Microsatellite instability (MSI), the spontaneous loss or gain of nucleotides from repetitive DNA tracts, is a diagnostic phenotype for gastrointestinal, endometrial, colorectal, and bladder cancers; yet a landscape of instability events across a wider variety of cancer types is beginning to be discovered. The epigenetic inactivation of the MLH1 gene is often associated with sporadic MSI cancers. Recent next-generation sequencing (NGS)-based analyses have comprehensively characterized MSI-positive (MSI+) cancers, and several approaches to the detection of the MSI phenotype of tumors using NGS have been developed. Bladder cancer (here we refer to transitional carcinoma of the bladder) is a major cause of morbidity and mortality in the Western world. Cystoscopy, a gold standard for the detection of bladder cancer, is invasive and sometimes carries unwanted complications, while its cost is relatively high. Urine cytology is of limited value due to its low sensitivity, particularly to low-grade tumors. Therefore, over the last two decades, several new “molecular assays” for the diagnosis of urothelial cancer have been developed. Here, we provide an update on the development of a microsatellite instability assay (MSA) and the development of MSA associated with bladder cancers, focusing on findings obtained from urine analysis from bladder cancer patients as compared with individuals without bladder cancer. In our review, based on over 18 publications with approximately 900 sample cohorts, we provide the sensitivity (87% to 90%) and specificity (94% to 98%) of MSA. We also provide a comparative analysis between MSA and other assays, as well as discussing the details of four different FDA-approved assays. We conclude that MSA is a potentially powerful test for bladder cancer detection and may improve the quality of life of bladder cancer patients.

Several studies have shown that microsatellite changes can be profiled in urine for the detection of bladder cancer. Use of microsatellite analysis (MSA) for bladder cancer detection requires a comprehensive analysis of up to 15 to 20 markers, which were based on amplification and interpretations of many individual MSA markers and can be technically challenging. Here, in a way to develop fast, more efficient, standardized and less costly MSA for detection of bladder cancer, we have developed 3 multiplex PCR based MSA assay, all of which were analyzed by genetic analyzer. First, we have selected 16 MSA markers based on 9 selected publications. Based on samples from Johns Hopkins University (JHU Sample, first set sample), we have attempted to develop MSA assay based on doublet, 2 tube based multiplex PCR combined with singlet, 1 tube based single plex PCR. While this assay was initially successful, we have encountered a reproducibility issue and we then developed MSA based on triplet, 3 tube based multiplex PCR (Triplet MSA assay). From second set samples (6 cancer patients’ and 14 normal individuals’ sample), our Triplet Assay with 15 MSA markers correctly predicted all of 6/6 cancer samples to be cancerous sample and 14/14 samples from normal individuals as normal samples. This result suggests that our Triplet MSA Assay combined with genetic analyzer is a potentially time and cost-effective genetic assay for bladder cancer detection and can be used potentially as a dependable assay in patient care.

People with severe mental illness (SMI) are at risk of chronic physical health conditions. However, physical health screening for this patient cohort is rarely conducted at primary or mental healthcare facilities because of gaps in health care and the stigma of mental illness. This article describes a quality improvement project, conducted at an integrated healthcare primary and mental healthcare facility in the United States. The facility provides primary and mental healthcare services, but physical health screening for patients with SMI was needed to identify their risk of developing health problems, such as cardiovascular disease and diabetes. The aims of the project were to identify potential physical health problems, use evidence-based recommendations to address the risks and improve patient outcomes.