Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer.

366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5-fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year. A significantly higher incidence of leuco-granulocytopenia was observed in the arm A (5 FU alone) inducing more frequent dose delays and adaptations as well as levamisole's withdrawal. Then dose-intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher (631 +/- 107 vs 557 +/- 99; p < 0.001). The median follow-up in the study was 4.5 years. Relapse free (RFS) and overall survivals (OAS) were prolonged in the 5 FU alone group peculiarly in those patients who had not been randomised for portal treatment. Curves diverged progressively with longer follows-up (at 8 years; RFS in arm A: 67-71% vs 59-53% in arm B; OAS in arm A: 72-74% vs 56-46% in arm B). Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone. The results are discussed in the light of other recent adjuvant trials. Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer. Levamisole may no longer be recommended in this setting.

Toxic effects of colloids in the intensive care unit.

Colloid fluid solutions are frequently used as plasma volume expanders in the critically ill. As a group, these nonblood volume replacement solutions have in common a number of potential adverse effects. Intravascular volume overload, dilutional coagulopathy, extravascular extravasation across leaky capillary membranes, and anaphylactoid reactions may all occur with administration of any colloid. In addition, individual agents have unique toxic effects. Renal dysfunction has been associated with dextran 40, myocardial depression with albumin, hypotension with purified plasma protein, and hyperamylasemia with hetastarch. Because no ideal colloidal solution exists, knowledge of type, severity, and clinical significance of adverse effects is important in determining the appropriate plasma volume expander and monitoring its effects.

Intrathecal effects of daclizumab treatment of multiple sclerosis.

OBJECTIVES: We previously reported that daclizumab, a humanized monoclonal antibody against CD25, reduced contrast-enhancing lesions (CEL) in patients with multiple sclerosis (MS) who were suboptimal responders to interferon-ß and that this response correlated with expansion of CD56(bright) NK cells. These data have been reproduced in a placebo-controlled multicenter trial (CHOICE study). The current study investigates whether daclizumab monotherapy reduces CEL in untreated patients with relapsing-remitting MS (RRMS) and the effects of daclizumab on the intrathecal immune system. METHODS: Sixteen patients with RRMS with high inflammatory activity were enrolled in an open-label, baseline-vs-treatment, phase II trial of daclizumab monotherapy for 54 weeks and followed by serial clinical and MRI examinations and immunologic biomarkers measured in the whole blood and CSF. RESULTS: The trial achieved predefined outcomes. There was an 87.7% reduction in brain CEL (primary) and improvements in Multiple Sclerosis Functional Composite (secondary), Scripps Neurologic Rating Scale, and Expanded Disability Status Scale (tertiary) outcomes. There was significant expansion of CD56(bright) NK cells in peripheral blood and CSF, with resultant decrease in T cells/NK cells and B cells/NK cells ratios and IL-12p40 in the CSF. Surprisingly, CD25 Tac epitope was equally blocked on the immune cells in the CSF and in peripheral blood. CONCLUSIONS: Daclizumab monotherapy inhibits formation of MS plaques in patients with RRMS and immunoregulatory NK cells may suppress activation of pathogenic immune responses directly in the CNS compartment. CLASSIFICATION OF EVIDENCE: The study provides Class III evidence that daclizumab reduces the number of contrast-enhancing lesions in treatment-naive patients with RRMS over a 54-week period.

Acute mesenteric vein thrombosis and pancreatitis. A rare association.

This article presents a case of acute mesenteric vein thrombosis with small bowel infarction associated with pancreatitis. Although a rare occurrence, the authors suggest this diagnosis should be considered as a possible complication of pancreatic inflammation.

Adjuvant intraportal chemotherapy for Dukes B2 and C colorectal cancer also receiving systemic treatment: results of a multicenter randomized trial. Groupe Régional d'Etude du Cancer Colo-Rectal (Belgium).

In a randomized trial, the authors evaluated the possible adjuvant activity of intraportal chemotherapy (with 5-fluorouracil 500 mg/m2/day in continuous infusion for 7 days and mitomycin C 10 mg/m2 at day 7) administered after surgery to half of the patients who underwent a full resection for Dukes B2 or C colorectal cancer. The procedure appeared manageable and safe. Two hundred and sixty patients were initially randomized, among whom 173 were finally considered as fully evaluable after having completed six courses of systemic chemotherapy. The reasons for withdrawal were basically tumoral ones and patients or doctors compliance. After a median follow-up of 4.5 years, no difference could be observed in the patients evolution assessed as relapses or deaths rate, or as relapse-free (at 5 years: 68% in the portal treatment group versus 70% in the control group) or overall survival (at 5 years: 76 versus 74%). The frequency of hepatic metastases (21 versus 18%) was also similar in both groups.