Who needs further evaluations to diagnose upper urinary tract urothelial cancers among patients with abnormal findings by enhanced CT?

Objective:We evaluated who would need further evaluations such as retrograde pyelography(RP)and/or ureteroscopy to diagnose upper urinary tract urothelial cancers(UUTUCs)when abnormal findings for the upper urinary tract(UUT)were detected by enhanced computed tomography(CT).Methods:We retrospectively analyzed 125 patients who underwent enhanced CT for various reasons and had abnormal findings for the UUT.Patients whose tumors were suspected to be of extraureteral origin were excluded.All patients received RP and/or ureteroscopy to evaluate the UUTUCs.Results:The median age of the 125 patients was 70 years and gross hematuria(26.4%)was the most frequently observed symptoms.RP,ureteroscopy and both were performed for 121,59 and 55 patients,respectively.CT revealed tumor-like lesions in 58 patients and the other patients had non-tumor-like lesions.UUTUCs were found in 43(34.4%)of the 125 patients.All of them had tumor-like lesions on CT.In 58 patients who had tumor-like lesions on CT,univariate and multivariate analyses revealed that tumor diameter and tumor enhancement were significant predictive factors for UUTUCs.ROC curve analysis of enhanced CT to diagnose UUTUCs revealed that a tumor diameter of 18 mm was the best cutoff point.The sensitivity,specificity and accuracy were 90.0%,98.8% and 92.7% for RP and 95.5%,100% and 97.1%for ureteroscopy,respectively.Both of them had high sensitivity,specificity and accuracy.Conclusion:We should decide to evaluate the UUT according to the tumor diameter on enhanced CT.When we evaluate the UUT in patients with tumor diameters of less than 20 mm,ureteroscopy is recommended.

Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker in Bladder Urothelial Cancer

Background： Tat-interacting protein 30 （TIP30） has been reported to be a tumor suppressor, with reduced or absent expression in various tumors. However, its role in bladder urothelial cancer （BUC） has not been investigated. Therefore, herein, we investigated the expression of T1P30 protein in BUC and normal bladder mucosa and the clinical significance of TIP30 expression in the prognosis of BUC. Methods： We reviewed data from 79 cases of BUC and 15 adjacent tissue samples from 79 patients treated at our institution between 2004 and 2007. TIP30 expression was examined by immunohistochemistry. The relationship between TIP30 expression and tumor stage, histological grade, and survival was analyzed. Differences between groups were evaluated using the t-test or matched-pairs test, and differences in the survival rates were analyzed with the log-rank test. Results： TIP30 protein expression was significantly reduced in BUC tissue （t = -6.91, P 〈 0.05） compared with normal tissue samples, and in invasive bladder cancer （t = 10.89, P 〈 0.05） compared with superficial bladder cancer. TIP30 protein expression differed significantly among different differentiated groups classified either according to the World Health Organization （2004, F = 17.48, P 〈 0.01） or World Health Organization （1973, F = 10.68, P 〈 0.01）. TIP30 protein expression was significantly reduced in high-grade papillary urothelial carcinoma compared with papillary urothelial neoplasm of low malignant potential （P 〈 0.05） and low-grade papillary urothelial carcinoma （P 〈 0.05）. Meanwhile, TIP30 protein expression was significantly reduced in Grade 111 BUC, compared with Grade I （P 〈 0.05） and Grade 11 （P 〈 0.05）. Patients with low T1P30 expression showed a higher incidence of disease progression than those with high TIP30 expression （t - 2.63, P 〈 0.05）. Kaplan-Meier survival analysis showed a strong positive relationship between TIP30 expression and overall survival （OS） （x^2 = 17.29, P 〈 0.05）. Conclusions： TIP30 expression was associated with clinical tumor stage in BUC, suggesting that it might play an important role in disease progression. Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be useful lbr predicting prognosis.

Biomarkers for therapy selection in metastatic urothelial cancer

The treatment of metastatic urothelial cancer(mUC)has been transformed by recent progress in clinical trials and drug development.There are now three therapeutic classes with proven benefits in mUC:chemotherapy,immunotherapy,and targeted therapy.The optimal sequence and combination of these classes remain to be defined.Biomarker development is essential to guide treatment selection at each therapeutic juncture.Two biomarkers,programmed death-ligand 1 expression and fibroblast growth factor receptor alterations,have been incorporated into the mUC treatment paradigm thus far.This review discusses predictive biomarkers in development and their potential to influence mUC treatment selection moving forward.

