Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.

PURPOSE OF REVIEW: This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS: Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.

Association between urologic malignancies and end-stage renal disease: A meta-analysis.

AIM: Previous studies have suggested a higher incidence of urologic malignancies in end-stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients. METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. Studies that reported incidence or odds ratios of urologic malignancies among ESRD patients were included. Pooled odds ratios (OR) and 95%CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067687). RESULTS: Nineteen observational studies with 1 931 073 ESRD patients were enrolled. The pooled estimated incidence of kidney cancer and urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) in ESRD patients were 0.3% (95%CI: 0.2-0.5%) and 0.5% (95%CI: 0.3-0.8%), respectively. Meta-regression showed significant positive correlation between incidence of urologic malignancies in ESRD patients and year of study (slopes = +0.05 and +0.07, P < 0.001 for kidney cancer and urothelial cancers, respectively). Compared to non-ESRD status, ESRD was significantly associated with both kidney cancer (pooled OR 6.04; 95% CI 4.70-7.77) and urothelial cancers (pooled OR 4.37; 95% CI 2.40-7.96). CONCLUSION: Our study demonstrates a significant association between ESRD and urologic malignancies. The overall estimated incidence rates of kidney cancer and urothelial cancers are 0.4% and 0.5%, respectively. There is a significant positive correlation between the incidence of urologic malignancies and year of study.

The status, limitation and improvement of adoptive cellular immunotherapy in advanced urologic malignancies.

In recent years, immunotherapy has been gradually established as the fourth frequently adopted antitumor therapy, following surgery, chemotherapy and radiotherapy, for advanced urologic malignancies with an improved understanding of theoretical basis, such as molecular biology and immunology. Thereinto, adoptive cellular immunotherapy (ACI) has become one of the hotspots, which comprises a variety of treatment approaches, such as TIL, CIK cell, γδ T cell, CAR-engineered T cell and Allogeneic stem cell transplantation (alloSCT). Although preclinical efficacy has been demonstrated remarkably, clinical trials could not consistently show the benefit due to multi-factors in complex immunosuppressive microenvironment in vivo compared to that of in vitro. Here we review some timely aspects of ACI for advanced urologic malignancies, and describe the current status and limitation of immunotherapy from the cellular level. It's our expectation to provide prompting consideration of novel combinatorial ACI strategies and a resurgence of interest in ACI for advanced urologic malignancies.

CD24 targeting with NK-CAR immunotherapy in testis, prostate, renal and (luminal-type) bladder cancer and identification of direct CD24 interaction partners.

Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, as well as urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. The present study aimed to decipher the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of a third-generation natural killer (NK) cell chimeric antigen receptor (CAR) against CD24 in urologic tumour cell lines. Up to 20 urologic tumour cell lines and several non-malignant control cells were included. XTT viability assays and annexin V/propidium iodide flow cytometry analyses were performed to measure cell viability and apoptosis rates, respectively. Co-immunoprecipitation followed by mass spectrometry analyses identified direct interaction partners of CD24. Luciferase reporter assays were used to functionally validate transactivation of CD24 expression by SOX2. N- and O-glycosylation of CD24 were evaluated by enzymatic digestion and mass spectrometry. The study demonstrates that SOX2 transactivates CD24 expression in embryonal carcinoma cells. In cells of different urological origins, CD24 interacted with proteins involved in cell adhesion, ATP binding, phosphoprotein binding and post-translational modifications, such as histone acetylation and ubiquitination. Treatment of urological tumour cells with NK-CD24-CAR cells resulted in a decreased cell viability and apoptosis induction specifically in CD24+ tumour cells. Limitations of the study include the in vitro setting, which still has to be confirmed in vivo. In conclusion, we show that CD24 is a promising novel target for immune therapeutic approaches targeting urologic malignancies.

Targeted Molecular Imaging as a Biomarker in Urologic Oncology.

