Search PubMed⌕ Search

Biomedical subjects

M Graefen

Publications and source records attributed to M Graefen.

At least 19 recordsLinked to original sources
PubMed2001

A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate-specific antigen in prostate cancer diagnosis.

BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43 microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio.

Adult↗
PubMed2001

[Nerve-sparing radical retropubic prostatectomy. Results of a patient survey].

Improved selection criteria have led to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localized prostate cancer. The results based on patient questionnaires regarding postoperative erectile function are described. Between January 1992 and March 1999, 366 patients (mean age: 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. For evaluation of postoperative patient-reported rates of sexual and erectile function, a questionnaire was used after a follow-up of at least 12 months. Data of five operation periods were analyzed. The results of the unilateral procedure for the five operation periods revealed consistent rates of 13-29% for erections sufficient for intercourse. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3 to 5; only four patients from period 2 underwent the bilateral procedure. The rates of intercourse-sufficient erections were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. The results of the unilateral procedure were disappointing. However, the bilateral nerve-sparing method achieved much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse.

Aged↗
PubMed2001

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens.

OBJECTIVES: To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. METHODS: We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. RESULTS: We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. CONCLUSIONS: The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

Adult↗
PubMed2001

A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy.

PURPOSE: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.

Humans↗
PubMed2000

[Prognostic markers for prostate cancer].

Careful consideration of therapy for prostate cancer needs an accurate analysis of prognostic markers to estimate success and benefit for the patient. Prognosis of prostate cancer is determined by the proportion of high grade cancer, many usually utilized prognostic characteristics were rejected by multivariate analysis as no independent prognostic information was delivered. For planning therapy it is crucial to estimate the proportion of high grade cancer as exact as possible. A standardized biopsy technique combined with a quantified analysis of the biopsy cores is most helpful to achieve this goal. The prognostic value of molecular biological and other factors is object of research, only a combination of some of these factors could be demonstrated so far to be superior to the estimation of the proportion of high grade cancer. However, at present their routine use in daily practise is precluded by a high technical and financial expense.

Biomarkers, Tumor↗
PubMed2000

[Mixed squamous epithelial and adenocarcinoma of the female urethra. A case report].

We report a case of mixed squamous-cell carcinoma with adenocarcinoma of the female urethra. A 37 year old women who presented with a 3-month' history of obstructive voiding symptoms. Clinical investigation showed a urethra tumor of 2.5 x 3.5 cm. Needle biopsy revealed a grade 3 carcinoma. Staging resulted in local cancer disease, a 2.5 x 3.5 cm tumor surrounding the whole urethra with protruding the trigonum. We performed urethrectomy with resection of the bladderneck and cystoneostomy. During bladderneck resection we performed regional staging lymphadenectomy of the obturator lymph nodes. Histological investigation revealed a mixed squamous-cell carcinoma with adenocarcinoma and undifferentiated carcinoma of the urethra. Periurethral tissue showed lymphangiosis carcinomatosa with negative lymph nodes. To exclude involvement of regional superficial lymph nodes we subsequently performed modified inguinal lymphadenectomy without evidence of advanced cancer disease.

Adult↗
PubMed2000

[Chemoprevention of prostatic carcinoma].

Chemoprevention of prostate cancer is the administration of agents to prevent, inhibit, or delay progression of prostate cancer. Asian men have a much lower incidence of prostate cancer than men in Europe or the USA. Asian food includes low-fat, high-fiber diets, which provide a rich supply of weak dietary estrogens. These estrogens have been proposed as chemopreventive agents. In addition to their estrogenic activity, many of these plant compounds can interfere with steroid metabolism and bioavailability and can also inhibit enzymes, such as tyrosine kinase or topoisomerase, which are important for cellular proliferation. In addition, nutritional factors such as reduced fat intake, vitamin E, vitamin D, and selenium may have a protective effect against prostate cancer. The fact was proven in large epidemiological studies as well as experimental observations. In the animal model, the progression of established tumors can be inhibited by these agents. A number of studies to investigate the effect of possible chemopreventive agents for men at high risk of prostate cancer are established. End points for evaluation are mainly based on changes in PSA, changes of histological precursors, or time of onset of clinical disease. The concept of chemoprevention in prostate cancer might have a significant impact on the incidence and mortality of this disease.

