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Biomedical subjects

A S Jones

Publications and source records attributed to A S Jones.

At least 55 records · Page 3Linked to original sources

Treatment of oropharyngeal carcinoma by irradiation or by surgery.

Of previously untreated patients with squamous cell carcinoma of the oropharynx, 145 are reviewed in this study. All were treated in the Department of Head and Neck Surgery at the University of Liverpool from 1990 to 1997. Seventy-seven patients were treated with irradiation, 28 patients by surgery and 40 patients were deemed not suitable for any curative treatment. Univariate analysis showed no difference in the two groups treated by curative modalities but multivariate analysis did suggest that the surgical group tended to have larger neck node metastases. The 5-year tumour specific actuarial survival for all patients was 53%, 65% for the radiotherapy group and 51% for the surgery group. The difference was not statistically significant (chi (1)2 = 1.5070). The modality of treatment had no affect on either the development of a primary or neck node recurrence or the survival after such a recurrence. Where neck node disease was present it was treated as appropriate. As is generally standard practice, lymph nodes over 2 cm were treated with radical neck dissection whether the patient was having irradiation therapy or surgery. If the patient was having irradiation therapy, the neck dissection was carried out before and irradiation after operation, both on the primary and on the neck, if appropriate. It is concluded that irradiation therapy in properly selected cases in combined head and neck clinics is a safe and effective treatment for squamous cell carcinoma of the oropharynx. Neck node disease should be treated appropriately, but there is no support for the old adage that whatever form of treatment is being used for the neck node should also be used for the primary site.

Analysis of Variance↗

Efficacy of external fixation following nasal manipulation under local anaesthesia.

Nasal fractures are one of the commonest reasons for patients being referred to ENT departments, but few studies have been published about the management of this condition. In particular, the efficacy of external splintage following manipulation has not been assessed. This was a prospective randomized study, which examined the results of manipulation under local anaesthetic and the benefit to be gained from external fixation with Plaster of Paris (POP) following this procedure. Accurate measurements of the degree of deviation of the nose pre- and post-manipulation were obtained using a camera mounted on a specially designed frame. Thirty-three out of 241 consecutive patients seen at a research clinic over the course of 12 months were included in the study. The mean deviation of the nasal bridge at presentation was 4.12 mm. Manipulation under local anaesthetic significantly improved the degree of deviation (mean 2.47 mm, P = 0.0011, 90% CI, 1-2 mm). Randomization of the patients, following manipulation, into POP/none-POP groups showed that external splintage of the nose appeared to be of little practical benefit.

Anesthesia, Local↗

Improved survival in patients with head and neck cancer in the 1990s.

It is generally felt amongst the medical profession and the lay public that cancer is being treated more successfully than in the past. This is certainly true for childhood malignancies and leukaemia but evidence that significantly improved survival is occurring in the common solid tumours is lacking. Since 1963 the University of Liverpool Department of Otolaryngology/Head and Neck Surgery has collected data on all patients with head and neck tumours presenting to the department. The present study investigates patients with histologically proven squamous cell carcinoma of the four main sites: larynx, hypopharynx, oral cavity and oropharynx. From 1963 until the end of 1989, 2738 patients were seen by the department and from 1990 a further 717 patients have been seen. Since 1990 patients have tended to be in better general physical condition but, on the other hand, have tended to have more advanced disease at the primary site. The department has latterly tended to see fewer laryngeal cancers and more cancers of the oropharynx. Significantly fewer patients have presented with neck node metastases. Multiple logistic regression suggests that the most significant difference between the two groups is the great reduction in neck node recurrence rates in the group of patients seen since 1990 (P = 0.0001). The recurrence of tumours at the primary site since 1990 has been 35% compared with 41% before 1990, and recurrence in the neck nodes since 1990 has been 12%, compared with 15% before 1990. These differences are significant (P = 0.0141 and P = 0.0494, respectively). When studying survival in the 1960s, 1970s and 1980s, the 5-year cure rate was 50%, whereas since 1990 the figure has risen to 60% tumour-specific 5-year survival--a significant difference. A similar effect was noted in observed survival. This improvement in cure rate occurred for all four main sites. The results were confirmed by Cox's proportional hazards model where year of treatment was highly significantly associated with improved survival (P = 0.0001). It has been demonstrated that locoregional recurrence has improved since 1990 and this is reflected in improved survival figures. Although there are differences in the parameters of tumours referred before 1990 and since 1990, multivariate analysis suggests that the improvement in neck node recurrence rates may be responsible for this improved survival rate. Multivariate analysis for survival also suggests that the improvement in cure rates is independent of compounding variables and dependent on the year of presentation of the tumour. This improved survival may be related to factors, such as the administration of radical postoperative radiotherapy.

