Inconsistent Surgical Implant Documentation: A Case Study in Total Knee and Hip Arthroplasty.

Value-based care initiatives require accurate quantification of resource utilization. This study explores hospital resource documentation performance for total knee and hip arthroplasty (TKA, THA) implants and how this may differ between hospitals. This retrospective study utilized the Premier discharge database, years 2006 to 2020. TKA/THA cases were categorized into 5 tiers based upon the completeness of implant component documentation: Platinum, Gold, Silver, Bronze, Poor. Correlation between TKA and THA documentation performance (per-hospital percentage of Platinum cases) was assessed. Logistic regression analyses measured the association between hospital characteristics (region, teaching status, bed size, urban/rural) and satisfactory documentation. TKA/THA implant documentation performance was compared to documentation for endovascular stent procedures. Individual hospitals tended to have very complete (Platinum) or very incomplete (Poor) documentation for both TKA and THA. TKA and THA documentation performance were correlated (correlation coefficient = .70). Teaching hospitals were less likely to have satisfactory documentation for both TKA (P = .002) and THA (P = .029). Documentation for endovascular stent procedures was superior compared to TKA/THA. Hospitals' TKA and THA-related implant documentation performance is generally either very proficient or very poor, in contrast with often well-documented endovascular stent procedures. Hospital characteristics, other than teaching status, do not appear to impact TKA/THA documentation completeness.

An Interoperable Similarity-based Cohort Identification Method Using the OMOP Common Data Model version 5.0.

Cohort identification for clinical studies tends to be laborious, time-consuming, and expensive. Developing automated or semi-automated methods for cohort identification is one of the "holy grails" in the field of biomedical informatics. We propose a high-throughput similarity-based cohort identification algorithm by applying numerical abstractions on Electronic Health Records (EHR) data. We implement this algorithm using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), which enables sites using this standardized EHR data representation to avail this algorithm with minimum effort for local implementation. We validate its performance for a retrospective cohort identification task on six clinical trials conducted at the Columbia University Medical Center. Our algorithm achieves an average Area Under the Curve (AUC) of 0.966 and an average Precision at 5 of 0.983. This interoperable method promises to achieve efficient cohort identification in EHR databases. We discuss suitable applications of our method and its limitations and propose warranted future work.

EliIE: An open-source information extraction system for clinical trial eligibility criteria.

OBJECTIVE: To develop an open-source information extraction system called Eligibility Criteria Information Extraction (EliIE) for parsing and formalizing free-text clinical research eligibility criteria (EC) following Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) version 5.0. MATERIALS AND METHODS: EliIE parses EC in 4 steps: (1) clinical entity and attribute recognition, (2) negation detection, (3) relation extraction, and (4) concept normalization and output structuring. Informaticians and domain experts were recruited to design an annotation guideline and generate a training corpus of annotated EC for 230 Alzheimer's clinical trials, which were represented as queries against the OMOP CDM and included 8008 entities, 3550 attributes, and 3529 relations. A sequence labeling-based method was developed for automatic entity and attribute recognition. Negation detection was supported by NegEx and a set of predefined rules. Relation extraction was achieved by a support vector machine classifier. We further performed terminology-based concept normalization and output structuring. RESULTS: In task-specific evaluations, the best F1 score for entity recognition was 0.79, and for relation extraction was 0.89. The accuracy of negation detection was 0.94. The overall accuracy for query formalization was 0.71 in an end-to-end evaluation. CONCLUSIONS: This study presents EliIE, an OMOP CDM-based information extraction system for automatic structuring and formalization of free-text EC. According to our evaluation, machine learning-based EliIE outperforms existing systems and shows promise to improve.

A multi-site cognitive task analysis for biomedical query mediation.

