UroVysion® predicts intravesical recurrence after radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: a prospective study.

BACKGROUND: Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUUT) is common. One of the mechanisms driving this is the implantation of cancer cells from the UCUUT at the RNUs. Therefore, their detection after RNU can assist in predicting IVR. This study aimed to examine the utility of UroVysion® as a tool for predicting bladder recurrence after RNU for UCUUT. METHODS: We prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017. RESULTS: Of the 65 patients, 54 (83.1%) who had both bladder urine samples available immediately after RNU (0 postoperative days: POD) and 5 days after RNU (5POD) were selected. We performed UroVysion® and cytology. Twenty-two patients showed IVR with 32 foci. UroVysion® results at 0POD (26 patients, 48.1%) and/or 5POD (31 patients, 57.4%) were positive in 42 (77.8%) patients. The sensitivity, specificity, positive predictive value, and negative predictive value of UroVysion® for included cases were measured for both 0POD and 5POD samples; they were determined to be 95.5% (21/22), 34.4% (11/32), 50.0% (21/42), and 91.7% (11/12), respectively. For cytology, these values were 75.0% (15/20), 52.9% (18/34), 48.4% (15/31), and 78.3% (18/23), respectively. Forty-two (64.6%) patients who were UroVysion®-positive demonstrated IVR. The IVR rate between the group positive for either 0POD or 5POD and that negative for both significantly differed for both UroVysion® (p = 0.019) and cytology (p = 0.046). CONCLUSION: Multiple urine tests using UroVysion® after RNU could be a useful predictor for IVR.

The highest Fuhrman and WHO/ISUP grade influences the Ki-67 labeling index of those of grades 1 and 2 in clear cell renal cell carcinoma.

Nuclear grade is one of the most important prognostic factors in clear cell renal cell carcinoma (CCRCC). Although CCRCCs usually have intratumoral heterogeneity with various nuclear atypia including nucleolar prominence, it is unclear whether a similar degree of nuclear grade component demonstrates the same proliferative activity. We aimed to reveal whether the presence of a higher nuclear grade has an effect on proliferative activity among each assigned nuclear grade in CCRCCs. We enrolled 129 CCRCC patients containing at least two different nuclear grades. We separately assessed nuclear grade using the Fuhrman and World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) grading systems. In addition, we selected blocks containing different nuclear grade and assessed the Ki-67 labeling index (LI) for each using a computer-based analysis system. Ki-67 LIs significantly correlated with both Fuhrman and WHO/ISUP grades (P < 0.001 and P < 0.001). Of note, the LIs among Fuhrman and WHO/ISUP grades 1 and 2 were also statistically significant according to the highest nuclear grade (P < 0.01 for both grades 1 and 2). Our data suggests that the highest nuclear grade influences the proliferative activity in tumor components regardless of the morphologically assigned nuclear grades. The exact evaluation of Ki-67 LI in CCRCC can provide a more precise information of the malignant potential.

Renal tumors in end-stage renal disease: A comprehensive review.

The incidence of end-stage renal disease has increased owing to the greater prevalence of patients with chronic kidney disease and diabetes mellitus. End-stage renal disease is usually accompanied by acquired cystic disease and is a risk factor for renal cell carcinoma. The present review discusses the etiology of renal cell carcinoma in end-stage renal disease patients, focusing on two unique renal cell carcinoma histological subtypes: acquired cystic disease-associated renal cell carcinoma and clear cell papillary renal cell carcinoma. Acquired cystic disease-associated renal cell carcinoma occurs almost exclusively in patients who underwent hemodialysis, especially long-term (>10 years) hemodialysis. Its histology is distinctive: a cribriform or sieve-like architecture with intra- or intracystic lumina; tumor cells containing abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli; and most notably, calcium oxalate crystal deposition. Recognition of the crystals is critical for diagnosing acquired cystic disease-associated renal cell carcinoma. Acquired cystic disease-associated renal cell carcinoma typically has an indolent clinical course, except in cases with sarcomatoid components. Clear cell papillary renal cell carcinoma also has an indolent course (no cases involving metastasis have been reported to date), and its features resemble those of both clear cell renal cell carcinoma and papillary renal cell carcinoma. Unlike acquired cystic disease-associated renal cell carcinoma, which occurs only in end-stage renal disease patients, clear cell papillary renal cell carcinoma occurs in non-end-stage renal disease patients as well. Additional renal tumors in end-stage renal disease patients include anastomosing hemangiomas. Long-term hemodialysis worsens the prognosis of end-stage renal disease patients with renal cell carcinoma, regardless of its original histological subtype, presumably by inducing oxidative stress and sarcomatoid transformation.

