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Biomedical subjects

N Stafford

Publications and source records attributed to N Stafford.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2005

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.

Aged↗
PubMed2005

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.

Biopsy↗
PubMed2004

Radioresistant laryngeal cancer: beyond the TNM stage.

Early stage squamous cell carcinoma of the larynx can be effectively cured by radiotherapy. Unfortunately treatment failures do occur and at present cannot be predicted by the clinician. This article reviews the potential molecular and cellular markers that may help to predict radioresistance in early stage laryngeal cancer.

Biomarkers, Tumor↗
PubMed2004

Expression of Cox-2 protein in radioresistant laryngeal cancer.

BACKGROUND: Radiotherapy is the principal modality used to treat early stage laryngeal cancer. Unfortunately treatment failures occur in 10-25% of patients. Subsequent salvage surgery is technically more difficult, with increased complication and failure rates. The ability to predict or prevent radioresistance would improve the poor survival associated with this disease. Cox-2 is an inducible enzyme involved with prostaglandin synthesis. We investigated a potential role for Cox-2 in predicting radioresistance in laryngeal cancer. PATIENTS AND METHODS: Using immunohistochemical techniques we examined the expression of Cox-2 protein in 122 pre-treatment laryngeal biopsies. All tumours were treated with single modality radiotherapy (curative intent). The group comprised of 61 radioresistant and 61 radiosensitive tumours matched for T stage, laryngeal subsite, gender and smoking history. RESULTS: Cox-2 expression was detected in 41 of 61 (67%) biopsy samples from patients with radioresistant tumours and 25 of 61 (41%) radiosensitive tumours. Overexpression was significantly associated with radioresistant tumours (P = 0.004). Cox-2 has a 67% accuracy in predicting radiotherapy failure. CONCLUSION: Cox-2 may have prognostic value in predicting response to radiotherapy. Cox-2 inhibitors such as NS-398 have been shown to enhance the effects of radiotherapy. We suggest that their use may be beneficial in patients who are destined to fail radiotherapy.

Aged↗
PubMed2004

A literature review of head and neck cancer patients information needs, experiences and views regarding decision-making.

This study reviews the body of existing research undertaken to explore head and neck cancer patients experiences of treatment for surgery, their information needs and their views regarding decision-making. Patients who suffer head and neck cancers and undergo surgery often report considerable psychological distress and impaired social functioning. To optimize survival, the decision about what treatment option to follow is often made quickly, with little support in terms of counsel or the provision of information. It is suggested that there is inadequate previous work exploring the content and delivery of information required by patients, their experiences and their views regarding decision-making to guide appropriate clinical interventions. By assimilating and critiquing existing work in this review an appropriate focus for further research is likely to be determined. An electronic search of relevant databases was undertaken including Cinahl, Medline, Psychinfo, Assia, the Cochrane Library and British Nursing Index. In addition, a grey literature search was also undertaken by hand. The search strategy was developed using recommendations from the Centre for Reviews and Dissemination 'Guidance for Those Carrying Out or Commissioning Reviews' (CRD Report Number 4, 2001). There is significant psychosocial and other functional disturbance amongst survivors of head and neck cancer surgery. Improved information giving may play a part in determining these outcomes.

Decision Making↗
PubMed1996

Recurrent aspergilloma of the frontoethmoid sinus in a non-immunocompromised patient.

Management of invasive aspergillosis of the paranasal sinuses requires sufficient experience to initiate appropriate investigations and then utilize the correct treatment protocol. Computed tomography (CT) or magnetic resonance imaging (MRI) is essential to show the extent of the disease and diagnosis is confirmed by histological analysis. Aspergillus flavus is a ubiquitous soil saprophyte in the Sudan and is responsible for many cases originating from this area. The literature is reviewed and treatment options discussed.

Adult↗
PubMed1995

Radiolabeled antibody combined with external radiotherapy for the treatment of head and neck cancer: reconstruction of a theoretical phantom of the larynx for radiation dose calculation to local tissues.

