Association of Medicaid expansion with 2-year survival and time to treatment initiation in gastrointestinal cancer patients: A National Cancer Database study.

INTRODUCTION: We evaluated whether Medicaid expansion (ME) was associated with improved 2-year survival and time to treatment initiation (TTI) among patients with gastrointestinal (GI) cancer. METHODS: GI cancer patients diagnosed 40-64 years were queried from the National Cancer Database. Those diagnosed from 2010 to 2012 were considered pre-expansion; those diagnosed from 2014 to 2016 were considered post-expansion. Cox models estimated hazard ratios and 95% confidence intervals (CIs) for 2-year overall survival. Generalized estimating equations (GEE) estimated odds ratios (OR) and 95% CI of TTI within 30- and 90 days. Multivariable Difference-in-Difference models were used to compare expansion/nonexpansion cohorts pre-/post-expansion, adjusting for patient, clinical, and hospital factors. RESULTS: 377,063 patients were included. No significant difference in 2-year survival was demonstrated across ME and non-ME states overall or in site-based subgroup analysis. In stage-based subgroup analysis, 2-year survival significantly improved among stage II cancer, with an 8% decreased hazard of death at 2 years (0.92; 0.87-0.97). Those with stage IV had a 4% increased hazard of death at 2 years (1.04; 1.01-1.07). Multivariable GEE models showed increased TTI within 30 days (1.12; 1.09-1.16) and 90 days (1.22; 1.17-1.27). Site-based subgroup analyses indicated increased likelihood of TTI within 30 and 90 days among colon, liver, pancreas, rectum, and stomach cancers, by 30 days for small intestinal cancer, and by 90 days for esophageal cancer. In subgroup analyses, all stages experienced improved odds of TTI within 30 and 90 days. CONCLUSION: ME was not associated with significant improvement in 2-year survival for those with GI cancer. Although TTI increased after ME for both cohorts, the 30- and 90-day odds of TTI was higher for those from ME compared with non-ME states. Our findings add to growing evidence of associations with ME for those diagnosed with GI cancer.

Transanal Endoscopic Platforms: TAMIS versus Rigid Platforms: Pros and Cons.

Transanal endoscopic surgery encompasses the minimally invasive surgical techniques used to operate in the rectum under magnification while maintaining pneumorectum via a resectoscope or port. The view, magnification, and surgical precision afforded by these advanced transanal techniques have resulted in excellent specimen quality and low recurrence rates, especially compared with traditional transanal surgery. For rigid platforms, the surgeon operates through a rigid 4-cm diameter steel proctoscope of varying lengths that is clamped to the operating table with an articulating arm. Transanal minimally invasive surgery (TAMIS) is a newer flexible platform using a disposable port which "hooks" into the anorectal ring to remain in place. The cost-effectiveness and versatility of the TAMIS platform have resulted in its popularity and use in more advanced applications such as transanal total mesorectal excision. Ultimately, the choice of operating platform should be based on surgeon preference, patient characteristics, availability, and cost. The pros and cons of each platform will be discussed in this article.

Surveillance, Epidemiology, and End Results (SEER) and SEER-Medicare Databases: Use in Clinical Research for Improving Colorectal Cancer Outcomes.

The Surveillance, Epidemiology, and End Results (SEER) program is a clinical database, funded by the National Cancer Institute (NCI), which was created to collect cancer incidence, prevalence, and survival data from U.S. cancer registries. By capturing approximately 30% of the U.S. population, it serves as a powerful resource for researchers focused on understanding the natural history of colorectal cancer and improvement in patient care. The linked SEER-Medicare database is a robust database allowing investigators to perform studies focusing on health disparities, quality of care, and cost of treatment in oncologic disease. Since its infancy in the early 1970s, the database has been utilized for thousands of studies resulting in novel publications that have shaped our management of colorectal cancer among other malignancies.

Enhanced recovery protocol improves postoperative outcomes and minimizes narcotic use following resection for colon and rectal cancer.

