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Simple Summary: Patients with metastasized, castration-resistant prostate cancer can be treated locally with radioactive radium-223, which usually comprises six cycles. We wanted to know whether this treatment affects immune function. We performed cell culture experiments with white blood cells from the patients and added components of microorganisms. We tested the ability of the cells to proliferate and produce two cytokines (interferon-gamma and interleukin-10) that are important for the balance of the immune system. Our data in 21 patients indicate that the immune cells show impairment in their defense against microorganisms after treatment. As determined by bone scintigraphy, a reduction in tumor burden was observed in 67% of patients. Interestingly, even before treatment, the number of cells producing interleukin-10, an anti-inflammatory cytokine, was an indicator of tumor burden at the end of treatment. Thus, a blood test can help assess whether the treatment is likely to be successful. Previous data indicate that one cycle of treatment with radium-223 (223Ra) did not significantly impair lymphocyte function in patients with metastasized, castration-resistant prostate cancer. The aim of the current study was to assess in 21 patients whether six cycles of this therapy had an effect on lymphocyte proliferation and interferon-γ and interleukin (IL)-10 ELISpot results. Lymphocyte proliferation after stimulation with microbial antigens and the production of interferon-γ continuously decreased after six cycles of radionuclide therapy, reaching statistical significance (p < 0.05) at months 1, 2, 4, and/or 6 after therapy. One month after the last cycle of therapy, 67% of patients showed a decrease in tumor burden. The tumor burden correlated negatively with IL-10 secretion at baseline, e.g., after stimulation with tetanus antigen (p < 0.0001, r = −0.82). As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment. [ABSTRACT FROM AUTHOR]

Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells. We purified and characterized tumorinfiltrating lymphocytes (TILs) and their patient-matched non-tumor counterparts from treatmentnaïve NSCLC patient biopsies to evaluate the effect of PD1 expression on the functional and molecular profiles of tumor-resident T cells. We show that PD1+ CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+ CD4 + memory TILs display transcriptional patterns consistent with both helper and regulator function, but can robustly facilitate B cell activation and expansion. Furthermore, we show that expanding ex vivo-prepared TILs in vitro broadly preserves their functionality with respect to tumor cell killing, B cell help, and TCR repertoire. Although purified PD1+ CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T-cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+ CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. These data unveil novel targets for tumor immunotherapy and have promising implications for the development of a personalized TIL-based cell therapy for lung cancer. [ABSTRACT FROM AUTHOR]

The usefulness of combined 2-[18F] fluoro-2-deoxy-D: -glucose positron emission tomography and computed tomography (FDG-PET/CT) in locating suspected recurrence in patients with iodine-negative differentiated thyroid cancer (DTC) was evaluated. Thirty-six patients with DTC and suspected iodine-negative recurrence underwent restaging with FDG-PET/CT. The images of CT, FDG-PET, both modalities viewed side by side (CT+PET), and FDG-PET/CT were evaluated by two physicians separately. Imaging results were correlated with either histology (n = 20) and/or clinical follow-up of at least 36 months. Recurrent disease was diagnosed in 22/36 patients. FDG-PET alone, CT alone, CT+PET, and FDG-PET/CT showed a sensitivity of 82%, 73%, 91%, and 96%, respectively. Specificities were 79%, 71%, 79%, and 100%, respectively. FDG-PET/CT significantly improved specificity compared with CT+PET and resulted in a further treatment modification in 5/36 patients (14%). CT alone was especially sensitive for lung metastases, FDG-PET alone for the remainder of the body. Accurate fusion of functional and morphologic data by FDG-PET/CT improves the staging accuracy of patients with suspected recurrence of iodine-negative DTC. This has an impact on patient management in a substantial number of patients. [ABSTRACT FROM AUTHOR]

Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in testicular cancer, but they have a limited sensitivity. Ongoing research may lead to the identification of novel biomarkers. Therefore, we review the experimental analyses for nucleic acids, circulating tumor cells, and proteins as potential biomarkers in the serum of testicular germ cell cancer patients. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only little and often contradictory data exist pertaining to the frequency and prognosis of patients with stage pT0 after radical cystectomy (RC). Furthermore there is discussion about the role of a radical transurethral resection of the urinary bladder (TURB) for complete tumour eradication. Within a RC population with clinical tumour stages cTa-cT2, cN0, cM0 and no neoadjuvant chemotherapy or radiotherapy, ≈6% had pathological stage pT0 with a 5-year cancer-specific survival (CSS) rate of 87%. Clinical tumour stage (advantage for non-invasive stages) and TURB time frame (advantage for more recent surgery) were independent predictors for stage pT0. A radical TURB is, assumedly, not the cause of this improved survival rate, but rather it is that individual tumour characteristics allow for complete tumour eradication through the TURB procedure. Concluding, a TURB with R0 resection is, as such, only a sign of a better tumour prognosis. OBJECTIVE • To evaluate the characteristics and long-term outcome of patients with pT0 stage after radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS • Clinical and pathological records of 2403 patients treated with RC for UCB were collected in a multi-institutional database. • The patients met the following criteria: clinical tumour stage cTa-cT2, cN0, cM0, no neoadjuvant chemotherapy or radiotherapy. • Overall (OS) and cancer-specific survival rates (CSS) were calculated for the various clinical tumour stages in relation to their corresponding pathological tumour stage in the RC sample. • Further to this, a multivariable prediction model was developed based onthe available clinical data to estimate the probability of tumour stage pT0. RESULTS • The mean follow-up was 53 months and 132 patients (5.5%) were stage pT0. • Patients withstage cT2-pT0 had a 5-year CSS of 87% vs 69% for cT2-pT2 ( P= 0.012) and 57% for cT2-pT+ ( P < 0.001). • In a multivariable Cox-model, stage pT0 led to a significant reduction of cancer-specific mortality (hazard ratio0.27; 95% confidence interval 0.12-0.61). • A logistical regression model identified clinical tumour stage (advantage for non-invasive stages) and transurethral resection of the urinary bladder (TURB) time frame (advantage for more recent surgery) as independent predictors for stage pT0. CONCLUSIONS • In muscle-invasive clinical tumour stages, patients with pathological tumour stage pT0 form a subgroup showing a significantly better CSS. • A radical TURB is, assumedly, not causative of this improved survival rate, but rather it is that individual tumour characteristics allow for complete tumour eradication through the TURB procedure. • A TURB with R0 resection is, as such, only a sign of a better tumour prognosis. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Epigenetic alterations play an essential role during carcinogenesis. While DNA methylation has been extensively studied in bladder cancer, the relevance of histone modifications remains to be clarified. Earlier studies suggested that global histone modification levels are predictive for patients' outcome in various tumour entities (e.g. prostate, lung, breast and kidney cancer). The possibility to determine global histone modification levels easily and inexpensively using immunohistochemistry increases a potential routine use in the future. Our aim was therefore to investigate the global levels of histone H3K4 and H4K20 mono-, di- and trimethylation. For this purpose we prepared tissue microarrays with non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), bladder cancer metastases (METS) and normal urothelium (NU) tissue to compare global H3K4 and H4K20 methylation in these tissues, as well to assess the prognostic value of histone modifications. We show that global histone modification levels (H3K4me1, H3K4me3, H4K20me1, H4K20me2, H4K20me3) are lower in bladder cancer than in NU tissue. Furthermore, there was a decrease of histone modification levels (H3K4me1, H4K20me1, H4K20me2, H4K20me3) from NU over NMIBC and MIBCto METS. Histone modifications are correlated to advanced pathological stage in NMIBC and MIBC. Furthermore, H4K20me3 appeared to be a significant and independent prognostic predictor of bladder cancer-specific survival in patients with MIBC undergoing radical cystectomy. Our findings therefore provide a rationale for further investigation of histone modifications and their manipulation in bladder cancer. OBJECTIVE • To determine the role of global histone methylation as a prognostic parameter in patients with bladder cancer. PATIENTS AND METHODS • We used a tissue microarray with samples from patients with non-muscle-invasive bladder cancer (NMIBC; n= 161), muscle-invasive bladder cancer (MIBC, n= 127), normal urothelium (NU; n= 31) and bladder cancer metastases (METS; n= 31) to determine global histone methylation (me) levels at histone H3 lysine 4 (H3K4) and H4K20. RESULTS • Global histone modification levels (H3K4me1, H3K4me3, H4K20me1, H4K20me2, and H4K20me3) were lower in bladder cancersamples than in NU tissue • Global levels of H3K4me1, H4K20me1, H4K20me2 and H4K20me3 were decreasing from NU over NMIBC and MIBC to METS. • H4K20me1 levels were increased in patients with NMIBC with advanced pTstage and less differentiated bladder cancer. • In patients with MIBC, pTstage was negatively correlated with H3K4me1, H4K20me1 and H4K20me2 levels. • H4K20me3 levels were significantly correlated in a univariate and multivariate model with bladder cancer-specific mortality after radical cystectomy in patients with MIBC. CONCLUSION • Global histone methylation levels may help to identify patients with bladder cancerwith poor prognosis after radical cystectomy. [ABSTRACT FROM AUTHOR]

