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Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 163 records · Page 9Linked to original sources

Diagnosis of metastases from testicular germ cell tumours using fine needle aspiration cytology.

The cytological features of testicular germ cell tumours were established in smears from 15 freshly resected tumours. These features were applied to the fine needle aspiration cytology diagnosis of metastases in 27 patients referred for chemotherapy. There were 16 positive reports in 32 aspirates of which 13 were taken before chemotherapy and three in patients with residual or new masses after chemotherapy. Teratomas and typical seminomas showed certain characteristic morphological features in cytological preparations which when present in fine needle aspiration cytology material enabled tumour types to be diagnosed. Spermatocytic and anaplastic seminoma were not represented in this series. It is unlikely that these could be distinguished from malignant teratoma undifferentiated (MTU) in the fine needle aspiration cytology material. Metastases from carcinomatous areas in MTU and malignant teratoma intermediate (MTI) may not be distinguishable in fine needle aspiration cytology material from metastatic adenocarcinoma or undifferentiated carcinoma from a different primary site. Positive cytological findings are of value to the oncologist in the management of patients with metastases from testicular germ cell tumours; negative cytology does not exclude the presence of viable tumour. The sampling of small foci of viable tumour in large necrotic masses persisting after chemotherapy is a problem for radiologists, cytologists, and histopathologists. This paper does not advocate the use of fine needle aspiration cytology for the diagnosis of primary testicular tumour.

Abdominal Neoplasms↗

Medical options in the management of stages 1 and 2 (N0-N3, M0) testicular germ cell tumors.

Retroperitoneal lymph-node dissection or radiotherapy have long been known to provide equivalent survival for early stage I and stage II nonseminomatous germ-cell tumors. Review of the results from intensive radiological and biochemical surveillance with salvage chemotherapy for stage I tumors demonstrates that the long-term survival rate is equivalent to that achievable by conventional treatment (i.e., 98 per cent survival at 4 years). As relapses have continued to occur in the third and fourth years at the rate of 4 per cent annually, and 4 years is the limit of follow-up, further follow-up is required to be sure of the long-term picture. Prognostic factor analysis demonstrates that venous and lymphatic invasion, the absence of yolk sac differentiation, and the presence of undifferentiated cells are independently important in predicting the frequency of relapse. Using these factors, it was possible to define low-risk groups with relapse rates less than that seen after lymph-node dissection and high-risk groups with 58 per cent frequency of relapse who probably are suitable for adjuvant chemotherapy studies. Review of the results from the use of surveillance in stage I seminoma demonstrated no advantages over prophylactic radiotherapy. However, late toxicity is being demonstrated after radiotherapy and evidence is emerging that the less toxic cisplatinum analogue carboplatin may be as good as radiotherapy for metastatic disease. This offers for the first time a viable alternative to radiotherapy for consideration in the adjuvant setting in stage I seminoma.

Combined Modality Therapy↗

The first clinical use of depot buserelin for advanced prostatic carcinoma.

The agonist analogues of the gonadotrophin-releasing hormone now provide an alternate medical treatment of prostatic cancer. For effect repeated administration is required, either by five or six times daily intranasal or once daily subcutaneous treatment. There is an obvious disadvantage to such regimens in elderly patients who may have difficulty complying with therapy. In order to circumvent these difficulties, sustained release formulations of the agonist analogues have been synthesized. We report the first clinical use of a long-acting formulation of D-Ser (TBU)6-LHRH Ethylamide (buserelin) using a novel polymer material. Twelve symptomatic patients with previously untreated carcinoma of the prostate were treated with depot buserelin, administered once monthly. In all patients, depot buserelin suppressed serum testosterone into the range seen in castrate men at a rate equivalent to that provided by five times daily intranasal therapy. No significant increase in serum testosterone, luteinizing hormone or follicle-stimulating hormone concentrations occurred during the period of follow-up. Long-acting formulations of buserelin offer an advance in the management of prostatic cancer with agonist analogues of the gonadotrophin-releasing hormone.

Aged↗

Methotrexate, cisplatin and carboplatin as single agents and in combination for metastatic bladder cancer.

A review of 78 previously untreated patients with bidimensionally measurable metastatic bladder cancer who were entered into a series of studies of cytotoxic chemotherapy has shown that complete response occurred in 1 of 23 patients receiving methotrexate, none of 15 receiving cisplatin, none of 20 receiving the platinum analogue carboplatin and 3 (2 with histological confirmation) of 20 receiving methotrexate in combination with cisplatin. WHO/UICC performance status 3 and 4, though a prediction of lower response, did not provide a means for excluding patients who might benefit from chemotherapy. Studies using serial cytology showed that 5 of 8 responders according to standard criteria had complete loss of malignant cells from the urine compared with none of 10 non-responders and there was a suggestion that duration of response was longer in those whose urine was negative for malignant cells than in those which remained positive.

Antineoplastic Agents↗

Indium-111 labelled monoclonal antibody to placental alkaline phosphatase in in the detection of neoplasms of testis, ovary, and cervix.

A monoclonal antibody (H17E2) against placental alkaline phosphatase (PLAP) and testicular placental-like alkaline phosphatase was labelled with indium-111 and used in radioimmunoscintigraphy of 15 patients known or suspected to have germ-cell carcinoma of the testis or carcinoma of the ovary or cervix. Good images of neoplastic lesions were obtained in most patients with active disease. In 1 patient with testicular teratoma and elevated human chorionic gonadotropin who had a normal computed tomography scan, the labelled antibody located microscopic disease in a lymph node, which was then removed. No false positive localisation was seen in patients with PLAP-negative tumours or sites of inflammation. This method may be helpful in the diagnosis, staging, and monitoring of PLAP-positive neoplasms of testicular, ovarian, and cervical origin.