OBJECTIVE: To apply cognitive task analyses of the Biomedical query mediation (BQM) processes for EHR data retrieval at multiple sites towards the development of a generic BQM process model. MATERIALS AND METHODS: We conducted semi-structured interviews with eleven data analysts from five academic institutions and one government agency, and performed cognitive task analyses on their BQM processes. A coding schema was developed through iterative refinement and used to annotate the interview transcripts. The annotated dataset was used to reconstruct and verify each BQM process and to develop a harmonized BQM process model. A survey was conducted to evaluate the face and content validity of this harmonized model. RESULTS: The harmonized process model is hierarchical, encompassing tasks, activities, and steps. The face validity evaluation concluded the model to be representative of the BQM process. In the content validity evaluation, out of the 27 tasks for BQM, 19 meet the threshold for semi-valid, including 3 fully valid: "Identify potential index phenotype," "If needed, request EHR database access rights," and "Perform query and present output to medical researcher", and 8 are invalid. DISCUSSION: We aligned the goals of the tasks within the BQM model with the five components of the reference interview. The similarity between the process of BQM and the reference interview is promising and suggests the BQM tasks are powerful for eliciting implicit information needs. CONCLUSIONS: We contribute a BQM process model based on a multi-site study. This model promises to inform the standardization of the BQM process towards improved communication efficiency and accuracy.

A data-driven concept schema for defining clinical research data needs.

OBJECTIVES: The Patient, Intervention, Control/Comparison, and Outcome (PICO) framework is an effective technique for framing a clinical question. We aim to develop the counterpart of PICO to structure clinical research data needs. METHODS: We use a data-driven approach to abstracting key concepts representing clinical research data needs by adapting and extending an expert-derived framework originally developed for defining cancer research data needs. We annotated clinical trial eligibility criteria, EHR data request logs, and data queries to electronic health records (EHR), to extract and harmonize concept classes representing clinical research data needs. We evaluated the class coverage, class preservation from the original framework, schema generalizability, schema understandability, and schema structural correctness through a semi-structured interview with eight multidisciplinary domain experts. We iteratively refined the schema based on the evaluations. RESULTS: Our data-driven schema preserved 68% of the 63 classes from the original framework and covered 88% (73/82) of the classes proposed by evaluators. Class coverage for participants of different backgrounds ranged from 60% to 100% with a median value of 95% agreement among the individual evaluators. The schema was found understandable and structurally sound. CONCLUSIONS: Our proposed schema may serve as the counterpart to PICO for improving the research data needs communication between researchers and informaticians.

Facilitating biomedical researchers' interrogation of electronic health record data: Ideas from outside of biomedical informatics.

Electronic health records (EHR) are a vital data resource for research uses, including cohort identification, phenotyping, pharmacovigilance, and public health surveillance. To realize the promise of EHR data for accelerating clinical research, it is imperative to enable efficient and autonomous EHR data interrogation by end users such as biomedical researchers. This paper surveys state-of-art approaches and key methodological considerations to this purpose. We adapted a previously published conceptual framework for interactive information retrieval, which defines three entities: user, channel, and source, by elaborating on channels for query formulation in the context of facilitating end users to interrogate EHR data. We show the current progress in biomedical informatics mainly lies in support for query execution and information modeling, primarily due to emphases on infrastructure development for data integration and data access via self-service query tools, but has neglected user support needed during iteratively query formulation processes, which can be costly and error-prone. In contrast, the information science literature has offered elaborate theories and methods for user modeling and query formulation support. The two bodies of literature are complementary, implying opportunities for cross-disciplinary idea exchange. On this basis, we outline the directions for future informatics research to improve our understanding of user needs and requirements for facilitating autonomous interrogation of EHR data by biomedical researchers. We suggest that cross-disciplinary translational research between biomedical informatics and information science can benefit our research in facilitating efficient data access in life sciences.

Use of Self-Service Query Tools Varies by Experience and Research Knowledge.

The lack of understanding of user experience with self-service query tools is a barrier to designing effective query tools and is what propelled this study. User actions were documented and transformed into networks of actions for qualitative analysis. Proficient use of self-service query tools requires significant technical experience. To decrease the user learning curve, additional user education is necessary for novice users.

What Is Asked in Clinical Data Request Forms? A Multi-site Thematic Analysis of Forms Towards Better Data Access Support.