We propose to use radiolabeled antibodies in combination with external beam radiotherapy to improve locoregional control of head and neck cancer. In this case radiation toxicity to mucosa may become a dose-limiting factor and a calculation of the possible compensatory decrease to the external beam radiotherapy would be needed. For this purpose, the following theoretical phantom of a representative organ of this anatomic region, the larynx, was reconstructed and local dosimetric data were derived for a selection of beta-emitting isotopes. The phantom was reconstructed as cylindrical concentric tubes using the established values of an outer diameter of 38 mm and a height of 44 mm. Published mean adult larynx weight (28 g) and cartilage weight (14.7 g) were used. Mean mucosa weight from 5 mucosa samples of our patients was calculated to be 2.0 +/- 0.4 (SD) g. The remaining weight was apportioned to a fat/muscle compartment (11.3 g). The specific gravity of cartilage (1.10 g/cm3), mucosa (1.04 g/cm3), and fat/muscle (1.04 g/cm3) were used to cross-check the volume/mass disparity of the theoretical tubular tissue shells. The established maximum glottic diameter of 24 mm was used to calculate the central air column volume. Mean laryngeal tumor volume from 8 representative laryngeal tumors was 4.4 +/- 3.1 cm3. Tissue compartment thickness was 660 microns for mucosa, 3100 microns for muscle/fat, and 3320 microns for cartilage. These values allowed the calculation of dose absorbed fractions for a number of theoretical radioimmunoconjugates by extending the established calculation of absorbed fractions for spheres of known diameter to absorbed fractions of tissue planes (annuli) of known thickness. We calculated a Deq for the respective tissues in the larynx for 131I-, 186Re-, 188Re-, 67Cu-, 90Y-, and 153Sm-labeled HMFG1. Compensatory decrease to the external radiotherapy dose is 1.1 Gy for each injection of the radioimmunoconjugate we propose to use (131I-HMFG1). This would be best implemented through the modification of the external radiotherapy fractions falling within 2 effective half-lives of this radioconjugate in the mucosa.

Aged↗
PubMed1995

Pharmacokinetics, biodistribution, and dosimetry of specific and control radiolabeled monoclonal antibodies in patients with primary head and neck squamous cell carcinoma.

The pharmacokinetics, biodistribution, and dosimetry of an IgG1 radiolabeled anti-mucin mAb (HMFG1) and an isotype-matched control (4D513) were studied in 29 patients with primary head and neck squamous cell carcinoma. Patients were given injections at 3 fixed time points prior to surgery, i.e., 24 (n = 12), 48 (n = 9), or 72 (n = 8) h. They were subsequently classified into two groups based on their immunohistochemical positivity for polymorphic epithelial mucin. Fourteen patients (48%) were positive, 5 of which were studied with both antibodies; and 15 patients were negative (52%), 7 of which were studied with both antibodies. There was no significant difference in serum pharmacokinetics and cumulative urinary clearance of the two antibodies. There was no significant difference in overall normal tissue uptake of specific and control antibody; however, when each component of the normal tissue category was analyzed individually, there was a significantly increased uptake of HMFG1 in mucosa as compared to control antibody. Immunohistochemical studies revealed positive staining of mucosa with HMFG1. There was significantly increased uptake of specific antibody in antigen-positive tumors as compared to uptake of control antibody (P < 0.02). A tendency for less label loss over time from positive tumors as compared to control was documented. Absolute antibody uptake and tumor/normal tissue ratios demonstrated significant overlap in individual patients from each category depending on the specific ratio (e.g., tumor/adipose tissue) or time point studied; hence arbitrary cutoff values could not be recommended as indicators of specific uptake. Specificity and localization indices were the most reproducible indicators of specific localization. Areas under the curve were calculated for all tissues, and local dosimetry for the two beta-emitting isotopes 131I and 90Y is presented. The Deq values for antigen-positive tumors were 2.9 cGy/mCi for 131I and 9.0 cGy/mCi injected for 90Y. For antigen-negative tumors these values were significantly lower at 0.83 and 2.4 cGy/mCi of 131I and 90Y, respectively. Bone marrow Deq was calculated to be 0.87 cGy/mCi of 131I-HMFG1 injected. Because the purpose of our ongoing research is to assess the therapeutic potential of the combination of radiolabeled antibody and external radiotherapy, detailed dose calculation to local dose-limiting tissues is required. Deq to mucosa was calculated to be 1.1 and 3.8 cGy/mCi of injected 131I and 90Y, respectively. We conclude that a 9-10-Gy dose increment may be achieved in two administrations of 150 mCi of 131I-HMFG1 during a course of external radiotherapy. This may lead to improved control of local disease in patients with head and neck cancer.