BACKGROUND: Enhanced recovery protocols are associated with improved recovery. However, data on outcomes following the implementation of an enhanced recovery protocol in colorectal cancer are limited. We set out to study the postoperative outcomes, opioid use patterns, and cost impact for patients undergoing colon or rectal resection for cancer. METHODS: A retrospective review of all elective colorectal cancer resections from January 2015 to June 2018 at a single institution was performed. Patient demographics, operative details, and postoperative outcomes were collected. Colon and rectal patients were studied separately, with comparison of patients before and after the implementation of an enhanced recovery protocol. RESULTS: One hundred ninety-two patients underwent elective colorectal resection for cancer. In January 2016, an enhanced recovery protocol was implemented for all elective resections - 71 patients (33 colon and 38 rectal) underwent surgery before implementation and 121 patients (56 colon and 65 rectal) underwent surgery after implementation of the enhanced recovery protocol. There were no differences with regard to age, gender, or body mass index before or after implementation (all P > .05). For both colon and rectal cancer patients, the enhanced recovery protocol reduced time to regular diet (both P < .05) and length of stay (colon: 3 vs 4 days; rectal: 4 vs 6 days; both P < .01). Enhanced recovery protocol patients also consumed fewer total narcotics (colon: 44 vs 184 morphine milligram equivalents, P < .01; rectal: 121 vs 393 morphine milligram equivalents, P < .01). CONCLUSIONS: Enhanced recovery protocol use reduced length of stay and narcotic use with similar total costs and no difference in 30-day complications for both colon and rectal cancer resections.

Biomarkers to estimate the probability of complicated appendicitis.

BACKGROUND: The conventional paradigm that all children with appendicitis require an appendectomy is being challenged by the idea that some patients may be successfully managed non-operatively. The study aimed to determine if matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are candidate biomarkers for estimating the probability of complicated appendicitis in pediatric patients. METHODS: The study was a single-institution, prospective cohort study. MMP and TIMP serum protein concentrations were measured in patients with suspected appendicitis. Three hundred and thirty-one patients were enrolled with appendicitis. Classification and Regression Tree (CART) analysis was used to determine the combination of candidate biomarkers that best predicted complicated appendicitis. RESULTS: The CART-generated decision tree for the derivation cohort included WBC count, MMP-8, MMP-9, MMP-12, TIMP-2, and TIMP-4 and had the following test characteristics for estimating the probability of complicated appendicitis (95% CI): AUC 0.86 (0.81-0.90); sensitivity 91% (83-96); specificity 61% (53-68); positive predictive value 58% (50-66); negative predictive value 92% (84-96); positive likelihood ratio (LR) 2.3 (1.9-2.8); and negative LR 0.15 (0.08-0.3). CONCLUSIONS: MMPs and TIMPs have the potential to serve as biomarkers to estimate the probability of complicated appendicitis in pediatric patients. The multi-biomarker-based decision tree has test characteristics suggesting clinical utility for decision making. LEVEL OF EVIDENCE: Level II: Study of Diagnostic Test.

Cancer Center Volume and Type Impact Stage-Specific Utilization of Neoadjuvant Therapy in Rectal Cancer.

BACKGROUND: Neoadjuvant chemoradiation reduces local recurrence in locally advanced rectal cancer, and adherence to national and societal recommendations remains unknown. OBJECTIVE: To determine variability in guideline adherence in rectal cancer treatment and investigate whether hospital volume correlated with variability seen. DESIGN: We performed a retrospective analysis using the National Cancer Database rectal cancer participant user files from 2005 to 2010. Stage-specific predictors of neoadjuvant chemotherapy and radiation use were determined, and variation in use across hospitals analyzed. Hospitals were ranked based on likelihood of preoperative therapy use by stage, and observed-to-expected ratios for neoadjuvant therapy use calculated. Hospital outliers were identified, and their center characteristics compared. RESULTS: A total of 23,488 patients were identified at 1183 hospitals. There was substantial variability in the use of neoadjuvant chemoradiation across hospitals. Patients managed outside clinical guidelines for both stage 1 and stage 3 disease tended to receive treatment at lower-volume, community cancer centers. CONCLUSIONS: There is substantial variability in adherence to national guidelines in the use of neoadjuvant chemoradiation for rectal cancer across all stages. Both hospital volume and center type are associated with over-treatment of early-stage tumors and under-treatment of more invasive tumors. These findings identify a clear need for national quality improvement efforts in the treatment of rectal cancer.

