Viral oncology of prostatic cancer

1. A method is described for the measurement of liver blood flow without hepatic venous catheterization by the injection of the a single dose of bromosulphthalein and the analysis of the graph of the plasma disappearance of the indicator. 2. The rationale of the method was tested in three systems which covered a wide range of flow rates. The first system was a physical model with a haemodialyser in which the calculated flow could be compared with the flow measured directly. The second was in anesthetized dogs, in which the calculated flow was compared with that measured by continuous infusion and hepatic venous catheterization, based on the Fick principle. The third system was in unanaesthetized turkeys, in which metabolism of bromosulphthalein does not occur. The calculated flow was compared with the flow measured simultaneously by the uptake of collodial particles by the Kupffer cells. 3. In all three systems the correspondence between the two methods of measuring liver blood flow was good, the differences between them being not statistically significant. 4. The method has been applied to measurements of liver blood flow in man and animals and gives results comparable with those reported by other workers.     

Molecular staging of prostatic cancer

Despite the improvement current evaluation techniques, approximately 30% of prostatic cancers clinically localized to the gland are understaged. RT-PCR is a sensitive and specific screening method for circulating prostatic cells, proposed as a molecular staging tool. The results obtained with this method and reported in the literature are critically discussed. These results, concerning the detection of circulating PSA- or PSMA-positive prostatic cells, are only indicative, as none of the teams used the same method. No consensus has been reached concerning the equipment used, the choice of oligonucleotide primers, the number of cycles to be applied or even the type of method, classical or "nested". Another possible application of this method is early detection of circulating prostatic cells, possibly neoplastic, during the follow-up of patients treated by radical prostatectomy. Once again, the results of the literature are contradictory. The reliability and reproducibility of molecular biology techniques in routine practice must therefore be demonstrated before these techniques can influence the therapeutic decision concerning prostatic cancer.     

Radical prostatectomy for localized prostatic cancer

Curatively intended surgical management of clinically localized prostate cancer has recently been introduced in Denmark. This literature review covers results of preoperative evaluation, impact of stage and grade on outcome, and the results following radical prostatectomy.     

Histological presence of viable prostatic glands on routine biopsy following cryosurgical ablation of the prostate

PURPOSE: Cryosurgical ablation of the prostate has recently received much attention as a therapeutic alternative for the treatment of localized prostatic adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes as well as unaltered prostatic glandular epithelial elements. Prostate specific antigen (PSA) remains undetectable in the majority of men. However, in some PSA increases without demonstrable local recurrence. MATERIALS AND METHODS: A total of 383 patients underwent 447 procedures between June 1990 and January 1994. Of 358 biopsies performed at our institution, 317 (2,075 cores) were available for review. Each core was examined for unaltered prostatic glandular epithelial elements and then scored for the percentage of epithelial glandular involvement according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50 to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements. RESULTS: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10% and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were positive for residual carcinoma. Among 55 cases with more normal epithelium per core 24 (43.6%) were positive for residual carcinoma. Patients with a positive biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124). CONCLUSIONS: Cryosurgical ablation of the prostate has the ability to ablate prostatic tissue completely, thus rendering it free of glandular elements as determined by biopsy. Increasing PSA can indicate residual glandular elements. Increases in unaltered prostatic glandular epithelial elements with time are not paralleled by increased rates of local disease recurrence. undetectable serum PSA has a low risk of residual unaltered prostatic glandular epithelial elements and localized carcinoma. Results as measured by unaltered prostatic glandular epithelial elements and PSA improve with the surgical experience.     

The hormonal and chemotherapy of prostatic cancer

Adenocarcinoma of the prostate is one of the most common malignant tumors in adult males. Hormonal therapy is the treatment of choice for patients with systemic disease concerning 80% response rate. Androgen ablation is now the first hormonal manipulation and can be achieved either by means of bilateral orchiectomy or of LH-HR agonist therapy: both are equally effective. Total androgen blockage (association between orchiectomy or LH-RH agonist and non-steroidal anti-androgens) would be reserved for controlled clinical trials only. Estrogens had the same efficacy, but revealed the serious cardio-vascular events. Endocrine therapy does not prolong survival but provides good palliation. Palliation should be given when there is something to palliate. Prostate cancer is usually not recognized as being sensitive to cytotoxic agents. Single agent or combination chemotherapy has not been shown to have a role as first line treatment of disseminated disease and is usually used for hormone refractory disseminated disease.     