Carcinoma, Squamous Cell↗

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival.

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.

Adult↗

A new short practical quality of life questionnaire for use in head and neck oncology outpatient clinics.

A new short questionnaire to assess the quality of life of head and neck patients has been designed at the University of Liverpool Head and Neck Oncology Department. The questionnaire is short, simple and can be easily completed by a patient whilst in the waiting room before consultation. It is filled in 6 months after completion of treatment and shows very good correlation with the standard long exhaustive questionnaires that are difficult to complete on every patient in a busy National Health Service clinic. The University of Liverpool questionnaire provides a simple score from 0%-100% which should prove valuable in the assessment of quality of care and help with decisions regarding treatment options in head and neck cancer patients.

Head and Neck Neoplasms↗

Impact of tracheotomy on colonization and infection of lower airways in children requiring long-term ventilation: a prospective observational cohort study.

STUDY OBJECTIVES: Determination of the following: (1) colonization and infection rates in children requiring long-term ventilation initially via a transtracheal tube and subsequently via a tracheotomy; (2) the number of infection episodes per 1,000 ventilation days, during both types of artificial airways; and (3) routes of colonization/infection of the lower airways, ie, whether the pathogenesis was endogenous (via the oropharynx) or exogenous (via the transtracheal tube or tracheotomy). DESIGN: Observational, cohort, prospective study over 2 1/2 years. SETTING: Pediatric ICU (PICU), Royal Liverpool Children's National Health Service Trust of Alder Hey, a tertiary referral center. PATIENTS: Twenty-two children requiring long-term mechanical ventilation initially transtracheally and subsequently via a tracheotomy. INTERVENTION: Nil. RESULTS: The lower airways were colonized in 71% of children during transtracheal ventilation; posttracheotomy, this was 95% (p=0.03). Children developed significantly fewer infections following colonization with a microorganism posttracheotomy (8/15 pretracheotomy vs 6/21 posttracheotomy; p=0.013). Throughout the study, there were a total of 17 episodes of infection, all of which were preceded by colonization. Haemophilus influenzae, Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa were the same four causative pathogens during mechanical ventilation both transtracheally and via tracheotomy. Forty-nine episodes of colonization were observed, 15 pretracheotomy and 34 posttracheotomy; of these, 12 (80%) and 19 episodes (56%), respectively, were primary endogenous, ie, present in the oropharynx on hospital admission and subsequently at tracheotomy. Only one colonization episode (7%) of exogenous pathogenesis was observed during transtracheal intubation, while 12 (35%) (p=0.02) occurred after tracheotomy. An equal number of secondary endogenous colonization episodes (two and three, ie, acquired in the oropharynx after PICU admission and after tracheotomy, respectively, were recorded. CONCLUSIONS: (1) Despite a high level of hygiene, exogenous colonization without subsequent infection was common. (2) Although all patients were colonized, the infection rate was lower after tracheotomy. This may be due to enhanced immunity (medically stable) and improved tracheobronchial toilet. (3) Microorganisms in children with tracheotomy differ from those in adults.

Adult↗

p53 mutations in squamous cell carcinoma of the head and neck predominate in a subgroup of former and present smokers with a low frequency of genetic instability.

We examined the p53 mutational profile of 65 squamous cell carcinomas of the head and neck (SCCHNs) from patients living in northwest England. Twenty-three p53 mutations were detected in 20 samples (31%). GC-->AT transitions were the predominant type of mutation. The p53 mutational profile of SCCHN tumors was similar to that of non-small cell lung tumors from patients within the same geographical area, supporting the idea of a common model for carcinogenesis in the upper respiratory tract. Statistical analysis showed that the incidence of p53 mutations among present and former smokers was significantly higher than that in nonsmokers (P < 0.02). In addition, p53 mutations were found to predominate in a group of SCCHN patients with low genetic damage, as indicated by the fractional allelic loss value. The above findings suggest an early initiating role for p53 and imply that at least two separate carcinogenic pathways may be involved in the development of SCCHN.

Alcohol Drinking↗

p53 mutations in relation to human papillomavirus type 16 infection in squamous cell carcinomas of the head and neck.