Many academic medical centers have aggregated data from multiple clinical systems into centralized repositories. These repositories can then be queried by skilled data analysts who act as intermediaries between the data stores and the research teams. To obtain data, researchers are often expected to complete a data request form. Such forms are meant to support record-keeping and, most importantly, provide a means for conveying complex data needs in a clear and understandable manner. Yet little is known about how data request forms are constructed and how effective they are likely to be. We conducted a content analysis of ten data request forms from CTSA-supported institutions. We found that most of the forms over-emphasized the collection of metadata that were not considered germane to the actual data needs. Based on our findings, we provide recommendations to improve the quality of data request forms in support of clinical and translational research.

Toward a cognitive task analysis for biomedical query mediation.

In many institutions, data analysts use a Biomedical Query Mediation (BQM) process to facilitate data access for medical researchers. However, understanding of the BQM process is limited in the literature. To bridge this gap, we performed the initial steps of a cognitive task analysis using 31 BQM instances conducted between one analyst and 22 researchers in one academic department. We identified five top-level tasks, i.e., clarify research statement, explain clinical process, identify related data elements, locate EHR data element, and end BQM with either a database query or unmet, infeasible information needs, and 10 sub-tasks. We evaluated the BQM task model with seven data analysts from different clinical research institutions. Evaluators found all the tasks completely or semi-valid. This study contributes initial knowledge towards the development of a generalizable cognitive task representation for BQM.

Characterization of the biomedical query mediation process.

To most medical researchers, databases are obscure black boxes. Query analysts are often indispensable guides aiding researchers to perform mediated data queries. However, this approach does not scale up and is time-consuming and expensive. We analyzed query mediation dialogues to inform future designs of intelligent query mediation systems. Thirty-one mediated query sessions for 22 research projects were recorded and transcribed. We analyzed 10 of these to develop an annotation schema for dialogue acts through iterative refinement. Three coders independently annotated all 3160 dialogue acts. We assessed the inter-rater agreement and resolved disagreement by group consensus. This study contributes early knowledge of the query negotiation space for medical research. We conclude that research data query formulation is not a straightforward translation from researcher data needs to database queries, but rather iterative, process-oriented needs assessment and refinement.

An Integrated Model for Patient Care and Clinical Trials (IMPACT) to support clinical research visit scheduling workflow for future learning health systems.

We describe a clinical research visit scheduling system that can potentially coordinate clinical research visits with patient care visits and increase efficiency at clinical sites where clinical and research activities occur simultaneously. Participatory Design methods were applied to support requirements engineering and to create this software called Integrated Model for Patient Care and Clinical Trials (IMPACT). Using a multi-user constraint satisfaction and resource optimization algorithm, IMPACT automatically synthesizes temporal availability of various research resources and recommends the optimal dates and times for pending research visits. We conducted scenario-based evaluations with 10 clinical research coordinators (CRCs) from diverse clinical research settings to assess the usefulness, feasibility, and user acceptance of IMPACT. We obtained qualitative feedback using semi-structured interviews with the CRCs. Most CRCs acknowledged the usefulness of IMPACT features. Support for collaboration within research teams and interoperability with electronic health records and clinical trial management systems were highly requested features. Overall, IMPACT received satisfactory user acceptance and proves to be potentially useful for a variety of clinical research settings. Our future work includes comparing the effectiveness of IMPACT with that of existing scheduling solutions on the market and conducting field tests to formally assess user adoption.

Evaluating the quality of Internet health resources in pediatric urology.

PURPOSE: Many patients and their parents utilize the Internet for health-related information, but quality is largely uncontrolled and unregulated. The Health on the Net Foundation Code (HONcode) and DISCERN Plus were used to evaluate the pediatric urological search terms 'circumcision,' 'vesicoureteral reflux' and 'posterior urethral valves'. MATERIALS AND METHODS: A google.com search was performed to identify the top 20 websites for each term. The HONcode toolbar was utilized to determine whether each website was HONcode accredited and report the overall frequency of accreditation for each term. The DISCERN Plus instrument was used to score each website in accordance with the DISCERN Handbook. High and low scoring criteria were then compared. RESULTS: A total of 60 websites were identified. For the search terms 'circumcision', 'posterior urethral valves' and 'vesicoureteral reflux', 25-30% of the websites were HONcode certified. Out of the maximum score of 80, the average DISCERN Plus score was 60 (SD = 12, range 38-78), 40 (SD = 12, range 22-69) and 45 (SD = 19, range 16-78), respectively. The lowest scoring DISCERN criteria included: 'Does it describe how the treatment choices affect overall quality of life?', 'Does it describe the risks of each treatment?' and 'Does it provide details of additional sources of support and information?' (1.35, 1.83 and 1.95 out of 5, respectively). CONCLUSIONS: These findings demonstrate the poor quality of information that patients and their parents may use in decision-making and treatment choices. The two lowest scoring DISCERN Plus criteria involved education on quality of life issues and risks of treatment. Physicians should know how to best use these tools to help guide patients and their parents to websites with valid information.