Quality assurance in radiotherapy of prostatic cancer

External beam radiotherapy is a widely experimented treatment modality in prostatic cancer. Recently published studies have documented a close dependence of clinical results, in terms of local control and toxicity in particular, on radiation therapy quality. Efforts to improve results of conventional radiotherapy were directed towards the identification of new therapeutic modalities (conformal therapy, fast neutron radiotherapy, neoadjuvant hormonotherapy) as well as towards the optimization of treatment accuracy. In this respect, the following procedures have been particularly effective: 1. the systematic use of CT and retrograde urethrography in PTV definition; 2. immobilization systems which allow a significant reduction in positioning errors; 3. checks before and during treatment by "portal imaging" which allow the identification and correction of a relevant percentage of inaccuracies. The general evolution in treatment planning occurred in recent years has introduced into prostatic cancer radiotherapy new methods and calculation algorithms. While at present the use of new and at the same time complex techniques makes the need for quality assurance of radiation treatments increasingly critical, it is in any case a daily requirement even in most conventional routine treatments.     

The quality of life of prostatic cancer patients

A questionnaire was used to assess the quality of life (QOL) of forty-two outpatients with prostate cancer. Most of the patients were old, so reduced physical comfort was correlated with bodily factors other than those caused by prostate cancer. Many patients with progressive disease reported disease--and treatment--related physical problems that tended to be correlated to the extent of the disease. Many patients treated with female hormones complained of breast induration or discomfort. Patient's sexual life was impaired remarkably. Our treatment for cancer pain would be especially inadequate to cancer pain relief. We must give positive aid to cancer pain relief from now on. Most patients lost sexual interest after developing prostate cancer. Only three of the patients were able to have sexual intercourse. Some of the patients who underwent radical prostatectomy suffered from urinary incontinence after the operation. Thus, the patients' social life was remarkably affected for relative good performance status. Many patients lived only with other elderly individuals. Therefore, it is also important to manage patients in the light of their living environment.     

Pharmacologic treatment of mild proliferation of prostatic cancer

In the paper, pathophysiological and clinical foundations of modern conservative therapy of mild proliferation of prostatic cancer are discussed in a short outline. The problems of treatment with hormonal and non-hormonal preparations are presented against the background of the mechanism of action of pharmacological preparations. The drugs, their dosage, effectiveness and also side effects are discussed. The importance is stressed of the drugs blocking the alpha-1 adrenergic receptors in the treatment of mild proliferation of prostatic cancer with additional beneficial mechanisms of action for the organism.     

TNM classification for urological cancer

The 5th edition of the new TNM classification for urological cancer has been published by UICC in 1997. Herein, the classification of 4 urological carcinomas (kidney, urinary bladder, renal pelvis and ureter, and urethra) is presented and discussed in comparison with the latest revisions in 1987 and 1992. In the 5th edition, the main revised points are as follows: As for kidney, the primary tumor cut off between T1 and T2 was changed from 2.5 cm to 7.0 cm, and the N classification was simplified as for urinary bladder, all muscle invasive tumors (T2 or T3a in the 1992 classification) are included in the T2 category, which is then subdivided into T2a and T2b; in the urethra, new T categories on transitional cell carcinoma of the prostate and prostatic urethra have been added, and the N classification is simplified; there is no change in the classification for the renal pelvis and ureter. According to these changes, a new system of stage grouping is proposed. There may still be widespread disagreement over the appropriateness of some of the changes introduced in the 5th edition of 1997. It is essential to continue efforts to improve the accuracy of determining the clinical extent of malignant tumors, and to work together in order to achieve our objectives for a unified system of TNM classification.     

