PubMed Health⌕ Search

Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 55 records · Page 3Linked to original sources
PubMed1998

Surgery as salvage therapy in chemotherapy-resistant nonseminomatous germ cell tumours.

OBJECTIVE: To review our experience of surgical staging for residual masses after chemotherapy in patients with nonseminomatous germ cell tumour (NSGCT) and positive tumour markers. PATIENTS AND METHODS: Of 107 patients with metastatic NSGCTs treated surgically after chemotherapy from 1978 to 1995, 30 (median age 30.5 years, range 20-52) had positive tumour markers. These patients were reviewed and the outcome compared with 77 patients who had normal tumour marker values. RESULTS: Of the 77 patients with negative markers undergoing surgical/pathological staging, 71 (92%) became continuously disease-free, including 37 of 50 (74%) with viable NSGCT in excised specimens. Seventeen of 30 (57%) with raised marker levels undergoing similar surgery for chemotherapy-resistant tumour became disease-free, including 11 of 22 with viable NSGCT in the excised specimens. CONCLUSION: Although the outcome after surgery is better in patients with negative tumour markers, it is clear that surgery is curative for patients with localized chemotherapy-resistant masses. There is a need for continued debate on the timing of salvage surgery and subsequent chemotherapy.

Adult↗
PubMed1998

Germ cell cancer of the testis.

Publications confirming a higher incidence of testicular germ cell cancer (GCC) in offspring of dizygous than in monozygous pregnancies and following pregnancies associated with severe maternal nausea show that transplacental-acting estrogen damage to fetal germ cells is becoming established as a major epidemiologic risk factor for these tumors. Endogenous retrovirus expression in GCC is a new observation that, given the confirmation that a high-frequency recessive gene was the best-fitting genetic model of familial GCC, opens up new areas for epidemiologic research. With two papers confirming the importance of excess p53 expression in determining GCC chemotherapy response, particularly in seminoma, the question of whether seminoma should be treated with different chemotherapy strategies re-emerges. Preclinical data on oxaloplatin suggest that it is active in cisplatin-resistant tumors, and justifies further trials to reduce our dependence on cisplatin. These trials will be difficult to undertake given the long time taken to prove the poor results from use of carboplatin--which 12 years after launch has now been shown to be 17% worse at 3 years in combination with bleomycin and etoposide.

Adult↗
PubMed1998

Squamous change in bladder cancer and its relevance to understanding clonal evolution in development of bladder cancer.

Using conventional morphological assessment, squamous change in bladder epithelium has been observed in 73% of bilharzial associated squamous cancers but only 28% of pure transitional cancers. However, more detailed studies of patients with TCC suggest that the latter figure may be an underestimate, since in one series it was reported to be more than 50%. The most significant risk factor for development of squamous carcinoma in the bladder is chronic persistent bacterial cystitis, although in the areas of the world where bilharzia is endemic this infestation also increases the risk of both squamous bladder cancer and chronic bacterial cystitis. Although it is clear that carcinogens are involved as co-factors in transformation from squamous metaplasia to cancer, the fact that in Zimbabwe one author has observed that TCC is more frequent in whites than squamous cancer is in bilharzia infected blacks is evidence that other unidentified risk factors are involved. This is increasing evidence for involvement of HPV subtypes in cervix, oropharynx and lung cancer. As all three of these tumours are associated with squamous metaplasia, there could be a case for investigation of bladder squamous tumours for HPV involvement. This is particularly so given the observation of the "hit and run" type of transient infection in cattle that develop BPV associated tumours and the tenfold difference (30% vs 3%) in frequency of HPV detection in squamous skin tumours developing in immunosuppressed individuals compared with those arising spontaneously. With new technology for cytological screening techniques using dot ELISA and evidence of differences in TP53 mutations that support the involvement of nitrous oxide, it is clear that there is more to learn from study of this tumour type that may be of general interest in understanding the clonal development of cancer.

Animals↗
PubMed1998

Malignancy associated papillomaviruses and morphology of human bladder cancer.

Animal studies in rabbit and cattle have clearly demonstrated the contribution of host genetics, chemical carcinogens and immunosuppression to the conversion of papillomavirus induced benign regressing warts into malignant cancers. More significant is the role of vaccination both with whole tumour cell suspensions with whole virus and viral proteins, particularly L2 molecules, in causing progressing warts to regress. Early results in small scale studies of HPV16 E6/E7 vaccine in patients with cervical cancer have provided evidence that tumour regression can be induced in human papillomavirus induced tumours. These observations provided added impetus for more research to firm up the increasing, but still principally anecdotal, evidence that papillomaviruses may be involved in the pathogenesis of bladder cancer. Studies of carcinomas arising in cattle after BBV 4 infection show absence of fully infectious virus in the majority of tumours, though the tumours have persistent E7, E8 and LCR sequences. As this is all that is required for transformation, it may require in vitro molecular studies in human bladder cancer screening for such elements before final proof of involvement is confirmed. However, even before this is achieved, given the success in animal models of whole tumour cell vaccines, serious thought should be given to how to develop protocols for study of crude tumour cell vaccines in vivo. Such studies would need in vitro assays to seek evidence for specific antitumour immunity, focusing on studies of tumour infiltrating lymphocytes and their T cell receptor polymorphisms.

