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Biomedical subjects

D Husband

Publications and source records attributed to D Husband.

At least 19 recordsLinked to original sources

Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms.

The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: (201)Tl P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study.

Adult↗

Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors.

BACKGROUND: The -1p/-19q genotype has been associated with prolonged survival and chemosensitivity in oligodendroglial neoplasms, but the predictive and prognostic significance of genotype in the routine clinic is not established. METHODS: The authors investigated allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in a cohort representative of clinical practice at their center (50 primary, 26 recurrent cases) given PCV chemotherapy between 2000 and 2003 and compared with response and outcome following PCV. RESULTS: 1p/19q loss was found in 12/19 OII, 10/23 OAII, 11/13 OIII, and 6/21 OAIII. Response, seen in 92% with 1p/19q loss, was associated with the -1p/-19q genotype (Fisher exact: p < 0.001) regardless of WHO grade or whether primary or recurrent. 1p/19q loss was an independent prognostic factor associated with longer progression-free (PFS) and overall survival (OS) (Cox regression: PFS and OS p < 0.001), with greater impact on PFS than OS in primary tumors, and OS at recurrence. 17p13 loss and p53 mutation were associated with poor prognosis in recurrent tumors and chromosome 10 loss was associated with short PFS and OS in primary tumors. Histologic subtype did not influence outcome in tumors of equivalent genotype. Genotype had greater association with response and outcome than conventional clinical factors. A total of 29% with intact 1p/19q and a variety of genetic or clinicopathologic characteristics responded in association with increased PFS and OS. CONCLUSIONS: The -1p/-19q genotype predicted response and favorable outcome following PCV chemotherapy corroborating genetic analysis to guide routine clinical management. However, some cases with intact 1p/19q also had clinical benefit.

Adult↗

Laboratory-based calculation of coronary heart disease risk in a hospital diabetic clinic.

AIMS: To develop an estimation of risk of coronary heart disease (CHD) based on the Framingham equation for use in a diabetes clinic, given concerns about the accuracy of the Sheffield risk tables in this setting. METHODS: A computer program using the Framingham equation based on patients' age, sex, systolic blood pressure, smoking history, presence of diabetes and left ventricular hypertrophy was applied to requests for lipid screening of patients attending the diabetes clinics of Birmingham Heartlands Hospital. The calculated risks for the population were compared with those estimated from the Sheffield tables. RESULTS: Of 1060 patients with diabetes mellitus, 215 (20%) had an annual CHD risk > or =3%, which is considered to be the threshold at which lipid-lowering drugs are cost-effective. Only 24 of these 215 patients (11%) were correctly identified by the Sheffield tables, which we conclude have an unacceptably low sensitivity in diabetes mellitus. CONCLUSIONS: A laboratory-based CHD risk calculation system is a practical alternative to the Sheffield system and may have a greater sensitivity in the diabetic clinic.

Adult↗

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↗

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↗

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients.

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.

Adult↗

Second primary tumors in patients with head and neck squamous cell carcinoma.

BACKGROUND: The concept that a patient could develop cancer twice was first put forward by Billroth. Second primary neoplasms are a particular feature of head and neck cancer. METHODS: This study examines the records of 3436 patients with squamous cell carcinoma of the head and neck, of whom 274 subsequently developed a second neoplasm. RESULTS: The actuarial second primary rate was 9.1% at 372 months, and median time to presentation for the second tumor was 36 months. Second tumors were more likely to occur in male patients younger than 60 years at the time of their index tumor, and who had laryngeal and oral cavity index tumors. Patients whose index tumor was small at diagnosis had a greater chance of developing a second tumor as did those with no cervical lymph node metastases to the neck. Radiotherapy to the index tumor was not associated with an increased risk of developing a second tumor. The commonest sites for second tumors were the head and neck (50%) and the lung (34%), and 86% were squamous cell carcinomas. The tumor-specific mortality for those who developed a second primary tumor was 20% after 15 years compared with 44% for patients who did not develop a second primary tumor. The 5-year survival for patients who developed a secondary tumor from the time of its diagnosis was 26%. CONCLUSIONS: Second primary tumors in the head and neck of patients with cancer are not uncommon. If the second tumor occurs in the head and neck region, the prognosis is reasonably good.

Actuarial Analysis↗

The treatment of node negative squamous cell carcinoma of the postcricoid region.

