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Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 145 records · Page 8Linked to original sources

Evaluation of the effect of continuous infusion recombinant interleukin-2 (bioleukin) on peripheral blood leucocytes of patients with terminal malignancy.

Seventeen patients with terminal malignancy have been entered into a sequential investigation of two doses of continuous infusion recombinant interleukin-2 (bioleukin) given in the setting of a general ward. After an initial experience of a dose of 300 micrograms m-2 in eight patients the remainder received 400 micrograms m-2. Temporary interruption of treatment at the first sign of any serious toxicity led to rapid resolution of side-effects. No patient needed intensive care support, although nine of 17 required temporary interruption of infusion, lasting on average 4 h. Median lymphocyte rebound on day 14 was 3.6 times the pre-treatment level. It remained above pre-treatment levels in four of five patients who had no shown disease progression at day 56 after more than 28 days off treatment. Minor responses occurred in five patients, lasting on average 4 months.

Adult↗

Unexplained spontaneous regression and alpha-interferon as treatment for metastatic renal carcinoma.

A series of 73 patients with measurable metastatic disease referred to a tertiary referral centre for consideration for an experimental treatment protocol were entered into a surveillance protocol in order to establish the incidence of spontaneous regression. Initially, patients were taken off the study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients went into therapy protocols only following the development of symptomatic progression. We observed 3 complete and 2 partial unexplained spontaneous regressions and a further 4 patients had prolonged stable disease for more than 12 months. A group of 21 patients on progression subsequently received treatment with alpha-interferon (Wellferon) as part of a multicentre study which included an additional 61 cases; 12 responded (3 surveillance relapse patients and 9 others). Patients with lung metastases only had the highest response rate (10/17 compared with 5 unexplained responses seen in 38 such patients on surveillance). These results confirm that alpha-interferon is active against metastatic renal carcinoma and that the responses are not totally explicable by spontaneous regression.

Humans↗

Radical retroperitoneal node dissection after chemotherapy for testicular tumours.

A group of 29 patients underwent salvage node dissection for residual retroperitoneal masses following orchiectomy and combination chemotherapy for advanced testicular cancer between 1980 and 1988. The results confirm that surgery for residual retroperitoneal masses following combination chemotherapy is worthwhile and whenever possible the sympathetic chain should be preserved.

Adolescent↗

Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer.

Beta human chorionic gonadotrophin (beta HCG) was measured in 127 urine and 85 serum samples from 175 untreated patients with urothelial cancer. Serum levels of beta HCG were substantially elevated in 16 of 21 patients (76%) with widespread metastases but in only 2 of 64 patients (3%) with disease confined to the pelvis. Urine beta HCG levels were moderately raised in 11 of 25 patients (44%) with locally advanced disease, but greatly elevated in 5 of 7 patients (71%) with metastases. Measurement of serum and/or urine beta HCG appears to be an efficient diagnostic marker for the presence of distant metastases in bladder carcinoma.

Adult↗

Findings in lymph nodes of patients with germ cell tumours after chemotherapy and their relation to prognosis.

One hundred and forty six patients with advanced germ cell testicular tumours (38 seminomas and 108 malignant teratomas) treated by combination chemotherapy were studied over 10 years. Most of the improvement seen was in patients with malignant teratoma undifferentiated. In the most recently treated patients (1984-1987) 75% of drug resistant cases were malignant teratoma intermediate compared with 26% in the series treated between 1978-1983. The microscopic features of 52 primary testicular tumours were compared with features seen in excised retroperitoneal lymph nodes after completion of chemotherapy. Primary malignant teratoma intermediate had a higher incidence of viable malignancy in the excised tissue than malignant teratoma undifferentiated. Mature teratoma or fibronecrotic tissue within resected tissue was associated with a good prognosis. If resection was complete patients with drug resistant malignant teratoma intermediate had a more favourable prognosis than drug resistant malignant teratoma undifferentiated. It is advised that retroperitoneal node dissection should be considered in the management of patients with advanced germ cell testicular tumours, and that as complete a resection as possible be attempted to avoid the danger of missing residual disease.

Adolescent↗

Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer.

One hundred and eighty-two patients with invasive (T2/T3) bladder cancer were treated by radical radiotherapy at the London Hospital between 1974 and December 1985. Cystectomy was reserved for patients whose tumours either did not respond completely to radiation or recurred later, provided they were fit for surgery and had not developed distant metastases. The overall corrected 5-year survival rate was 40%; 75 patients responded to radiation and did not relapse during the period of follow-up; 20 patients had an initial response to radiation but subsequently relapsed, with a 5-year survival rate following relapse of 20%. Of these, 11 patients had a cystectomy with a 5-year survival following relapse of 36%, whereas all 9 patients who did not have a cystectomy died within 3 years; 87 patients who did not respond to radiation had a 5-year survival rate of 18%. Of these, 22 patients underwent salvage cystectomy with a 5-year survival of 47%, whereas the 65 patients who did not have a cystectomy had a 5-year survival of 3%. These results justify a policy of radical radiotherapy and salvage cystectomy rather than elective cystectomy in the treatment of invasive bladder cancer.

Adult↗

Short-course etoposide, bleomycin and cisplatin in the treatment of metastatic germ cell tumours. Appraisal of its potential as adjuvant chemotherapy for stage 1 testis tumours.

