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Biomedical subjects

D W Newling

Publications and source records attributed to D W Newling.

At least 37 records · Page 2Linked to original sources
PubMed1997

Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free survival in a rat model.

OBJECTIVES: The present study was initiated to explore the effects of hydroxyethylidene diphosphonate labeled with rhenium 186(186Re-HEDP) treatment on the progression of lumbar skeletal metastasis in an animal model and to correlate the eventual treatment efficacy with the radioisotope tissue distribution. METHODS: The effect of 186Re-HEDP on the progression of lumbar metastasis from prostate cancer was investigated in the Copenhagen rat model. Metastatic prostate tumor deposits were induced in male rats by tail vein injection of R3327-MATLyLu prostate tumor cells under concomitant clamping of the inferior caval vein. The development of clinical symptoms such as onset of hind leg paralysis and urinary bladder swelling was monitored and related to the presence of tumor cells within histologic sections of L-5 and L-6 vertebrae. RESULTS: The 186Re-HEDP administration, given either 1 day or 8 days after surgical induction of lumbar metastasis, could significantly increase the symptom-free survival of the animals. These results were confirmed by a significant decrease in the presence of histologically detectable tumor tissue. Biodistribution studies demonstrated the uptake of the major part of the radioisotope within bone tissue. Uptake of radioactivity within the lumbar vertebrae on a microscopic scale, as shown by phosphor screen autoradiography, was concentrated in areas of bone formation and turnover. Signs of radiotoxicity, such as bone marrow replacement by fat cells and the absence of megakaryocytes, were observed. CONCLUSIONS: The results show that radionuclide treatment using 186Re-HEDP is a potentially efficacious treatment option in prostate cancer disseminated to the skeleton. The optimal treatment dose should be determined carefully and aimed at acceptable levels of myelotoxicity.

Animals↗
PubMed1997

The palliative therapy of advanced prostate cancer, with particular reference to the results of recent European clinical trials.

The palliative therapy of advanced prostate cancer still remains a perplexing problem. If advanced prostate cancer is defined either as a primary advanced-stage tumour (T3, T4, N0-N1), or a rising PSA level after primary and hopefully curative therapy, or the traditional patient presenting with small- or large-volume metastases with or without symptoms, then some 60% of all patients have advanced disease when first seen. There is still a need for the continuation of large prospective, randomized studies in all stages of this common illness, to define the role of the different therapeutic options at our disposal. The urological and urooncological worlds must be patient and not jump to too many early conclusions over the benefit of the various therapies until a statistical advantage for both individual and combined therapeutic options has been shown.

Androgen Antagonists↗
PubMed1997

Facing progressive localized prostatic cancer.

Patients diagnosed with locally progressive prostate cancer can be divided into three groups according to the stage of their disease. The first group includes patients with locally progressive cancer presenting initially as either T3 or T4; the second group involves individuals treated curatively who then develop local progression in the pelvis; the third group includes patients who present with metastatic disease and who develop recurrence of locally advancing disease in the pelvis despite undergoing hormonal therapy. This article reviews the treatment options currently available for patients in these three groups. The factors involved in deciding which is the most appropriate therapy are discussed, and the effectiveness of each treatment and the complications associated with it are presented.

Combined Modality Therapy↗
PubMed1997

Clinical assessment and management of stage T3 prostate cancer.

The early recurrence of prostate cancer originally staged as locally more than T2 and nonmetastatic, cast doubts over the adequacy of the staging of this form of the disease. Monotherapy with curative intent, either by radical prostatectomy or radiotherapy, results in around half of the patients failing within 5 years. While improvements in staging of the disease are essential, the early results of combined modality therapy, particularly the combination of neo-adjuvant hormones and surgery, have been disappointing. Neo-adjuvant maximal androgen blockade followed by radiotherapy does appear to offer survival benefit for patients with locally advanced disease, and other studies combining radiotherapy adjuvant hormonal therapy and surgery with routine postoperative with radiotherapy are eagerly awaited. Combination therapy might not give the hoped-for additive effects of the two therapies, but almost certainly will give an increased incidence of complications.

Androgen Antagonists↗
PubMed1996

Primary signet-ring cell carcinoma of the urinary bladder.

Signet-ring cell carcinoma of the urinary bladder is a rare tumour, accounting for approximately 0.24% of all bladder malignancies. In this study, the clinicopathological findings in 13 cases are described. This malignancy is far more common in men than in women (ratio 11:2). The distribution by age and clinical symptoms can not distinguish it from transitional cell carcinoma. The tumour behaves like other high grade malignancies, presenting frequently at an advanced stage, and having an unfavourable clinical outcome. No special therapy seems superior to another.

Adult↗
PubMed1996

Transplantation of the testis; from the past to the present.

Since the development of surgery, the possibility of testis transplantation has fascinated man for centuries. Hunter and Berthold are considered to be the most important investigators in this field and, in addition, to be the founders of modern endocrinology. The association of testis transplantation with rejuvenation led to widespread popularity for this treatment in the first three decades of the twentieth century. At the same time, controversies concerning the aim of the treatment have coloured the early years of endocrinology. In the 1960s renewed interest in the subject arose for experimental reasons, leading to the development of microsurgical techniques for autotransplantation of high-lying undescended testes in children. Homologous testis transplantation has never become a subject of great interest, probably for ethical reasons. This possible treatment for hypogonadism, however, has been developed experimentally and has been performed in man only in Russia and China, evidently with success. The details of these studies and their outcomes are discussed.