Animals↗
PubMed2000

[Mucinous adenocarcinoma of the urachus. Case report and review of the literature].

We report on a 44-year-old man with the rare case of a mucin-positive carcinoma of the urachus. We performed extended partial cystectomy with regional staging lymphadenectomy of the obturator lymph nodes. Histological investigation revealed a mucin-positive carcinoma of the urachus with negative lymph nodes. For this case, we present symptoms, a plan for diagnosis, and treatment of these tumors.

Adenocarcinoma, Mucinous↗
PubMed2000

Human glandular kallikrein 2: a potential serum marker for predicting the organ confined versus non-organ confined growth of prostate cancer.

PURPOSE: We measured serum levels of human glandular kallikrein 2 (hK2) in patients with prostate cancer treated with radical retropubic prostatectomy for clinically localized prostate cancer to determine whether preoperative hK2 levels discriminate stage pT2a/b from pathological stage T3a or greater cancer. This finding would help to predict preoperatively the organ confined versus non-organ confined growth of prostate cancer. MATERIALS AND METHODS: A total of 68 consecutive men underwent radical retropubic prostatectomy for clinically localized prostate cancer. Serum was obtained 1 day preoperatively before prostatic manipulation. hK2, and total and free prostate specific antigen (PSA) were measured using immunofluorometric assays. Mean, median and range of hK2, total and free PSA, and the ratio of free-to-total PSA (percent free PSA) were calculated. Each analyte or combination of analytes was evaluated to determine whether it significantly contributed to enhance the discrimination of organ confined from non-organ confined cancer. We calculated the statistical significance of observed differences using the Mann-Whitney U and Kruskal-Wallis tests. Sensitivity and specificity calculations were performed for hK2, total PSA and the algorithm, (hK2) x (total PSA/free PSA) in addition to receiver operating characteristics curves and the respective areas under the curves. Multivariate logistic regression analysis was done for hK2, and total and free PSA RESULTS: Disease was organ and non-organ (extraprostatic extension) confined in 38 and 30 men, respectively. In organ confined cancer mean hK2 was significantly lower than in non-organ confined cancer (0.09 ng./ml., range less than 0.03 to 0.23 versus 0.30, range 0.04 to 0.94, p <0.0001). In addition, there was significantly higher free and total but not percent free PSA in non-organ than in organ confined cases. There were also statistically significant differences in hK2, free PSA and total PSA at each pathological disease stage (p <0.001, <0.01 and <0.05, respectively). Sensitivity for detecting organ confined disease was 37% at 100% specificity (correct identification of all non-organ confined cancer) using hK2 measurements compared with a sensitivity of 14% for total PSA. At a specificity of 95%, sensitivity was 40% for hK2 versus 23% for total PSA, which was a statistically significant gain in sensitivity (p <0.05). Receiver operating characteristics curves demonstrated that hK2 had the largest area under the curve, followed by the algorithm, (hK2) x (total PSA/free PSA), and total PSA (0.76, 0.75 and 0.72, respectively). However, none of area under the curve differences was statistically significant. CONCLUSIONS: Compared with total and free PSA hK2 testing improved the preoperative evaluation of patients who underwent radical retropubic prostatectomy due to the superior discrimination of organ from non-organ confined cancer.

Adenocarcinoma↗
PubMed2000

Stage migration in clinically localized prostate cancer.

OBJECTIVES: To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer. METHODS: 1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes. RESULTS: Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm(3)) remained stable between 2 and 5% over the last 5 years. CONCLUSION: The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.

Humans↗
PubMed2000

Advanced prostate cancer is associated with a decrease in serum luteinizing hormone.

OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone-sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available. METHODS: Patients with biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters. CONCLUSIONS: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T- or DHT-mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.

Adult↗
PubMed2000

Detection rate of histologically insignificant prostate cancer with systematic sextant biopsies and fine needle aspiration cytology.

