Colonoscopic injection for murine solid cecal cancer model.

BACKGROUND: The validity of current animal colon cancer models is questionable. This study was performed to evaluate whether colonoscopic injection of a murine colon cancer cell line into the cecal wall of immunocompetent rats leads to a solid tumor. METHODS: A bolus of bowel prep was given to BD-IX rats. Anesthesia was injected intraperitoneally. Video fiberscope allowed for irrigation and suction. Failure was inability to reach/inject cecum. Procedure was performed by four surgeons; 100 µl of colon tumor cell suspension (DHD/K12TRb; 10 million cells in 0.1 ml) was injected into cecal wall with 23-gauge needle placed on 3 mm wire resulting in a blister. Rats were allowed to recover. Solid tumor growth was measured at scheduled necropsy at 4 weeks. Sample size (107 rats: type I error 0.05; power 80%) was based on a pilot study. Data were presented as median (range). RESULTS: A total of 107 male BD-IX retired breeders weighing 356 g (range 256-432 g) underwent colonoscopy with submucosal injection of cecal wall. A single solid cecal cancer was identified in 98 (91.5%) rats at scheduled necropsy. Histology confirmed adenocarcinoma with tumor size of 4 mm (range 2.6-8.4 mm). Peritoneal carcinomatosis was found in ten (9.3%) rats. Distant metastases were found in three (2.8%) rats. Complications occurred in four (3.8%) rats: two aspirations and two colon perforations. CONCLUSIONS: A solid cecal tumor without carcinomatosis or metastasis has been developed by colonoscopic injection of a rat colon cancer cell line in 79% of immunocompetent rats.

Failure to rescue in the era of the lung allocation score: The impact of center volume.

BACKGROUND: Failure to Rescue (FTR) is a valuable surgical quality improvement metric. The aim of this study is to assess the relationship between center volume and FTR following lung transplantation. METHODS: Using the database of the United Network for Organ Sharing (UNOS) all adult, primary, isolated lung recipients in the United States between May 2005 and March 2016 were identified. FTR was defined as operative mortality after any of five specific complications. FTR was compared across terciles of transplantation centers stratified based on operative volume. RESULTS: 17,185 lung recipients met study criteria. The composite FTR rate (Death following at least one complication) was 20.7%. Following stratification by volume, FTR rates increased from high to middle tercile centers (19.3% vs. 23.0%). Multivariate logistic regression models suggested an independent relationship between higher center volume and lower FTR rates (p < 0.001). CONCLUSION: Higher volume lung transplantation centers have lower rates of failure to rescue.

Failure to Rescue Contributes to Center-Level Differences in Mortality After Lung Transplantation.

BACKGROUND: The clinical response to postoperative complications after lung transplantation (LTx) may contribute to mortality differences among transplantation centers. The ability to avoid mortality after a complication-failure to rescue (FTR)-may be an effective quality metric in LTx. METHODS: The United Network for Organ Sharing database was queried for adult, first-time, lung-only transplantations from May 2005 to December 2015. Transplantation centers were stratified into equal-sized terciles on the basis of observed operative mortality rates. Several postoperative complications were identified, including stroke, acute rejection, acute kidney injury requiring hemodialysis, airway dehiscence, and extracorporeal membrane oxygenation 72 hours after surgery. Rates of FTR were calculated as the number of operative mortalities in patients who had complications divided by the number of patients who had any postoperative complications. RESULTS: Our study population included 16,411 LTx operations performed at 69 transplantation centers. LTx centers were stratified into terciles with average perioperative mortality of 4.0% for low-mortality centers, 6.9% for intermediate-mortality centers, and 12.4% for high-mortality centers. Low-mortality centers had slightly lower complication rates (low, 15.0% vs intermediate, 17.1% vs high, 19.1%; P < .001). Differences in FTR rate were significantly more pronounced (low, 14.9% vs intermediate, 23.9% vs high, 34.2%; P < .001). Multivariable logistic regression and generalized linear models demonstrated an independent association between high FTR rates and high mortality in LTx (P < .001). CONCLUSIONS: Differences in rates of FTR contribute significantly to per-center variability in mortality after LTx. FTR can serve as a quality metric to identify opportunities for improvement in management of perioperative adverse events.

Long-term follow-up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease.

On the basis of studies in experimental animals demonstrating that AdVEGF121, an E1(-)E3(-) serotype 5 adenovirus coding the 121 isoform of vascular endothelial growth factor (VEGF), could mediate the generation of new blood vessels and reverse coronary ischemia, a clinical study of direct myocardial administration of AdVEGF121 was initiated in patients with late-stage, diffuse coronary artery disease. This study provides long-term (median, 11.8 years) follow-up on these patients. From 1997 to 1999, AdVEGF121 was administered by direct myocardial injection to an area of reversible ischemia in 31 patients with severe coronary disease, either as an adjunct to conventional coronary artery bypass grafting (group A) or as minimally invasive sole (MIS) therapy, using a minithoracotomy (group B). There was no control group; the study participants served as the control subjects. The 5- and 10-year survival was 10 of 15 (67%) and 6 of 15 (40%) for the group A patients, and 11 of 16 (69%) and 5 of 16 (31%) for group B sole therapy patients, respectively. In comparison, maximal medical therapy in comparable groups in the literature have a 3- to 5-year survival rate of 52 to 59%. For the survivors, the angina score for group A was 3.4±0.5 at time 0 and 1.9±1.0 at last follow-up, and for group B it was 3.4±0.6 and 2.0±1.1, respectively. The incidences of malignancy and retinopathy were no greater than that expected for the age-matched general population. We conclude that adenovirus-mediated VEGF direct myocardial administration to patients with severe coronary artery disease is safe, and future larger trials are warranted to assess efficacy.