Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis.

BACKGROUND: Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis. METHODS: Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival. RESULTS: The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months). CONCLUSIONS: The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection.

Detection of active gastrointestinal hemorrhage with CT angiography: a 4(1/2)-year retrospective review.

PURPOSE: To retrospectively evaluate the performance of computed tomography (CT) angiography in the detection and localization of clinically active gastrointestinal (GI) hemorrhage of an unknown source. MATERIALS AND METHODS: Eighty-six CT angiograms were obtained in 74 patients with the clinical diagnosis of acute GI hemorrhage of an unknown source. Results of CT angiography were recorded, and the patients' electronic medical records were reviewed for documentation of subsequent interventional procedures performed within 24 hours of the reference CT angiogram to diagnose or control ongoing GI hemorrhage. Surgical, endoscopic, and final pathologic reports, if available, were reviewed. RESULTS: Twenty-two of the 86 CT angiograms (26%) were positive for active hemorrhage, with findings confirmed in 19 of the 22 cases (86%). Thirteen cases were confirmed with angiography, five cases were confirmed with surgery, and one case was confirmed with autopsy. Sixty-four of the 86 CT angiograms were negative, and 59 (92%) of the CT angiograms required no further intervention. These patients were discharged without incident. There were no cases in which CT angiography was negative and subsequent angiography within 24 hours was positive. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of CT angiography in the detection of active GI hemorrhage within this study population were 79%, 95%, 91%, 86%, and 92%, respectively. CONCLUSIONS: CT angiography provides valuable information that can be used to determine the appropriateness of catheter angiography and guide mesenteric catheterization if a bleeding source is localized. The authors' experience with this study cohort supports its use before angiography in those patients with acute GI bleeding of an unknown source who are being considered for catheter-directed intervention.

Acute gastrointestinal bleeding: emerging role of multidetector CT angiography and review of current imaging techniques.

Acute gastrointestinal bleeding is a common cause of hospitalization, morbidity, and mortality in the United States. The evaluation and treatment of acute gastrointestinal bleeding are complex and often require a multispecialty approach involving gastroenterologists, surgeons, internists, emergency physicians, and radiologists. The multitude of pathologic processes that can result in gastrointestinal bleeding, the length of the gastrointestinal tract, and the often intermittent nature of gastrointestinal bleeding further complicate patient evaluation. In addition, there are multiple imaging modalities and therapeutic interventions that are currently being used in the evaluation and treatment of acute gastrointestinal hemorrhage, each with its own strengths and weaknesses. Initial experience indicates that multidetector computed tomographic angiography is a promising first-line modality for the time-efficient, sensitive, and accurate diagnosis or exclusion of active gastrointestinal hemorrhage and may have a profound impact on the evaluation and subsequent treatment of patients who present with acute gastrointestinal bleeding.

Changes with malnutrition in the concentration of plasma vitamin D binding protein in growing rats.

The work presented here examines the possible effects of nutritional deficiencies on the characteristics of the plasma transport protein for vitamin D and its metabolites (vitamin D binding protein, DBP) in the growing rat. Deficiencies in both dietary protein intake and dietary energy intake may decrease the concentration of DBP in the circulation, although plasma DBP was not affected by dietary Ca deficiency. None of the dietary factors examined appears to influence the affinity of DBP for its major ligand, 25-hydroxycholecalciferol (25(OH)D(3)). Protein-deficient rats seemed to have difficulty in maintaining adequate concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)) in the circulation. The sensitivity of DBP to dietary protein and energy intake may constitute a novel mechanism that may help to explain the observed associations between malnutrition and the development of metabolic bone disease, through alterations to the cellular availability of vitamin D ligands to DBP.