Study Type – Prognosis (inception cohort) Level of Evidence 1b OBJECTIVES To validate the association of lymphovascular invasion (LVI) with disease recurrence and cancer-specific survival (CSS) in a multicentre cohort of patients treated with radical cystectomy (RC) for urothelial bladder cancer (UBC). PATIENTS AND METHODS We collected pathological and clinical data on 1099 lymph node-negative patients treated with RC at six German institutions. LVI was defined as the presence of tumour cells within an unequivocal endothelium-lined space in haematoxylin and eosin-stained sections. RESULTS LVI was present in 295 (26.8%) patients; the presence of LVI correlated significantly with increasing tumour stage, i.e. pT1, 65 (29.4%); pT2, 88 (31.5%); pT3 110 (31.8%); and pT4 32 (38.1%) ( P= 0.002) and grade ( P < 0.001). In univariable analysis the presence of LVI was significantly associated with reduced recurrence-free survival ( P= 0.008) and reduced CSS ( P= 0.039). On multivariable Cox regression analysis tumour stage ( P < 0.001), age (>75 vs ≥75 years; P= 0.018) and LVI ( P < 0.001) were identified as independent predictors of CSS. CONCLUSIONS Our large multicentre study confirms the independent prognostic value of LVI in patients with node-negative UBC. LVI can be regarded as a surrogate variable for lymphatic micrometastasis in node-negative UBC. Assessment of LVI might improve the selection of patients who are likely to benefit from adjuvant therapy after RC. The identification of factors involved in the process of LVI could reveal new therapeutic targets for UBC. [ABSTRACT FROM AUTHOR]

Purpose: Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. Materials and Methods: In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. Results: In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Conclusions: Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality. [Copyright &y& Elsevier]

