Jesco Pfitzenmaier

Positive surgical margins after radical prostatectomy: do they have an impact on biochemical or clinical progression?

To prospectively examine the effects of the margin status after radical prostatectomy (RP), the location, and the number of positive surgical margins (PSMs) on biochemical and clinical outcome, as even if there seems to be little debate that there is a higher risk of both local and distant recurrence of prostate cancer in the face of a PSM the significance of a PSM after RP is only followed for biochemical progression in most studies.

Vaporization of prostates of ≥80 mL using a potassium-titanyl-phosphate laser: midterm-results and comparison with prostates of <80 mL

To compare the safety and outcome of potassium‐titanyl‐phosphate (KTP) GreenlightTM (Laserscope, AMS, Minnetonka, MN, USA) vaporization for treating benign prostatic hyperplasia (BPH) in prostates of ≥80 vs <80 mL.

Glucocorticoid use in prostate cancer and other solid tumours: implications for effectiveness of cytotoxic treatment and metastases

Glucocorticoids have been used widely in conjunction with other treatment for patients with cancer because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, glucocorticoids are used in a supportive-care role, even though to our knowledge no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that glucocorticoids induce treatment resistance in solid tumours, including prostate cancer. Research has focussed on disseminated cells that have been shed by the tumour: the potential of glucocorticoids to render these cells resistant to apoptosis--and to downregulate the immune response--might contribute to tumour metastasis. Here, we review the benefits of glucocorticoids and their negative effects, such as induction of resistance in tumour cells and concomitant induction of apoptosis in immune cells, with particular emphasis on prostate cancer.

The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells.

The enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue (p ≤ 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the EZH2 gene plays a role for both the proliferation and the apoptosis resistance of RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy to improve the therapeutic response of RCC.

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors

Background: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. Material and Methods: We performed an overall statistical analysis of our new and recent data obtained with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. Results: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two non-steroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in co-treatment of carcinoma patients. Conclusion: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signaling.

The influence of body mass index on the long‐term survival of patients with renal cell carcinoma after tumour nephrectomy

To assess whether under‐ or overweight at the time of surgery has any effect on the survival of the patients with renal cell carcinoma (RCC), as obesity increases the risk of developing RCC.

Desmosomal Plakophilins in the Prostate and Prostatic Adenocarcinomas: Implications for Diagnosis and Tumor Progression

The plakophilins, members of the armadillo-repeat family, consist of three different proteins (PKP1-3) that are specifically recruited to desmosomal plaques in a highly cell type-specific manner. Using immunofluorescence, immunoelectron microscopy, and immunoblot, we found that all three plakophilins occurred in luminal and basal cells of the pseudostratified prostate epithelium. The analysis of 135 cases of prostatic adenocarcinomas grouped into tumors with low (Gleason score < or = 6), intermediate (Gleason score 7), and high Gleason score (8 < or = Gleason score < or = 10) showed that the expression of PKP1 was reduced or lost in adenocarcinomas with high Gleason scores. The expression of PKP2 was unchanged in all prostatic adenocarcinomas analyzed. In contrast, PKP3 expression was increased in carcinomas with high Gleason scores in comparison with carcinomas with low Gleason scores. In DU 145 cell lines with either overexpression or knockdown of PKP3, both imbalances resulted in fewer desmosomal cell contacts. In addition, overexpression of PKP3 in DU 145 cells led to an augmentation in proliferation rate. Our data imply that both loss of PKP1 and up-regulation of PKP3 expression are biologically important events in prostate cancer and are associated with a more aggressive phenotype.

Treatment decision-making in localized prostate cancer: why patients chose either radical prostatectomy or external beam radiation therapy

Study Type – Therapy (case series)

Intestinal reconstruction of the lower urinary tract as a prerequisite for renal transplantation

To report a two‐stage protocol for children in whom bladder reconstruction was followed by kidney transplantation, as about a quarter of children requiring a kidney transplantation show significant lower urinary tract dysfunction, and consequently their bladder is unsuitable for a kidney transplant.

En bloc stapler ligation of the renal vascular pedicle during laparoscopic nephrectomy

To evaluate, in a prospective series of laparoscopic nephrectomies (LNs), the safety and feasibility of en bloc stapling for resection and occlusion of the vascular renal pedicle.