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Biomedical subjects

J W Hetherington

Publications and source records attributed to J W Hetherington.

18 recordsLinked to original sources
PubMed2001

Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group.

PURPOSE: Time to progression (TTP), overall survival, and quality of life (QL) were compared in patients with hormone-resistant prostate cancer (HRPC) treated with prednisone (5 mg orally, four times a day) or flutamide (250 mg orally, three times a day). PATIENTS AND METHODS: Symptomatic patients were randomized to receive either prednisone (101 patients) or flutamide (100 patients). Subjective response was assessed based on performance status, the use of analgesics, and the need to apply alternative palliative treatment. Prostate-specific antigen (PSA)-based biochemical response (>or= 50% reduction of baseline PSA) was recorded. At baseline and at 6-week intervals during follow-up, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. RESULTS: There was no difference between the groups in median TTP (prednisone, 3.4 months; flutamide, 2.3 months) or overall survival (prednisone, 10.6 months; flutamide, 11.2 months). In the prednisone group, 56% of the patients experienced a subjective response, compared with 45% in the flutamide group (P: = .18). The median response duration was 4.8 months for prednisone and 4.2 months for flutamide. A biochemical response was observed in 21% and 23% of the prednisone and flutamide groups, respectively. Gastrointestinal toxicity was the reason for trial discontinuation in seven patients receiving flutamide and two patients receiving prednisone. The QL assessment parameters favored the use of prednisone with statistically significant differences in pain, fatigue, role functioning, appetite loss, gastrointestinal distress, and overall QL. CONCLUSION: In symptomatic HRPC, treatment with prednisone or flutamide leads to similar rates of TTP and overall survival and no difference in subjective or biochemical response. The QL results favor the use of low-cost prednisone in patients with HRPC.

Aged↗
PubMed1998

A pilot study of intermittent androgen deprivation in advanced prostate cancer.

OBJECTIVE: To assess the feasibility of intermittent hormone therapy for metastatic prostate cancer. PATIENTS AND METHODS: Sixteen patients with metastatic carcinoma of the prostate were treated using a protocol of intermittent hormone therapy with the luteinizing hormone-releasing hormone (LHRH) analogue leuprorelin at a dose of 3.75 mg every 4 weeks. The protocol required that hormone therapy be stopped when the response was stable, and was designed to assess the duration of the unmaintained response and the probability of a second response to re-initiation of leuprorelin. RESULTS: Eleven of the 16 patients had a stable hormone response and stopped therapy 3-9 months (mean 5.5) from the start of treatment. The mean (range) duration of the unmaintained response, as judged by monitoring symptoms and serum prostate specific antigen (PSA) levels every month was 4 (2-8) months in the seven patients who had bone metastases and was 3, 3 and 6 months in the three with only loco-regional disease (one patient temporarily discontinued follow-up). As the immediate re-induction of hormone therapy was not mandatory in asymptomatic patients at the time of progression, the mean (range) period off hormone therapy was 8 (3-13) months in those eight patients with bone metastases and was 3, 36 and 42 + months in the three presenting with loco-regional disease. All 10 patients who re-initiated hormone therapy had a second hormone response, in six of which led to a decline in PSA level to < 2 ng/mL. During the period off hormone therapy no patient developed irreversible symptoms. CONCLUSIONS: The temporary cessation of hormone therapy early during the response in patients with metastatic carcinoma of prostate is associated with biochemical evidence of relatively early progression in most cases, but can be associated with significant periods off therapy and with a high chance of a second hormone response. The value of this approach to the quality and duration of patients' lives requires a prospective comparative evaluation.

Androgen Antagonists↗
PubMed1994

Molecular genetic investigation of sporadic renal cell carcinoma: analysis of allele loss on chromosomes 3p, 5q, 11p, 17 and 22.

To investigate the role of tumour-suppressor genes on the short arm of chromosome 3 in the mechanism of tumorigenesis in non-familial renal cell carcinoma, we analysed 55 paired blood-tumour DNA samples for allele loss on chromosome 3p and in the region of known or putative tumour-suppressor genes on chromosomes 5, 11, 17 and 22. Sixty-four per cent (35/55) of informative tumours showed loss of heterozygosity (LOH) of at least one locus on the short arm of chromosome 3, compared with only 13% at the p53 tumour-suppressor gene and 6% at 17q21. LOH at chromosome 5q21 and 22q was uncommon (2-3%). Detailed analysis of the regions of LOH on chromosome 3p suggested that, in addition to the VHL gene in chromosome 3p25-p26, mutations in one or more tumour-suppressor genes in chromosome 3p13-p24 may be involved in the pathogenesis of sporadic renal cell carcinoma (RCC). We also confirmed previous suggestions that chromosome 3p allele loss is not a feature of papillary RCC (P < 0.05).

Adult↗
PubMed1993

Para-aortic lymphadenectomy after chemotherapy for metastatic non-seminomatous germ cell tumours: prognostic value and therapeutic benefit.