Purpose: DNA hypermethylation is a common cancer associated alteration. We analyzed methylation patterns of cell-free serum DNA in patients with testicular cancer. Materials and Methods: Hypermethylation at APC, GSTP1, PTGS2, p14(ARF), p16(INK) and RASSF1A was analyzed using real-time polymerase chain reaction following methylation sensitive restriction endonuclease treatment in 73 patients with testicular cancer and 35 healthy individuals. Results: Hypermethylation was more common in patients with testicular cancer than in healthy individuals, including APC 57% and 6%, p16(INK) 53% and 17%, p14(ARF) 53% and 0%, RASSF1A 47% and 0%, PTGS2 45% and 0%, and GSTP1 25% and 0%, respectively (each p <0.01). Methylation frequencies at the investigated gene sites were similar in nonseminoma and seminoma cases (p >0.05). Diagnostic information was increased when multiple gene sites were analyzed in combination (ROC AUC 0.834, 67% sensitivity and 97% specificity). Diagnostic information was superior to the analysis of AFP/HCG/PLAP/LDH (combined sensitivity 58% and AUC 0.791). The sensitivity of hypermethylation in patients with unsuspicious conventional tumor markers was 71% (AUC 0.871, 97% specificity). Hypermethylation at PTGS2 was more common in patients with pT1 stage tumors (p = 0.011). Conclusions: The detection of hypermethylated cell-free serum DNA has the potential of a useful additional diagnostic parameter in patients with testicular germ cell cancer. Furthermore, in cases without conventional tumor marker increases testing CpG island hypermethylation in cell-free circulation DNA may improve the ability to detect early and/or recurrent testicular cancer. [Copyright &y& Elsevier]

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Background: Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as 'foreign') cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016.Methods: During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment.Results: No significant differences regarding the patients' survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis.Conclusions: In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression. [ABSTRACT FROM AUTHOR]

Valid prognostic tools are needed to guide risk-adjusted treatment approaches in patients with diffuse large B-cell lymphoma (DLBCL). We assessed total metabolic tumor volume (TMTV) and standardized uptake value (SUV)-based interim positron emission tomography (iPET) response in 510 patients with DLBCL participating in the positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL) trial (NCT00554164). TMTV was analyzed with a relative (SUV 41max) and a fixed thresholding method (SUV 4), and iPET was evaluated using the ΔSUV max procedure. We determined associations between TMTV and international prognostic index (IPI) factors using Welch's t -test, investigated effects of TMTV, iPET response, and the IPI factors on time to progression (TTP), progression-free survival (PFS), and overall survival (OS) by Cox regression, and estimated the outcome using Kaplan–Meier curves. TMTV was associated with all IPI factors except age. Irrespective of the thresholding method used, TMTV and iPET response were correlated with TTP, PFS, and OS, and remained the only independent outcome predictors in Cox regression analysis. By dichotomizing TMTV (cut-off: 328 cm³ by SUV 41max) and iPET response (cut-off: 66% SUV max reduction), we defined three groups at different risk of treatment failure (low [57.1% of patients]: low TMTV/good iPET response; intermediate [37.8%]: high TMTV/good iPET response or low TMTV/poor iPET response; and high [5.1%]: high TMTV/poor iPET response), with corresponding 2-year probabilities of 93.8% vs. 67.3% vs. 38.5% for TTP, 90.9% vs. 62.5% vs. 29.9% for PFS, and 95.5% vs. 77.4% vs. 37.1% for OS. The PET-based risk model proposed may help identify patients who may benefit from treatment modifications or novel approaches. • All IPI factors except age are surrogates of tumor burden that can be more accurately displayed by TMTV. • TMTV and iPET response predict TTP, PFS, and OS. • Combining TMTV and iPET response optimizes outcome prediction in DLBCL. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cell-free circulating mitochondrial DNA (mtDNA) has been proposed as universal diagnostic and prognostic biomarker in cancer patients. Patients and methods: Cell-free DNA was isolated from 1 ml serum from patients with bladder cancer (BCA, n = 84), renal cell carcinoma (RCC, n = 33), and prostate cancer (CaP, n = 23), and compared with healthy individuals (n = 79). Quantitative real-time PCR was used to analyze the levels of a 79 bp (mtDNA-79), and 220 bp (mtDNA-220) fragment of the mitochondrial specific 16S-RNA. The mitochondrial DNA integrity (mtDNA-integrity) was defined as ratio of mtDNA-220 to mtDNA-79 fragments. Results: In healthy controls, mtDNA-79 levels were increased in male volunteers; mtDNA-230 levels and mtDNA-integrity were correlated with age. Neither mtDNA levels nor mtDNA-integrity were correlated with age or gender in cancer patients. Circulating mtDNA-79 (median 8.75 × 106 vs. 0.43 × 106 copies/ml) and mtDNA-230 (8.11 × 106 vs. 0.27 × 106 copies/ml) levels were significantly increased in cancer patients and allowed sensitive (84%) and specific (97%) discrimination from healthy controls. mtDNA levels were unequally distributed among the different cancer entities (mtDNA-79: BCA 9.54 × 106 vs. RCC 6.69 × 106 vs. CaP 4.48 × 106 copies/ml; mtDNA-230: BCA 9.78 × 106 vs. RCC 6.74 × 106 vs. CaP 1.94 × 106 copies/ml). The mtDNA-integrity was increased in RCC and BCA patients compared to control subjects and CaP patients. Serum mtDNA-integrity was correlated with pathological stage in RCC and with tumor grade in BCA patients. Conclusion: Circulating mtDNA levels are associated with gender and age in healthy individuals, but not in cancer patients. Quantification of circulating mtDNA may help identify patients with urologic malignancies. [Copyright &y& Elsevier]