Adult↗

Comparison of the cytotoxic activities of chemotherapeutic drugs using a human bladder cancer cell line.

Many chemotherapeutic drugs have been used to treat patients with advanced bladder cancer, but few of these have been evaluated adequately in phase II clinical trials. Continuous cell lines provide one means for comparing the in vitro cytotoxicities of anticancer agents. In this study, a continuous cell line derived from a transitional cell cancer of the human bladder, which still produces tumours histologically similar to the tumour of origin on xenotransplantation, was used to measure the in vitro cytotoxicities of twelve chemotherapeutic drugs by clonogenic assay. The most cytotoxic agents tested were methotrexate, mitoxantrone, adriamycin, mitomycin C and cisplatin. These in vitro findings are compatible with the activity of these drugs given systemically as single agents in phase II clinical trials in patients with advanced bladder cancer.

Animals↗

Serum marker potential of placental alkaline phosphatase-like activity in testicular germ cell tumours evaluated by H17E2 monoclonal antibody assay.

A monoclonal antibody (H17E2) was used in a solid-phase localisation of enzyme activity (ILEA) assay to evaluate placental-like alkaline phosphatase (PLAP) as a serum marker of testicular germ cell tumours. Single or repeated assays were performed on 213 normal blood donor and a smaller number of term pregnancy and testicular cancer sera. The detection limit of PLAP by this system was 0.14 O.D. units equivalent to 0.04iul-1. Of 50 patients with established metastatic disease tested before treatment, 88% of 16 with seminoma, 54% of 13 with mixed seminoma and malignant teratoma and 33% of 21 with malignant teratoma had serum PLAP greater than 0.2 O.D. units. This compared to an incidence of 2% in non-smokers and of 29% in smokers who had been free of disease for more than 12 months. In 15 of 22 successfully treated patients, pre-treatment serum PLAP exceeded 0.2 O.D. units (mean 0.69 O.D.) and varying (53-97%) reductions in the initial levels occurred with treatment. These results with monoclonal antibody ILEA assay suggest that measurement of PLAP levels will be useful in the management of patients with germ cell tumours, particularly seminoma.

Alkaline Phosphatase↗

Chemotherapy of invasive carcinoma of the bladder.

Cytotoxic chemotherapy does not yet have a service role in the management of invasive carcinoma of the bladder, though the minor palliation achievable in patients with symptomatic recurrent primary or metastatic disease does justify its use in patients whose symptoms are not controlled by standard analgesia. For the future, progress will depend on more intense screening of new drugs in centres specializing in undertaking Phase 2 Trials on patients with measurable metastases. However, there is in addition a need for studies measuring primary tumour response to drugs in combination with radiotherapy which still remains the most active single agent in the non-surgical treatment of carcinoma of the bladder.

Antineoplastic Agents↗

The value of fine needle aspiration cytology in the management of metastatic germ cell tumours.

Review of 19 patients with advanced metastatic malignant teratomas has revealed five serious complications possibly related to the surgical biopsy procedure, three of which led to the patient's death. Preliminary results from a small series of patients diagnosed by fine needle aspiration (FNA) cytology suggest that this procedure is a reliable alternative method for diagnosing these patients. In addition, when used after chemotherapy this procedure may save patients with residual malignancy from having to undergo post-treatment surgical staging. However, the absence of malignant cells in the aspirate cannot exclude malignancy because of the focal distribution of residual tumour in these masses.

Biopsy↗

Serum and tissue tumour markers in seminomas.

The serum expression of the tumour markers hydroxybutyric dehydrogenase (HBD), beta human chorionic gonadotrophin (beta HCG), alphafetoprotein (alpha FP) and placental alkaline phosphatase (PLAP) has been assessed in a consecutive series of 50 patients with pure seminoma. In pre-orchiectomy sera from 15 patients with stage I disease, HBD was elevated in 5, beta HCG in 3, alpha FP in 1 and PLAP in 1 (of 3 only). In 27 patients with stage 2 or 3 disease, prior to chemotherapy, serum HBD was elevated in 19, beta HCG in 11, alpha FP in 2 and PLAP in 10 (of 18). The presence of beta HCG was investigated immunocytochemically in primary tumour tissue from 39 patients. It was demonstrated in 6 of 21 tumours from patients with stage I disease and 5 of 18 with stage 2 or 3 disease.

Alkaline Phosphatase↗

A long term follow-up of patients with advanced prostatic cancer treated with buserelin.

Thirty consecutive patients with newly diagnosed symptomatic, locally advanced or metastatic prostate cancer were treated with intranasal buserelin, a long-acting analogue of gonadotrophin releasing hormone, in divided dosages of either 600, 1000 or 1200 micrograms daily. Suppression of testosterone occurred in 1 of 5 patients treated with 600 micrograms daily and in all of 25 patients receiving 1000 or 1200 micrograms regimens. Two of 5 patients treated with the 600 micrograms regimen and 23 of 25 patients receiving the higher dosage regimens showed subjective and objective evidence of response. Follow-up was from 1 to 31 months. During this period 11 patients have relapsed. The mean duration of remission was 16 months. Buserelin offers an effective alternative of equivalent efficacy to conventional treatments for prostatic cancer, without any significant side effects.

Buserelin↗