The cancer stem cell (CSC) hypothesis of tumor genesis suggests that unlike most cancer cells within tumor CSC resist chemotherapy and can regenerate various cell types in tumor thereby causing relapse. Hence drugs that selectively target CSC may offer great promise for cancer therapy especially when combined with chemotherapy. Current treatment options for colorectal cancer (CRC) and other gastrointestinal (GI) tumors rely on combination of surgical resection, cytotoxic and targeted drugs. Recent findings showed that metformin, an ant diabetic drug was associated with a significantly lower risk of CRC (0.63 [0.47 - 0.84]; P = 0.002) in patients with type 2 diabetes. We therefore hypothesize that administration of metformin will reduce CSC.Patients with CRC and other GI cancers undergoing resection were enrolled. Metformin was administered at 500 mg orally twice daily for up to 14 days and terminated 24 hours, prior to planned surgery. Both tumor and normal tissue was procured. Adverse events (AEs) were graded according to NCI CTCAE Version 3.0. Primary objective was to establish the safety of administering metformin prior to resection. Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry.A total of 10 patients (4 Male; 6 Female) received metformin. Grade 3 AEs included anemia, hypoalbuminemia, alanine aminotransferase elevation, abdominal pain and nausea but none of these were related to metformin. No hypoglycemia and lactic acidosis were observed. No unexpected post-operative complications were witnessed. Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin.Our pilot study showed feasibility of metformin before surgery in GI cancers and indicated impact on CSC. This preliminary data warrants further investigation in a larger randomized placebo-control study to assess these markers and their correlation with survival.
Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome.HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P
The era of managed care has spawned a national debate over the allocation of health care resources. We hypothesized that routine postjejunostomy jejunogram rarely provides additional clinical information or changes patient management and, therefore, is unwarranted. We retrospectively reviewed the charts of 128 consecutive patients undergoing feeding jejunostomy tube insertion between January 1995 and December 1996. All patients had postinsertion jejunograms. Eighty-five (66%) of the jejunograms were performed after operative insertion of the jejunostomy, and 43 (33%) were performed after percutaneous reinsertion of a previously placed jejunostomy. Data extracted from the charts include age, sex, indication for jejunogram, length of time prior jejunostomy was in place at time of reinsertion, and results of jejunogram. There were no patients (0%) with misplaced jejunostomy or extravasation of dye, as noted on jejunogram. There were no management changes implemented as a result of jejunogram readings (P < <0.05). The use of routine jejunogram after operative insertion or reinsertion of a prior jejunostomy that has become dislodged or occluded does not alter patient management, incurs unnecessary costs, and, therefore, is unwarranted.
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