Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer.

BACKGROUND: Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question. PATIENTS AND METHODS: This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann-Whitney U and Fisher's exact tests. Survival information was summarized using standard Kaplan-Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals. RESULTS: A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group's (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001). CONCLUSIONS: The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.

Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

BACKGROUND: Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI2)-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. METHODS: BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI2-dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. RESULTS: As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI2 production. CONCLUSIONS: In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI2 pathway.

Innovation-Oriented Medical School Curricula: Review of the Literature.

Innovation and entrepreneurship (I&E) programs in medical education have become available as medical schools recognize the need to train forward-thinking physicians. There is considerable diversity in the design and implementation of these curricula, which represents a challenge and possibly serves as a deterrent for the development of additional I&E programs. A comprehensive search of medical school I&E programs and review of all Association of American Medical Colleges member websites (n = 171) were conducted. This review sought to (1) identify all American and Canadian allopathic medical schools with I&E curricula, (2) evaluate their structure/integration in the context of medical education, (3) outline core learning themes, and (4) describe the evaluative metrics. Information was collected through published or publicly available websites and through a questionnaire sent to identified I&E program leaders. Twenty-eight I&E-oriented medical education programs were identified from 26 schools; all of the programs integrated faculty leadership with backgrounds in medicine, engineering, and/or business/entrepreneurship. Of the programs, 57% (16/28) had been launched within the past four years and 75% (21/28) based program enrollment on a selective application process. Nearly all (27/28) incorporated lecture series and/or hands-on modules as a teaching technique. The most prevalent metric was completion of a capstone project (22/28; 79%). At least 15.2% (26/171) of American and Canadian allopathic medical schools include the option for students to participate in an I&E curriculum-based program. This review can be used to help medical school faculty with developing I&E curricula.

Prognostic models for stage I-III esophageal cancer: a comparison between existing calculators.

BACKGROUND: Determining the best approach for esophageal cancer and predicting accurate prognosis are critical. Multiple studies evaluated characteristics associated with overall survival, and several prediction models have been developed. This study aimed to evaluate existing models and perform external validation of selected models. METHODS: A retrospective investigation of a multi-site institutional enterprise for patients with a diagnosis of esophageal cancer between 2013-2014 was performed. Selected survival prediction models included the Roswell Park Comprehensive Cancer Center (RPCCC) calculator, Oregon Health & Science University (OHSU) calculator, and two nomograms published by Shapiro et al. and Sun et al. One-year overall survival, level of agreement, and performance for each model were evaluated. RESULTS: A total of 104 patients were included and used to assess the prediction models. One-year overall survival was 0.76. Different calculators tended to rank patients similarly; however, they did not agree on predicted overall survival. The least disparity in correlation was observed between OHSU and Shapiro calculators. Shapiro's model achieved the highest performance [area under the curve (AUC) =0.63]. CONCLUSIONS: Selected models showed fair results in estimating individual overall survival, although none achieved a high performance. While these tools may support the decision-making process for esophageal cancer patients, their implementation in clinical practice requires improved refinement to optimize their clinical utility.

Does Surgical Intervention Help with Neurological Recovery in a Lumbar Spinal Gun Shot Wound? A Case Report and Literature Review.

The third leading cause of spinal injuries are gunshot wounds to the spine, accounting for 15.2% of all spinal cord injuries. Treatment for gunshot wound spinal cord injuries (GSWSCI) remains variable, with indications for surgery being controversial. There is no clear evidence or guidelines that can help spine surgeons decide and direct surgical intervention. With the paucity of available literature, we report an interesting case of a gunshot injury to the lumbar spine at L1-L2, discuss the presentation and outcome, and evaluate relevant literature. A 27-year-old incarcerated male patient presented with a conus cauda equina asymmetrical injury involving the lower extremities and required initial medical stabilization in the intensive care unit (ICU). He subsequently underwent delayed surgical treatment with decompression and fragment resection at L1-L2. The patient improved neurologically to the American Spinal Injury Association (ASIA) Classification D and eventually regained nearly all lower extremity neurological function. Despite considerable evidence favoring the conservative management of GSWSCI and the absence of guidelines or recommendations on surgical interventions, our case report demonstrates that surgical intervention in appropriately selected patients can yield good recovery of neurological function and improvement in the quality of life. The key remains careful patient selection, the appropriate location of the retained fragment, and the extent of neurological injury that occurred. We feel surgical decompression and fragment removal, along with debridement, can result in good neurological recovery and long-term outcomes.