Background: Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. Methods: Published reports relevant to use of tumor markers for 4 cancer sites—liver, bladder, cervical, and gastric—were critically reviewed. Results: α-Fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 μg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3

BACKGROUND:The current study was conducted to develop a pretreatment prognostic model for patients with unresectable and/or metastatic urothelial cancer who were treated with first-line, cisplatin-based chemotherapy. METHODS: Individual data were pooled from 399 patients who were enrolled on 8 phase 2 and 3 trials evaluating cisplatin-based, first-line chemotherapy in patients with metastatic urothelial carcinoma. Variables selected for inclusion in the model were combined in a Cox proportional hazards model to produce a points-based nomogram with which to predict the median, 1-year, 2-year, and 5-year survival. The nomogram was validated externally using data from a randomized trial of the combination of methotrexate, vinblastine, doxorubicin plus cisplatin versus docetaxel plus cisplatin. RESULTS: The median survival of the development cohort was 13.8 months (95% confidence interval, 12.1 months-16.0 months); 68.2% of the patients had died at the time of last follow-up. On multivariable analysis, the number of visceral metastatic sites, Eastern Cooperative Oncology Group performance status, and leukocyte count were each found to be associated with overall survival (P <.05), whereas the site of the primary tumor and the presence of lymph node metastases were not. All 5 variables were included in the nomogram. When subjected to internal validation, the nomogram achieved a bootstrap-corrected concordance index of 0.626. When applied to the external validation cohort, the nomogram achieved a concordance index of 0.634. Calibration plots suggested that the nomogram was well calibrated for all predictions. CONCLUSIONS: Based on routinely measured pretreatment variables, a nomogram was constructed that predicts survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy. This model may be useful in patient counseling and clinical trial design. Cancer 2013;119:3012-9. V C 2013 American Cancer Society.KEYWORDS: urothelial cancer; bladder cancer; prognosis; metastatic; chemotherapy; cisplatin. INTRODUCTIONContemporary cisplatin-based combination chemotherapy regimens achieve objective responses in approximately 50&percnt to 60% of patients with metastatic urothelial cancer.1,2 Although response durations are generally short, and the median overall survival of patients with unresectable and/or metastatic urothelial cancer is only approximately 14 months, significant heterogeneity exists with regard to patient outcomes.2 Long-term follow-up of clinical trials has demonstrated that approximately 10% to 20% of patients are alive at 5 years.1,3 The ability to predict individual patient outcomes has clear implications with regard to both patient counseling and patient stratification on clinical trials.Prognostic models have previously been developed for chemotherapy-naive patients with unresectable and/or metastatic urothelial cancer. In 1998, Bajorin et al identified Karnofsky performance status and the presence of visceral metastases as independent predictors ...

Ki67 SI and NED should be advocated to be rendered by the histopathologist because both parameters can be immunohistochemically determined without much additional expense in time and cost involved. This concept is rewarded by an additional gain of prognostic accuracy in evaluating individual risk profile after surgery.

IntroductionPenile carcinoma has an incidence of 4,000 cases in Europe. The therapy and prognosis depend decisively on the lymph node status. Lymph node metastases are detected in 23–65% cases depending on the histopathological pattern. Due to improved diagnostic methods an early detection of tumor stage is possible. Multimodal therapeutic concepts can offer curability for a subset of patients, even those suffering from advanced disease.Material and methodsCurrent data on penile cancer based on a selective review of the literature by PubMed and the EAU guidelines 2009.ResultsInvasive diagnostic tools, such as fine–needle biopsy (FNB) and dynamic sentinel node biopsy (DSNB), improved the diagnosis of lymph node status considerably and reduced the morbidity in specialized centers. The application of 18F–FDG–PET/CT for metastases detection needs further evaluation due to inconsistent results. Inguinal lymphadenectomy is the therapeutic standard in case of metastases proof. It was possible to reduce the complications due to the new modified operation techniques. Patients with extended lymph node and distant metastases have a poor prognosis. Different systemic polychemotherapy regimes are applied currently and are associated with poor outcome (response rates <50%) and high morbidity. Neoadjuvant chemotherapy is recommended in patients with unresectable and relapsing lymph node metastases.ConclusionsCurrently, inconsistent therapy regimens are applied for metastatic penile cancer. Standardization is urgently needed through the development of high–quality studies and long–term registers in order to lower the morbidity and increase the efficiency of diagnosis and therapy.

KISS1 is a metastasis suppressor gene that is lost in several malignancies, including bladder cancer. We tested the epigenetic silencing hypothesis and evaluated the biological influence of KISS1 methylation on its expression and clinical relevance in bladder cancer. KISS1 hypermethylation was frequent in bladder cancer cells analyzed by methylation-specific PCR and bisulfite sequencing and was associated with low gene expression, being restored in vitro by demethylating azacytidine. Hypermethylation was also frequently observed in a large series of bladder tumors (83.1%, n ‫؍‬ 804). KISS1 methylation was associated with increasing stage (P ‫؍‬ 0.001) and tumor grade (P ‫؍‬ 0.010). KISS1 methylation was associated with low KISS1 transcript expression by quantitative RT-PCR (P ‫؍‬ 0.037). KISS1 transcript expression was also associated with histopathological tumor stage (P < 0.0005). Low transcript expression alone (P ‫؍‬ 0.003) or combined with methylation (P ‫؍‬ 0.019) was associated with poor disease-specific survival (n ‫؍‬ 205).KISS1 transcript expression remained an independent prognosticator in multivariate analyses (P ‫؍‬ 0.017). KISS1 hypermethylation was identified in bladder cancer, providing a potential mechanistic explanation (epigenetic silencing) for the observed loss of KISS1 in uroepithelial malignancies. Associations of KISS1 methylation and its expression with histopathological variables and poor survival suggest the utility of incorporating KISS1 measurement using paraffin-embedded material for tumor stratification and clinical outcome prognosis of patients with uroepithelial neoplasias.

Introduction. Aim of this study was to assess the safety and efficacy of injection of autologous muscle-derived cells into the urinary sphincter for treatment of postprostatectomy urinary incontinence in men and to characterize the injected cells prior to transplantation. Methods. 222 male patients with stress urinary incontinence and sphincter damage after uroloical procedures were treated with transurethral injection of autologous muscle-derived cells. The transplanted cells were investigated after cultivation and prior to application by immunocytochemistry using different markers of myogenic differentiation. Feasibility and functionality assessment was achieved with a follow-up of at least 12 months. Results. Follow-up was at least 12 months. Of the 222 treated patients, 120 responded to therapy of whom 26 patients (12%) were continent, and 94 patients (42%) showed improvement. In 102 (46%) patients, the therapy was ineffective. Clinical improvement was observed on average 4.7 months after transplantation and continued in all improved patients. The cells injected into the sphincter were at least ~50% of myogenic origin and representative for early stages of muscle cell differentiation. Conclusions. Transurethral injection of muscle-derived cells into the damaged urethral sphincter of male patients is a safe procedure. Transplanted cells represent different phases of myogenic differentiation.

UBC Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.