Biomedical subjects

Christian Eichelberg

Publications and source records attributed to Christian Eichelberg.

7 recordsLinked to original sources

PubMed2007

Tumour volume and high grade tumour volume are the best predictors of pathologic stage and biochemical recurrence after radical prostatectomy.

INTRODUCTION: Our goal was to examine to what extent tumour volume (TV) and percentage of high grade tumour volume (%HGTV) affect the rate of positive surgical margins and the rate of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: TV and %HGTV were routinely planimetrically quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7 months. Multivariable regression models addressed two separate endpoints: positive surgical margins and biochemical recurrence. The increase in model predictive accuracy related to the addition of TV and %HGTV to radical prostatectomy stage and grade was assessed, after 200 bootstrap resamples to reduce overfit bias. RESULTS: In multivariable logistic regression models addressing positive surgical margins rate, predictive accuracy increased by 1.9% (p<0.001) when TV was added to other covariates. No further increment was noted when %HGTV was added (p=0.3). In multivariable Cox regression models addressing biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added. CONCLUSION: Tumour bulk reflected by TV affects local cancer control rate, which is reflected in the rate of positive surgical margins. Conversely, high grade cancer determines the rate of biochemical recurrence. These two variables represent the most powerful predictors of cancer control in men treated for localised prostate cancer. Moreover, they increase the ability of established predictors to predict the outcomes of interest. In consequence, they warrant consideration in future predictive and prognostic tools.

Adult↗

PubMed2007

Development and external validation of an extended repeat biopsy nomogram.

PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately predicted. We tested this hypothesis in a contemporary cohort from 3 centers. MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany was used for nomogram development as well as for internal 200 bootstrap validation in 721 and external validation in 361. Two additional external validation cohorts, including 87 men from Milan, Italy and 142 from Seattle, Washington, were also used. Predictors of prostate cancer on repeat biopsy were patient age, digital rectal examination, prostate specific antigen, percent free prostate specific antigen, number of previous negative biopsy sessions and sampling density. Multivariate logistic regression models were used to develop the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5 (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1 (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate analyses all predictors were statistically significant (p < or =0.028). After internal validation the nomogram was 76% accurate. External validation showed 74% (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer variables (6) and shows superior accuracy in European men. Accuracy in American men is substantially lower. Racial, clinical and biochemical differences may explain the observed discrepancy in predictive accuracy.

Adult↗

PubMed2006

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients.

OBJECTIVE: To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single-institution European cohort of patients. PATIENTS AND METHODS: In all, 2402 men had a RP by a group of 11 surgeons, all of whom were trained by the surgeon with the highest SV; all surgeons used the same surgical technique. Variables assessed before RP were prostate-specific antigen (PSA) level, clinical stage and biopsy Gleason sum; variables assessed after RP were PSA level, extracapsular extension, seminal vesicle invasion, lymph node invasion and pathological Gleason sum. These were used to predict the rate of PSM in models before or after RP. Multivariate models were complemented with SV to test its independent and multivariate statistical significance and to quantify its impact on the model's overall (and 200 bootstrap-corrected) predictive accuracy. RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly statistically significant independent predictor of PSM (P < 0.001) and increased the predictive accuracy in multivariate models both before (2.0%) and after RP (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who contributed to 1293 cases, was removed from the analyses, the multivariate independent prediction and the gains in predictive accuracy related to adding SV, disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that patients treated by surgeons with a very high volume can expect to have a significantly lower rate of PSM, after accounting for clinical and pathological case-mix differences. However, SV is not a predictor of PSM when analyses are restricted to intermediate- and low-volume surgeons.

Clinical Competence↗

PubMed2006

Nerve distribution along the prostatic capsule.

OBJECTIVES: Recent literature describes indications for a more-complex course of fibres of the neurovascular bundle (NVB), despite the widely held assumption that it is gathered at the rectolateral side of the prostate. The objective of this study therefore was to determine the typical pattern of nerve distribution along the prostatic capsule. MATERIALS AND METHODS: Permanent sections of 31 patients, who underwent non-nerve-sparing radical prostectomy (RP) at our institution, were investigated. A total of 186 slides taken from the apex, mid-part, and base of the prostate was analyzed by microscopy. Before microscopy, slides were divided into 12 sectors and numbered clockwise starting from "1" for left ventral sides to "6" for the rectal sides (accordingly, "12"-"7" for right half). Every single nerve and ganglion in the prostatic capsule and the periprostatic tissue was counted in each sector. RESULTS: The majority of nerves found in the sectors corresponded to the typical location of the NVB at the rectolateral sides of the prostate (4/5 or 8/9 o'clock sectors). In these two sectors, a median of 45.9-65.6% of counted nerves per half was found. However, a significant amount of nerves (21.5%-28.5%) was detected above the horizontal line. CONCLUSIONS: We conclude that 1/5-1/4 of nerves can be found along the ventral circumference of the prostatic capsule. To preserve a maximum number of nerves, we therefore recommend a modification of the surgical technique by focusing on a high incision for nerve sparing on the ventral parts of the prostate.