Surviving rectal cancer: examination of racial disparities surrounding access to care.

BACKGROUND: The aim of this study was to evaluate whether survival differences are attributable to disproportionate access to stage-specific rectal cancer treatment recommended by the National Comprehensive Care Network. METHODS: A retrospective analysis of the National Cancer Data Base between 1998 and 2006 was performed. A series of Kaplan-Meier survival analyses were used to compare 5-y survival among race cohorts. Propensity score matching was used to compare Caucasian and African American patients who received the same treatment by accounting for covariates. RESULTS: 5-y overall survival in African Americans was 50.7% versus 56.2% in Caucasians (P < 0.001). In patients with stage I-III disease, 5-y survival was 58.7% in African Americans versus 63.1% in Caucasians (P < 0.001). Analysis of patients receiving surgery for stage I-III disease, revealed a 61.1% 5-y survival in African Americans versus 65.8% in Caucasians (P < 0.001). Propensity score matching did not eliminate the racial disparity. The median survival for Caucasian patients was 109.6 mo as compared to 85.8 mo for African Americans (P < 0.001). CONCLUSIONS: These data show that access to standard care appears to decrease but not eliminate the survival differences between African Americans and Caucasians with rectal cancer.

Hospital Variability in Use of Adjuvant Chemotherapy for Patients with Stage 2 and 3 Colon Cancer.

BACKGROUND: Following oncologic resection, adjuvant chemotherapy is associated with decreased recurrence and improved survival in stage 3 colon cancer. However, there is controversy regarding its use in stage 2 colon cancer with high-risk features (tumor depth T4, poorly differentiated, positive margin, and/or inadequate lymph node retrieval). Consensus guidelines recommend no adjuvant chemotherapy in the absence of these high-risk features (low-risk stage 2). OBJECTIVE: This study aimed to examine hospital characteristics associated with poor risk-adjusted, stage-specific guideline compliance for the use of adjuvant chemotherapy in stage 3 and low-risk stage 2 colon cancer. DESIGN: This was a retrospective study. Stepwise logistic regression was used to identify patient and hospital factors associated with administration of adjuvant chemotherapy. Hierarchical regression models were used to calculate risk- and reliability-adjusted rates of chemotherapy use and observed-to-expected ratios in each hospital's stage 2 low-risk and stage 3 patients. SETTINGS: Data were retrieved from the National Cancer Database. PATIENTS: Patients selected were adults treated with oncologic resection for stage 2 to 3 colon cancer between 2004 and 2010. MAIN OUTCOME MEASURES: The primary outcome measured was receipt of adjuvant chemotherapy. RESULTS: A total of 167,345 patients were identified at 1395 hospitals. The mean overall risk-adjusted adjuvant chemotherapy rate was 65.3% for stage 3 and 15.2% for low-risk stage 2. Analysis of low outlier hospitals for stage 3 colon cancer, where adjuvant chemotherapy was underutilized, demonstrated that 62.8% were low-volume centers and 51.4% were community centers. Of high outlier hospitals for stage 2 low-risk disease, where adjuvant chemotherapy was overutilized, 87.2% were low-volume hospitals and 67.2% were community centers. LIMITATIONS: Selection bias and the inability to compare specific chemotherapy regimens were limitations of this study. CONCLUSIONS: Following oncologic resection, administration of adjuvant chemotherapy for low-risk stage 2 and stage 3 disease varies substantially among hospitals in the United States. Outlier hospitals were most likely to be low-volume community centers.

Role of matrix metalloproteinase-8 as a mediator of injury in intestinal ischemia and reperfusion.

