Biomedical subjects

Markus Graefen

Publications and source records attributed to Markus Graefen.

65 records · Page 4Linked to original sources

PubMed2002

Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer.

PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor College of Medicine. This nomogram uses readily available clinical and pathologic variables to predict 7-year freedom from recurrence after radical prostatectomy. We evaluated the predictive accuracy of the nomogram when applied to patients of four international institutions. PATIENTS AND METHODS: Clinical and pathologic data of 2,908 patients were supplied for validation, and 2,465 complete records were used. Nomogram-predicted probabilities of 7-year freedom from recurrence were compared with actual follow-up in two ways. First, the area under the receiver operating characteristic curve (AUC) was calculated for all patients and stratified by the time period of surgery. Second, calibration of the nomogram was achieved by comparing the predicted freedom from recurrence with that of an ideal nomogram. For patients in whom the pathologic report does not distinguish between focal and established extracapsular extension (an input variable of the nomogram), two separate calculations were performed assuming one or the other. RESULTS: The overall AUC was 0.80 when applied to the validation data set, with individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of the nomogram was apparently higher in patients who were operated on between 1997 and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC, 0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate when applied at international treatment institutions. Our results suggest that accurate predictions may be expected when using this nomogram across different patient populations.

Adult↗

PubMed2002

Prospective validation of an algorithm with systematic sextant biopsy to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma.

PURPOSE: We prospectively validate an algorithm to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma. MATERIAL AND METHODS: A total of 293 patients with prostatic cancer were identified before pelvic lymph node dissection according to an algorithm developed with the classification and regression tree analysis as high-greater than 3 sextant biopsies containing any Gleason grade 4 or 5 cancer, intermediate-at least 1 biopsy dominated by Gleason grade 4 or 5 cancer but not high risk and low risk-all other patients. Observed and predicted frequencies of pelvic lymph node metastasis were compared. RESULTS: The observed frequencies of lymph node metastasis were remarkably similar to the predicted frequencies, including 2.8% versus 2.2% in 85.7% of patients in the low risk group, 16.7% versus 19.4% in 10.2% intermediate and 41.7% versus 45.5% in 4.1% high, respectively. If patients in the low risk group were considered to have node negative disease the specificity and negative predictive value of the algorithm were 88.4% and 97.2%, respectively. CONCLUSIONS: Our algorithm is valid as a simple and accurate tool for the prediction of pelvic lymph node metastasis in patients with clinically localized prostatic cancer. Those 85.7% of patients classified by the algorithm to have a low risk of lymphatic spread should not undergo pelvic lymph node dissection before definitive local treatment.

Algorithms↗

PubMed2002

Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen.

PURPOSE: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. MATERIALS AND METHODS: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng./ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. RESULTS: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng./ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704,p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). CONCLUSIONS: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.

Biomarkers, Tumor↗

PubMed2002

Clinical use of urinary markers for the detection and prognosis of bladder carcinoma: a comparison of immunocytology with monoclonal antibodies against Lewis X and 486p3/12 with the BTA STAT and NMP22 tests.

PURPOSE: The noninvasive detection of urothelial carcinoma remains challenging. We prospectively evaluated urine markers for bladder carcinoma. We compared the NMP22 (Matritech, Cambridge, Massachusetts) and BTA Stat (Bard Diagnostics, Redmond, Washington) tests with immunocytology using mAbs 486p3/12 and BG7 against Lewis X antigen. MATERIALS AND METHODS: The NMP22 and BTA Stat tests were performed in urine samples and immunocytology with mAbs 486p3/12 and BG7 staining were performed in bladder washing specimens in 146 samples of 115 patients undergoing transurethral resection for suspected bladder carcinoma (70) or 45 undergoing followup cystoscopy for a history of bladder carcinoma (76). Bladder carcinoma was detected in 54 patients, including stages pTa in 25, pT1 in 20, pT2 in 8 and carcinoma in situ in 1, while 61 had no evidence of bladder carcinoma. The cutoff was 10 units per ml. for the NMP22, 30% positive cells for 486p3/12 and 5% positive cells for the Lewis X tests. RESULTS: BTA Stat was positive in 65 samples (44.5%) and NMP22 was positive in 69 (47.3%). Immunocytology with mAbs 486p3/12 and BG7 against Lewis X was positive in 52 (35.6%) and 109 (74.7%) samples, respectively. Sensitivity was 70.3% for BTA Stat, 68.5% for NMP22, 68.5% for 486p3/12 and 94.4% for Lewis X. Specificity was 70.6% for BTA Stat, 65.2% for NMP22, 83.6% for 486p3/12 and 36.9% for Lewis X. Area under the receiver operating characteristics curve was 0.6804 for NMP22, 0.7226 for Lewis X and 0.8002 for 486p3/12. False-positive results on BTA Stat in 2 of 22 patients (9%), on NMP22 in 2 of 25 (8%), on 486p3/12 in 3 of 11 (27%) and on Lewis X in 4 of 43 (9.3%) were associated with tumor recurrence. Furthermore, negative results on BTA Stat in 2 of 39 patients (2%), on NMP22 in 2 of 36 (0.5%), on Lewis X in 0 of 18 (0%) and on 486p3/12 in 1 of 50 (2%) was associated with tumor recurrence during followup. CONCLUSIONS: Immunocytology with mAbs against Lewis X showed higher sensitivity than all commercially available tests evaluated. Because of its high sensitivity and high negative predictive value, it may be useful for screening in a high risk population. Patients with a false-positive 486p3/12 test results are at increased risk for tumor recurrence compared with those with negative results.

