Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline

Biomarkers are described as characteristics that provide information about biological conditions whether normal or pathological. Detection of biomarkers at the earliest stage of the cancer is of utmost importance for clinical diagnosis. Electrochemical biosensors allow detecting the low levels of specific analytes in blood, urine or saliva and providing a sensitive approach for direct measurement for cancer biomarker detection. Moreover, the integration of electrochemical devices with nanomaterials, such as carbon nanotubes, gold and magnetic particles offer amplification and multiplexing capabilities for simultaneous measurements of cancer biomarkers very sensitively. This review summarizes the recent developments of electrochemical biosensors systems for the detection of cancer biomarkers with emphasis on voltammetric, amperometric and impedimetric biosensors. A special attention is paid to aptamers and miRNAs that are very promising for the ultra-sensitive and specific cancer biomarker detection.

Electrochemical Biosensors for Cancer Biomarkers Detection: Recent Advances and Challenges

The clinical relevance of variant histology in urinary bladder cancer has been increasing, resulting in new classifications of urothelial cancers by the WHO in 2016 and highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice. Histological variants can generally be divided into urothelial and nonurothelial. Urothelial variants often have similar features that also have specific morphological phenotypes, whereas nonurothelial variants have independent features. Overall, histological variants follow a more aggressive clinical course than conventional urothelial carcinoma, but conclusive data on their effect on survival are currently lacking. The clinical relevance of variant histology can manifest at three different levels: diagnostic, as identification is challenging and misinterpretation is not uncommon; prognostic, for patient risk stratification and outcome estimation; and therapeutic, as particular variants could be responsive to specific treatment strategies. An accurate morphological description of histological variants is necessary for patient consultation and therapy planning. Moreover, the association of variant histology with specific mutation patterns promises to be helpful in discovering targeted therapeutic approaches based on specific molecular pathways.

Characteristics and Clinical Significance of Histological Variants of Bladder Cancer

Objective The prognostic significance of squamous and glandular elements, the most common histologic variants of urothelial carcinoma of the bladder (UCB), is unclear. This study aimed to examine the sole influence of squamous or glandular or both differentiation on UCB outcome following cystectomy and to identify factors that explain the relatively poor prognosis observed in UCB patients with these differentiation elements. Materials and methods A total of 2,444 patients who underwent radical cystectomy with extended lymph node dissection at a single referral center between 1976 and 2008 were considered. We identified 141, 97, and 21 patients with squamous, glandular, and squamous + glandular differentiation elements, respectively (“cases”). Pure UCB patients without differentiation were matched 1:1 to these cases for demographic, tumor, and treatment characteristics (“controls”). Cases were also compared with an independent cohort of 1,244 pure UCB controls. Recurrence-free and overall survivals were compared between cohorts using univariable and multivariable Cox proportional hazards analyses. Results Median follow-up for cases, controls, and independent control cohort was 15.2, 11.0, and 12.2 years, respectively. Cases were matched to controls for pathologic stage (chi-square P = 1.00) and administration of intravesical agents ( P ≥0.85), neoadjuvant ( P ≥0.31), and adjuvant ( P ≥0.96) chemotherapy. Cases were also balanced with controls for age, gender, and race ( P ≥0.30). Following this intensive matching, no differences in outcomes between cases and controls were observed (log-rank P ≥0.12). Pathologic stage was predictive of outcome in cases with differentiation by multivariable analysis ( P ≤0.004). When compared to an independent control cohort, cases with differentiation were observed to present with higher pathologic stage at cystectomy (chi-square P ≤0.005). Conclusions Outcomes of UCB patients with squamous or glandular or both differentiation are similar to those of patients with pure UCB, given comparable demographic, clinicopathologic, and management characteristics. However, UCB with differentiation present with higher pathologic stage, thus explaining the aggressive clinical course in these patients.

Does presence of squamous and glandular differentiation in urothelial carcinoma of the bladder at cystectomy portend poor prognosis? An intensive case-control analysis

Background
Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention.

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Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068).Patients with non-muscle invasive variants of bladder cancers can be managed with intravesical immunotherapy if tumor is not bulky (>4 cm). Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients, life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer.

Urinary calculi have been recognized as one of the most painful medical disorders. Tenable knowledge of the phase composition of the stones is very important to elucidate an underlying etiology of the stone disease. We report here the results of quantitative X-ray diffraction phase analysis performed on 278 kidney stones from the 275 patients treated at the Department of Urology of Hadassah Hebrew University Hospital (Jerusalem, Israel). Quantification of biominerals in multicomponent samples was performed using the normalized reference intensity ratio method. According to the observed phase compositions, all the tested stones were classified into five chemical groups: oxalates (43.2%), phosphates (7.7%), urates (10.3%), cystines (2.9%), and stones composed of a mixture of different minerals (35.9%). A detailed analysis of each allocated chemical group is presented along with the crystallite size calculations for all the observed crystalline phases. The obtained results have been compared with the published data originated from different geographical regions. Morphology and spatial distribution of the phases identified in the kidney stones were studied with scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). This type of detailed study of phase composition and structural characteristics of the kidney stones was performed in Israel for the first time.

X-ray diffraction and SEM study of kidney stones in Israel: quantitative analysis, crystallite size determination, and statistical characterization

Plasmacytoma of the Testis in a Patient With Previous Multiple Myeloma: Is the Testis a Sanctuary Site?

Aim: To examine the hypothesis that the risk of high-grade bladder cancer can be predicted using noninvasively obtained data. Patients and Methods: We retrospecti

Predicting the risk of high-grade bladder cancer using noninvasive data.

OBJECTIVE To evaluate the importance of stone composition and crystallite size in the formation of ultimatestone burden. Crystallite is the smallest building block, which is unique in size and architecturefor each type of stone component. Currently, the knowledge about the clinical importance ofcrystallite size is very limited.METHODS The results of quantitative X-ray diffraction phase analysis performed on 286 kidney stonesextracted during endourological surgery or expelled spontaneously were retrospectively analyzed.Stone composition and crystallite size were determined and were compared to the burdenoccupying the pelvicalyceal system.RESULTS A total of 286 renal stones were analyzed. Stones were low burden and high burden in 242 and44 of cases, respectively. We observed statistically signiﬁcant association of phosphates andurates with high-burden stones in contrast to oxalates, which formed mainly low-burden stones.Crystallite sizes were available for 179 stones. Large-sized crystallites of calcium oxalate mono-hydrate and hydroxyl apatite formed low-burden stones, whereas small-sized crystallites formedstaghorn stones. Struvite and urates had a uniform average size of crystallites.CONCLUSION Oxalatestoneshavestatisticallysigniﬁcantassociationwithsmallerstones,whereashigh-burdencalculiaresigniﬁcantly associated with urates and phosphates, especially the struvite type. The smaller the crystallitesize is to start with, the larger will be the ultimate stone burden. This rule is followed by calcium oxalatemonohydrate and Apatite minerals.

Nandakishore Shapur

Papers

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer.

X-ray diffraction and SEM study of kidney stones in Israel: quantitative analysis, crystallite size determination, and statistical characterization

Plasmacytoma of the Testis in a Patient With Previous Multiple Myeloma: Is the Testis a Sanctuary Site?

Predicting the risk of high-grade bladder cancer using noninvasive data.

Endourology and Stones Crystallite Size—Is It a New Predictor for Renal Stone Burden?