Hospital safety-net burden does not predict differences in rectal cancer treatment and outcomes.

BACKGROUND: Safety-net hospitals have been shown to have inferior short-term surgical outcomes. The aim of this study was to compare rectal cancer management and survival across hospitals stratified by payer mix. MATERIALS AND METHODS: Rectal cancer patients (n = 296,068) were identified using the 1998-2010 National Cancer Data Base. Hospitals were grouped into safety-net burden categories, according to the proportion of patients with Medicaid or no health insurance, as follows: low-, medium-, and high-burden hospitals (HBHs). Patient and tumor characteristics, processes of care, and outcomes were evaluated, and regression analysis was used to investigate correlations between hospital safety-net burden on patient survival. RESULTS: HBH encountered patients with more advanced disease (P < 0.001). Despite this, stage I-III patients at HBH had equal likelihood of receiving surgery and guideline-appropriate radiation and chemotherapy (all P > 0.05). The 30-day readmissions and mortality were also similar across safety-net groups (all P > 0.05). Multivariate analysis showed no difference in survival between HBH and low-burden hospital (P = 0.164). CONCLUSIONS: Hospital payer mix may not adversely influence management of rectal cancer. This study highlights potential areas to improve cancer care for vulnerable patient populations.

Mediating millisecond reaction time around particles and cells.

Precise spatiotemporal control of how particles and cells interact with reagents is critical for numerous laboratory and industrial processes. Novel tools for exerting this control at shorter time scales will enable development of new chemical processes and biomedical assays. Previously, we have developed a generalized approach to manipulate cells and particles across fluid streams termed rapid inertial solution exchange (RInSE), which utilizes inertial lift forces at finite Reynolds number and high Peclet number to transfer particles from an initial solution to another within a millisecond. Here, we apply these principles toward developing a continuous flow microfluidic platform that enables transient chemical treatments of cells and particles (on the order of 1 ms). We also demonstrate how the reactant stream can be employed as a diffusion barrier, preventing adverse reactions between coflowing solutions. In order to demonstrate the utility of the method, we applied it to various operations in molecular biology and automated cell staining including cell permeabilization, fluorescent staining, and molecular delivery to viable cells. We expect this method will enable previously unexplored studies of the dynamics of molecular events, improve uniformity of reactions carried on the surface of beads, and increase uniformity in cell-based assays through automation.

Understanding the "Weekend Effect" for Emergency General Surgery.

BACKGROUND: Several studies have identified a "weekend effect" for surgical outcomes, but definitions vary and the cause is unclear. Our aim was to better characterize the weekend effect for emergency general surgery using mortality as a primary endpoint. METHODS: Using data from the University HealthSystem Consortium from 2009 to 2013, we identified urgent/emergent hospital admissions for seven procedures representing 80% of the national burden of emergency general surgery. Patient characteristics and surgical outcomes were compared between cases that were performed on weekdays vs weekends. RESULTS: Hospitals varied widely in the proportion of procedures performed on the weekend. Of the procedures examined, four had higher mortality for weekend cases (laparotomy, lysis of adhesions, partial colectomy, and small bowel resection; p < 0.01), while three did not (appendectomy, cholecystectomy, and peptic ulcer disease repair). Among the four procedures with increased weekend mortality, patients undergoing weekend procedures also had increased severity of illness and shorter time from admission to surgery (p < 0.01). Multivariate analysis adjusting for patient characteristics demonstrated independently higher mortality on weekends for these same four procedures (p < 0.01). CONCLUSIONS: For the first time, we have identified specific emergency general surgery procedures that incur higher mortality when performed on weekends. This may be due to acute changes in patient status that require weekend surgery or indications for urgent procedures (ischemia, obstruction) compared to those without a weekend mortality difference (infection). Hospitals that perform weekend surgery must acknowledge and identify ways to manage this increased risk.

Can Biologic Augmentation Improve Clinical Outcomes Following Microfracture for Symptomatic Cartilage Defects of the Knee? A Systematic Review.