Antibodies, Monoclonal↗

PubMed2002

Major postoperative complications secondary to use of the Bookwalter self-retaining retractor.

OBJECTIVES: To report on five serious intraoperative damages to nonprocedure-related organs during 10 years of experience with the Bookwalter device. Self-retaining retractors are helpful devices, particularly during major transperitoneal and retroperitoneal operations. Various retractors are available and allow the use of all combinations of blades to maintain exposure during each step of an operation. Furthermore, by using these devices, most operations can be performed by two surgeons only. METHODS: With the help of the operation protocols, more than 4000 applications of the Bookwalter device between January 1992 and December 2001 were retrospectively reviewed. Four cases with damage to the large bowel and one of femoral neuropathy were documented. RESULTS: In one transperitoneal and three retroperitoneal approaches, serious damage to the large bowel occurred. None was recognized before postoperative days 2 and 7. One femoral neuropathy was noted. CONCLUSIONS: The Bookwalter self-retaining retractor is a helpful and safe device in exposing the intraoperative situs. However, care must be taken in patients with risk factors, such as immunosuppression and diverticulitis, and particularly in retroperitoneal operations when tightening the blades. When the intra-abdominal cavity is not exposed, damage to other organs may not be directly noted, which could explain the delay of several days to the onset of symptoms.

Adult↗

PubMed2002

Prediction of tumor heterogeneity in localized prostate cancer.

Clinical T1 and T2 prostatic carcinoma is a heterogeneous tumor with respect to pathologic stage and outcome. In the authors' experience, 60% of patients have a pT2 prostatic carcinoma, and 2% to 4% have tumors less than 0.5 cm3 in volume. The latter group cannot be predicted by the use of preoperative parameters with a sufficient sensitivity and specificity. Quantitative analysis of six systematic biopsies, that is, reporting the number of biopsies with any Gleason grade 4 or 5 cancer or the number of biopsies with more than 50% Gleason grade 4 and 5 cancer, together with preoperative PSA levels can be used to predict the different pathologic stages and risk groups of patients with T1 or T2 prostatic carcinoma. CART analysis that using these preoperative parameters can predict the lymph node stage and the capsular penetration on each side of the prostate with a sufficient positive and negative predictive value and a sufficient specificity to avoid routine lymphadenectomy in approximately 80% of the patients classified as a low-risk group for having lymph nodes positive for disease. CART analysis also allows a solid identification of patients in whom the unilateral or bilateral nerve may be spared during surgery. These algorithms may be improved further by determining the HK-2 level in the blood or by including other molecular biologic markers in the analysis of the biopsies. Clinical T1 or T2 prostatic carcinoma is a heterogeneous but fairly predictable tumor.

Biopsy↗

PubMed2002

Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone.

OBJECTIVES: Transition zone (TZ) carcinomas of the prostate are thought to have less malignant potential than tumours that arise in the peripheral zone (PZ). It is unclear, however, whether this can be put down to anatomical reasons alone, or if there are further differences between tumours of both zones. METHODS: We examined Gleason scores, proliferation and apoptosis rates, microvessel density (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic cells. Proliferation, MVD, p53, and bcl-2 were investigated by immunohistochemistry. RESULTS: There were significant differences between TZ tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P < 0.0001), the proliferation rate (3.2% versus 5.2%; P = 0.0003), and the MVD (68.5 versus 104; P = 0.0002), but the median apoptosis rate was quite similar (0.8% versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively). CONCLUSION: There is evidence for lower Gleason scores as well as lower expression of markers related to tumour growth in TZ carcinomas of the prostate, which might contribute to a less malignant clinical behaviour as compared to PZ cancers.

Aged↗

PubMed2002

Assessment of clinical and pathologic characteristics predisposing to disease recurrence following radical prostatectomy in men with pathologically organ-confined prostate cancer.

