A Pilot Study Assessing the Potential Role of non-CD133 Colorectal Cancer Stem Cells as Biomarkers

Introduction: Over 50% of patients with colorectal cancer (CRC) will progress and/or develop metastases. Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells are thought to be responsible for tumor initiation, dissemination and treatment failure. Therefore, we hypothesized that CRC cancer stem cell markers (CRCSC) will identify a group of patients at high risk for progression

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease.</p> <p>A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy.</p> <p>Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer.</p> <p>Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer.</p> <p>Design</p> <p>This is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01294358">NCT01294358</a></p

The evolution of reproductive isolation in a simultaneous hermaphrodite, the freshwater snail Physa

<p>Abstract</p> <p>Background</p> <p>The cosmopolitan freshwater snail <it>Physa acuta </it>has recently found widespread use as a model organism for the study of mating systems and reproductive allocation. Mitochondrial DNA phylogenies suggest that <it>Physa carolinae</it>, recently described from the American southeast, is a sister species of <it>P. acuta</it>. The divergence of the <it>acuta/carolinae </it>ancestor from the more widespread <it>P. pomilia </it>appears to be somewhat older, and the split between a hypothetical <it>acuta/carolinae/pomilia </it>ancestor and <it>P. gyrina </it>appears older still.</p> <p>Results</p> <p>Here we report the results of no-choice mating experiments yielding no evidence of hybridization between <it>gyrina </it>and any of four other populations (<it>pomilia, carolinae</it>, Philadelphia <it>acuta</it>, or Charleston <it>acuta</it>), nor between <it>pomilia </it>and <it>carolinae</it>. Crosses between <it>pomilia </it>and both <it>acuta </it>populations yielded sterile F1 progeny with reduced viability, while crosses between <it>carolinae </it>and both <it>acuta </it>populations yielded sterile F1 hybrids of normal viability. A set of mate-choice tests also revealed significant sexual isolation between <it>gyrina </it>and all four of our other <it>Physa </it>populations, between <it>pomilia </it>and <it>carolinae</it>, and between <it>pomilia </it>and Charleston <it>acuta</it>, but not between <it>pomilia </it>and the <it>acuta </it>population from Philadelphia, nor between <it>carolinae </it>and either <it>acuta </it>population. These observations are consistent with the origin of hybrid sterility prior to hybrid inviability, and a hypothesis that speciation between <it>pomilia </it>and <it>acuta </it>may have been reinforced by selection for prezygotic reproductive isolation in sympatry.</p> <p>Conclusions</p> <p>We propose a two-factor model for the evolution of postzygotic reproductive incompatibility in this set of five <it>Physa </it>populations consistent with the Dobzhansky-Muller model of speciation, and a second two-factor model for the evolution of sexual incompatibility. Under these models, species trees may be said to correspond with gene trees in American populations of the freshwater snail, <it>Physa</it>.</p

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Medicaid beneficiaries undergoing complex surgery at quality care centers: Insights into the Affordable Care Act

© 2016 Elsevier Inc. All rights reserved. Background Medicaid beneficiaries do not have equal access to high-volume centers for complex surgical procedures. We hypothesize there is a large Medicaid Gap between those receiving emergency general vs complex surgery at the same hospital. Methods Using the Nationwide Inpatient Sample, 1998 to 2010, we identified high-volume pancreatectomy hospitals. We then compared the percentage of Medicaid patients receiving appendectomies vs pancreatectomies at these hospitals. Hospital characteristics associated with increased Medicaid Gap were evaluated using generalized estimating equation models. Results A total of 602 hospital-years of data from 289 high-volume pancreatectomy hospitals were included. Median percentages of Medicaid appendectomies and pancreatectomies were 12.1% (interquartile range: 5.8% to 19.8%) and 6.7% (interquartile range: 0% to 15.4%), respectively. Hospitals that performed greater than or equal to 40 pancreatic resections per year had higher odds of having significant Medicaid Gap (odds ratio 2.3, 95% confidence interval 1.1 to 5.0). Conclusions Gaps exist between the percentages of Medicaid patients receiving emergency general surgery vs more complex surgical care at the same hospital and may be exaggerated in hospitals with very high volume of complex elective surgeries

Multimorbidity and access to major cancer surgery at high-volume hospitals in a regionalized era

© 2016 Elsevier Inc. All rights reserved. Background The Institute of Medicine has recently prioritized access of quality cancer care to vulnerable persons including multimorbid patients. Despite promotional efforts to regionalize major surgical procedures to high-volume hospitals (HVHs), little is known about change in access to HVH over time among multimorbid patients in need of major cancer surgery. We performed a time-trend appraisal of access of multimorbid persons to HVH for major cancer surgery within a large nationally representative cohort. Methods We identified 168,934 patients who underwent 6 major cancer surgeries from the Nationwide Inpatient Sample (1998 to 2010). Comorbidities were identified using Elixhauser\u27s method. HVHs were defined as hospitals of highest procedure volumes that treated 1/3 of all the patients. Logistic regression models and predictive margins were used to assess the adjusted effects of comorbidity on receiving major cancer surgeries at HVH. Results Of all, 45.7% of the patients had 2 comorbidities or more. Multimorbidity predicted decreased access to HVH for esophagectomy, total gastrectomy, pancreatectomy, hepatectomy, and proctectomy, but not for distal gastrectomy, after controlling for covariates. A comorbidity level by year interaction analysis also showed that little disparity existed for receiving distal gastrectomy at an HVH, whereas the predicted difference in probability of receiving any of the other 5 major cancer procedures remained prominent between the years 1998 and 2010. Conclusions In this large 12-year time-trend study, multimorbid cancer patients have sustained low access to HVH for major cancer surgery across many oncologic resections. These results continue to reinforce and highlight the need for policy targeted research and intervention aimed at improving these access gaps

Readmissions after major cancer surgery among older adults

© 2015 Elsevier Inc. All rights reserved. Background Decreasing readmissions has become a focus of emerging efforts to improve the quality and affordability of health care. However, little is known about reasons for readmissions after major cancer surgery in the expanding elderly population (65 years) who are also at increased risk of adverse operative events. We sought to identify (1) the extent to which older age impacts readmissions and (2) factors predictive of 30- and 90-day readmissions after major cancer surgery among older adults. Methods We identified 2,797 older adults who underwent 1 of 7 types of major thoracic or abdominopelvic cancer surgery within a large multihospital system from 2003 to 2012. Multivariate logistic regression analyses were conducted to identify predictors of 30- and 90-day readmission controlling for covariates. Results Overall 30- and 90-day readmission rates were 16% and 24% with the majority of readmissions occurring within 15-days of discharge. Principal diagnoses of 30-day readmissions included gastrointestinal, pulmonary, and infections complications. The 30-day readmissions were associated with \u3e2 comorbid conditions and 2 postoperative complications. Readmissions varied significantly according to cancer surgery type and across treating hospitals. Readmissions did not vary by increasing age. Factors associated with 90-day readmission were comparable to those observed at 30 days. Conclusion In this large, multihospital study of older adults, multiple morbidities, procedure type, greater number of complications, and the treating hospital predicted 30- and 90-day readmissions. These findings point toward the potential impact of hospital-level factors behind readmission. Our results also heighten the importance of assessing the influence of readmission on other important cancer care metrics, namely, patient-reported outcomes and the completion of adjuvant systemic therapies