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Biomedical subjects

P M Stell

Publications and source records attributed to P M Stell.

At least 19 recordsLinked to original sources

Multiple cytogenetic aberrations in squamous cell carcinomas of the head and neck.

Chromosomal abnormalities in short term cultures have been investigated in 10 squamous cell carcinomas of the head and neck. Of these tumours, three demonstrated clonal chromosomal abnormalities, two showed random abnormalities and 5 patients' tumours had normal karyotypes. The 5 patients with aberrant karyotypes were all from previously treated tumours, of these, 4 patients had received radiotherapy and 1 surgery. On analysis of the three clonal tumours, two were found to be polyclonal, each with five separate clones. 116 breakpoints were demonstrated from the clonal data of these tumours, and all of the chromosomes were involved, apart from number 18. In this study we found three or more breakpoints at sites 1p36, 9q32 and 11q23. 1 of the patients investigated showed a clonal abnormality involving a breakpoint at the 11q13 site, with a further 2 patients having breakpoints at 1p22--sites previously reported to have marked clustering of cytogenetic abnormalities in oral cancer patients. Only further studies will demonstrate whether the breakpoints found are of clinical significance.

Carcinoma, Squamous Cell

Prognosis in mouth cancer: host factors.

A personal series of 842 patients with a tumour of the oral cavity is presented. Five hundred and twelve of these patients had a histologically proven squamous cell carcinoma, and were previously untreated. Increasing age was associated with worsening performance status. Women were older at presentation than men, and tumours of the upper part of the mouth were more common in the elderly, but there was no relation between age and histological grade or stage grouping. Sex had no correlation with performance status or histological grade. However, men were more likely to have an advanced tumour, and tumours of the floor of the mouth and alveolus were much commoner in men. There was no correlation between performance status and site or histological grade, but patients in poor general condition were more likely to have stage III-IV tumours. Multivariate analysis showed that sex had no impact whatever on survival, but survival fell with increasing age and worsening performance status. The effect of age and performance status disappeared when the survival of treated patients was adjusted for deaths due to other causes.

Age Factors

Cisplatin-albumin complex for treatment of cancer of the head and neck.

Many patients with cancer of the head and neck are unable to receive or continue treatment with cisplatin, which is nephrotoxic, because of poor renal function. We present here, however, the case of a patient who underwent conventional cisplatin therapy but who then had to be withdrawn from treatment because of renal toxicity despite having undergone partial remission. Treatment was then changed to cisplatin in the form of a cisplatin-albumin complex which is not nephrotoxic. The patient went on to a histologically confirmed complete response and we suggest that although the cisplatin-albumin complex may not be as effective as the conventional form of the drug it offers a possible form of treatment of patients with compromised renal function who could not otherwise be treated.

Aged

Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry.

The cell kinetics of 82 squamous cell carcinomas of the head and neck were studied by in vivo administration of the thymidine analogue, bromodeoxyuridine (BrdUrd). Ploidy, BrdUrd labelling index (LI), duration of S-phase (Ts), potential doubling time (Tpot) and S-phase fraction (SPF) were measured by flow cytometry on 50 microns paraffin embedded sections. The range of values obtained compared well with other in vivo cell kinetic studies of head and neck cancer. Aneuploid tumours had a significantly higher BrdUrd labelling index and SPF, and a short Tpot than diploid tumours. To validate the use of 50 microns sections for measuring cell kinetic parameters by flow cytometry a comparison of values obtained by 50 microns sections and small blocks of tissue was made. No significant difference was found between the two methods. Reproducibility of values between two consecutive thick sections was also good. We conclude that reproducible cell kinetic measurements can be made in tumour samples using 50 microns sections of BrdUrd labelled tissue.

Aneuploidy

Phase I trial of a cisplatin-albumin complex for the treatment of cancer of the head and neck.

1. A phase I trial of a cisplatin-albumin complex for the treatment of end-stage squamous cell carcinoma of the head and neck is reported. The complex was prepared by overnight incubation of cisplatin with human albumin at 37 degrees C. This resulted in more than 98% of the drug being bound to protein at the start of treatment. The patients were either unable to continue with or had refused conventional therapy with cisplatin. 2. The trial began at a dose of 100 mg cisplatin m-2 and was increased in 25 mg m-2 increments to 650 mg m-2. Despite the absence of the customary protective measures of pre-hydration and anti-emetic treatment no serious toxicity was encountered. 3. Unbound plasma platinum concentrations were lower than after conventional cisplatin treatment but total plasma platinum and tumour platinum concentrations were much higher. Urinary excretion of platinum was low and the incidence of nephrotoxicity was greatly diminished. Two responses were seen (one complete and one partial) in 38 patients treated and the median survival time was 109 days, compared with 151 days for patients treated conventionally with cisplatin and 56 days for untreated patients. 4. The complex is not as effective as conventional cisplatin therapy but is much less toxic, offers improved quality of life during treatment and may prove to be of benefit in patients who could not otherwise be treated.

