Expression patterns and prognostic role of transketolase-like 1 in muscle-invasive bladder cancer

Purpose

The pentose phosphate pathway (PPP) has been shown to play an important role in the metabolism of cancer cells. The transketolase-like 1 gene (TKTL1) encodes an enzyme representing an essential component of this pathway. Its expression has been demonstrated to correlate with stage and outcome in various tumors. The aim of the present study was to assess expression patterns and the prognostic role of TKTL1 in muscle-invasive bladder cancer (MIBC).

Patients and methods

The expression of TKTL1 was assessed in a tissue microarray consisting of histopathologically benign and malign tissue of 112 patients who underwent radical cystectomy due to MIBC. Cytoplasmatic and nuclear expression were assessed by immunohistochemistry and compared separately with clinicopathologic parameters and outcome.

Results

Cytoplasmatic expression of TKTL1 was exclusively present in tumor tissue. In contrast, the proportion of nuclei positive for TKTL1 was higher in histopathologically benign tissue compared with malign tissue. No correlation was observed between cytoplasmatic or nuclear TKTL1 expression and tumor stage, grade or the presence of metastases. Patients with lymph node involvement showed a decreased frequency of cytoplasmatic expression compared with node-negative patients (p = 0.01). However, no further correlation was observed between the expression of TKTL1 and clinical outcome of patients.

Conclusions

The present study shows that the cytoplasmatic expression of TKTL1 is specific for MIBC tissue compared with histopathologically benign urothelium. This specific expression is present in a subgroup of MIBC potentially identifying patients with activated PPP suitable for a targeted inhibition of sugar metabolism. In contrast to other malignancies, TKTL1 shows no prognostic significance in MIBC.

     

Primäre monosymptomatische Enuresis

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.     

Metastasiertes kastrationsresistentes Prostatakarzinom

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life.     

The prognostic role of pre-cystectomy hemoglobin levels in patients with invasive bladder cancer

Purpose

To determine whether pre-treatment hemoglobin (Hb) levels in patients with bladder cancer impact on oncological outcomes after radical cystectomy (RC).

Methods

A consecutive, contemporary series of 246 patients undergoing RC and pelvic lymph node dissection for bladder cancer. Decreased Hb level was defined as ≤12 g/dL. The Kaplan–Meier method was used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). The Fisher exact/Chi-square test was used to investigate differences between both groups. Uni- and multivariable Cox regression analysis addressed risk factors for recurrence, cancer-specific death and overall death. The median follow-up was 30 months (2–116).

Results

Of the 246 patients, 182 (74 %) had normal (>12 g/dL) and 64 decreased (≤12 g/dL) preoperative Hb (26 %). In univariable analysis, decreased Hb was associated with increased age, extravesical disease, hydronephrosis (all p < 0.001), node-positive disease and positive resection margins (both p = 0.01). Subanalyzed for patients with organ-confined disease (defined as ≤pT2bN0R0; N = 109), the 3-year RFS, CSS and OS was significantly lower in patients with decreased (34.9, 35.5 and 19.8 %) compared to normal Hb level (69.7, 86.3 and 77.6 %; p = 0.01/p = 0.002/p < 0.001). In multivariable analysis, RFS, CSS and OS were significantly lower in patients with decreased Hb (p = 0.007, p = 0.001 and p = 0.002), pathologically locally advanced tumor (≥pT3a; p = 0.023, p = 0.036 and p = 0.065) and nodal stage (p < 0.001, p = 0.006 and p = 0.001) and positive soft tissue surgical margins (p = 0.040, p = 0.004 and 0.012).

Conclusions

Pre-cystectomy Hb levels are associated with adverse histopathologic characteristics and provide additional prognostic information especially for patients with pathologically localized bladder cancer.

     

Is there an anti-androgen withdrawal syndrome for enzalutamide?

Background

The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495–503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.

Methods

In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.

Results

Mean withdrawal follow-up was 6.5 weeks (range 1–26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5–440.7 %) with a median of 44.9 %.

Conclusions

If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.     

Anatomical radical retropubic prostatectomy: 'curtain dissection' of the neurovascular bundle

OBJECTIVE: To investigate the topographical relationship of the cavernosal nerves (CNs) to seminal vesicles, prostate, rhabdosphincter and urethra during the development of the prostate, and to use the resulting morphological data to modify the surgical technique of nerve-sparing radical prostatectomy. MATERIALS AND METHODS: The study included 29 male fetuses (gestational age 9-37 weeks) and eight adult specimens assessed anatomically and histologically. Using the plastination technique and anatomical dissection, the course of the CNs was investigated in all specimens. Based on these morphological results, the technique of dissecting the CNs during nerve-sparing radical retropubic prostatectomy was modified. RESULTS: During early fetal development the fibres of the CNs enclose the prostatic and membranous urethra dorsally and laterally. During the growth of the prostate, the CNs running along the prostate become displaced further anteriorly and spread, thus forming a concave shape (like a 'curtain') of the neurovascular bundles (NVB). Therefore, dissection of the NVB has to start anteriorly to preserve all the nerve fibres that are spread along the surface of the lateral lobes of the prostate. CONCLUSIONS: From these anatomical findings we propose a modified 'curtain dissection' to improve preservation of the CNs running in the NVB, in which the incision of the periprostatic fascia and dissection of the NVB is far more anterior than previously described.