Urologic malignancies constitute a large portion of annually diagnosed cancers. Timely diagnosis, accurate staging, and assessment of tumor heterogeneity are essential to devising the best treatment strategy for individual patients. The high sensitivity of molecular imaging allows for early and sensitive detection of lesions that were not readily detectable using conventional imaging techniques. Moreover, molecular imaging enables the interrogation of molecular processes used in targeted cancer therapies and predicts cancer response to treatment. Here we review the current advancements in molecular imaging of urologic cancers, including prostatic, vesical, renal testicular, and ureteral cancers.

[Trends in uro-oncological surgery in Germany-comparative analyses from population-based data]. / Entwicklung der operativen Uroonkologie in Deutschland ­ vergleichende Analysen aus populationsbasierten Daten.

Although urologic cancer represents a relevant health economic burden with about 100,000 new cases per year, hardly any knowledge exists about the structure and development of the corresponding uro-oncological interventions at the more than 400 urological surgical hospitals in Germany. Thus, we identified all cases of 5 major tumor surgery procedures in Germany from the DRG (diagnosis-related group) database of the Federal Statistical Office (prostatectomy, cystectomy, renal tumor surgery, retroperitoneal lymphadenectomy, penis surgery) from 2006-2013 (or 2016) by database query and investigated the influences of technical innovations, as well as guideline changes on the developments of case numbers. In addition, we analyzed the correlations between annual case numbers and perioperative outcomes. The results showed a clear correlation between case volume (and thus expertise) of a hospital and an improved perioperative outcome. Nevertheless, there is hardly any tendency towards centralization in these uro-oncological interventions. The development in the number of cases seems to depend more on the effect of advertising by means of technical innovations or the regional relation of the patients to a certain clinic. In the past, centrally controlled attempts to introduce minimum case numbers or voluntary certification of centers had little influence on the distribution of case numbers.

HISTOMORPHOLOGICAL PATTERN OF UROLOGIC MALIGNANCIES IN ILE-IFE, SOUTH-WESTERN NIGERIA.

INTRODUCTION: The last decade witnessed a remarkable rise in the prevalence of several malignant diseases in Nigeria. Whether Urologic malignancies (UM) have followed the same trend remains to be studied. The pattern of UM diagnosed in a Nigerian tertiary hospital is hereby presented. Our aim was to determine the pattern and prevalence of histologically diagnosed UM in Obafemi Awolowo University Teaching Hospitals Complex. Ile-Ife, Nigeria. MATERIALS AND METHODS: A 10-year retrospective review of all patients diagnosed with UM was carried out between January 2005 and December 2014. Data was obtained from the patients' case files and the Ife-Ijesha Cancer registry. Information obtained included demographic characteristics, site of origin and histology. Data was analysed with Statistical package for Social sciences (SPSS) Version 20. RESULTS: A total of 4675 malignancies were histologically confirmed during the study period. UM accounted for 420 (8.9%) of total malignancies. Prostate cancer was the commonest UM with 315 (75%) cases. Others include renal tumours 62(14.8%), bladder tumours 29 (6.9%), testicular tumours 13(3.1%) and scrotal tumour 1(0.2%). UM were commoner in males (348, 88.8%) than females (47, 11.2%) and accounted for 13.8% and 2.18% of all tumours in males and females respectively. CONCLUSION: This study revealed a rising prevalence of UM most especially Prostate and Renal Cancers among other malignancies in Ile-Ife.

Use of administrative data for comparative effectiveness research in the treatment of non-prostate genitourinary malignancies.

Comparative effectiveness research (CER) is imperative for objective and balanced assessment of treatment outcomes. CER that uses administrative databases (AD-CER) affords unique opportunities for large scale data analyses that potentially transcend limitations of small institutional datasets. Prostate cancer has received much attention from the AD-CER research community, whereas non-prostate genitourinary malignancies are less well-studied. The objective of this article is to review the currently available AD-CER that has been published in the non-prostate genitourinary malignancies space.

The Hedgehog pathway: potential biomarker and therapeutic applications in urologic malignancies.

The Hedgehog pathway has been implicated in the development of several non-urologic malignancies. Recent work suggests that the activation of the glioma-associated GLi family of zinc finger transcription factors may play a role in some urologic malignancies. This review surveys the potential role of the Hedgehog pathway as a new class of biomarker in some urologic cancers.

Palliative management of malignant upper urinary tract obstruction.

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field.