Increased HRD score in cisplatin resistant penile cancer cells.

BACKGROUND/INTRODUCTION: Penile cancer is a rare disease in demand for new therapeutic options. Frequently used combination chemotherapy with 5 fluorouracil (5-FU) and cisplatin (CDDP) in patients with metastatic penile cancer mostly results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance against standard therapy could help to understand molecular mechanisms underlying chemotherapy resistance and to identify candidate treatments for an efficient second line therapy. METHODS: We generated a cell line from a humanpapilloma virus (HPV) negative penile squamous cell carcinoma (UKF-PEC-1). This cell line was subject to chronic exposure to chemotherapy with CDDP and / or 5-FU to induce acquired resistance in the newly established chemo-resistant sublines (PEC-1rCDDP2500, adapted to 2500 ng/ml CDDP; UKF-PEC-1r5-FU500, adapted to 500 ng/ml 5- FU; UKF-PEC1rCDDP2500/r5-FU500, adapted to 2500 ng/ml CDDP and 500 ng/ml 5 -FU). Afterwards cell line pellets were formalin-fixed, paraffin embedded and subject to sequencing as well as testing for homologous recombination deficiency (HRD). Additionally, exemplary immunohistochemical stainings for p53 and gammaH2AX were applied for verification purposes. Finally, UKF-PEC-1rCDDP2500, UKF-PEC-1r5-FU500, UKF-PEC1rCDDP2500/r5-FU500, and UKF-PEC-3 (an alternative penis cancer cell line) were tested for sensitivity to paclitaxel, docetaxel, olaparib, and rucaparib. RESULTS AND CONCLUSIONS: The chemo-resistant sublines differed in their mutational landscapes. UKF-PEC-1rCDDP2500 was characterized by an increased HRD score, which is supposed to be associated with increased PARP inhibitor and immune checkpoint inhibitor sensitivity in cancer. However, UKF-PEC-1rCDDP2500 did not display sensitivity to PARP inhibitors.

The routine use of LCD-Array hybridisation technique for HPV subtyping in the diagnosis of penile carcinoma compared to other methods.

BACKGROUND: Routine human papillomavirus (HPV) testing is performed in cervival cancer and is required for classification of some head and neck cancers. In penile cancer a statement on HPV association of the carcinoma is required. In most cases p16 immunohistochemistry as a surrogate marker is applied in this setting. Since differing clinical outcomes for HPV positive and HPV negative tumors are described we await HPV testing to be requested more frequently by clinicians, also in the context of HPV vaccination, where other HPV subtypes are expected to emerge. METHOD: Therefore, a cohort of archived, formalin-fixed paraffin embedded (FFPE) penile neoplasias was stained for p16 and thereafter tested for HPV infection status via PCR based methods. Additionally to Sanger sequencing, we chose LCD-Array technique (HPV 3.5 LCD-Array Kit, Chipron; LCD-Array) for the detection of HPV in our probes expecting a less time consuming and sensitive HPV test for our probes. RESULTS: We found that LCD-Array is a sensitive and feasible method for HPV testing in routine diagnostics applicable to FFPE material in our cohort. Our cohort of penile carcinomas and carcinomas in situ was associated with HPV infection in 61% of cases. We detected no significant association between HPV infection status and histomorphological tumor characteristics as well as overall survival. CONCLUSIONS: We showed usability of molecular HPV testing on a cohort of archived penile carcinomas. To the best of our knowledge, this is the first study investigating LCD-Array technique on a cohort of penile neoplasias.

Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas.

Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

Decreasing susceptibility of bacteria to ampicillin/ sulbactam and third generation cephalosporins in urinary tract infections.

Background: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and have become more difficult to treat over the years. Inappropriate antibiotic use has led to increased antibiotic resistance. Materials and methods: We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility. We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years. Results: In our hospital-based analysis, cystitis was the most frequently diagnosed UTI in women (76%) and men (79%). Escherichia coli (48%) was the most commonly identified uropathogen. Samples demonstrated an increase in the proportion of E. coli (p < 0.001) and a decrease in Enterococcus faecalis (p < 0.001) over the study time period. Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam (p < 0.001) and to third-generation cephalosporins cefotaxime (p = 0.043) and ceftazidime (p < 0.001). Conclusions: Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs. When selecting an optimal antimicrobial treatment regimen for patients with UTIs, it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns. Therefore, continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.