Abstract: Patients with malignancies often possess increased concentrations of cell-free serum DNA. In this study, we investigated serum DNA levels in each 45 patients with bladder cancer (BCA) undergoing radical cystectomy and with benign prostate hyperplasia. A quantitative real-time PCR was used to amplify a 124bp (PTGS2; mostly apoptotic origin) and a 271bp (Reprimo; mostly necrotic origin) DNA fragment. Changes in the origin of DNA fragments were specified as the Apoptosis Index (AI, ratio of 124bp/271bp fragments). Small and large fragments were increased (p <0.001 and p =0.041) in BCA patients. The AI increase suggests that DNA fragmentation was mostly (p <0.001) caused by apoptosis. High levels of small DNA fragments distinguished between BCA and BPH with high sensitivity (96%) and moderate specificity (62%). DNA levels and the AI were not correlated with clinicopathological parameters. However, an increased AI was correlated with BCA-specific mortality in a multivariate analysis (p =0.011) indicating that the AI is an independent prognostic factor. Thus, cell-free DNA seems to be a useful prognostic marker in patients with BCA. [Copyright &y& Elsevier]

Objectives: CpG island hypermethylation causes gene silencing and could be decisive in prostate carcinogenesis and progression. We investigated its role at multiple gene sites during prostate carcinogenesis. Methods: A quantitative, methylation-specific polymerase chain reaction was used to analyze the hypermethylation patterns at nine gene loci (Annexin2, APC, EDNRB, GSTP1, PTGS2, MDR1, RARbeta, Reprimo, and TIG1) in 80 patients with prostate cancer (PCa) and 26 patients with benign prostatic hyperplasia (BPH). Results: Hypermethylation was more frequent in PCa than in BPH tissues (EDNRB, 100% versus 88%; TIG1, 96% versus 12%; RARbeta, 95% versus 35%; GSTP1, 93% versus 15%; APC, 80% versus 50%; MDR1, 80% versus 31%; PTGS2, 68% versus 15%; Reprimo, 59% versus 19%; and Annexin2, 4% versus 0%). TIG1 and GSTP1 hypermethylation distinguished between PCa and BPH with a specificity of greater than 85% and sensitivity of greater than 93%. Hypermethylation at a single gene locus did not correlate with any clinicopathologic variables. In contrast, hypermethylation at two genes (eg, APC and TIG1, APC and GSTP1, APC and PTGS2, APC or MDR, GSTP1 or PTGS2) correlated significantly with the pathologic stage and/or Gleason score (P = 0.033 to 0.045). Hypermethylation at APC and Reprimo, as well as DNA hypermethylation at more than five genes, correlated significantly with the rate of prostate-specific antigen recurrence after radical prostatectomy (P = 0.0078 and P = 0.0074, respectively). Conclusions: Our results have confirmed that the hypermethylation patterns are helpful in the diagnosis and prognosis of PCa. Increases in CpG island hypermethylation at multiple gene sites occur during PCa progression and indicate early biochemical recurrence after radical prostatectomy. [Copyright &y& Elsevier]