Pathological confirmation of nerve-sparing types performed during robot-assisted radical prostatectomy (RARP).

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Incremental nerve-sparing techniques (NSTs) improve postoperative erectile function after robot-assisted radical prostatectomy (RARP). However, there are no studies to date that histologically confirm the surgeon intended NST. Thus, in the present study, we histologically confirmed that the surgeon performed the nerve preservation as his intended NSTs during RARP. Also, we found that there was more variability in fascia width outcome on the left side compared with the right. Therefore, when performing nerve preservation on the surgeon's non-dominant side, we need to pay more close attention. OBJECTIVES: To confirm that the surgeon achieved true intended histological nerve sparing during robot-assisted radical prostatectomy (RARP) by studying RP specimens. To aid the novice robotic surgeon to develop the skills of RARP. PATIENTS AND METHODS: Between June 2008 and May 2009, 122 consecutive patients underwent RARP by a single surgeon (K.K.B.). The degree of nerve sparing (wide resection [WR], interfascial nerve sparing [ITE-NS], intrafascial nerve sparing [ITR-NS]) on both sides was recorded. The posterior sectors of RP specimens from distal, mid, and proximal parts were evaluated. Fascia width (FW) of each position in RP specimens were compared across nerve-sparing types (NSTs). FW was recorded at 15 ° intervals (3-9 o'clock position), measured as the distance between the outermost prostate gland and surgical margin. The slides were reviewed by an experienced uropathologist who was 'blinded' to the NST. RESULTS: In all, 93 men were included. The overall mean (sd) FW was the greatest in the order of WR, ITE-NS, and ITR-NS, at 2.42 (1.62), 1.71 (1.40) and 1.16 (1.08) mm, respectively (P < 0.001). FW was statistically significantly correlated with the surgical technique used. When the surgeon intended to perform various levels of nerve sparing, these were reflected in the FW. Interestingly, the left-side FW showed more variability than the right side. We suspect that this was a result of the surgeon's right-hand dominance. Erectile function (EF) recovery rate according to NST was 88.9%, 77.3%, 65.6%, 56.3%, and 0% in bilateral ITR-NS, ITR-NS/ITE-NS, bilateral ITE-NS, ITE-NS/WR, and bilateral WR, respectively. To further validate and confirm these preliminary findings, additional studies involving multicentre cohorts would be required. CONCLUSIONS: The surgeon intended dissection and FW correlate, with ITR-NS providing the narrowest FW and the EF recovery rate was the highest in bilateral ITR-NS. There was more variability in FW outcome on the left side than the right. The novice robotic surgeon should consider this variability when performing RARP. It may have implications for technique improvement on nerve preservation for EF.

Partial nephrectomy online: a preliminary evaluation of the quality of health information on the Internet.