Animals↗
PubMed1998

Clonal development of bladder cancer and its relevance to the clinical potential of HLA antigen and TP53 based gene therapy.

In the last decade there has been major progress in understanding the multiple steps involved in cancer cells developing their malignant potential. Study of bladder cancer has provided important information during this period and helped to identify HLA class I and wild type normal TP53 as potential probes for gene therapy studies. Given the magnitude of genetic damage that is associated with the clonal development of bladder cancer, and particularly the number of cellular mechanisms that have been highjacked in the development of terminal metastatic disease, it is obviously highly unlikely that a single gene therapy involving HLA class I alone would work in terminal metastatic disease. However, it seems possible that HLA-B7 treatment of patients with bladder cancer who are candidates for salvage cystectomy would benefit such patients. If it were to work, it could provide a whole new approach to managing superficial tumours. However for patients with extensive metastatic disease, progress could come from investing more effort in uncoverinlg the genetic basis of the chemosensitivity of germ cell tumours and understanding the basis of the normal checkpoints of meiosis and the role of TP53. This could provide a completely new approach to gene therapy that might be exploited even in patients with advanced metastatic disease. Such a tetraploidal construct combined with allogeneic HLA class I and incorporated into a low pathogenic lytic viral construct to induce oncolysis with some form of tissue promoter to focus the cell types in which the genes will be activated could provide ideal effective gene therapy.

Carcinoma, Renal Cell↗
PubMed1998

The role of surgery in the multimodality treatment of bladder cancer.

There has been little change in bladder cancer survival for more than 40 years, although earlier diagnosis is now detecting more cases at an early, potentially curable stage. Radical cystectomy remains the most effective single treatment, although in the past the morbidity and mortality of treatment and the age of patients made it less favoured as primary treatment. Progress in continent bladder reconstruction is changing attitudes. However, because tissue damage from preoperative radiation, particularly when combined with chemotherapy, makes such operations less safe in patients with advanced disease, reconstruction is primarily of value in high risk superficial and early invasive cancers, though there remains a need for randomized trials or immediate vs deferred use of these operations to establish when they give most benefit. With new knowledge about the role of trauma released tissue repair cytokines and immunosuppressive effect of prolonged anaesthesia on increasing tumour recurrence after surgery, new approaches such as treatment with TNFA, anti-EGF antibody or neoadjuvant chemo/immunotherapy before TURBT to improve on the benefits of surgery need to be explored in randomized trials in both advanced invasive and early superficial disease. With progress in vaccine and gene therapy on the horizon, the central role of the urologist in both harvesting tumours for molecular diagnosis and monitoring response of local disease to treatment is undisputed. The relative underusage and value of bladder washings cytology to provide cells for such studies is also highlighted.

Combined Modality Therapy↗
PubMed1997

Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer.

OBJECTIVES: The increasing interest in exploring the use of intermittent androgen deprivation in prostate cancer has prompted a retrospective review of patients who elected to stop treatment. METHODS: Case records were reviewed. RESULTS: Twenty patients after 3 to 48 months (median 12) of endocrine therapy elected to stop therapy. Thirteen subsequently relapsed after a median observation of 9 months. Seven of 20 patients continue progression-free for 9 to 42 months (median 33). After second-line therapy, 75% of patients with a relapse remain progression-free at 2 years. Progression-free survival was higher in patients at Stage M0 (82% at 1 year) versus M+ (29% at 1 year). CONCLUSIONS: With 10 of 13 patients demonstrating an ongoing second PSA response, 45% of patients showing no progression, and 85% alive at 3 years, these results support findings from previous publications that suggest that there are no major risks with use of intermittent hormone therapy. However, in the future, there is an urgent need that such studies should be randomized and done in the context of audit-based research and development programs. The resources released could then be invested with respect to further improvements in treatment of prostate cancer, possibly considering such a combined approach with immunotherapy as an alternative to surgery or radiotherapy for early disease in elderly patients with long PSA-doubling time.

Aged↗
PubMed1997

Future trials in germ cell malignancy (GCM) of the testis.

With overall cure in excess of 95%, there is a debate about how to conduct further trials. Three areas are reviewed: (1) Relapse and high risk patients. With a plethora of new drugs and high dose salvaging one in three second-line failures, there is plenty of choice. Substituting taxol for etoposide in etoposide, ifosfamide and cisplatin (VIP), followed by high dose, is one possibility. (2) For low-risk metastatic disease the current priority is to recruit large numbers to the EORTC/MRC three vs four courses bleomycin, etoposide and cisplatin (BEP) and 3 vs 5 day etoposide trial to evaluate the safety of risking less toxic treatment. (3) For stage 1 disease, non-seminoma, quality of life assessments and evaluating patient participation in decisions about adjuvant therapy are the principal priorities. For seminoma one course carboplatin, the first realistic alternative to radiotherapy, is currently being tested in a MRC trial. During the next decade there will be two areas of interest in addition to those above. Firstly, trials of testis conservation to reduce the use of orchidectomy on diagnosis. For advanced drug-resistant disease, gene therapy using candidate genes found to be responsible for a chemotherapy response, and exploration of their role within non-germ cell cancer.