Prompted by recent reports of the increasing incidence of late relapses in Stage 1 patients with both malignant teratoma and seminoma on surveillance, a low toxicity regimen combining etoposide, bleomycin and cisplatin [EBCi(3)] with prolonged infusion of bleomycin, given daily for 3 days, has been developed for possible use as adjuvant treatment. Forty of 44 patients treated remain free of disease with a median follow-up of 21 months and actuarial disease free survival at 2 years of 91%. There have been no respiratory problems attributable to bleomycin lung toxicity in this study compared with four (3 associated with patient deaths) seen in 91 previously treated patients. The relatively low toxicity and high efficacy of this regime indicate that it may be suitable as adjuvant treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Chemotherapy for carcinoma in situ of the bladder.

In an 8-year period, 71 patients were diagnosed as having carcinoma in situ of the bladder. Twenty patients with primary carcinoma in situ were treated with systemic cyclophosphamide or intravesical mitomycin C and 19 of them survived 3 years. Three patients required cystectomy: 1 for invasive cancer and 2 for intractable symptoms in the absence of tumour. Fifty-one patients had either secondary or concomitant carcinoma in situ. Systemic or intravesical chemotherapy was given to 28 patients in whom carcinoma in situ was associated with G1 or G2 exophytic superficial tumour: there was only one cancer death in 3 years. Fifteen patients with G3 carcinoma in situ associated with a G3 or invasive exophytic tumour were treated with radiotherapy: 9 responded but 4 of the 6 with radio-insensitive tumours died of cancer within 3 years. Eight patients with secondary carcinoma in situ were managed by transurethral resection alone: in 6 there was spontaneous regression and 2 developed muscle invasion within 1 year. These results compare well with those of immunotherapy or early radical surgery and suggest that chemotherapy should be given a trial in patients with carcinoma in situ.

Administration, Intravesical↗

Clinicopathological significance of immunoreactive beta-hCG production by bladder cancer.

Immunocytochemical screening of bladder tumors with an antibody to beta-human chorionic gonadotrophin (hCG) demonstrates a correlation with malignant behavior in that 0 of 20 G1M0, 5 of 20 G3M0, and 11 of 20 G2/3M + showed strong staining, while only 2/20 G3 Ca prostate and 0/18 renal cell carcinoma showed weak staining. There was a suggestion that hCG positive bladder cancer responded less well to chemotherapy (1 of 12 hCG positive and 6 of 13 hCG negative patients achieved a complete or partial response) and also patients whose tumors showed strong hCG staining did less well after radiotherapy, though paradoxically patients showing only occasional stained cells did better than patients whose tumor showed no staining. The possible significance of these observations in relation to recent observations on the mechanisms of trophoblast escape from immune surveillance is discussed.

Biomarkers, Tumor↗

A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression.

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.

BCG Vaccine↗

Histopathology in the prediction of relapse of patients with stage I testicular teratoma treated by orchidectomy alone.

259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orchidectomy alone and monitored at one often centres in the United Kingdom were followed for a median of 30 months. 62 of the 70 relapses occurred in the first 18 months after orchidectomy. The 2-year relapse-free rate was 74%, falling to 68% at 4 years. Histological sections from 233 of the orchidectomy specimens were reviewed centrally. Four features independently predicted relapses: invasion of testicular veins, invasion of testicular lymphatics, absence of yolk-sac elements, and presence of undifferentiated tumour. An index, based on the number of these features observed, identified a high-risk subgroup of 55 patients who had a 42% relapse-free rate at 2 years.

Follow-Up Studies↗

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells.

Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU l(-1). All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production.

Cell Line↗

HLA phenotype and clinicopathological behaviour of germ cell tumours: possible evidence for clonal evolution from seminomas to nonseminomas.

Analysis of 101 patients with germ cell tumours of the testis who have been typed for HLA DR antigens has provided confirmatory evidence for an association of DR5 with the development of seminoma and demonstrated an association of DR7 with metastases. These observations taken with the suggestion of HLA linkage in the small numbers of familial cases reviewed, does suggest that there is an HLA linked gene involved in the clinicopathological behaviour of germ cell tumours. Though of only theoretical interest at present these observations may be of considerable importance in the future given the observation in mice that transfection of missing MHC genes into a malignant tumour can produce a vaccine that enables previously unexposed animals to resist the original malignant tumour (Hui et al., 1984).

Dysgerminoma↗

Limitations to the use of surveillance as an option in the management of stage I seminoma.

Improved definition of seminoma using step sections and tumour markers makes such patients a more selected group than when radiotherapy was first introduced. This and the improvements in radiological staging and the exquisite sensitivity of metastatic seminoma to chemotherapy justifies reappraisal of the role of prophylactic radiotherapy. To investigate this, twenty-six patients have been entered onto a programme of prospective biochemical and radiological surveillance. Though only four (15%) have relapsed, and all easily salvaged by chemotherapy, the relative difficulty and lateness of establishing the diagnosis makes this approach unsuitable for service use. Whether given the chemosensitivity of seminomas, radiotherapy would remain the treatment of choice compared to short courses of adjuvant carboplatin requires testing in a randomized trial.

Carcinoma in Situ↗