A 27-Year-Old Primigravida with a Right Renal Cell Carcinoma Removed at 30 Weeks of Gestation by Robot-Assisted Retroperitoneoscopic Partial Nephrectomy.

BACKGROUND Large renal tumors during pregnancy are rare findings (0.07-0.1%). Current guidelines recommend surgical removal. This surgery should be carefully planned in an interdisciplinary team and involves special risks for mother and fetus. This report describes a case of a 27-year-old primigravida woman with a right renal cell carcinoma involving the lower pole of the kidney, which was removed at 30 weeks of gestation by robot-assisted retroperitoneoscopic partial nephrectomy (RARPN). CASE REPORT The patient was referred by the treating obstetrician with a newly diagnosed right lower pole renal mass of 6×4 cm in greatest diameter extending deeply into the parenchyma. No metastasis or enlarged lymph nodes were described in subsequent magnetic resonance tomography. Clinical and laboratory examinations documented a healthy mother and fetus. A right-sided RARPN was advised and planned by an interdisciplinary team of treating physicians (gynecologists, oncologists, and urologists). The surgery was conducted under general anesthesia with an obstetrician on stand-by. Surgery was performed without any complications (operation time 95 min, renal-ischemia time 15 min, and negligible blood loss) and histopathology confirmed the diagnosis of a chromophobe renal cell carcinoma. Further follow-up consultations showed regular wound healing and normal progression of pregnancy, and the patient gave birth to a healthy child at term. Follow-up examinations of the patient were uneventful. CONCLUSIONS This case shows that RARPN can be a safe and effective surgical procedure for partial nephrectomy during pregnancy, where surgery is performed in a specialist center and by an interdisciplinary experienced surgical team. It seems to offer advantages and better risk profile over the laparoscopic approach.

Retrospective Evaluation of the Clinical Values of Minimally Invasive Marsupialization of Symptomatic Giant Renal Cysts.

Background: To evaluate the indication and benefit of minimally invasive laparoscopic marsupialization (MIS) of symptomatic giant renal cysts. Materials and Methods: Sixty-four consecutive patients who underwent MIS for large renal cysts (Bosniak I; 4 × 5-16 × 12 cm) by one surgeon were included in the study. Presenting symptoms were renal pain (100%), associated with hypertension (28%), renal dysfunction (4.7%), hematuria (4.7%), ureteropelvic junction obstruction (UPJO) (7.8%), ipsilateral urolithiasis (4.7%), polycystic kidney (6.3%), adrenal cyst (1.6%), and retroperitoneal cysts (1.6%). Seven patients with peripelvic cysts and previous retroperitoneal operations were treated by a laparoscopic approach; all other patients underwent retroperitoneoscopic marsupialization. Single-port retroperitoneoscopy was performed in 4 patients. Follow-up included clinical examination, abdominal ultrasound, and computed tomography scan. Postoperative radiologic success was defined as a minimum of 50% in size reduction and no recurrence. Results: Mean patients' age was 46 (21-65) years. All procedures were successfully completed without conversion or revision. Mean operative time was 55 (40-85) minutes with a mean hospital stay of 3 days. All patients underwent uneventful postoperative recovery. Observed minor complications (transitory fever/pain) were found in 4 patients during the first postoperative month. Median follow-up was 12 months (10 months-2 years). About 98.5% of patients reported of no relevant postoperative pain. A relief from UPJO and hematuria was achieved in 100% of patients. Ten patients with known hypertensive disease (55.6%) had a significant reduction of mean blood pressure resulting in a reduction of antihypertensive medication. Ureterorenoscopic stone extractions were performed successfully afterward. No cyst recurrences were detected during the follow-up period. Conclusion: Treatment indications for symptomatic renal cysts could include not only symptoms but also associated diseases like UPJO and hypertension. Retroperitoneoscopic MIS may be curative for these cyst-associated pathologies. The feasibility, safety and efficacy of these techniques could be demonstrated.

Evaluation of Testicular Self Examination and Testicular Partner Examination in Medical versus Non-Medical Students.