The relationship between human papillomavirus (HPV) type 16 infection and p53 gene mutations was investigated in squamous cell carcinomas of the head and neck (SCCHN). HPV was detected by general primer-mediated and type-specific PCR. Alterations in the p53 gene were investigated using single-strand conformation polymorphism and sequence analysis in 27 SCCHN, of which 12 were HPV 16-positive and 15 were HPV-negative. Mutations were detected in 2/12 (16.7%) HPV 16-positive and 7/15 (46.7%) HPV-negative tumours; this difference was not statistically significant. The predominant mutations were deletions and C --> T transitions; G --> T transversions were found in only 2 tumours. Our results indicate that the presence of HPV 16 and p53 mutations is not mutually exclusive and detection of a p53 mutation does not exclude a potential role for HPV 16 in the pathogenesis of a subset of SCCHN.

Carcinoma, Squamous Cell↗

Four cases of aggressive MRSA wound infection following head and neck surgery.

Four cases of serious MRSA wound infection following head and neck surgery have been identified. One patient died. At post mortem a mediastinal abscess containing MRSA was found to have eroded into the innominate artery causing fatal haemorrhage. The other three suffered serious wound infections, two requiring further surgery. Once MRSA had been identified they were treated with intravenous teicoplanin and all made a full recovery.

Adult↗

Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases.

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.

Aged↗

Mandibular invasion in patients with oral and oropharyngeal squamous carcinoma.

Invasion of the mandible in squamous carcinoma of the oral cavity and oropharynx has always proved a problem for head and neck oncologists. We studied 82 patients who had mandibulectomies as part of their primary surgical treatment for cancer of these sites. In 40 patients, the tumour appeared to be invading the mandible on clinical grounds and 33 patients had tumours invading the mandible when the latter was examined histopathologically. Multivariate analysis showed that tumour was more likely to be fixed to and clinically invading the mandible in the presence of cancer of the oral cavity, compared with oropharyngeal cancer (P < 0.0001). There was a high degree of correlation between clinical invasion of the mandible and histopathological invasion of the mandible (P = 0.0059). In addition, clinical invasion of the mandible correlated with radiological findings (P = 0.0284). The 5-year survival of those patients with tumour that appeared not to be invading the mandible was 53% compared with 25% for those where tumour did appear to be invading the mandible (P < 0.02). The sensitivity and specificity of clinical evidence of mandibular invasion was calculated with the final arbiter of invasion being the histopathological findings. The sensitivity of clinical examination was 91% and the specificity 80%. The positive predictive value was 75% and the negative predictive value 93%. Mandibular invasion is a poor prognostic sign in cancer of the oropharynx and oral cavity. Detection of invasion prior to operation is obviously extremely important and it appears that clinical findings are an accurate method of predicting invasion.

Adult↗

The nasal response to axillary pressure in non-eosinophilic intrinsic rhinitis.

The exact pathophysiology of intrinsic rhinitis is not fully understood. The generally held belief is that it is due to an imbalance between the outflow of the sympathetic and parasympathetic nervous systems to the nose, perhaps due to excessive parasympathetic or reduced sympathetic activity. In this study the nasal airway response to a predominantly sympathetic stimulus, axillary pressure was studied in 19 patients with intrinsic rhinitis and compared with 16 normal patients. Axillary pressure was applied using a crutch. Following sustained pressure, a significant fall in nasal resistance in the normal group (0.823 kPas/l) and an insignificant fall in the patients with rhinitis (0.0725 kPas/l) was found. Pulse and blood pressure changes were similar in both groups with a significant rise in pulse rate and diastolic blood pressure. The study shows that there is an abnormal response to axillary pressure in intrinsic rhinitis, perhaps due to relative nasal sympathetic hyposensitivity.

Airway Resistance↗

Adenoid cystic carcinoma of the head and neck.

Adenoid cystic carcinoma has a long natural history but frequently proves fatal. The present study describes 108 patients with an adenoid cystic carcinoma of the head and neck seen over a 30-year period. Analysis of the data utilized both univariate and multivariate methods. Forty per cent of patients had tumours arising from the oral cavity and half of these were in the hard palate; 29% occurred in the major salivary glands; 41% of tumours were locally advanced at presentation and 11% had lymph node metastases at this time. The histological pattern was solid in 25%, cribriform in 40% and tubular in 20%. In addition, 15% of patients had a polymorphous low-grade adenocarcinoma and these were analysed separately. Primary site recurrence was more common in the presence of locally advanced tumours at presentation (T3-4) (P = 0.0093). Only six patients had surgery with adjuvant radiotherapy. Six patients had no curative treatment, 21 had primary radiotherapy, 39 had local excision and 42 radical excision. The actuarial primary site recurrence rate was 100% at 30 years. The neck node recurrence rate was 23% at 15 years. Tumour specific survival was 40% at 20 years. Solid histology had a worse prognosis than other histological types (P = 0.0429) but those patients with polymorphous low-grade adenocarcinomas fared very well. Patients with tumours of the hard palate fared better than those patients with tumours at other sites (P = 0.0301). Early disease at the primary site (T1-2) was a good prognostic sign (P = 0.0013). Patients with neck node metastases at presentation tended to do badly (P = 0.009).

