Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study ...reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.
To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) ...engine that abstracts pathology data from full-text pathology reports.
Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer.
When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer.
NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data.
Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are ...limited.
DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering.
Immune hot and cold groups had different immune compositions in the TME but not in circulating blood. Two clusters of patients identified with consensus clustering had different immune compositions not only in the TME but also in blood.
Detailed immune profiling via methylation cytometry reveals the significance of understanding tumor and systemic immune relationships in cancer patients.
Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant ...morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC.
We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients (N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97-1.00; CD8T: HR = 0.97, 95% CI = 0.95-1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00-1.07; mdNLR: HR = 1.12, 95% CI = 1.04-1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death (P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites.
Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.
Bladder cancer is the fourth most common cancer among men in the United States and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically ...informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA‐34a (miR‐34a) is a short noncoding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population‐based prognostic study of bladder cancer in New Hampshire, United States to evaluate miR‐34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long‐term for recurrence, progression and survival. Fluorescence‐based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (n = 229). A larger proportion of the nonmuscle invasive tumors had high levels of miR‐34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR‐34a levels in their baseline nonmuscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio 0.57, 95% confidence interval 0.34–0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR‐34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR‐34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder.
What's new?
About half a million people in the United States are living with a history of urothelial carcinoma, the most common form of bladder cancer. Many of those patients will experience disease recurrence, screening for which poses a significant challenge for patient management. In the present study, increased levels of a marker known as miR‐34a were associated with a decreased risk of tumor recurrence. Functions for miR‐34a that are consistent with a tumor suppressive role were identified in vitro. The findings suggest that miR‐34a may be of value in the surveillance of urothelial carcinoma, having both prognostic and therapeutic potential.
Adrenal masses are commonly found on radiographic studies performed for unrelated reasons. We report on a case of a non-functioning adrenal mass from which a needle biopsy showed a nonspecific ...infiltrate of polyclonal plasma cells and small lymphocytes. A definitive diagnosis of the plasma cell variant of Castleman lymphadenopathy was made only after surgical excision. While the hyaline vascular variant of Castleman lymphadenopathy has been identified in adrenal glands, this is the first report of the plasma cell variant in an adrenal mass. This case particularly underscores the importance of an excisional biopsy for proper diagnosis.
To evaluate CD4(+)CD25(+)FOXP3(+) T regulatory cells (T(REG)) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and ...healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating T(REG) combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis.
Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. T(REG) phenotype was examined using flow cytometry (FCM). T(REG) were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis.
We observed higher numbers of T(REG) in pre-treatment PBL of mRCC patients compared to controls. A significant increase in T(REG) was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of T(REG) was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort.
Immune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying T(REG) with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies.
Objectives To describe the costs associated with the learning curve of robotic-assisted prostatectomy (RAP). Methods A theoretical model of the cost of operative time during the learning curve for ...RAP was constructed. Within the theoretical model varying rates of improvement were considered, and once the learning curve was complete, the total cost of operative time was calculated. This cost was then compared with an actual series of RAP, whose operative time and associated costs during the learning curve were also calculated. Results In the theoretical model, surgeons improved at rates of 1, 5, or 10 minutes per case, and began the learning curve that required 8 or 9 hours to perform a single RAP. At the end of the learning curve it took either 3 or 4 hours. The most expensive learning curve was 360 cases long and cost $1.3 million; the least expensive learning curve was 24 cases and cost $95,000. The literature search involved 8 series, with a range of learning curves from 13 to 200 cases. The least expensive learning curve was $49,613 and the most expensive learning curve was $554,694. The average learning curve was 77 cases and cost $217,034. Conclusions Costs associated with operative time while learning RAP are substantial, and should be considered when deciding whether to implement RAP at an individual institution. RAP may best be suited to high volume prostatectomy centers, in which the learning curve can be rapidly traversed, and associated costs minimized.
Despite the high prevalence of bladder cancer, research on optimal bladder cancer care is limited. One way to advance observational research on care is to use linked data from multiple sources. Such ...big data research can provide real-world details of care and outcomes across a large number of patients. We assembled and validated such data including (1) administrative data from the Department of Veterans Affairs (VA), (2) Medicare claims, (3) data abstracted by tumor registrars, (4) data abstracted via chart review from the national electronic health record, and (5) full text pathology reports.
Based on these combined data, we used administrative data to identify patients with newly diagnosed bladder cancer who received care in the VA. To validate these data, we first compared the diagnosis date from the administrative data to that from the tumor registry. Second, we measured accuracy of identifying bladder cancer care in VA administrative data, using a random chart review (n = 100) as gold standard. Lastly, we compared the proportion of patients who received bladder cancer care among those who did versus did not have full text bladder pathology reports available, expecting that those with reports are significantly more likely to receive care in VA.
Out of 26,675 patients, 11,323 (42%) had tumor registry data available. 90% of these patients had a difference of 90 days or less between the diagnosis dates from administrative and registry data. Among 100 patients selected for chart review, 59 received bladder cancer care in VA, 58 of which were correctly identified using administrative data (sensitivity 98%, specificity 90%). Receipt of bladder cancer care was substantially more common among those who did versus did not have bladder pathology available (96% vs. 43%, p < 0.001).
Merging administrative with electronic health record and pathology data offers new possibilities to validate the use of administrative data in bladder cancer research.
Interpretation of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer diagnosis and staging can be challenging and, in some cases, benign prostate disease can mimic locally ...advanced malignancy. We present the case of a 57 year-old male with biopsy-proven Gleason 3 + 4 prostate cancer and a preoperative mpMRI showing extraprostatic extension who was later found to have infiltrating malakoplakia on final surgical pathology. This case highlights the importance of recognizing that malakoplakia of the prostate can present as a PI-RADS 5 lesion with extracapsular extension on mpMRI. Such cases can result in wide-excision, non-nerve sparing radical prostatectomies that may be unwarranted.
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