OBJECTIVES: Although testicular cancer (TC) is the most common tumor in young men in Western countries, there is no official cancer detection/screening program for young men in Germany. The most important TC detection tool is self-examination of the testis. Hypothetically medical students may have a diagnosis lead time and detection superiority. This study was designed to analyze whether medical students have a possible knowledge advantage over students of other faculties concerning TC and to compare male and female cancer screening demeanor and mentality. METHODS: Male and female students of various faculties at the Goethe University Frankfurt/Main, Germany were invited to participate in this internet-based anonymous questionnaire with questions about TC awareness/knowledge, testicular (self) examination, and cancer screening behavior. RESULTS: In total 1,049 students (329 medical and 716 non-medical students) completed the questionnaire. In general, medical students had a significantly higher TC knowledge, especially in the more advanced stages of their medical studies (year 3-6). About 50% of medical students had knowledge of TC whereas only 21.3% of non-medical students knew about the disease (p < 0.01). In addition, medical students conducted scrotal examinations more frequently (34.7%) than non-medical students (18.8%). CONCLUSION: The knowledge about TC is low among students. In general, medical students are more aware of TC and perform more frequent testicular examinations compared to non-medical students. Female TC knowledge rises in the clinical part of studies to the same level as their male counterparts, with the result of more testicular partner examinations.

Quality of Patient Information by Urologists Is Associated with Mental Distress in Bladder Cancer Patients.

AIMS: The study aimed to evaluate the prevalence of mental distress in patients with newly diagnosed bladder cancer, the cancer-information search behavior, and the influence of information seeking on distress. METHODS: One hundred and one bladder cancer patients answered 2 established questionnaires ("Hospital Anxiety and Depression Scale" [HADS] and the "Fragebogen zur Belastung von Krebskranken" [FBK-R23]) for evaluation of mental distress and a self-developed questionnaire with questions concerning information seeking and socioeconomic facts. RESULTS: Regarding risk group stratification, 57.4% were classified as high-risk and 42.6% as low-risk tumor-bearing patients. Analysis of mental distress showed that 23.2% had a score above the HADS-A cutoff, 25.3% above the HADS-D cutoff, and 21.4% showed a pathologic FBK-R23 score. Overall, 75% felt well informed about their illness. Risk group stratification did not correlate with HADS-A, HADS-D, or FBK-R23 score. Furthermore, active search for information or the use of the Internet did not correlate with the HADS-A, HADS-D, or FBK-R23 score. However, the quality of the urologist's information and the feeling of being informed correlated with the grade of mental distress. CONCLUSION: Besides the treatment of bladder cancer, informing the patient about the disease in a psychologically wholesome manner and working together with psycho-oncologically trained psychologists are essential tasks for the treating urologist.

Tumor necrosis factor­related apoptosis­inducing ligand as a therapeutic option in urothelial cancer cells with acquired resistance against first­line chemotherapy.

Patients with urothelial carcinoma frequently fail to respond to first­line chemotherapy using cisplatin and gemcitabine due to development of resistant tumor cells. The aim of the present study was to investigate whether an alternative treatment with tumor necrosis factor­related apoptosis­inducing ligand (TRAIL) that induces tumor cell death via the extrinsic apoptotic pathway may be effective against chemotherapy­resistant urothelial cancer cell lines. The viability of the urothelial cancer cell line RT112 and its chemotherapy­adapted sublines was investigated by MTT assay. The expression of anti­apoptotic proteins was determined by western blotting and the individual roles of cellular inhibitor of apoptosis protein (cIAP)1, cIAP2, x­linked inhibitor of apoptosis protein (XIAP) and induced myeloid leukemia cell differentiation protein (Mcl­1) were investigated by siRNA­mediated depletion. In particular, the bladder cancer sublines that were resistant to gemcitabine and cisplatin were cross­resistant to TRAIL. Resistant cells displayed upregulation of anti­apoptotic molecules compared with the parental cell line. Treatment with the second mitochondrial activator of caspases (SMAC) mimetic LCL­161 that antagonizes cIAP1, cIAP2 and XIAP resensitized chemoresistant cells to TRAIL. The resensitization of tumor cells to TRAIL was confirmed by depletion of antiapoptotic proteins with siRNA. Collectively, the findings of the present study demonstrated that SMAC mimetic LCL­161 increased the sensitivity of the parental cell line RT112 and chemotherapy­resistant sublines to TRAIL, suggesting that inhibiting anti­apoptotic molecules renders TRAIL therapy highly effective for chemotherapy­sensitive and ­resistant urothelial cancer cells.

HDAC Inhibition Counteracts Metastatic Re-Activation of Prostate Cancer Cells Induced by Chronic mTOR Suppression.