Objective To perform a systematic review of clinical outcomes following microfracture augmented with biological adjuvants (MFX+) compared with microfracture (MFX) alone. Design The MEDLINE, Scopus, and Cochrane databases were searched for clinical studies on MFX+ for chondral defects of the knee. Study characteristics and clinical outcome score data were collected. Subjective synthesis was performed using data from randomized controlled studies to determine effect size of MFX+ procedures performed with either injectable or scaffold-based augmentation compared with MFX alone. Results A total of 18 articles reporting on 625 patients (491 MFX+, 134 MFX) were identified. Six studies were level II evidence and 1 study was level I evidence. Mean patient age range was 26 to 51 years, and mean follow-up ranged from 2 to 5 years. All studies demonstrated significant improvement in reported clinical outcome scores at follow-up after MFX+ therapy, and 87% of patients reported satisfaction with treatment. The most commonly reported treatment complication was postoperative stiffness (3.9% of patients). Subjective synthesis on randomized controlled trials demonstrated that 2/2 injectable MFX+ interventions had significantly greater improvements in International Knee Documentation Committee Subjective Knee Form (IKDC; P = 0.004) and Knee injury and Osteoarthritis Outcome Score (KOOS; P = 0.012) scores compared with MFX alone, while 2/2 trials on scaffolding MFX+ adjuvants showed comparable postoperative improvements. Conclusions MFX+ biological adjuvants are safe supplements to marrow stimulation for treating cartilage defects in the adult knee. Early literature is heterogenous and extremely limited in quality. Individual trials report both equivalent and superior clinical outcomes compared with MFX alone, making definitive conclusions on the efficacy of MFX+ difficult without higher quality evidence.

Opportunities to Improve Care of Hepatocellular Carcinoma in Vulnerable Patient Populations.

BACKGROUND: Hepatocellular carcinoma (HCC) patients with Medicaid or no health insurance have inferior survival compared with privately insured patients. Safety-net hospitals that care for these patients are often criticized for their inferior outcomes. We hypothesized that HCC survival was related to appropriate surgical management. STUDY DESIGN: The American College of Surgeons National Cancer Database was queried for patients diagnosed with HCC (n = 111,481) from 1998 to 2010. Hospitals were stratified according to safety-net burden, defined as the percentage of patients with Medicaid or no insurance. The highest quartile, representing safety-net hospitals, was compared with lower-burden hospitals with regard to patient demographics, cancer presentation, surgical management, and survival. RESULTS: Patients at safety-net hospitals were less often white, had less income and education, but presented with similar stage HCC. Safety-net hospital patients were less likely to receive surgery (odds ratio 0.77; p < 0.01), and among curable patients (stages 1 and 2) who underwent surgical intervention, liver transplantation and resection were performed less often at safety-net hospitals than at other hospitals (50.7% vs 66.7%). Procedure-specific mortality rates were also higher at safety net hospitals (p < 0.01). However, multivariate analysis adjusting for cancer stage and type of surgery revealed similar survival for safety-net hospital patients who had surgery and survived for longer than 30 days (p = 0.73). CONCLUSIONS: Vulnerable patients with HCC are commonly treated at safety-net hospitals, are less likely to receive curative surgery, and have worse short-term outcomes. However, safety-net patients who can endure liver surgery have a similar prognosis as patients at nonsafety-net hospitals. Providing equal access to surgery may improve survival for vulnerable populations of HCC patients.

Addressing the High Costs of Pancreaticoduodenectomy at Safety-Net Hospitals.

Importance: Safety-net hospitals care for vulnerable patients, providing complex surgery at increased costs. These hospitals are at risk due to changing health care reimbursement policies and demand for better value in surgical care. Objective: To model different techniques for reducing the cost of complex surgery performed at safety-net hospitals. Design, Setting, and Participants: Hospitals performing pancreaticoduodenectomy (PD) were queried from the University HealthSystem Consortium database (January 1, 2009, to December 31, 2013) and grouped according to safety-net burden. A decision analytic model was constructed and populated with clinical and cost data. Sensitivity analyses were then conducted to determine how changes in the management or redistribution of patients between hospital groups affected cost. Main Outcomes and Measures: Overall cost per patient after PD. Results: During the 5 years of the study, 15 090 patients underwent PD. Among safety-net hospitals, low-burden hospitals (LBHs), medium-burden hospitals (MBHs), and high-burden hospitals (HBHs) treated 4220 (28.0%), 9505 (63.0%), and 1365 (9.0%) patients, respectively. High-burden hospitals had higher rates of complications or comorbidities and more patients with increased severity of illness. Perioperative mortality was twice as high at HBHs (3.7%) than at LBHs (1.6%) and MBHs (1.7%) (P < .001). In the base case, when all clinical and cost data were considered, PD at HBHs cost $35 303 per patient, 30.1% and 36.2% higher than at MBHs ($27 130) and LBHs ($25 916), respectively. Reducing perioperative complications or comorbidities by 50% resulted in a cost reduction of up to $4607 for HBH patients, while reducing mortality rates had a negligible effect. However, redistribution of HBH patients to LBHs and MBHs resulted in significantly more cost savings of $9155 per HBH patient, or $699 per patient overall. Conclusions and Relevance: Safety-net hospitals performing PD have inferior outcomes and higher costs, and improving perioperative outcomes may have a nominal effect on reducing these costs. Redirecting patients away from safety-net hospitals for complex surgery may represent the best option for reducing costs, but the implementation of such a policy will undoubtedly meet significant challenges.