TNM classification: cancer of the stomach

The 5th edition of TNM Classification was published by the UICC (International Union Against Cancer) in 1997. In the classification of gastric cancer, anatomical subsites and N category were newly published. The new classification and role of the Japanese TNM Joint Committee were described in this paper. The Japanese committee had strongly advocated to continue "the anatomical N classification", because the hazard ratios were more significant for prognosis of patients with gastric cancer, and had many reasonable and scientific advantages. However, the UICC introduced "a new N classification by number of metastatic lymph nodes" because of the difficulty in studying nodes by anatomical classification. The new TNM can not be considered an improved classification, and so we are looking for a more scientific, practical, and internationally acceptable classification.     

Endocrine effects of oestrogen treatment in patients with prostatic cancer

In 36 men with prostatic cancer, the following findings were obtained: intravenous administration of 12.0 g diethylstilboestrol diphosphate (DSDP) induced a relatively slight decrease of the LH plasma level from 22.7 +/- 11.8 to 7.7 +/- 3.6 mIU/ml (34%), whereas the total testosterone plasma level decreased from 435.3 +/- 187.8 to 29.9 +/- 16.4 ng/100 ml (6.7%) suggesting a direct inhibitory effect of the oestrogen on testicular testosterone secretion. The apparently free, biologically active testosterone plasma level even decreased from 6.2 +/- 3.7 to 0.21 +/- 0.16 ng/100 ml (3.4%), due to the oestrogen-induced increase of the concentration of testosterone-binding beta-globulin (from 9.6 +/- 4.4 to 20.6 +/- 10.7-10(-8) M). 3--7 days after additional orchidectomy plus subcutaneous implantation of 100 mg dienoestrol diacetate a further decrease of the apparently free testosterone plasma level from 0.21 +/- 0.16 to 0.14 +/- 0.07 ng/100 ml was found. In contrast, 6 weeks after orchidectomy without oestrogen implantation a significant increase of th- apparently free testosterone plasma level -rom 0.21 %/- 0.16 to 0.34 +/- 0.15 ng/100 ml was observed (p less than 0.01). In view of these findings the biologically active free testosterone plasma level appears to be even more suppressed by intravenous administration of high DSDP than by orchidectomy. The most effective suppression of apparently free testosterone was achieved, however, by oestrogen treatment combined with orchidectomy.     

Prostate-specific antigen in the follow-up of conservatively treated prostatic cancer

The determination of serum prostate specific antigen (PSA) has made the diagnosis of prostate cancer easier. PSA is also used extensively in the follow-up of patients, both treated and untreated. On the basis of material from 308 patients who were mainly managed conservatively, we discuss the usefulness of this practice. It is important to monitor PSA after radical treatment because an increase may indicate local recurrence. In some patients this may lead to further treatment with cure as the aim. For patients under observation only, or those being treated by endocrine intervention, the value of regular PSA measurements is less certain. Where such patients were followed up for at least three years, we found considerable overlaping of PSA values among patients with different outlooks. Within the present therapeutic possibilities it may be better to base their management on clinical signs rather than on PSA. Regular measurements of PSA lead to focusing on this variable, causing unnecessary distress to patients months, or even years, before clinical progression of the disease.     

Effect of cell differentiation in prostatic cancer on basal PSA

The effect of cell differentiation on PSA production in patients with prostate cancer has been evaluated. With this intention 70 patients were included and were analyzed for age, T stage, cell differentiation, bone scan involvement and PSA level prior to therapy. In well-differentiated tumours mcan PSA was 31.3 ng/mL, 56.6 in those with moderate differentiation and 31.6 in poorly differentiated ones (p > 0.05). Multivariate analysis shows no significant differences between both variables, but and inverse relationship between cell differentiation and PSA production (r = -0.27, p > 0.05) can be seen. The most influential variable on PSA levels was de extent of bone scan involvement. Cell differentiation as confusion variable to interpret PSA values in poorly differentiated tumours deserves further study to know the exact role of this protein as a treatment response criterion in prostate cancer.