Antimetabolites, Antineoplastic↗
PubMed1997

Prognostic factors for patients with advanced seminoma treated with platinum-based chemotherapy.

Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity.

Adult↗
PubMed1997

Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party.

In a retrospective study, data from 302 patients with metastatic testicular seminoma treated with chemotherapy between 1978 and 1990 in 10 European centres were analysed to evaluate the role, if any, of postchemotherapy treatment with irradiation. The primary endpoint of this study was the progression-free survival rate after chemotherapy with or without additional radiotherapy. This was related to the type of primary chemotherapy, sites and sizes of pre- and postchemotherapy masses, the extent of surgical resection after chemotherapy and the use of radiotherapy. 174 patients had residual disease at the end of chemotherapy. The most important prognostic factors for progression were the presence of any visceral metastases or raised LDH prechemotherapy, and the presence of residual disease at visceral sites after chemotherapy. Approximately half the patients with residual masses underwent postchemotherapy radiotherapy, with selection based predominantly on institutional practice. In patients receiving platinum-based chemotherapy, no significant difference was detected in progression-free survival whether or not radiotherapy was employed. Patients receiving BEP (bleomycin, etoposide and cisplatin) had a progression-free survival rate of 88% (95% CI, 80-96%) uninfluenced by postchemotherapy radiotherapy. In patients with residual masses confined to the abdomen after platinum-based chemotherapy, the absolute benefit to radiotherapy was estimated to be 2.3%. The potential benefit of postchemotherapy radiotherapy is minimal, and so it is concluded that the use of adjuvant radiotherapy to residual masses after platinum-based chemotherapy for metastatic seminoma is unnecessary.

Abdominal Neoplasms↗
PubMed1997

Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter.

Fourteen patients with previously treated, locally advanced/metastatic transitional cell carcinoma (TCC) of the bladder or ureter received paclitaxel at a dose of 200 mg m-2 administered as a 3-h infusion every 21 days. The activity of paclitaxel in this group of patients was modest. The response rates were one partial response (PR) (7%) and three stable disease (SD). There were two early deaths.

Adult↗
PubMed1997

A single-centre observational study of surgery and late malignant events after chemotherapy for germ cell cancer.

OBJECTIVE: To review the impact of surgical staging after treatment on the late malignant events in an unselected group of patients treated with chemotherapy for germ cell cancer of the testis over the last 16 years. PATIENTS AND METHODS: The study comprised 256 patients treated between 1978 and 1994 who were reviewed for late relapse and development of second germ cell and non-germ cell cancer. RESULTS: At diagnosis, 142 patients had clinical stage 2, 30 stage 3 and 84 stage 4 disease; 57 patients relapsed within 20 months of treatment, while late germ-cell cancer relapses (> or = 24 months after treatment) occurred in six patients. Of patients relapsing early or late, 42% and 33%, respectively, received surgery after treatment. Only two of those relapsing late remain progression-free with further treatment. Four patients developed germ cell cancer in the contralateral testis, while six developed second non-germ cell cancers. CONCLUSION: Late events occurred in 6.2% of 256 patients in this series, from 29 to 141 months after treatment. Given that the late relapse rate of six of 256 (2.3%) is less than the incidence of mature teratoma at routine retroperitoneal lymph node dissection, more patients may eventually relapse. These results suggest that there might be a case to evaluate the use of ultrasonographic surveillance of the retroperitoneum and testis at 5, 10 and 20 years, in addition to extending routine surveillance.

Adult↗
PubMed1997

A new approach using tissue alkaline phosphatase activity to identify early testicular cancer.

OBJECTIVE: To establish the specificity and sensitivity of alkaline phosphatase activity in testicular tumours for the early detection of testicular germ cell tumours (GCTs). MATERIALS AND METHODS: Samples from patients with GCTs of the testis were sectioned and stained using the nitroblue tetrazolium salt (NBT)/5 bromo-4-chloro-3-indolylphosphate (BCIP) Sigma Fast substrate technique (referred to as MEDC) and peroxidase antiperoxidase (PAP) assay. Additionally, several cell lines from GCTs and other tumours were cultured using standard techniques and stained using both methods, and lysates from all samples were stained after gel electrophoresis. RESULTS: MEDC showed strong and specific staining of testicular tumours only. The activity on gel electrophoresis appeared as two bands, one at 75 and one at 95 kDa, which was a unique combination for testicular tumours and testis cell lines. CONCLUSION: The MEDC method has extreme sensitivity and intensity for testicular tumour tissue and has potential use as a powerful tool for the early detection of testicular GCTs by analysing semen samples, particularly in patients with equivocal findings on testicular ultrasonography.

Alkaline Phosphatase↗