Carcinoma, Squamous Cell

Squamous carcinoma of the head and neck in the young adult.

We present a series of 2305 previously untreated histologically proven squamous carcinomas of the mucosal surfaces of the upper aerodigestive tract managed by one of us in a 27-year period. 62 (2.7%) of the patients were aged 40 years or younger. The sex ratio between young and old patients was similar but, as expected, the younger patients were in better physical condition. Furthermore, 90% of young patients were treated, compared with only 78% of the older patients. Younger patients had a higher incidence of oropharyngeal tumours and lymph node metastases, but the proportion of poorly differentiated tumours, and stage T3-T4 tumours, was similar, as was the metastatic rate. The crude survival of the younger patients was 10% better than that of the older group, and adjusted (life-table) survival was 9% better, and this better survival in younger patients was significant when differing site incidence and N-stage were allowed for by multivariate analysis. The recurrence rate at the primary site was 19% in the younger patients and 15% in older patients, but this difference was not significant. The recurrence rate in cervical lymph nodes was similar in both age groups: 37% at 2 years in young patients and 38% in older patients.

Adult

Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma.

We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).

Animals

Recurrence after radiotherapy for glottic carcinoma.

A series of 478 patients with T1-3N0 glottic carcinoma treated by irradiation is presented. Of these patients, 320 were previously untreated, whereas 158 patients were referred for treatment of a recurrence after receiving radiotherapy elsewhere. The primary recurrence rate in the previously untreated patients was 10%. The rate was higher in T2 and T3 tumors, poorly differentiated tumors, and in patients who were in poor general condition. Over 80% of the recurrent tumors were Stage pT3 or pT4, whereas 12% of total laryngectomy specimens showed necrosis only with no evidence of tumor. The necrosis rate in previously untreated patients was 1% for T1 tumors, 4% for T2 tumors, and 3% for T3 tumors. Of all tumors, 60% were transglottic when they recurred, whereas only 29% were confined to the glottis at recurrence. Histologic diagnosis had a high sensitivity but a low specificity, indicating that a negative histologic report is unreliable. Of patients with a recurrent primary tumor, 13% were untreatable. The 5-year survival after a primary recurrence was 39%, and the main prognostic factors were sex, T stage at recurrence, and time to recurrence. Of patients available for follow-up at 5 years 49% were alive with a larynx, 5% were alive without a larynx, 13% were dead of the original cancer, and 33% had died of other causes. In those suffering a primary recurrence, the commonest cause of death was a subsequent lymph node metastasis, followed in order of frequency by stomal recurrence and recurrence in the pharyngeal remnant. The hospital mortality rate after laryngectomy was 3%, and 30% of patients undergoing laryngectomy developed a pharyngocutaneous fistula. The recurrence rate in lymph nodes was 14% at 5 years, general condition and T stage being the only significant predictors of recurrence. Only 17% of patients had small (N1) nodes by the time the diagnosis of cervical lymph node recurrence was made, and 27% of all patients were unsuitable for treatment. Host, tumor factors, and time to recurrence were not significant predictors of survival after node recurrence. The survival rate 5 years after node recurrence was 16%, and the main cause of death in those who died was uncontrolled disease in the neck. The hospital mortality after salvage neck dissection was 4.7%.

Adolescent

Recurrence of oropharyngeal carcinoma after radiotherapy.

Two-hundred-and-twenty-one patients with squamous carcinoma of the oropharynx treated by irradiation are presented. The primary recurrence rate at five years in the previously untreated patients was 27%, but was dictated by neither host factors (age, sex and general condition) nor tumour factors (site, T-stage and histological grade). Pre-operative histological diagnosis had a very high sensitivity but a low specificity, indicating that false positives are common but false negatives unusual. Twenty per cent of patients with a recurrent primary tumour were untreatable. The five year survival after a primary recurrence was 31 per cent. Sixty-eight per cent of patients undergoing major surgery recovered without a major complication, and the hospital mortality rate was three per cent, due entirely to major medical catastrophes. The major complication rate in those undergoing flap repair after major resection was seven per cent. The metastatic rate in lymph nodes was 44 per cent at five years, and again this did not depend on any host or tumour factors. The survival at five years after node recurrence was a mere 19 per cent, and the length of survival was related to the primary site of the original tumour and the presence of extranodal disease. Two-thirds of patients had advanced disease (N2 and N3) when node recurrence was diagnosed and about 15 per cent were unsuitable for surgery.