PURPOSE: We evaluate the detection rate of insignificant prostate cancer and the rate of significant prostate cancer overlooked in the results of systematic sextant biopsy and fine needle aspiration biopsy of the prostate of asymptomatic men with serum prostate specific antigen concentrations less than 4.0 ng./ml. MATERIALS AND METHODS: We analyzed specimens from 133 consecutive patients with a mean age of 60 years undergoing cystoprostatectomy for bladder cancer. Six systematic biopsy specimens and 2 fine needle aspiration cytology samples were taken from the prostate immediately after cystoprostatectomy. The specimens were step sectioned and examined for prostate cancer. Insignificant prostate cancer was defined as any cancer with an aggregate volume 0.5 cm.3 or less. RESULTS: Incidental prostate cancer was found in 58 of the 133 patients (44%). Tumor volume was 0.5 cm.3 or less in 47 cases. Sextant biopsy detected 7 cancers, including 4 of 47 (9%) that were insignificant and 3 of 11 (27%) that were significant. Fine needle aspiration cytology also detected 7 cancers, including 3 (6%) and 4 (36%) that were insignificant and significant, respectively. CONCLUSIONS: Systematic sextant biopsy and fine needle aspiration cytology each diagnose prostate cancer in about 5% of asymptomatic men who have normal digital rectal examination and serum prostate specific antigen less than 4.0 ng./ml. However, many of the cancers thus detected are insignificant and most of the significant cancers are missed. Therefore, routine screening of such patients with sextant biopsy or aspiration cytology does not appear to be justified.

Adenocarcinoma↗
PubMed1999

Early prostate-specific antigen relapse after radical retropubic prostatectomy: prediction on the basis of preoperative and postoperative tumor characteristics.

OBJECTIVES: This study was undertaken to distinguish between patients who will and will not benefit from a retropubic radical prostatectomy (RRP) for clinically localized prostatic carcinoma (PCa) on the basis of preoperative and postoperative tumor characteristics. METHODS: Data of 318 consecutive patients who underwent RRP for clinically localized PCa were reviewed. Preoperative characteristics used included clinical stage, findings on transrectal ultrasonography, prostate-specific antigen (PSA) values, Gleason grade, number of positive biopsies, number of biopsies containing any Gleason grade 4 and/or 5 cancer, and number of biopsies with predominant (>50% of cancerous tissue) Gleason grade 4 and/or 5 cancer. Postoperative characteristics included pathologic stage, Gleason grade, margin status, cancer volume, and volume of Gleason grade 4 and/or 5 cancer. The impact on biochemical relapse after RRP were calculated by Cox regression and CART (classification and regression tree) analysis to establish low, intermediate, and high risk of recurrence. RESULTS: Of patients who underwent RRP, 66% showed no evidence of relapse after a follow-up of 42 months. All preoperative and postoperative characteristics showed a significant association with biochemical relapse. Cox regression of preoperative characteristics showed the number of positive biopsies with predominant Gleason grade 4 and/or 5 cancer to be the most accurate predictor of failure (p < 0.0001), followed by the number of positive biopsies and PSA. CART analysis distinguished between four risk groups on the basis of the same characteristics as in the Cox regression. The low-risk group consisted of 232 patients (75.1%) and the high-risk group of 17 patients (5.5%); corresponding Kaplan-Meier curves showed a 2-year PSA-free survival rate of 97% for the low-risk group and 20% for the high-risk group. Cox regression of postoperative characteristics recognized the volume of Gleason grade 4 and/or 5 as the characteristic with the strongest association with biochemical failure. CART analysis distinguished between four risk groups, using the volume of high-grade cancer as the most influential characteristic. The corresponding Kaplan-Meier curves showed for the low-risk group (n = 79; 29.6%) a PSA-free survival rate of 96% after 42 months and for the high-risk group (n = 47; 17.6%) a 21% PSA-free survival rate after 42 months. CONCLUSION: For preoperative and postoperative estimation of biochemical recurrence after RRP, a quantitative analysis of high-grade cancer, expressed by the number of preoperative biopsy cores containing high-grade cancer and the volume of cancer, proved to be the best predictor of relapse. CART analysis might be useful in advising patients for their best therapy options. However, defined characteristics of risk groups should be evaluated with new prospective data before they are used routinely.

Adenocarcinoma↗
PubMed1999

Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy.

PURPOSE: We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS: Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant. RESULTS: Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard assay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapses were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurrence. CONCLUSIONS: Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.

Follow-Up Studies↗