This study was designed to investigate whether epigenetic modulation by histone deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell model. Parental (par) and temsirolimus-resistant (res) PC3 prostate cancer cells were exposed to the HDAC inhibitor valproic acid (VPA), and tumor cell adhesion, chemotaxis, migration, and invasion were evaluated. Temsirolimus resistance was characterized by reduced binding of PC3res cells to endothelium, immobilized collagen, and fibronectin, but increased adhesion to laminin, as compared to the parental cells. Chemotaxis, migration, and invasion of PC3res cells were enhanced following temsirolimus re-treatment. Integrin α and ß receptors were significantly altered in PC3res compared to PC3par cells. VPA significantly counteracted temsirolimus resistance by down-regulating tumor cell⁻matrix interaction, chemotaxis, and migration. Evaluation of integrin expression in the presence of VPA revealed a significant down-regulation of integrin α5 in PC3res cells. Blocking studies demonstrated a close association between α5 expression on PC3res and chemotaxis. In this in vitro model, temsirolimus resistance drove prostate cancer cells to become highly motile, while HDAC inhibition reversed the metastatic activity. The VPA-induced inhibition of metastatic activity was accompanied by a lowered integrin α5 surface level on the tumor cells.

Influence of Body Mass Index on Clinical Outcome Parameters, Complication Rate and Survival after Radical Cystectomy: Evidence from a Prospective European Multicentre Study.

Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). METHODS: Clinical and histopathological parameters of patients have been prospectively collected within the "PROspective MulticEnTer RadIcal Cystectomy Series 2011". BMI was categorized as normal weight (<25 kg/m2), overweight (≥25-29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. RESULTS: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the -American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). CONCLUSIONS: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled -accordingly.

Nationwide analysis on the impact of socioeconomic land use factors and incidence of urothelial carcinoma.

BACKGROUND: Incidence rates for urothelial carcinoma (UC) have been reported to differ between countries within the European Union (EU). Besides occupational exposure to chemicals, other substances such as tobacco and nitrite in groundwater have been identified as risk factors for UC. We investigated if regional differences in UC incidence rates are associated with agricultural, industrial and residential land use. METHODS: Newly diagnosed cases of UC between 2003 and 2010 were included. Information within 364 administrative districts of Germany from 2004 for land use factors were obtained and calculated as a proportion of the total area of the respective administrative district and as a smoothed proportion. Furthermore, information on smoking habits was included in our analysis. Kulldorff spatial clustering was used to detect different clusters. A negative binomial model was used to test the spatial association between UC incidence as a ratio of observed versus expected incidence rates, land use and smoking habits. RESULTS: We identified 437,847,834 person years with 171,086 cases of UC. Cluster analysis revealed areas with higher incidence of UC than others (p=0.0002). Multivariate analysis including significant pairwise interactions showed that the environmental factors were independently associated with UC (p<0.001). The RR was 1.066 (95% CI 1.052-1.080), 1.066 (95% CI 1.042-1.089) and 1.067 (95% CI 1.045-1.093) for agricultural, industrial and residential areas, respectively, and 0.996 (95% CI 0.869-0.999) for the proportion of never smokers. CONCLUSION: This study displays regional differences in incidence of UC in Germany. Additionally, results suggest that socioeconomic factors based on agricultural, industrial and residential land use may be associated with UC incidence rates.

Impact of vasectomy on the sexual satisfaction of couples: experience from a specialized clinic.

INTRODUCTION: Vasectomy is the simplest, safest, and most effective form of definitive fertility control in men [1]. Vasectomy is used for 10% of contraception worldwide but only for 2% in Germany [2]. The aim of this study was to investigate the impact of vasectomy on the sexual satisfaction of sterilized men and their partners. MATERIAL AND METHODS: Vasectomized men and their partners were surveyed by means of the IIEF (International Index for Erectile Function) and the FSFI (Female Sexual Function Index) questionnaires. A total of 294 couples were surveyed; 90 men answered the IIEF, and 74 women answered the FSFI. The results of the questionnaires were compared to a historical comparison group. The men were also surveyed with a not validated questionnaire, which was returned by 95 men. The two-sample t-test for independent samples, the chi-squared test, and the Wilcoxon-Mann-Whitney test were carried out. RESULTS: The vasectomized men had significantly better results than the healthy historical comparison group in the IIEF domains of erectile function, orgasm, sexual desire, and intercourse satisfaction. For the female partners of the sterilized men, there were almost no significant differences in any questions of the FSFI in comparison to the control group. A significant difference was observed only in the domain 'arousal'. CONCLUSIONS: Vasectomy does not have a negative impact on the sexual satisfaction of the affected couples. In fact, sexual satisfaction improved for the sterilized men, while the satisfaction of the women was not reduced by the vasectomy.

