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Thirty-six eerie short tales, most of which were originally published on the blog of the same name, relate to an imaginary museum of creepy artifacts and are arranged into such thematic \"drawers\" as love, luck, song, and fairy tales.

Key Points Laser techniques are increasingly being used in favour of transurethral resection of the prostate (TURP) and open prostatectomy as a treatment for benign prostatic obstruction Several laser-based surgical methods have been developed, using different wavelengths of light that have different physical properties and, accordingly, different uses in the clinic Laser enucleation with the holmium laser and green light laser vaporization lead to immediate improvement of voiding symptoms and parameters comparable to TURP With regard to intra-operative safety, green light laser vaporization seems to be superior to TURP Thulium laser enucleation shows encouraging results regarding efficacy and safety and early functional outcomes appear comparable to TURP Early diode lasers were associated with increased postoperative complications; in later models a trend towards enucleating techniques with less morbidity can be noticed Over the past decade, laser techniques have become an established alternative to transurethral resection for the treatment of benign prostatic obstruction. Rieken and Bachmann provide a comprehensive, evidence-based overview of laser treatment, including the physical properties of lasers that lend themselves to prostatic surgery and the clinical differences between the techniques. Laser-based prostatectomy for benign prostatic obstruction has emerged over the past decade as a treatment alternative to transurethral resection of the prostate (TURP) and open prostatectomy. These techniques set new standards in minimally invasive surgery and aim to obviate the complications of open surgery while ensuring durability of outcomes. Enucleation, which mimics open prostatectomy in that the whole prostate adenoma is removed, and vaporization, which involves ultra-rapid heating of superficial tissue layers and subsequent ablation, are the most often used surgical techniques in laser prostatectomy. The wavelength and the power output of the laser influence the tissue–laser interactions, which determine the physical properties and the safety profile of the technique. Holmium laser enucleation of the prostate (HoLEP) and GreenLight ™ laser vaporization of the prostate are the two reference techniques for laser prostatectomy, both of which have been shown to be as effective as TURP, while offering advantages in the safety profile in various randomized trials. Thulium laser enucleation of the prostate (ThuLEP) shares similarities with HoLEP and has shown encouraging results. However, more controlled trials with longer follow-up assessment are needed. Diode lasers come in various wavelengths and fibre designs and have been used for vaporization and enucleation, but require high-quality data to support their clinical use.

Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6. Inflammation-driven production and functions of PCa-TDFSs were tested \" \" by stimulating established cell lines (CA-HPV-10 and PC3) with IFN-γ or TNF-α. Expression of genes encoding IDO, IL-6, IFN-γ, TNF-α, and their receptors was investigated in tumor tissues of PCa patients undergoing radical prostatectomy, in comparison with benign prostatic hyperplasia (BPH) specimens. IFN-γ and TNF-α-treatment resulted in the induction of IDO and IL-6 gene expression and release in established cell lines, suggesting that the elicitation of PCa-TDSFs by these cytokines might contribute to progression of cancer into an untreatable phenotype. An analysis based on timing of biochemical recurrence revealed the prognostic value of IDO but not IL-6 gene expression in predicting recurrence-free survival in patients (RFS) with PCa. In addition, a urine-based mRNA biomarker study revealed the diagnostic potential of IDO gene expression in urines of men at risk of PCa development.

Introduction Laser techniques for the treatment of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE) have emerged as an alternative to transurethral resection of the prostate (TURP) and open prostatectomy (OP). Materials and methods A Medline search over the past 4 years was performed to assess the safety, intra- and postoperative morbidity of various laser techniques. Results Data on holmium laser enucleation of the prostate (HoLEP) show the highest grade of evidence with two meta-analyses available and prove the low intra- and postoperative morbidity with reproducible long-term results. Photoselective vaporization of the prostate (PVP) with the Greenlightlaser (potassium titanyl phosphate, KTP or lithium borate, LBO) is characterized by excellent haemostatic properties in patients with or without oral anticoagulation. Long-term results show a reoperation rate comparable with TURP; however, there is a lack of randomized trials. Various types of diode lasers with different wavelengths are available for laser vaporization; despite their favourable haemostatic properties, a higher invasion depth seems to result in necrosis of the tissue leading to a higher rate of reoperation. Thulium-laser resection of the prostate shows promising intra- and postoperative morbidity, but data are limited and initial results need to be confirmed in large-scale trials. Conclusion In summary, HoLEP- and KTP-, or LBO-laser vaporization of the prostate are the most mature techniques of laser prostatectomy and treatment alternatives to TURP and OP, whereas the clinical value and durability of procedures with diode laser systems and the thulium laser need to be confirmed in high-quality prospective RCTs.

Purpose To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. Methods Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). Results Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage ( P  < 0.001), higher grade ( P  < 0.001), lymph node metastasis ( P  = 0.006), lymphovascular invasion ( P  < 0.001), concomitant carcinoma in situ ( P  < 0.001), multifocality ( P  = 0.004), tumor necrosis ( P  = 0.020) and sessile architecture ( P  < 0.001). Within a median follow-up of 30 months (interquartile range 15–57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival ( P  < 0.001) and cancer-specific survival CSS ( P  = 0.006); however, in multivariable analyses, it was not ( P  = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses. Conclusion In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin’s association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Background Chronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera. Methods Eighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ 2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers. Results IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign disease. Serum titres of C reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute phase proteins were similar in both groups of patients. Conclusions Expression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH.

Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.

Intravesical Bacillus Calmette Guérin (BCG) immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1) duration between resection and the first instillation; (2) BCG dose; (3) indwelling time; and (4) treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

To use combinatorial epitope mapping (\"fingerprinting\") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.

Purpose To asses the (1) outcomes and (2) intraoperative, perioperative, and long-term complications of photoselective vaporization of the prostate (PVP) with Greenlight laser. Methods A systematic review of outcomes and complications of PVP was conducted. The article selection process was performed according to PRISMA guidelines and included publications published between 2009 and 2014. Results All generations of PVP (80, 120, 180 W) lead to a significant improvement of micturition symptoms (IPSS, QoL) and voiding parameters (Q max, PVR volume) during follow-up. Data on sexual function are heterogeneous and suggest a trend toward decline in erectile function in men with sustained preoperative erection. The rate of intraoperative complications is low. Data on peri- and postoperative complications show a large variation that mainly can be attributed to heterogeneity in documentation. Conclusions PVP leads to a statistically significant and clinically relevant improvement of voiding parameters and micturition symptoms in patients with prostates <100 ml. The technique is characterized by a high degree of intra- and perioperative safety. Long-term evidence on functional outcomes and complications beyond 3 years from RCTs is currently missing for all generations of the Greenlight laser.