Abstract: Objectives: Peripheral primitive neuroectodermal tumor (PNET) is a highly aggressive neoplasm belonging to the Ewing family of tumors. It is characterized by the expression of MIC2 and neural markers (eg, neuron-specific enolase, synaptophysin, S-100, vimentin, Leu-7), and the presence of the EWS-FLI1 translocation. Methods: We performed a MEDLINE search for PNET in urologic malignancies. Additionally, we report on 2 cases of renal and 1 case of bladder PNET. The data obtained by reviewing patients with renal PNET were analyzed using Kaplan-Meier analysis. Results: Renal PNET is diagnosed in young adults (median age 24 years). In contrast, the incidence of bladder PNET seems to be dependent on a defective immune mechanism. Patients often present with pain (84%), palpable tumor (60%), and hematuria (38%). The radiologic findings are uncharacteristic; therefore, the diagnosis should be based on the histologic and immunohistochemistry findings. Renal and bladder PNET are both often diagnosed at an advanced stage and, therefore, the prognosis is poor, despite aggressive multimodal treatment (surgery, polychemotherapy, radiotherapy). We identified palpable tumor masses (log-rank test, P = 0.0027) and synaptophysin expression (log-rank test, P = 0.0422) as prognostic unfavorable markers for renal PNET. Conclusions: Renal PNET should be considered in young patients who present with the classic triad of renal cancer, hematuria, and pain and palpable tumor. Once PNET is diagnosed, multimodal treatment (radical surgery, multidrug chemotherapy, radiotherapy) must be initiated. Despite this, the prognosis is poor if distant metastases are present. Furthermore, palpable tumor masses and synaptophysin expression are associated with a shorter cancer-specific survival. [Copyright &y& Elsevier]

Introduction and objectives: The purpose of this study was to estimate the health-related quality of life (HRQoL) following modified ureterosigmoidostomy (Mainz Pouch II) urinary diversion.Materials and methods: Between March 1995 and February 2003 the procedure was performed in 83 patients (67 male and 16 female, median age 62 years, range 2–78 years) at the Departments of Urology in Bonn, Germany, and Pesaro, Italy. Patients were asked during follow-up to complete a validated, cancer-specific quality of life questionnaire, namely the EORTC QLQ C-30 Version 3. Forty-one patients (29 male, 12 female) completed the QLQ C-30. Twenty-eight patients were dead at the time of the study and 14 patients were lost to follow-up. A non-validated questionnaire was answered by 31 patients (75%) of the Bonn series to determine specific urinary diversion items. Mean follow-up time was 24.4 months (6 to 84 months).Results: No statistically significant differences (p < 0.05) in functional and symptom scales or global health status were detected between males and females. All scales but diarrhea showed good results and the outcome was comparable to health-related quality of life in a reference population of Germany. Continence rate was 100% at daytime; all but one patient had to get up for urination at night. About one third of the patients have to urinate more than six times during the day and more than three times during the night. Sixty-three percent of the patients in the Bonn series were able to distinguish between stool and urine.Conclusion: The Mainz Pouch II serves as a satisfying continent urinary diversion for both sexes in selected patients in terms of quality of life. Patients seem to adapt to their “individual” form of urinary diversion. In terms of continence modified ureterosigmoidostomy can lead to daytime continence rate of 100%. The relatively high voiding frequency during night-time was not felt to be disturbing by the patients and demonstrates the adaptability of the patients. [Copyright &y& Elsevier]