[Recent advances in prostate pathology].

Gleason score was revised in 2005 by International Society of Urological Pathology (ISUP). This revision has great impacts on prostate cancer diagnosis and treatment. However, some issues were not reached to consensus. In addition, some modifications are needed to adapt recent advanced prostate cancer therapies, especially for patients with active surveillance and very high risk prostate cancer. The authors review recently updated Gleason grading system by ISUP, which will fit to recent prostate cancer treatment. There are few prognostic factors to predict cancer specific survival and overall survival. The authors show the concept and diagnostic criteria of IDC-P. The authors also discuss clinical usefulness and problems of IDC-P in practice.

Urothelial carcinoma: variant histology, molecular subtyping, and immunophenotyping significant for treatment outcomes.

Although urothelial carcinoma (UC) has been recognised as a homogenous disease entity until recently, it exhibits widely diverse histological variants. Recent studies have revealed that some histological variants may serve as markers of very high risk for advanced cancers and poor prognoses. Certain histological variants can generate a pathological T stage, which may result in unnecessary surgery. Though platinum based chemotherapy is the standard treatment, the use of immune checkpoint inhibitors (ICIs) for UC treatment has become a major trend in oncology. UCs showing specific histological variants have responded exceptionally well to chemotherapy and ICIs. Currently, molecular studies base molecular classification on gene expression profile signatures in order to make diagnoses or predict responses to chemotherapies and ICIs. Notably, some histological variants correlate with specific molecular subtypes. The usefulness of immunophenotyping for classification purposes was recognised only recently. Immunophenotypes are classified into three categories according to lymphocyte distribution in or around the cancer cell nest: desert, excluded, and inflamed. This immunophenotyping has been increasingly shown to be of value in predicting the response to ICIs. This review describes the morphological characteristics of histological variants as well as the advantages and limitations in determining them, with particular reference to clinical benefits. Subsequently, we describe the concept of molecular classification and immunophenotypes, and their morphological features, which are easily interpreted and amenable to daily practice via hematoxylin and eosin staining. We also consider the clinical advantages, limitations, and issues encountered while using these in routine clinical practice.

Diagnostic Utility of UroVysion Combined With Conventional Urinary Cytology for Urothelial Carcinoma of the Upper Urinary Tract.

OBJECTIVES: We prospectively evaluated the utility of UroVysion in urothelial carcinomas of the upper urinary tract (UCUUTs). METHODS: Ninety patients who received nephroureterectomy for UCUUT were enrolled. We performed urinary cytology and UroVysion before nephroureterectomy. We also performed the assays on 23 volunteers without a history of urothelial carcinoma. RESULTS: Seventy-five high-grade urothelial carcinomas (HGUCs), 10 low-grade urothelial carcinomas, and five other conditions were enrolled. Sensitivity, specificity, positive predictive value, and negative predictive value for HGUC detection by urinary cytology were 28.0%, 100.0%, 100.0%, and 31.6%, respectively; for detection by fluorescence in situ hybridization, these values were 60.0%, 84.0%, 93.8%, and 41.2%, respectively. UroVysion detected the only deletion of 9p21 in eight of 23 samples negative for HGUC by urinary cytology and in three of 23 volunteers. CONCLUSIONS: Combining urinary cytology and UroVysion can improve the diagnostic accuracy of UCUUT. Caution is advised in diagnosing UCUUT based only on deletion of 9p21.