Acute mesenteric ischemia is associated with high morbidity and mortality. In recent studies, we found that the intestine is an important source of matrix metalloproteinase (MMP)8 during intestinal injury. We hypothesized that genetic ablation or pharmacological inhibition of MMP8 would reduce intestinal injury in mice subjected to intestinal ischemia-reperfusion (I/R) injury. Male mice aged 8-12 wk were subjected to intestinal I/R injury by transient occlusion of the superior mesenteric artery for 30 min. MMP8 was inhibited by genetic and pharmacological approaches. In vivo study endpoints included several functional, histological, and biochemical assays. Intestinal sections were assessed for barrier function and expression of tight junction proteins. I/R injury led to increased intestinal and systemic expression of MMP8. This increase was associated with increased intestinal neutrophil infiltration, epithelial injury, and permeability. I/R injury was associated with increased systemic inflammation and weight loss. These parameters were ameliorated by inhibiting MMP8. I/R injury caused a loss of the tight junction protein claudin-3, which was ameliorated by genetic ablation of MMP8. MMP8 plays an important role in intestinal I/R injury through mechanisms involving increased inflammation and loss of claudin-3. Inhibition of MMP8 is a potential therapeutic strategy in this setting.-Daly, M. C., Atkinson, S. J., Varisco, B. M., Klingbeil L., Hake, P., Lahni, P., Piraino, G., Wu, D., Hogan, S. P., Zingarelli, B., Wong, H. R. Role of matrix metalloproteinase-8 as a mediator of injury in intestinal ischemia and reperfusion.

The effect of hospital volume on resection margins in rectal cancer surgery.

BACKGROUND: We hypothesized that after controlling for case-mix differences, the rates of positive resection margin after rectal cancer surgery vary substantially in the United States and that high-volume hospitals have lower margin positivity rates. MATERIALS AND METHODS: Patients treated with oncologic resection for stage I-III rectal cancer were selected from the 1998-2010 National Cancer Data Base. Hierarchical regression models were used to calculate risk- and reliability-adjusted positive margin rates and hospital level variability in positive margin rates using Empirical Bayes techniques. RESULTS: A total of 113,113 patients were treated at 1446 hospitals. The mean overall risk- and reliability-adjusted positive margin rate was 7.3%. High-volume hospitals did not have a lower rate of adjusted margin positivity (7.4%, P = 0.75). When both case mix and hospital volume differences were factored into the model, variability in margin positivity rates increased by 9.8%, implying that referral to high-volume hospitals alone would not improve margin positivity rates. CONCLUSIONS: Rectal cancer margin positivity rates vary substantially in the United States, despite adjusting for differences in case mix. These results support standardization of surgical technique and pathologic assessment as part of a broader initiative that identifies and refers patients to higher performing hospitals rather than simply to higher volume hospitals.

ß-globin matrix attachment region improves stable genomic expression of the Sleeping Beauty transposon.

The liver is an attractive target for gene therapy due to its extensive capability for protein production and the numerous diseases resulting from a loss of gene function it normally provides. The Sleeping Beauty Transposon (SB-Tn)(1) system is a non-viral vector capable of delivering and mediating therapeutic transgene(s) insertion into the host genome for long-term expression. A current challenge for this system is the low efficiency of integration of the transgene. In this study we use a human hepatoma cell line (HuH-7) and primary human blood outgrowth endothelial cells (BOECs) to test vectors containing DNA elements to enhance transposition without integrating themselves. We employed the human ß-globin matrix attachment region (MAR) and the Simian virus 40 (SV40) nuclear translocation signal to increase the percent of HuH-7 cells persistently expressing a GFP::Zeo reporter construct by ∼50% for each element; while combining both did not show an additive effect. Interestingly, both elements together displayed an additive effect on the number of insertion sites, and in BOECs the SV40 alone appeared to have an inhibitory effect on transposition. In long-term cultures the loss of plasmid DNA, transposase expression and mapping of insertion sites demonstrated bona fide transposition without episomal expression. These results show that addition of the ß-globin MAR and potentially other elements to the backbone of SB-Tn system can enhance transposition and expression of therapeutic transgenes. These findings may have a significant influence on the use of SB transgene delivery to liver for the treatment of a wide variety of disorders.