UNLABELLED: What's known on the subject? and What does the study add? Patients are highly likely to access the Internet for health information, and studies have reported that inaccurate or low-quality information may alter patients' expectations and negatively impact informed decision-making. In a unique collaboration with the Health On the Internet (HON) Foundation, we evaluated the top 20 search results for the urology search term 'partial nephrectomy,' and identified the highest and lowest scoring criteria to increase awareness of areas of concern and improvement. OBJECTIVE: To further evaluate the quality of information available on the Internet with regard to the management of localized renal cancer, we evaluated websites providing information on 'partial nephrectomy' in conjunction with the Health On the Internet (HON) Foundation. Many patients now utilize the Internet as a resource to provide further information on disease, treatments and outcomes, and health information on the Internet is largely unregulated. Inaccurate information may contribute to unrealistic expectations and dissatisfied patients. PATIENTS AND METHODS: A google.com search identified the top 30 websites for the search term 'partial nephrectomy'. The HON Foundation evaluated each website according to the eight principles for Health on the Internet code of conduct (HONcode) certification and reported the overall frequency of certification, as well as individual website compliance with each of the principles. RESULTS: Overall, seven (23.3%) of 30 websites met the requirements of HONcode certification and an additional two (6.7%) websites were under review to maintain their certification based on updating their resources. The remaining 21 (70%) websites did not meet the standards for certification. The lowest performing criteria included proper citation of medical information and a clear distinction of advertising from editorial content. CONCLUSIONS: The low rate of HONcode compliance for these websites illustrates the poor quality of information that patients may encounter when researching options for nephron-sparing surgery, which may have a significant impact on patient decision-making and treatment choices. Physicians should be aware of the quality of Internet resources and how to best use these tools to help guide patients to websites with valid information.

Socioeconomic and clinical factors influence the interval between positive prostate biopsy and radical prostatectomy.

OBJECTIVE: To examine socioeconomic and clinical factors that may predict a longer interval between prostate biopsy and radical prostatectomy (RP). METHODS: The Columbia University Urologic Oncology Database was queried for patients who underwent RP from 1990-2010. Time to surgery (TTS) was defined as the period between the most recent positive prostate biopsy and date of surgery. Clinical factors examined included: age, D'Amico risk group, year of surgery, body mass index, and comorbidities. Socioeconomic factors included race/ethnicity, relationship status, income, and distance to treatment center. The relationship between clinical/socioeconomic factors and TTS was evaluated using univariate and multivariate regression models. RESULTS: Two-thousand five-hundred seventy-three patients were included in the analysis. Median TTS was 48 days (IQR 35-70, range 43-1103), and 71% of patients underwent RP within 60 days after the most recent positive biopsy. On multivariate analysis, living further from the medical center was associated with shorter TTS (P = .01), whereas more recent year of surgery (P = .01), comorbid cardiovascular disease (P = .007), African-American (P = .005) or Hispanic race (P = .005), divorced relationship status (P = .01), and lower income (P = .003) were all associated with longer TTS. CONCLUSION: Patients often experience widely variable intervals between the diagnosis and treatment of localized prostate cancer. Longer intervals before surgery may point to disparities in access to prostate cancer care, and not increased decision-making time by the patient.

Comparison of biochemical failure definitions for predicting local cancer recurrence following cryoablation of the prostate.

BACKGROUND: Various definitions of biochemical failure (BF) have been used to predict cancer recurrence following prostate cryoablation. However to date, none of these definitions have been validated for this use. We have reviewed several definitions of BF to determine their accuracy in predicting biopsy-proven local recurrence following prostate cryoablation. METHODS: The Columbia University Urologic Oncology Database was queried for patients who underwent prostate cryoablation between 1994 and 2010, and who subsequently underwent surveillance biopsy due to clinical suspicion of prostate cancer recurrence. Serial postoperative prostate-specific antigen (PSA) results were used to determine BF according to various definitions of BF. Biopsy results were used to determine local recurrence. Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curve area were calculated for each of the BF definitions. RESULTS: A total of 110 patients met inclusion criteria for the study. These patients were treated with primary full-gland (n = 38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer. The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and 0.64, respectively. CONCLUSIONS: Overall, the Phoenix definition best predicted local cancer recurrence following prostate cryoablation. These preliminary data may be useful for researchers evaluating the short-term efficacy of cryoablation, and for urologists assessing their patients for potential cancer recurrence.

Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer.

