 12 months of therapy. Radiosensitive tumours (n = 22), defined as no recurrence with a minimum follow-up of 36 months. MAIN OUTCOME MEASURES: Density of S-100 staining DC on three x200 magnified microscopic fields. RESULTS: DC were present in approximately equal numbers in both radioresistant and radiosensitive laryngeal tumour pre-treatment biopsies and therefore density did not correlate with radiotherapy treatment outcome (P = 0.420). CONCLUSION: There is no intrinsic deficiency in DC number in radioresistant laryngeal tumours meaning that such tumours could potentially benefit from vaccination strategies that enhance the specific anti-tumour immune response.

Dendritic cells and HNSCC: a potential treatment option? (Review).

Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response.