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N D Stafford

Publications and source records attributed to N D Stafford.

At least 19 recordsLinked to original sources
PubMed2006

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.

Aged↗
PubMed2005

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.

Antigen Presentation↗
PubMed2004

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.

Adult↗
PubMed2004

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.

Carcinoma, Squamous Cell↗
PubMed2004

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.

Cartilage↗
PubMed2004

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.

Adult↗
PubMed2003

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.

Biomarkers, Tumor↗
PubMed2003

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2001

The expression of vascular endothelial growth factor (VEGF) and VEGF-C in early laryngeal cancer: relationship with radioresistance.

Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF-C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty-two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow-up was 2 years after radiotherapy. Expression of VEGF and VEGF-C was evaluated by immunohistochemistry of formalin-fixed, paraffin-embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF-C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF-C (P < 0.001). In addition, the expression of VEGF-C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF-C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF-C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.

Adult↗
PubMed2001

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.

Attitude of Health Personnel↗
PubMed2000

Angiogenesis in head and neck squamous cell carcinoma.

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.

Angiogenesis Inducing Agents↗
PubMed1999

Genetic analysis of head and neck squamous cell carcinoma and surrounding mucosa.

OBJECTIVE: Comparative genomic hybridization was performed on head and neck squamous cell carcinoma and surrounding mucosa to determine whether common chromosomal aberrations could be detected that would predispose an individual to developing a second primary tumor. DESIGN: Biopsy specimens were taken from 19 patients with squamous cell carcinoma of the head and neck, 3 samples from each person: 1 specimen from the tumor site and 1 each from 1 and 5 cm from the macroscopic tumor margin. Samples were snap frozen in liquid nitrogen. A portion of each distant sample and tissue taken from immediately adjacent to the site of the tumor specimen were sectioned and stained with hematoxylin-eosin, either to search by light microscopy for tumor cells or signs of dysplasia in the distant samples, or to determine whether the tumor specimen had substantial non-tumor cell content. Tissue adjacent to the tumor biopsy site was used because the biopsy specimens were relatively small. Comparative genomic hybridization was performed on all samples. SUBJECTS: Nineteen patients with newly diagnosed carcinomas of the head and neck. RESULTS: The tumor biopsy specimens showed no substantial nontumor cell content, and the distant specimens were all histologically normal. The tumors showed multiple mutations: mean (SD) number of deletions, 5.4 (4.3); amplifications, 5.2 (4.6). Deletion of chromosome 3p was seen in 13 of 19 cases and was associated with amplification of 3q in 10 cases. No mutations were seen in the distant biopsy specimens. CONCLUSIONS: Frequently occurring chromosomal aberrations were seen in the tumor cells, suggesting a key role for these mutations in tumor development. Screening histologically normal upper aerodigestive tract mucosa with comparative genomic hybridization does not provide information on early genetic events that predispose a patient to developing a second primary tumor.

Aged↗
PubMed1999

Pleomorphic adenoma of the nasal septum.

Pleomorphic adenoma is the commonest benign tumour of the major salivary glands. It can also occur in minor salivary glands, mainly in the oral cavity, but also in other sites in the head and neck both within and outwith the upper aerodigestive tract. We present a rare case of pleomorphic adenoma of the nasal septum with consideration of the clinical management and a review of the literature.

Adenoma, Pleomorphic↗
PubMed1999

The effect of pH of douching solutions on mucociliary clearance.

The effect of the pH of hypertonic saline nasal douching solutions on mucociliary clearance was studied in order to investigate the common notion that such solutions should be buffered alkaline. Thirty normal subjects were included in a randomised controlled crossover trial. Mucociliary clearance was measured by the saccharin clearance time. There was no difference in mucociliary clearance after douching with a non-buffered solution and a solution buffered to pH 8. However both solutions significantly improved mucociliary clearance compared to the baseline (P < 0.001) probably on account of their hypertonicity.

Adult↗
PubMed1999

Serum vascular endothelial growth factor in patients with head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is a key pro-angiogenic cytokine expressed by most human tumours. Two isoforms, VEGF121 and VEGF165, are soluble and can be assayed in serum. Serum VEGF has been shown to be significantly raised in patients with solid tumours and shows some promise as a potentially useful tumour marker. Serum levels of VEGF were assayed in 52 patients with untreated head and neck squamous cell carcinoma (HNSCC) and 104 healthy controls. Serum VEGF is significantly raised in patients with HNSCC (P < 0.001), but there was no association with either tumour stage or specifically the presence of nodal metastases. Sixteen patients (31%) had a higher serum VEGF than 95th centile of controls, suggesting that serum VEGF measurement is of little practical use as an initial diagnostic tool. The finding that patients with HNSCC have significantly raised serum VEGF probably relates to enhanced platelet aggregation in these patients.

Aged↗