OBJECTIVE: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). METHODS: Clinical and pathological characteristics of 331 consecutive men with pT2N0 PCa treated solely with RP were used in Cox proportional hazard models to identify independent predictors of prostate specific antigen (PSA) failure (PSA > or = 0.1 ng/ml). All pathologic specimens were step sectioned at 3 mm. RESULTS: Twelve patients (3.6%) failed at a median follow-up of 26 months (range 0.2-99.6 months) and 120 men remained at risk 3 years after RP. In univariate Cox models PSA (P < 0.001), percentage of high-grade cancer (P < 0.001) total and high-grade cancer volume (P = 0.001 and P < 0.0001, respectively) and RP Gleason sum (P = 0.003) represented significant predictors of PSA failure. Clinical stage (P = 0.4), surgical margin status (P = 0.3), age (P = 0.2), and pathologic evidence of unilateral versus bilateral PCa (P = 0.6) failed to reveal significance. In receiver operator curve (ROC) analyses, high-grade cancer volume achieved highest outcome predictive accuracy (area under the curve (AUC 0.93)), which was not exceeded by Cox regression-based nomogram combining serum PSA, RP Gleason sum, margin status and pathologic evidence of unilateral versus bilateral PCa (AUC 091). Predictive accuracy of this multivariate nomogram was not enhanced by adding total cancer volume (AUC 0.93), high-grade cancer volume (AUC 0.90), or percentage of high-grade cancer (AUC 0.90). CONCLUSIONS: In pT2N0 PCa high-grade cancer volume appears to represent the most important pathologic factor for prediction of outcome following RP. However, similar predictive accuracy may be achieved by combining routinely available tumor characteristics.

Area Under Curve↗

PubMed2002

Patient-reported sexual function after nerve-sparing radical retropubic prostatectomy.

OBJECTIVE: Improved selection criteria have lead to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localised prostate cancer (PCA). Patient questionnaire based outcome analysis on post-operative erectile function after uni- or bilateral nerve-sparing RRP is described. METHODS: Between January 1992 and March 1999, 366 patients (mean age 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. Indication for nerve-sparing procedure was based on the results of a multivariate classification and regression tree analysis (CART). For evaluation of post-operative patient-reported rates of sexual and erectile function non-validated and validated questionnaires (IIEF 5) were administered after a follow-up of 12 months. Data of five operation periods were analysed. RESULTS: The unilateral procedure resulted in rates of 13-29% of erections sufficient for unassisted intercourse. Some degree of tumescence was reported by 37-73% of the remaining patients. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3-5, only four patients of period 2 received the bilateral procedure. Here, rates of erections sufficient for intercourse were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. Patients with grades 4 and 5 erections had IIEF scores of 19.2 and 20.2 and patients without rigidity or tumescence had scores of 5.7 and 7.0 after uni- and bilateral nerve-sparing procedure, respectively. Patients <60 years of age had better erections than those > or =60 (unilateral: 19% versus 13%, bilateral 45% versus 38%). CONCLUSION: Compared to a unilateral nerve-sparing procedure, the bilateral nerve-sparing technique revealed much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse without use of sexual aids.

Adult↗

PubMed2002

Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy.

PURPOSE: We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. MATERIALS AND METHODS: We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS: On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). CONCLUSIONS: Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.

Humans↗

PubMedDate not supplied

A validation of two preoperative nomograms predicting recurrence following radical prostatectomy in a cohort of European men.

Kattan et al. at Baylor College of Medicine and D'Amico et al. at Harvard Medical School have each developed preoperative nomograms for prostate cancer recurrence after radical prostatectomy based on readily available clinical variables. Calibration and validation of those tools was achieved using North American patient cohorts, and their validity has not yet been shown in patients from other continents. We investigated the predictive accuracy of these nomograms when applied to European men with localized prostate cancer. Clinical data from patients who underwent radical prostatectomy at the University-Hospital Hamburg and fitted the respective derivation criteria were used for external validation (n = 1003 for the Kattan-Nomogram, n = 932 men for the D'Amico-Nomogram). Nomogram predictions of the probability for 2-years and 5-years freedom from recurrence predicted by the D'Amico-Nomogram and the Kattan-Nomogram respectively were compared with actual follow-up. The predictive accuracy of the nomograms was tested using areas under the receiver-operating-characteristic curves (AUC). The D'Amico-Nomogram AUC predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction with an AUC of 0.83. Using the 932 patients who exactly fit the derivation criteria of both nomograms, the predictive accuracy of the Kattan-Nomogram was 0.81. The superiority in predictive accuracy of the Kattan-Nomogram was statistically significant (p = 0.0274) but of unclear clinical significance. The two nomograms predicted recurrence with similar accuracy when applied to men diagnosed with localized prostate cancer in Germany. The high predictive accuracy of both nomograms demonstrates that these predictive tools derived in the U.S. can be applied to non-U.S. patients.

Cohort Studies↗