The role of modern immunotherapy in metastatic urothelial cancer:mini review

The approval of immune checkpoint inhibitors(ICIs)has changed the treatment landscape in many aspects of urothelial cancer(UC),in both non-muscle-invasive bladder cancer and muscle-invasive bladder cancer and has introduced the concept of long-term remission for some patients in the metastatic setting.Front-line chemotherapy remains superior at achieving initial control of disease compared to front-line immune therapy.However,long-term durable responses are limited by chemotherapy resistance.The maintenance approach,sequencing chemotherapy with ICIs,could be considered a best of both worlds approach,achieving initial control with chemotherapy,which is maintained in some individuals with avelumab.However,outcomes for patients with metastatic UC remain poor.There are three steps to improving outcomes for these patients;the first is to develop better drugs and combinations of therapies,the second is the development of novel biomarkers and techniques to better select patients for treatment,and the third area of development is to give the drugs in the most optimal setting.

High Grade Muscle-Invasive Urinary Bladder Cancer in A 36 Year Old Male Patient:A Case Report&Review of Literature

We are reporting a case of urothelial bladder cancer in a 36 year old male patient with no history or exposure to any risk factors.The incidence of urothelial bladder cancer is very low in young individuals i.e.below 40 years of age with reported rate of incidence around 0.1-0.4%.Most of the times,these young individuals present with non-muscle invasive bladder cancer with low grade and low stage.As the age increases,the incidence of high grade bladder cancer increases along with it.The index case presented with high grade muscle invasive bladder cancer at the time of diagnosis without any known risk factors.The 5-year survival of urothelial bladder cancer is better in young patients(93.8%)as compared to older people(85.1%).Cigarette smoking is responsible for development of bladder cancer in majority of patients followed by exposure to occupational carcinogens.Role of genetic alterations in development of bladder cancer is still under research and process of urothelial bladder carcinogenesis is unanswered in young individuals.

Urothelial bladder cancer progression: lessons learned from the bench

Urothelial bladder carcinoma(UBC)is an intricate malignancy with a variable natural history and clinical behavior.Despite developments in diagnosis/prognosis refi nement and treatment modalities,the recurrence rate is high,and progression from non-muscle to muscle invasive UBC commonly leads to metastasis.Moreover,patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment,and overall survival rates are poor.Thus,UBC remains a challenge in the oncology fi eld,representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence,progression,and chemo-refractoriness.However,progress toward personalized medicine has been hampered by the unique genetic complexity of UBC.Recent genome-wide expression and sequencing studies have brought new insights into its molecular features,pathogenesis and clinical diversity,revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups.Hence,it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation.In this review,we have summarized ours and others’research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer:tumor neovascularization,invasion and metastasis,and energy metabolism reprogramming of the tumor microenvironment.

What we have learned from urinary bladder cancer models

Urinary bladder cancer(UBC)is a heterogeneous disease with highly variable clinical outcomes and responses to chemotherapy.Despite some advances in the molecular understanding of UBC,this knowledge still has not been translated to the clinic in terms of improvements in the prognosis and treatment of patients.Suitable urinary bladder tumor models representative of the human disease in terms of histology and behavior are needed to study factors involved in tumor initiation,progression and metastasis.Further,accurate model systems would facilitate identification of new therapeutic targets and predictive markers that could lead to optimization of existing therapies and development of new ones.Many established cancer cell lines derived from human urinary bladder tumors representing different grades and stages have been used as experimental models for UBC study.These cell lines reflect some of the genetic and morphologic alterations observed in human urothelial carcinoma and serve as simplified models to study the behavior of cancer cells in vitro.However,their translational potential is limited due to the artificial conditions,in which the cells are maintained,grown and tested.Animal models offer a more complex and realistic model for the establishment,development,and progression of tumors as well as to evaluate new therapeutic approaches.Over the years,the authors'group has worked with several UBC cell lines,established and characterized chemically induced UBC models,and patient-derived xenografts models.In this study,the authors will provide a summary of the UBC models developed by their group,analyze their translational potential and weaknesses,and define areas that remain to be explored.