Label-free enumeration, collection and downstream cytological and cytogenetic analysis of circulating tumor cells.

Circulating tumor cells (CTCs) have a great potential as indicators of metastatic disease that may help physicians improve cancer prognostication, treatment and patient outcomes. Heterogeneous marker expression as well as the complexity of current antibody-based isolation and analysis systems highlights the need for alternative methods. In this work, we use a microfluidic Vortex device that can selectively isolate potential tumor cells from blood independent of cell surface expression. This system was adapted to interface with three protein-marker-free analysis techniques: (i) an in-flow automated image processing system to enumerate cells released, (ii) cytological analysis using Papanicolaou (Pap) staining and (iii) fluorescence in situ hybridization (FISH) targeting the ALK rearrangement. In-flow counting enables a rapid assessment of the cancer-associated large circulating cells in a sample within minutes to determine whether standard downstream assays such as cytological and cytogenetic analyses that are more time consuming and costly are warranted. Using our platform integrated with these workflows, we analyzed 32 non-small cell lung cancer (NSCLC) and 22 breast cancer patient samples, yielding 60 to 100% of the cancer patients with a cell count over the healthy threshold, depending on the detection method used: respectively 77.8% for automated, 60-100% for cytology, and 80% for immunostaining based enumeration.

Size-selective collection of circulating tumor cells using Vortex technology.

A blood-based, low cost alternative to radiation intensive CT and PET imaging is critically needed for cancer prognosis and management of its treatment. "Liquid biopsies" of circulating tumor cells (CTCs) from a relatively non-invasive blood draw are particularly ideal, as they can be repeated regularly to provide up to date molecular information about the cancer, which would also open up key opportunities for personalized therapies. Beyond solely diagnostic applications, CTCs are also a subject of interest for drug development and cancer research. In this paper, we adapt a technology previously introduced, combining the use of micro-scale vortices and inertial focusing, specifically for the high-purity extraction of CTCs from blood samples. First, we systematically varied parameters including channel dimensions and flow rates to arrive at an optimal device for maximum trapping efficiency and purity. Second, we validated the final device for capture of cancer cell lines in blood, considering several factors, including the effect of blood dilution, red blood cell lysis and cell deformability, while demonstrating cell viability and independence on EpCAM expression. Finally, as a proof-of-concept, CTCs were successfully extracted and enumerated from the blood of patients with breast (N = 4, 25-51 CTCs per 7.5 mL) and lung cancer (N = 8, 23-317 CTCs per 7.5 mL). Importantly, samples were highly pure with limited leukocyte contamination (purity 57-94%). This Vortex approach offers significant advantages over existing technologies, especially in terms of processing time (20 min for 7.5 mL of whole blood), sample concentration (collecting cells in a small volume down to 300 µL), applicability to various cancer types, cell integrity and purity. We anticipate that its simplicity will aid widespread adoption by clinicians and biologists who desire to not only enumerate CTCs, but also uncover new CTC biology, such as unique gene mutations, vesicle secretion and roles in metastatic processes.

Microfluidic purification and concentration of malignant pleural effusions for improved molecular and cytomorphological diagnostics.

Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology. However, a large background of smaller leukocytes and/or erythrocytes can make accurate diagnosis difficult and reduce specificity in identification of mutations of interest for targeted anti-cancer therapies. Here, we describe an automated microfluidic system (Centrifuge Chip) which employs microscale vortices for the size-based isolation and concentration of cancer cells and mesothelial cells from a background of blood cells. We are able to process non-diluted pleural fluids at 6 mL/min and enrich target cells significantly over the background; we achieved improved purity in all patient samples analyzed. The resulting isolated and viable cells are readily available for immunostaining, cytological analysis, and detection of gene mutations. To demonstrate the utility towards aiding companion diagnostics, we also show improved detection accuracy of KRAS gene mutations in lung cancer cells processed using the Centrifuge Chip, leading to an increase in the area under the curve (AUC) of the receiver operating characteristic from 0.90 to 0.99. The Centrifuge Chip allows for rapid concentration and processing of large volumes of bodily fluid samples for improved cytological diagnosis and purification of cells of interest for genetic testing, which will be helpful for enhancing diagnostic accuracy.