Humans↗

PubMed2006

Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy.

OBJECTIVES: The intraoperative finding of palpable tumor lesions has been described as a contraindication for nerve-sparing (NS) radical prostatectomy (RP). However, its evaluation is subjective. Especially in patients with a strong demand to regain postoperative erectile function, a surgeon might be reluctant to sacrifice neurovascular bundles (NVBs) based on this information. We investigated the use of frozen section (FS) analysis to monitor the safety and efficiency of NS during RP in patients with intraoperatively identified subcapsular tumor lesions. METHODS: In 83 of 608 patients, who underwent NS-RP, intraoperative FS was performed because of a lesion palpable close to the capsule. A wedge of 4cm in diameter including the lesion was cut off and stained differently for capsule and intraprostatic margin. In case of presence of carcinoma adherent to the capsule, the NVB was resected; otherwise, the NVB remained in situ. RESULTS: Patients with palpable tumor lesions had pT3 tumors in 36% and 61% had Gleason 4 pattern, compared to 18% and 42% for the control group. Carcinoma was found in 93% of the FS specimens. In 42% of the FS samples, tumor had contact with the capsule and 14% of secondary resected NVB specimens demonstrated a carcinoma invasion. In 52% NVBs could be preserved despite an ipsilateral nodule without negatively affecting the margin status. However, the false-negative rate of the FSs was 6%. Conversely, FSs set the intraoperative decision to remove the NVB in 42% of FS patients, resulting in an additional 36% of negative margins. CONCLUSIONS: In patients with intraoperatively detected tumor lesions during a NS planned RP, FS objectively supports the decision of secondary NVB resection as well as preservation.

Carcinoma↗

PubMed2006

The 2002 AJCC pT2 substages confer no prognostic information on the rate of biochemical recurrence after radical prostatectomy.

INTRODUCTION: We examined the prognostic value of AJCC pT2 substages in prediction of biochemical recurrence (BCR) after radical prostatectomy (RP), in European patients. METHODS: A cohort of 1726 RP patients with pT2N0 prostate cancer (PCa) was studied. Multivariate Cox regression models addressed the association between either the 1997 or 1992/2002 pT2 substages after controlling for total PSA, primary and secondary pathologic Gleason scores and surgical margin status and time to PSA recurrence (PSA >0.1 and rising) after RP. Regression coefficients were then used to test the predictive accuracy of multivariate models in a nomogram setting. RESULTS: PSA recurrence occurred in 80 (4.6%) patients. Mean and median times to recurrence were respectively 28.9 and 24.4 months. In univariate analyses, neither the 1997 (p = 0.48) nor the 1992/2002 pT2 substages (p = 0.054) were predictive of recurrence. In multivariate analyses the lack of significance persisted (1997 p = 0.709; 1992/2002 p = 0.124). When either the 1997 or 1992/2002 pT2 substages were added to a multivariate nomogram without pT2 substage information, its accuracy respectively decreased by 0.8% and 1.1%. CONCLUSION: Our data indicate that pT2 substages offer no incremental value relative to pre-treatment total PSA, surgical margin status and pathologic Gleason scores. Therefore, it might be postulated that it is sufficient to confirm organ confinement according to Partin's pathologic staging.

Analysis of Variance↗

PubMed2002

Characterization of cells prepared by dendritic cell-tumor cell fusion.

Dendritic cells (DCs) are professional antigen-presenting cells currently being discussed as a potent tool for antitumor vaccination strategies. The approach consisting of the in vitro generation of DC-tumor cell hybrids may be advantageous for individualized vaccines since there is no need for the determination of MHC-restricted tumor-associated antigens recognized by T cells. As recent vaccination studies gave varying results, we tested the impact of the fusion treatment on the cells used. Polyethylene glycol-induced fusion, as well as electrofusion, proved to be suitable for generating hybrid cells although at a low frequency. Of note, both methods also gave rise to DCs having phagocytosed apoptotic tumor cells. The expression of surface molecules relevant for specific T cell stimulation was not altered by the fusion procedure and the DCs were still functionally active as demonstrated by the secretion of IL-12 and the uptake of antigen. The cells were able to induce a tumor-specific T cell response in vitro and therefore deserve further investigation as potent tools for immunotherapy trials.

Antigens, CD↗