Carcinoma, Adenoid Cystic↗

The magnitude of random errors in acoustic rhinometry and re-interpretation of the acoustic profile.

By measuring the effect of incomplete acoustic seal and increasing nosepiece insertion depth on the derived nasal acoustic profile, this study quantifies the random errors that may arise in the course of the clinical practice of acoustic rhinometry using the insert nosepiece. The relative movement of the nose and nosepiece also enables us to separate the contribution of each to the acoustic curve. Sixteen volunteers were tested using a commercial rhinometer. As a consequence of this study we are able to formulate the following conclusions: (1) The first minimum of the nasal acoustic profile is due to the end of the nosepiece, but may be further diminished by the position of the nosepiece tip on or within the nose. (2) The second minimum is due to the nasal valve, to which the head of the inferior turbinate contributes. (3) Acoustic rhinometry is extremely sensitive to acoustic leaks and results obtained without a fluid acoustic sealant cannot be considered valid. (4) The errors associated with the nosepiece insertion technique are very small unless the nosepiece is forced into the nasal vestibule.

Acoustics↗

Informed consent: patients' and junior doctors' perceptions of the consent procedure.

The important task of obtaining informed consent is often left to the most junior member of the surgical team, whose understanding of the surgical procedures involved may be limited. Little is known about patients' and junior doctors' satisfaction with the consent procedure, which was studied with the use of questionnaires. The vast majority of patients (95%) were satisfied with the explanation given to them prior to obtaining consent although 45% thought that the doctor who signed the consent form would be performing the surgery. Thirty-seven per cent of the junior doctors questioned admitted to obtaining consent for procedures of which they had little understanding. The majority of both junior doctors and patients felt that the surgeon performing surgery should sign the consent form. Junior doctors cannot be expected to obtain informed consent for procedures they do not fully understand and patients's; expectations must be taken into consideration if the seemingly inexorable rise in medico-legal litigation is to be halted.

Attitude of Health Personnel↗

An immunohistochemical analysis of p53 protein expression in pre-malignant and malignant tissues of the oral cavity.

This study looks at p53 protein expression in dysplastic and malignant lesions of the oral cavity using an immunohistochemical staining technique. Archival biopsy specimens of oral dysplasia of squamous cell carcinoma from 64 patients were analysed immunohistochemically. Sections from 90 oral biopsy specimens were examined in all. Positive immunohistochemical detection of the p53 protein, demonstrated by brown nuclear staining, was detectable in over 80% of mild, moderate and severe dysplastic tissues as well as carcinoma-in-situ and squamous carcinoma specimens. We concluded that p53 protein expression occurs frequently in both malignant and dysplastic lesions of the oral cavity, suggesting that abnormally detectable p53 protein is present at the very early stages of development of oral squamous carcinoma. Oral cancer may provide a good model for the study of multistage tumorigenesis in head and neck cancer as the lesions are frequently detected at the pre-invasive stage and are accessible to biopsy.

Carcinoma, Squamous Cell↗

Autonomic reflexes and non-allergic rhinitis.

Functions traditionally ascribed to the nose include warming, humidification, and filtration of inspired air prior to its passage to the lower respiratory tract. The nose thus conditions inspired air, making it suitable for pulmonary gas exchange. In order to carry out these functions, the nose is subject to a complex series of reflexes mediated via the autonomic nervous system. The effector tissues are the nasal blood vessels and glands. Perennial non-allergic rhinitis may be divided into two types based on the presence or absence of eosinophilia in nasal secretions. Much circumstantial evidence suggests that non-eosinophilic non-allergic rhinitis (NENAR) may be a disease of autonomic imbalance. In a series of studies carried out at the University of Liverpool, patients with perennial non-allergic rhinitis, and NENAR in particular, were found to have qualitative and quantitative abnormalities in their nasal response to various stimuli as manifested by changes in nasal patency. The nasal response to axillary pressure is much reduced in NENAR patients compared with normal controls, and the normal decrease in nasal resistance in response to standing is abrogated. Isometric exercise has little effect in normal subjects, but those with NENAR demonstrate an increase in nasal resistance. A similar effect is seen in response to the cold pressor test. Of great importance for therapy is the effect of topical fluticasone propionate in patients with NENAR. Treatment normalizes the damaged nasal reflexes seen in this condition, whereas placebo has no effect. However, abnormalities in other non-nasal autonomic reflexes (systemic parameters) are not affected by treatment.

Administration, Topical↗