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.

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.

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.

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.

Defining the criteria for radioresistant laryngeal cancer.

Survival rates for head and neck cancer are comparatively poor, typically 40% at 5 years. Radiotherapy is one of the most common modalities used to cure early-stage cancers. It has the advantage in that it preserves anatomical structure and function. However, treatment failures do occur necessitating salvage surgery if a cure is to be achieved. A universally accepted definition of radioresistant cancer does not exist. Second primaries and occult metastasis are common in head and neck cancer, and can be confused with true radioresistant tumours. We suggest a strict definition for radioresistant laryngeal cancer and characterize 66 radioresistant tumours stage matched to 66 radiosensitive tumours. It was not possible to differentiate the radioresistant group from the radiosensitive groups using tumour differentiation. By using an agreed set of criteria defining radioresistant head and neck tumours, researchers will be better able to investigate molecular and cellular markers of radioresistance.

Computerised tomography vs. pathological staging of laryngeal cancer: a 6-year completed audit cycle.

The aim of this audit was to examine the accuracy of computerised tomography (CT) staging of advanced laryngeal tumours. CT staging was evaluated against the T staging of laryngeal tumours as determined by pathological examination. Data from 38 patients, between 1996 and 2000 with laryngeal squamous cell cancer that fulfilled the audit criteria, were collected and compared. Subjects had to have a pre-operative CT scan of the larynx and a total laryngectomy specimen for pathological staging. The audit demonstrated that 45% of the patients were over staged and 10% were under staged using CT criteria as compared to pathological staging. Fourteen patients had been erroneously up staged to T4 on the basis of laryngeal cartilage invasion as judged by the radiological sign of cartilage sclerosis. While this radiological sign is used as a marker of neoplastic invasion in the literature, it was found to have a low sensitivity of 62% and low specificity of 42% in this study. Arytenoid cartilage sclerosis in isolation was no longer used as a radiological sign of neoplastic cartilage invasion. Following the change in practice, the CT staging of laryngeal cancer was re-evaluated in a second audit cycle. Correct CT staging of the tumour improved from 45 to 71%. Arytenoid cartilage sclerosis is no longer used as a sole CT criterion for predicting neoplastic cartilage invasion at our institution.

Can a genetic signature for metastatic head and neck squamous cell carcinoma be characterised by comparative genomic hybridisation?

Survival from head and neck squamous cell carcinoma (HNSCC) has remained static for the last 20 years. The development of lymph node metastasis (LNM) significantly reduces the 5-year survival rate, thus the ability to identify tumours with the potential to metastasise would allow more aggressive treatment regimes to be directed at these patients regardless of negative clinical and radiological findings at the time of presentation. Comparative genomic hybridisation (CGH) can identify chromosomal aberrations that may lead to metastasis. DNA from 23-paired specimens of primary tumour (PT) and LNM were analysed. Nonrandom copy number changes were identified in all paired samples. Similar numbers of aberrations were identified on PT and LNM samples. The most common aberrations were 3q (90%), 8q (65%), 1q (50%), 5p (43%), 2q (41%) and 11q (41%) and deletions 3p (57%), 1p (54%), 4p (48%), 13q (48%), 11q (41%) and 10q (37%). A number of differences were also detected. No aberration was found to be preferentially associated with the LNM, although gains on 6q (48 vs 22%) and 22q (26 vs 9%) were found at higher frequencies. Clonality studies demonstrated that LNM develop from the dominant population of cells in the PT. These results were compared with two similar publications. No combination of chromosomal aberrations, as detected by CGH, was associated with metastatic progression in HNSCC.

The immunohistochemical localisation of somatostatin receptors 1, 2, 3, and 5 in acoustic neuromas.

AIMS: Acoustic neuroma is a benign tumour, which develops through an overproliferation of Schwann cells along the vestibular nerve. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane bound receptor subtypes. The aim of this study was to determine whether somatostatin receptor subtypes (SSTRs) 1, 2, 3, and 5 are present in acoustic neuromas. METHODS: The expression of SSTRs 1, 2, 3, and 5 was studied in both the Schwann cells and blood vessels of eight acoustic neuroma specimens, by means of immunohistochemistry using novel rabbit polyclonal antibodies raised against human SSTR 1, 2, and 5 subtype specific peptides, and a commercial anti-SSTR3 antibody. RESULTS: SSTR2 was the most prevalent subtype in Schwann cells (seven of eight), with intermediate expression of SSTR3 (six of eight), and lower expression of SSTRs 1 and 5 (four of eight and five of eight, respectively). There was ubiquitous vascular expression of SSTR2, with no evidence of SSTR 1, 3, or 5 expression in blood vessels. CONCLUSION: SSTRs 1, 2, 3, and 5 are differentially expressed in acoustic neuromas. Somatostatin analogues may have a therapeutic role in the management of this rare and challenging condition.

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation.

A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. Kaplan-Meier survival analysis revealed significant correlations between gain of 3q25-27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.

The expression of somatostatin receptors 1 and 2 in benign, pre-malignant and malignant laryngeal lesions.

The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane-bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre-malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre-malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low-to-moderate levels in only 2/6 (33%) pre-malignant and 3/12 (25%) malignant specimens (P < 0.01). This 'loss' of epithelial SSTR2 expression may provide a growth advantage in pre-malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre-malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.

Circulating angiogenic cytokines as tumour markers and prognostic factors in head and neck squamous cell carcinoma.

This pilot study investigated the potential use of three circulating angiogenesis-related cytokines, basic fibroblast growth factor (bFGF), angiogenin (ANG) and endostatin, as tumour markers and prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). A total of 30 patients with HNSCC treated with curative intent and 15 healthy controls were studied. Serum (bFGF and ANG) and plasma (endostatin) was assayed by enzyme-linked immunoabsorbance assay (ELISA). None of the cytokines was raised in HNSCC patients when compared with controls. Serum bFGF was not associated with any clinico-pathological or outcome parameters, although there was a trend towards higher levels in more advanced and aggressive tumours. Lower serum angiogenin (sANG) levels were associated with loco-regional disease recurrence (P = 0.036). Using a cut-off level of 400 pg/mL, a low level of sANG predicted tumour recurrence with a relative risk of 4.0 (95% CI: 0.7-24.0). Plasma endostatin was associated with higher histological grade (P = 0.01) and with both disease recurrence (P = 0.045) and death from disease (P = 0.021). Plasma endostatin above a cut-off point of 70 ng/mL could predict tumour recurrence with a relative risk of 4.7 (95% CI: 1.1-19.7). These data suggest that plasma endostatin and sANG have potential roles as prognostic factors and require further investigation.

Surgeon information giving practices prior to laryngectomy: a national survey.

Prior to the proposed development of a pretreatment counselling package for patients with cancer of the larynx or pharynx, a study was undertaken to determine current information giving practice prior to laryngectomy. A postal questionnaire was sent to all UK ENT consultants registered in the Medical Directory. The response rate was 88%, with 48% meeting the study's entry criteria. Counselling practice varies widely. Surgeons report an average of 15 min available for discussion with the patient: 84% gave the diagnosis and discussed the treatment options at the same consultation. The size of the department, as measured by cases seen per year, did not correlate with the consultation time although it did with the numerous different issues discussed. Whilst the survey supports the need and desire for an appropriate counselling package, many surgeons feel that they alone know what the patient's information needs are.