Adult↗
PubMed1992

Complications following fast neutron therapy for head and neck cancer.

Serious complications resulting from the use of fast neutrons to treat head and neck malignancies are reported in 38 patients. The average interval between treatment and onset of complications was 5.5 years. Significant airways obstruction, requiring a tracheostomy, occurred in two patients, and a gastrostomy or pharyngostomy was performed for intractable dysphagia in six. Eight patients developed osteoradionecrosis: carotid artery rupture occurred in three patients following surgery for residual or recurrent disease. Our experience suggests that complications following fast neutron therapy for head and neck tumours are more severe, more common and occur after a longer time interval than those seen following conventional radiotherapy. Subsequent surgery in the irradiated area is compromised by severely impaired wound healing. When radical surgery is necessary for residual or recurrent disease the entire volume of irradiated tissue must be removed if healing is to be achieved.

Airway Obstruction↗
PubMed1992

Ligation of the external carotid artery for severe epistaxis.

Epistaxis which is not controlled by anterior and posterior nasal packing is usually treated by ligation or embolization of the arterial supply to the nose. Transantral ligation of the maxillary artery, or embolization of its branches, have recently been considered the treatments of choice. Ligation of the external carotid artery has the advantage of being a short procedure which can be readily performed under local anesthesia, and does not require particular surgical expertise or the use of specialized equipment. This procedure, in combination with ligation of the ipsilateral anterior ethmoidal artery, controlled the bleeding in 14 of 15 patients over a nine-year period. There were no deaths and no significant complications. Although ligation and embolization of the maxillary artery are of proven efficacy, ligation of the external carotid artery is similarly effective and its simplicity may still make it the procedure of choice in some situations.

Adult↗
PubMed1991

Papillary carcinoma in thyroglossal duct remnants.

About 100 cases of carcinoma arising in thyroglossal remnants have been reported in the world literature. Five additional cases were discovered incidentally on histopathological examinations of specimens following Sistrunk's operation for removal of thyroglossal cysts and are now reported. The possibility of preoperative clinical diagnosis and the modalities of treatment are discussed.

Adenocarcinoma↗
PubMed1989

Recent experience with reconstructive surgery following major glossectomy.

In an attempt to monitor the impact of new reconstructive procedures and shifting interest away from routine preoperative radiotherapy, we have reviewed the 81 patients undergoing major glossectomy and reconstruction (MGR) at the Royal Marsden Hospital, London and Surrey, England, between 1975 and 1987. While there were four marginal and 13 major reconstructive failures, 11 of the latter were successfully managed with an alternative flap, thus providing a prompt and effective palliation for most of these patients. An evolution in our choice of reconstructive procedures as well as a recent trend toward using MGR as a primary therapeutic modality were noted. Data relating to speech following reconstruction and diet rehabilitation were encouraging, particularly with the use of the latissimus dorsi flap. Survival following MGR, however, was dismal due to early local and regional recurrence.

Adult↗
PubMed1988

Treatment of 'inoperable' neck nodes using surgical clearance and postoperative interstitial irradiation.

The inability to remove all disease at the time of a radical neck dissection, or inoperable recurrent disease after a neck dissection, are both familiar problems for the head and neck surgeon. All too frequently the conventional treatment options have already been used, the patient having received external beam radiotherapy and possibly cytotoxic chemotherapy. In such circumstances, and provided that the primary tumour remains under control, a positive approach to the further management of the neck metastases should be adopted, given that the patient is in otherwise reasonable health and does not have gross distant metastatic disease. We describe our experience with postoperative interstitial irradiation (brachytherapy) using after-loaded iridium-192 (192Ir) wires positioned at the site of the tumour after its surgical exposure and debulking or clearance. All the treated patients had previously received external beam irradiation to the neck and in the first three cases local skin necrosis occurred as a sequel to interstitial implantation. Therefore, in the other five patients, cutaneous or myocutaneous flaps were used to resurface the area at the time of implant placement. This combination of techniques, which has not been described previously, provided local tumour control in four out of the five cases without irradiation necrosis occurring in any of them.

Adult↗
PubMed1986

The treatment of recurrent tonsillitis in adults.

A prospective study comparing surgical and antibiotic treatment for recurrent tonsillitis in adults suggests that, whilst tonsillectomy is very effective, adequate medical treatment provides an equally good alternative in the majority of patients.

Adolescent↗