Blocking integrin ß1 decreases adhesion in chemoresistant urothelial cancer cell lines.

Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, ß1, ß3, and ß4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin ß1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin ß1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin ß1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin ß1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin ß1 may influence adhesion, further studies are warranted to evaluate integrin ß1 as a potential therapeutic target for bladder cancer in vivo.

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells.

Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab-paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC-SUP, as well as sub-lines with acquired resistance against gemcitabine (T24rGEMCI20 and TCC-SUPrGEMCI20) and vinblastine (T24rVBL20 and TCC-SUPrVBL20) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1-inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab-paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.

Prostate Cancer on the Web-Expedient Tool for Patients' Decision-Making?

Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.

Do we have biomarkers to predict response to neoadjuvant and adjuvant chemotherapy and immunotherapy in bladder cancer?

Radical cystectomy (RC) is the standard of care treatment of localized muscle-invasive bladder cancer (BC). However, about 50% of patients develop metastases within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival (OS) in patients with muscle-invasive BC. Pathological response to neoadjuvant treatment is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from chemotherapy. The identification of reliable biomarkers enabling clinicians to identify patients who might benefit from chemotherapy is a very important clinical task. An identification tool could lead to individualized therapy, optimizing response rates. In addition, unnecessary treatment with chemotherapy which potentially leads to a loss of quality of life and which might also might cause a delay of cystectomy in a neoadjuvant setting could be avoided. The present review aims to summarize and discuss the current literature on biomarkers for the prediction of response to systemic therapy in muscle-invasive BC. Tremendous efforts in genetic and molecular characterization have led to the identification of predictive candidate biomarkers in urothelial carcinoma (UC), although prospective validation is pending. Ongoing clinical trials examining the benefit of individual therapies in UC of the bladder (UCB) by molecular patient selection hold promise to shed light on this question.

What should be the patient's preference regarding the choice of hospital in the case of radical cystectomy? Evaluation of early complications after open radical cystectomy in a medium and high volume setting in one hospital.

PURPOSE: This study compares early complications after cystectomy and urinary diversion (UD) stratified by the surgical focus and case load of two different department chairpersons in a single institution in two time periods. Creating clear data about complications that can affect the quality of life is an important tool for patients to decide whether and where to perform this extensive surgery. HYPOTHESIS: A team of surgeons with a clear focus on pelvic surgery leads to lower complication rates in radical cystectomy. MATERIALS AND METHODS: Radical cystectomy was performed in two separate time periods under the patronage of two different chairmen in the same university hospital. The patient data were analyzed retrospectively and the complications 30 days after surgery were assessed using the Clavien-Dindo classification. RESULTS: Statistical analysis showed a significant difference in the severity of complications between the two time periods, A and B, in total (P<0.001). When placing patients into subgroups, significantly more complications in period A were also seen concerning sex (male, P<0.001; female, P=0.003), age (<70 years, P<0.001; >70 years, P≤50.001) tumor grade (low grade, P<0.001; high grade, P≤0.001), and UD (ileal conduit, P<0.001; neobladder, P<0.001). In a multivariable analysis, age (P=0.031) and type of UD (P=0.028) were determined as independent predictors for complications in period A. When joining the two periods together, the type of UD (P=0.0417), age (P=0.041), and the time periods (A/B) (P<0.001) show a significant association with the presence of complications. CONCLUSION: This study compares for the first time surgical complications in two time periods with different case load and surgical focus in one department. Categorization shows that patients should prefer radical cystectomy in centers of excellence or a high-volume hospital in order to keep complications at the lowest possible level and thus have the highest benefit for oncologic outcome and quality of life.

Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts.

BACKGROUND: Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112rGEMCI20 in vitro and in vivo. METHODS: RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112rGEMCI20) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. RESULTS: Dasatinib exerted similar effects on Src signaling in RT112 and RT112rGEMCI20 cells but RT112rGEMCI20 cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC50) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC50 of dasatinib in RT112rGEMCI20 cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112rGEMCI20 tumors. CONCLUSION: Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.