This study includes 155 patients with T1-4N0 carcinoma of the postcricoid region seen between 1963 and 1993. Sixty-seven were treated by primary surgery, 50 by primary irradiation therapy, 36 were unsuitable for curative treatment and two patients were lost to follow-up. Reasons for deciding against curative therapy were: advanced age, poor general condition and advanced disease at the primary site. This study included only those patients who had no neck node metastases at presentation. Patients receiving surgery tended to be in better general physical condition and tended to have more advanced disease than those treated by irradiation in this series. The tumour-specific five-year survival rate for those treated by surgery was 43 percent (95 percent confidence interval (CI) 23-60 percent). For those patients treated by irradiation the five-year survival rate was 48 percent (95 percent CI 27-66 percent) and for those receiving no treatment the median survival rate was three months (95 percent CI two-six months). The observed survival for the surgery group was only 18 percent and for the radiotherapy group 25 percent at five years. Multiple logistic regression showed no significant difference in proportions of host and tumour factors between the group receiving radiotherapy and the group receiving surgery. Recurrence at the primary site and the appearance of neck node metastases were not predicted by any host or tumour factor. Twenty-one patients out of 67 receiving primary surgery had recurrence at the primary site compared with 26 patients out of 50 receiving primary irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Lymphoma presenting to a head and neck clinic.

Lymphomas generally have a good prognosis compared with squamous carcinomas. The present study investigates a series of 185 lymphomas of the head and neck seen over a 30-year-period. The records of 236 patients were examined and the histology slides reviewed. The lymphomas were classified according to the working formulation method and staged using the Ann Arbor system. A total of 185 patients had a non-Hodgkin's lymphoma, of those 43 were low grade, nine intermediate and 103 high grade. The histology slides of 30 patients were not available for review. In addition, 51 patients had Hodgkin's disease. One hundred and fifty patients were stage 1 or 2 and 74 stage 3 or 4. In 12 patients insufficient data was available for staging; 152 were extranodal and 84 nodal. The 5-year survival of those patients with Hodgkin's disease was 73%. For the patients with non-Hodgkin's lymphoma the 5-year survival was 43% for low grade and 48% for high grade lesions. The survival of patients with Hodgkin's disease was significantly better than for non-Hodgkin's lymphoma (P < 0.01). The 5-year survival of patients with extranodal disease was 54% and for patients with nodal disease 65% (P = NS). Treatment was by irradiation for localized lesions and by chemotherapy or a combination for more advanced lesions. Lymphomas have a relatively good prognosis in the head and neck as elsewhere in the body and every effort should be made to provide adequate diagnosis and treatment in combined clinics.

Aged↗

Diagnostic value of a guaiac occult blood test and faecal alpha 1-antitrypsin.

This study evaluates the diagnostic accuracy of a faecal occult blood test and faecal alpha 1-antitrypsin in the investigation of patients with gastrointestinal symptoms or iron deficiency anaemia. One hundred and seventy nine patients with either iron deficiency anaemia (n = 67), changed bowel habit and aged > 39 years (n = 107), or a history suggestive of melaena (n = 5) provided faecal samples. After investigation, 32 patients had a diagnosis of possible gastrointestinal bleeding and 139 patients had no evidence of gastrointestinal bleeding. Eight patients had a cause of enteric protein loss in the absence of gastrointestinal bleeding and were excluded from subsequent analysis. The faecal alpha 1-antitrypsin test was diagnostically more accurate than the guaiac test in identifying probable gastrointestinal bleeding (82% and 72% respectively, p < 0.05). This faecal alpha 1-antitrypsin test was also more specific (83% and 72% respectively, p < 0.05), but was not significantly more sensitive (78% and 72% respectively). The sensitivity of these tests was insufficient to recommend their use for most patients in this study.

Adult↗

Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer.

Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products.

Aged↗

Increased levels of vaccenic acid in bronchogenic carcinoma tissue.

Employing capillary gas liquid chromatography the levels of palmitic, palmitoleic, stearic, oleic, cis-vaccenic, linoleic, arachidonic and docosahexaenoic acids were measured in lung tissue and lung tumours from 28 patients undergoing surgery for bronchogenic carcinoma. There were significant increases in the majority of fatty acids in tumour tissue compared to normal tissue when the results were expressed in absolute units. However, when the relative changes in fatty acid concentration were studied, the most consistent findings were a significant rise in vaccenic acid and a fall in palmitic acid in tumour tissue compared to normal tissue. This change in the vaccenic:palmitic acid ratio may reflect specific changes in fatty acid metabolism in bronchogenic carcinoma tissue involving a delta-9 desaturase.

Adult↗