Between 1976 and 1990, 231 patients had excision of para-aortic lymph node masses remaining after chemotherapy for metastatic non-seminomatous germ cell tumours. The overall 5-year survival rate was 80%. Multivariate analysis of survival after surgery was performed and the following were found to be independent prognostic variables: completeness of surgical excision, pathology of excised mass, timing of surgery after chemotherapy (elective versus salvage) and year of treatment (before or after 1984). Para-aortic lymphadenectomy provided both therapeutic benefit and histological information of prognostic value in planning future treatment and follow-up. Size of mass and serum markers at the time of surgery were of no additional prognostic value once completeness of excision and pathology were taken into account. We therefore recommend that all residual masses should be removed soon after completion of chemotherapy.

Adolescent↗
PubMed1990

A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic.

The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic.

Adolescent↗
PubMed1988

Contribution of bone scintigraphy, prostatic acid phosphatase and prostate-specific antigen to the monitoring of prostatic cancer.

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.

Acid Phosphatase↗
PubMed1987

Urinary fibrin/fibrinogen degradation products in transitional cell carcinoma of the bladder.

Urinary fibrin/fibrinogen degradation products (FDPs) were measured in 210 specimens from 174 patients with newly or previously diagnosed transitional cell carcinoma of the bladder. They were detected in 94% of patients with deeply invasive bladder tumours (pT2-4) compared with 17% of superficial tumours. Microalbuminuria (greater than 50 micrograms/g creatinine) was also found in 80% of patients with pT2-4 lesions. Both were compared with urine cytology. Urinary FDPs are markers of bladder tumour invasion. Our results suggest that urinary FDPs are not of value in screening for the presence of bladder neoplasia but their role may be in following patients with superficial bladder tumours to detect those tumours which become invasive. The mode of excretion of the FDPs in the urine is discussed.

Adult↗
PubMed1987

Surgical salvage of advanced testicular tumours.

After combination chemotherapy, 19 patients underwent salvage surgery for testicular neoplasia. Active malignancy was found in nine patients, three of whom have died of the disease. Those with benign residual disease have had a good prognosis without further treatment. Biopsy alone of the residual masses proved reliable in determining which patients were to be simply followed or given further chemotherapy. If active malignancy was not resected fully, the prognosis was very poor. Our policy continues to be to attempt complete excision of residual masses after induction chemotherapy and to give salvage chemotherapy to patients with residual active malignancy.

Adolescent↗
PubMed1987

Intravesical mitomycin C for the treatment of recurrent superficial bladder tumours.

Forty-three patients with recurrent multiple superficial bladder tumours (Tis, Ta and Tl) were treated with Mitomycin C 20 mg in 20 ml water intravesically weekly for 8 to 12 weeks, and monthly instillations were continued for 5 to 6 months. Residual tumour was resected at 12 weeks, at which time 40 patients (93%) showed a response to treatment. A complete response was seen in 24 (56%) and 16 (37%) showed a partial response. After a follow-up of 12 to 48 months (median 19), 19 of 33 evaluable patients (58%) have shown tumour recurrence. Invasive tumour has developed in seven (17%) and transitional cell tumours of the ureter in two of those patients who showed an initial response to treatment.

Administration, Intravesical↗
PubMed1987

Prevalence of chlamydial infection in acute epididymo-orchitis.

The prevalence of sexually transmitted infection was studied in 40 men presenting with acute epididymo-orchitis in Leeds. Chlamydia trachomatis infection was identified in 13 of 29 men (45%) aged under 35 years. Neisseria gonorrhoeae was isolated from four of these 13 men with chlamydial urethritis. C trachomatis was isolated from the urethra of only one of 11 men (9%) aged over 35. Appreciable bacteriuria was found in six of these 11 men (55%). Noting details of sexual history and screening for sexually acquired pathogens is advocated in younger men with acute epidiymo-orchitis.

Acute Disease↗
PubMed1986

Biochemical monitoring of carcinoma of prostate treated with an LH-RH analogue (Zoladex).

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.

Acid Phosphatase↗
PubMed1986

Modified nephroureterectomy: a risk of tumour implantation.

The standard surgical management of patients presenting with transitional cell carcinoma of the upper urinary tract is nephroureterectomy with excision of a cuff of bladder around the ureteric orifice. Recently a modified technique of resecting the lower ureter endoscopically and completing the nephroureterectomy through a single loin incision has been advocated as a safe and simple procedure. We consider that this technique may have a risk of tumour implantation at the site of the resected lower ureter. We report our experience of this operation in five patients, two of whom developed invasive tumour at the site of the ureteric orifice after only a short follow-up.

Aged↗
PubMed1986

Evaluation of a double-monoclonal radioimmunoassay for the measurement of carcinoembryonic antigen in the urine of patients with bladder cancer.

A double-monoclonal radioimmunoassay (RIA) has been used to detect urinary carcinoembryonic antigen (CEA) in 204 patients attending for diagnostic cystoscopy. Elevated levels of urinary CEA were found in 50% of patients with bladder tumours, and these levels correlated with both the grade and stage of the tumour. The sensitivity proved to be 58% and the specificity 74%, which compares with previous studies using polyclonal RIA kits. As a monitoring test, urinary CEA proves to be as useful as urine cytology. The use of a more specific assay does not increase the clinical value of the test which still lacks the sensitivity and specificity needed to allow it to be used to monitor recurrence of low grade tumours (Ta, Tis and T1).

Aged↗