Animals↗
PubMed1996

The management of hormone refractory prostate cancer.

Prostate cancer patients deemed unsuitable for curative therapy by means of radical prostatectomy or radiation are offered androgen ablation or suppression therapy, which normally results in an inhibition of prostate cellular growth for a period of 12-18 months. Death of patients from prostate cancer is directly related to the development of clones of cells capable of multiplying and metastasising without androgen stimulation, and to date efforts to suppress these cells have been singularly unsuccessful. There are a number of treatment options available, and these include secondary hormone therapy, growth factor inhibition, chemotherapy, combination therapies and interstitial radiotherapy. The merits and disadvantages of these management approaches are discussed.

Androgen Antagonists↗
PubMed1996

The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up.

PURPOSE: We determined the role, if any, of 1 and 5 instillations of intravesical mitomycin C in the treatment of newly diagnosed superficial bladder cancer. MATERIALS AND METHODS: A multicenter randomized clinical trial was done involving 502 patients with newly diagnosed superficial bladder cancer. After complete transurethral resection patients with newly diagnosed superficial bladder cancer. After complete resection patients were randomized into 1 of 3 treatment arms: no further treatment, 1 instillation of mitomycin C at resection and 1 instillation at resection and at 3-month intervals for 1 year (total 5 instillations). The dose of mitomycin C used was 40 mg./40 ml. water. End points were interval to first superficial recurrence, recurrence rate (defined as the number of positive cystoscopies per year) and progression-free interval rate (progression defined as the development of muscle invasive or metastatic disease, or death from bladder cancer). RESULTS: After median followup of 7 years 1 and 5 instillations of mitomycin C resulted in decreased recurrence rates and increased recurrence-free interval. The benefit of mitomycin C was observed in patients at low, medium and high risk for subsequent recurrence. There was suggestive but not conclusive evidence that 5 instillations of mitomycin C offered a slight advantage over 1 instillation. CONCLUSIONS: Our analysis confirms the positive benefit of mitomycin C to decrease the number of subsequent recurrences and increase the recurrence-free interval.

Administration, Intravesical↗
PubMed1995

Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group.

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

Administration, Oral↗
PubMed1995

Bilateral intravesical duplex system ureteroceles with multiple calculi in an adult patient.

We present a case report of an adult female patient with bilateral duplex system ureteroceles, containing multiple small stones. There was no history of urinary tract infections or stone disease. Treatment consisted of right upper pole heminephrectomy because of non-function and transurethral incision of the left ureterocele, resulting in almost complete removal of the calculi. Furthermore no vesicoureteral reflux was seen 3 months postoperatively. Transurethral incision is a safe and effective treatment in removing stones in ureteroceles without necessitating further treatment because of vesicoureteral reflux.

Adult↗
PubMed1995

[Clinical protocols in treatment of prostatic carcinoma in Europe. The role of EORTC and other organizations].

In the last few years the EORTC has conducted multiple clinical studies on the therapy of prostate cancer. In most cases with incidental unifocal prostate cancer, no therapy is necessary, as the disease is rarely progressive or the cause of death. Current EORTC studies are evaluating the timing of hormone therapy, as it is still unknown whether therapy should be started at the time of diagnosis or when the patient becomes symptomatic. Different hormone therapies are useful for locally progressive prostate cancer and as effective than radiotherapy in the case of progression and survival. The preliminary results of a current study on total androgen blockade for 3 months before radical prostatectomy show a positive effect for some of the patients with a T2 carcinoma. Inconclusive results in studies on total androgen blockade versus orchiectomy in metastasising prostate cancer have lead to a meta-analysis of 22 studies by the EORTC. This only showed a trend towards better survival time and longer interval till progression with total androgen blockade but the group of patients with small volume metastatic disease benefit greatly from this treatment. The importance of estrogen therapy and the treatment with high dose non steroidal antiandrogens as well as the use of intermittent hormonal therapy in progressive disease will have to be assessed in future studies. Chemotherapy is not very effective due to its low response rate and its short lived effect.

Androgen Antagonists↗
PubMed1995

The geography of prostate cancer and its treatment in Europe.

The search for more efficient treatments for prostate cancer continues. In localized prostate cancer, the combination of neo-adjuvant or adjuvant hormone therapy with surgery may improve curability rates. In the palliation of advanced prostate cancer, novel concepts of varying forms of maximal androgen blockade, including the re-introduction of safer forms of oestrogen therapy, should be capable of lengthening the time to progression and improving the quality of life of patients with advanced disease. The chemotherapy of prostate cancer remains experimental, but its earlier introduction may enable better dosing schedules to further limit advanced disease.

Europe↗
PubMed1995

The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate.

This report is the final analysis of an EORTC Genito-Urinary Group Phase III trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate 50 mg 3 times a day and stilboestrol 1 mg daily in the management of metastatic carcinoma of the prostate. Three hundred and twenty-eight eligible patients admitted into the study have been followed up for a median period of 4 years. There was no difference in time to metastatic progression and overall survival between the treatment arms. The cardiovascular toxicity of stilboestrol 1 mg daily has resulted in more cardiovascular deaths as compared with the orchidectomy treatment arm. The outcome for individual patients has been determined by on-study prognostic factors, especially the performance status, rather than the treatment given.

Adenocarcinoma↗