Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.
Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer.
Percutaneous needle core biopsy is the definitive procedure by which essential diagnostic and prognostic information on acute and chronic renal allograft dysfunction is obtained. The diagnostic value of the information so obtained has endured for over three decades and has proven crucially important in shaping strategies for therapeutic intervention. This Review provides a broad outline of the utility of performing kidney graft biopsies after transplantation, highlighting the relevance of biopsy findings in the immediate and early post-transplant period (from days to weeks after implantation), the first post-transplant year, and the late period (beyond the first year). We focus on how biopsy findings change over time, and the wide variety of pathological features that characterize the major clinical diagnoses facing the clinician. This article also includes a discussion of acute cellular and humoral rejection, the toxic effects of calcineurin inhibitors, and the widely varying etiologies and characteristics of chronic lesions. Emerging technologies based on gene expression analyses and proteomics, the in situ detection of functionally relevant molecules, and new bioinformatic approaches that hold the promise of improving diagnostic precision and developing new, refined molecular pathways for therapeutic intervention are also presented.
Background. Restless leg syndrome (RLS) is one of the prevalent complaints of
patients with end stage renal diseases suffering chronic hemodialysis. Although there are some
known pharmacological managements for this syndrome, the adverse effect of drugs causes a
limitation for using them. In this randomized clinical trial we aimed to find a nonpharmacological
way to improve signs of restless leg syndrome and patients' quality of life.
Material and Methods. Twenty-six patients were included in the
study and divided into 2 groups of control and exercise. The exercise group used
aerobic exercise during their hemodialysis for 16 weeks. The quality of life and severity
of restless leg syndrome were assessed at the first week of study and final week. Data
were analyzed using SPSS software. Results. The difference of means of
RLS signs at the first week of study and final week was −5.5 ± 4.96 in exercise group and −0.53 ± 2.3 in control group. There was not any statistical difference between control group
and exercise group in quality of life at the first week of study and final week. Conclusions. We
suggest using aerobic exercise for improving signs of restless leg syndrome, but no evidence was found for its efficacy on patient's quality of life.
An idiopathic capillary leak syndrome (“engraftment syndrome”) often occurs in recipients of hematopoietic cells, manifested clinically by transient azotemia and sometimes fever and fluid retention. Here we report the renal pathology in 10 recipients of combined bone marrow and kidney allografts. Nine developed graft dysfunction on day 10–16 and renal biopsies showed marked acute tubular injury, with interstitial edema, hemorrhage and capillary congestion, with little or no interstitial infiltrate (≤10%) and marked glomerular and peritubular capillary (PTC) endothelial injury and loss by electron microscopy. Two had transient arterial endothelial inflammation; and 2 had C4d deposition. The cells in capillaries were primarily CD68+MPO+ mononuclear cells and CD3+CD8+ T cells, the latter with a high proliferative index (Ki67+). B cells (CD20+) and CD4+ T cells were not detectable, and NK cells were rare. XY FISH showed that CD45+ cells in PTCs were of recipient origin. Optimal treatment remains to be defined; two recovered without additional therapy, six were treated with anti-rejection regimens. Except for one patient, who later developed thrombotic microangiopathy and one with acute humoral rejection, all fully recovered within 2–4 weeks. Graft endothelium is the primary target of this process, attributable to as yet obscure mechanisms, arising during leukocyte recovery.
Background:The Immense cost of cancer treatment is one of the main challenges of health care systems all over the world including Iran. The aim of this study was to analyze the direct treatment costs of colorectal cancer patients in Isfahan, Iran.Methods:In this cross sectional study, the medical records of colorectal cancer (CRC) patients admitted to the Seyyed-al-Shohada Hospital “SSH” from 2005-2010 were reviewed. The profiles of 452 patients were examined. However based on inclusion, exclusion criteria a total number of 432 profiles were analyzed. All records including age, sex, treatment processes and treatment costs were extracted from the patients’ profiles and analyzed using Kruskal-Wallis test.Findings:The results showed that 56.1% of CRC patients were male. The mean age of patients suffering from CRC was 56 ± 13.4. More than Thirty-six percent of the patients were in stages 1-3 of CRC and more than half of them (64.4%) were in the 4th stage. The higher the stage of the cancer the higher the percentage of treatments used. 5-Fluorouracil and Leucovorin (5FU/LV) was the most common used chemical treatment protocol. The mean treatment cost for stage one was 10715 (±4927), for stage two 15920 (±3440), stage three 16452 (±2828) and for stage four was 16723 (±2555) US Dollars. The cost of drug treatment was the first cost driven between the medical services.Conclusion:CRC in Iranian population starts in younger age than people in western countries. This imposed considerable direct and indirect economic cost to the society. The direct medical cost of colorectal cancer in Iran is very higher than 38 million $. Screening programs could reduce the economic cost of CRC significantly.
The knowledge of Iranian population about CKD and its risk factors is low. Future public health education programs should put efforts in educating Iranian community about the asymptomatic nature of CKD in its initial stages and highlighting the importance of regular renal care counseling. The high-risk individuals should receive tailored education and be encouraged to adopt lifestyle modifications to prevent or slow the progression of CKD.
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