BACKGROUND: It is becoming increasingly evident that microRNAs (miRNAs) are associated with the development and progression of prostate cancer (PCa). METHODS: We examined the hypothesis that plasma miRNA levels can differentiate patients by aggressiveness in 82 PCa patients. Taqman based quantitative RT-PCR assays were performed to measure copy number of target miRNAs. RESULTS: miR-20a was significantly overexpressed in plasma from patients with stage 3 tumors compared to stage 2 or below (P = 0.03). The expression levels for miR-20a and miR-21 were significantly increased in patients with high risk CAPRA scores (16,623 and 1,595 copies, respectively). Significantly increased miR-21 and miR-145 expression were observed for patients with intermediate or high risk D'Amico scores compared to patients with low risk scores (P = 0.047 and 0.011, respectively). The relapse rates for CAPRA scores ranged from 1.9% for low risk to 9.5% for intermediate risk and to 22.2% for high risk patients (P = 0.023). For D'Amico scores, the relapse rates ranged from 0.0% for low risk to 7.4% for intermediate risk and 17.6% for high risk patients (P = 0.039). Expression of miR-21 and miR-221 significantly differentiated patients with intermediate risk from those with low risk CAPRA scores (AUC = 0.801, P = 0.002). Four miRNAs (miR-20a, miR-21, miR-145, and miR-221) could also distinguish high versus low risk in PCa patients by D'Amico score with an AUC of 0.824. CONCLUSIONS: These preliminary data suggest that altered plasma miRNAs may be useful predictors to distinguish PCa patients with varied aggressiveness. Further larger studies to validate this promising finding are warranted.

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion.

UNLABELLED: What's known on the subject? and What does the study add? In an array of urological and non-urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20-year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI-positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI-positive disease have overall survival outcomes similar to those of patients with muscle-invasive LVI-negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC. OBJECTIVE: To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified. These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log-rank tests and Cox proportional hazards regression models. Actuarial survival curves were calculated using the Kaplan-Meier method. RESULTS: LVI was observed in 68 patients (32.2%). The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5- and 10-year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively. In multivariate analysis, age, race and LVI were independent predictors of overall survival. CONCLUSIONS: The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC. LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options. With confirmation from large international studies, inclusion of LVI in the tumour-node-metastasis staging system for UTUC should be considered.

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer.

BACKGROUND: Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2-T4aN0-N2M0 bladder cancer. METHODS: In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum-based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin-based chemotherapy compared with carboplatin-based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin-based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01-112.2). CONCLUSION: In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum-based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin- or carboplatin-based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy.

DNA methylation changes correlate with Gleason score and tumor stage in prostate cancer.

DNA methylation, a widely used epigenetic mark, has been associated with many tumors. However, few studies have addressed the role of cell-free plasma DNA methylation in discriminating aggressive prostate cancer (PCa) from indolent cases. We conducted a case series and a case-control study among histologically confirmed stage II/III cases and matched controls recruited at Columbia University Medical Center. The aim of this study was to investigate whether plasma DNA methylation levels are appropriate surrogate biomarker of PCa tumor tissue levels and whether these markers are associated with worse clinicopathological tumor characteristics, which correlate with poorer prognosis. Quantitative pyrosequencing was used to detect methylation levels of p16 (CDKN4A), APC, GSTP1, and LINE-1 in 24 pairs of prostate tumor and adjacent tissues, as well as 27 plasma samples of PCa patients and 24 of controls. DNA methylation levels were significantly higher in tumor tissue than in adjacent nontumor tissue for p16 (CDKN4A), GSTP1, and APC; GSTP1 had a higher average percentage methylation in tumor tissue (38.9%) compared with p16 (CDKN4A) (5.9%) and APC (14.5%). GSTP1, p16 (CDKN4A), and APC methylation in tumor tissue was statistically significantly higher for cases with Gleason score ≥7 compared with those with Gleason score <7 [49.0% vs. 21.9% (p=0.01), 6.6% vs. 4.5% (p=0.04), and 19.1% vs. 7.4% (p=0.02), respectively]. Plasma LINE-1 methylation levels were higher in those with higher Gleason (67.6%) than in those with Gleason's below 7 (64.6%, p=0.03). Significant plasma-tissue correlations were observed for GSTP1 and LINE-1 methylation. These data, although preliminary, suggest that aberrant methylation may be a useful marker to identify PCa patients with clinically aggressive disease.