Carcinoma, Squamous Cell

Blood transfusion and survival after laryngectomy for laryngeal carcinoma.

Survival of patients with surgically treated malignancy may be adversely affected by blood transfusion. Immune suppression due to transfusion has been implicated but remains unproven. We conducted a study of 240 patients with squamous cell carcinoma of the larynx undergoing laryngectomy to assess the effect of per-operative blood transfusion on survival.

Carcinoma, Squamous Cell

Emergency laryngectomy.

From 1974 to 1990, 31 patients underwent emergency laryngectomy for airway obstruction due to laryngeal carcinoma, in an effort to avoid the complication of stomal recurrence. This group of patients had a greater proportion of multiregional tumours (35 per cent vs 13 per cent) than a comparison group of elective laryngectomies. In other respects the two groups were similar. Early post-operative mortality (6.5 per cent vs 3 per cent), stomal recurrence rates (4.2 per cent vs 4.8 per cent) and survival (53 per cent vs 55 per cent) were not significantly different between the emergency laryngectomy group and the comparison group undergoing elective laryngectomy.

Aged

Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck.

Expression of the tumour suppressor gene p53 was examined in squamous cell carcinoma of the head and neck using two p53 antibodies, PAb 421 and PAb 1801. Elevated p53 expression was found in 67% of the 73 patients investigated. P53 expression was not found to correlate with whether the patient had been previously treated or not, nor any of the clinico-pathological parameters. However a correlation was found between the patients smoking history and positive p53 staining. Six out of seven non-smokers did not express p53 whereas 29 of 37 heavy smokers were found to have elevated p53 expression (P less than 0.005). Also, of a group of ten patients who had given up smoking more than 5 years ago, nine had elevated expression. Epidemiological studies have shown a correlation between heavy smoking and head and neck cancer. The present study indicate a genetic link for this correlation.

Carcinoma, Squamous Cell

Disposition and tumour concentrations of platinum in hypoalbuminaemic patients after treatment with cisplatin for cancer of the head and neck.

1 Platinum concentrations in the tumour reached a peak of 3.8 +/- 1.5 micrograms g-1 wet weight tissue at the end of an 8 h intravenous infusion of cisplatin. The tumour concentrations of platinum were higher than the corresponding plasma concentrations (2.5 +/- 0.9 micrograms ml-1) and declined more slowly. 2 Patients with squamous carcinoma of the head and neck had a significantly shorter median survival time if they had low plasma albumin concentrations (less than 40 g l(-1) compared with patients in the normal range, 133 days and 768 days respectively (P less than 0.05) after treatment with cisplatin. 3 No changes in the pharmacokinetics of platinum were detected to account for this poor response of hypoalbuminaemic patients, but plasma albumin concentration was found to be negatively correlated with the first order elimination rate constant. 4 The cumulative urinary excretion of platinum in the first 24 h was not altered by lowered plasma albumin. 5 The concentration of platinum in the tumour did not correlate with the survival time of the patient, but was found to be correlated with the volume of distribution in the post-distributive phase.

Adult

Is laterality important in neck node metastases in head and neck cancer?

We present a series of 2219 previously untreated squamous carcinomas of the head and neck, 141 (6.5%) of whom had bilateral nodes at presentation. Bilateral nodes became progressively less common with increasing age but were not related to other host factors. They were also strongly related to the site of the primary tumour, its T-stage and its histological grade, being more common in tumours of the oro or naso-pharynx, in poorly or moderately differentiated tumours, and in tumour stages T3 or T4 at presentation. There were also interactions between these tumour factors, and patients with all three factors had a 25% incidence of bilateral nodes. 126 of these patients could be matched for the main prognostic factors with 126 patients with unilateral neck node disease. The survival rate of the latter group was 9% better than that of the unilateral group. Further breakdown showed that the survival of patients with nodes smaller than 6 cm is not affected by laterality, whereas it is for patients with massive nodes.

Carcinoma, Squamous Cell