Lars Karlberg

Prognostic value of the Gleason score in prostate cancer

Objective To investigate the prognostic value of the Gleason score in prostate cancer.

Prevalence of lower urinary tract symptoms in men aged 45–79 years: a population-based study of 40 000 Swedish men

There is a strong epidemiological background to this section. In the first article, a Swedish group assess the prevalence of LUTS in a population‐based study of 40 000 Swedish men aged 45–79 years. The second is a community‐based study from India into the natural history of LUTS. Both papers contain some surprising results which are of interest to urologists, add to the general debate and to our knowledge of the symptoms associated with prostatic disease.

Cell Proliferation Assessed by Ki-67 Immunoreactivity on Formalin Fixed Tissues is a Predictive Factor for Survival in Prostate Cancer

PURPOSE Proliferation rate may be an important determinant of tumor progression. To evaluate the predictive value of proliferation, immunoreactivity for the proliferation associated antigen Ki-67 was related to survival in a series of patients with prostate cancer. MATERIALS AND METHODS Formalin fixed tissue, obtained by transurethral resection from 125 previously untreated prostate tumors, was examined with an immunohistochemical method for Ki-67. Ki-67 index was defined as the percentage of immunoreactive cells in a tumor. Patients were followed with surveillance after transurethral resection. The cause of death was determined by examination of patient records 11 to 19 years postoperatively (mean followup 71 months). At evaluation 17 patients (14%) were still at risk and 55 (44%) had died of prostate cancer. RESULTS Mean Ki-67 index was 2.1. Ki-67 index correlated with grade (p < 0.0005) and weakly with stage (p = 0.019). Mean survival of patients with a Ki-67 index of more than 3 was less than half that of patients with a Ki-67 index of less than 3 (53 versus 132 months, p < 0.00005). The difference in survival remained in an analysis of the intermediately differentiated tumors (61 versus 126 months, p = 0.0032). In a Cox multiple regression analysis for cancer specific survival, including Ki-67 index, grade, stage, metastasis and age, Ki-67 index remained an independent predictive factor. CONCLUSIONS Our study indicates that proliferation rate, assessed by Ki-67 immunoreactivity in formalin fixed tissues, is a predictive marker for outcome in prostate cancer.

Percent Gleason grade 4/5 as prognostic factor in prostate cancer diagnosed at transurethral resection.

PURPOSE We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. MATERIALS AND METHODS A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. RESULTS At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. CONCLUSIONS Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.

Erythrocyte and Albumin Distribution in the Kidney Following Warm Ischemia: A Study in Rats

A dark zone of probably stagnant erythrocytes, localised primarily to the inner stripe of the outer medulla, is always found in acute renal failure caused by clamping of the renal artery for 45 min. To test the possible accumulation of red cells, the regional renal red cell content was investigated with 51Cr labelled red cells injected before, during and 10 min after the recirculation. Analyses were made of the volumes of (1) cells remaining from the period of clamping, (2) cells aggregated 0--10 min after recirculation and (3) cells still circulating 10--20 min after recirculation. In the inner stripe the total red cell volume was 21.8 +/- 2.2 microliter . 100 mg-1 (control value 9.3 +/- 0.6), where 26% remained from the period of clamping, 46% had accumulated 0--10 min after recirculation, and only 28% had entered the region 10--20 min after recirculation. The same pattern of response, though less pronounced, was also found in the inner zone. In the cortex the total red cell volume was 6.3 +/- 1.2 microliter . 100 mg-1 (control value 4.4 +/- 0.3), where 24% remained from the period of clamping, 32% were accumulated and 44% remained circulating. The plasma volume as investigated from 131I-labelled albumin was markedly increased in all zones, probably due to extravasation of the tracer. It is suggested that red cell accumulation plays an important role for the medullary ischemia found in ischemic acute renal failure.

Long-Term Outcome of Patients Treated for Hydrocele with the Sclerosant Agent Sodium Tetradecyl Sulphate

The long-term outcome of 106 patients treated for hydrocele with the sclerosing agent sodium tetradecyl sulphate was examined. In a questionnaire distributed at a mean time of 40 months after therapy 83/86 (96%) of the eligible patients responded and 95% of them were satisfied with the treatment and its long term results. The treatment associated pain was evaluated on a visual analogue scale (0-10) the mean pain score was found to be 1.8 and the mean duration of the pain 2.4 days. When all hydroceles were considered the overall success rate was 88%. Side-effects were minor apart from two patients (1.9%) with diabetes mellitus who had an intense inflammatory reaction necessitating orchidectomy after sclerotherapy.

Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance.

Abstract Objective. The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975–1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf). Results. In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours. Conclusions. Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.

p53 immunoreactivity as prognostic marker for cancer-specific survival in prostate cancer.

OBJECTIVES The objective of this study was to evaluate the role of p53 immunoreactivity as a prognostic marker in prostate cancer. METHODS The nuclear accumulation of the aberrant p53 protein was determined by immunohisto-chemistry on surgical specimens and related to stage, grade and cancer-specific survival in 186 prostate cancer patients treated with transurethral resection and subsequent surveillance. RESULTS There was a significant correlation between p53 staining and grade: 2% of the highly differentiated, 8% of intermediately, and 21% of the poorly differentiated tumors stained. Patients with p53-positive tumors had a significantly shorter survival (52 months) than the p53-negative group (123 months). However, in a Cox multiple regression analysis of p53 status, tumor stage, grade, metastasis and age, p53 lost its significance as an independent predictor. CONCLUSIONS p53 is a rare and late event in prostate cancer, indicating that other molecular mechanisms may be of greater importance in the development of prostate cancer. The predictive value of p53 apparently depends on its association with high grade and advanced stage, and it is not a useful prognostic marker in prostate cancer. However, p53 status could play a role in the evaluation of patients prior to radiotherapy since p53 inactivation may produce radioresistant tumors.