Angiogenic switch in earliest stages of human colonic tumorigenesis.

BACKGROUND: Angiogenesis is activated in numerous physiological and pathological conditions. We examined whether new vessel formation exists in the earliest stages of colonic tumorigenesis. MATERIALS AND METHODS: Microvascular density (MVD) was examined in 176 formalin-fixed and paraffin-embedded aberrant crypt foci (ACF) dissected from macroscopically-normal mucosa obtained from patients with colorectal cancer. ACF were classified as non-hyperplastic, non-dysplastic (NH-ACF, n = 80), hyperplastic (H-ACF, n = 72) and dysplastic (D-ACF, n = 24). Mucosal strips were stained with methylene blue solution and screened under x 40 magnification for ACF. The identified ACF were microdissected and stained with an anti-CD-34 monoclonal antibody. MVD in ACF were compared to that of normal corresponding mucosa. RESULTS: The mean MVD for normal mucosa and ACF were 13.7 +/- 7.7 and 23 +/- 13, respectively. Microvessel counts increased in NH-ACF versus normal mucosa (18.7 +/- 10 vs. 13.7 +/- 7.7, p = 0.05), in H-ACF versus NH-ACF (24.8 +/- 14 vs. 18.7 +/- 10, p = 0.002) and in D-ACF versus H-ACF (31.7 +/- 10 vs. 24.8 +/- 14, p = 0.014). We further evaluated the effect of low-dose aspirin on MVD in ACF. No effect of aspirin on microvessel counts could be detected. CONCLUSION: Our data suggest that angiogenesis occurs in ACF which are the earliest morphologically identifiable preneoplastic and early neoplastic lesions in colonic mucosa. With progression from NH-ACF to D-ACF there is a progressive, statistically significant increase in MVD, suggesting active angiogenesis during the earliest steps of colorectal tumorigenesis.

Should aspirin therapy be withheld before insertion and/or removal of a permanent peritoneal dialysis catheter?

The necessity of withdrawal of aspirin [acetylsalicylic acid (ASA)] for fear of perioperative or postoperative bleeding in patients about to undergo surgery is as yet controversial. In this study we prospectively evaluated the effect of ASA on postoperative bleeding in end-stage renal failure patients who underwent insertion, removal, and/or replacement of a peritoneal dialysis (PD) catheter at our institution from November 1999 to March 2001. During the study period 52 of the above procedures were consecutively performed in 46 patients. Patients whose catheters were removed as a result of refractory peritonitis were excluded from the study. In all cases the PD catheter used was the coiled two-cuff Tenckhoff (NIPRO, Manchester, GA) catheter and the surgery was performed in the operating room under local anesthesia. No drains were left in the operating wound. Postoperative bleeding (wound hematoma or persistent oozing from the incision or exit site) was classified as either minor (requiring no professional intervention and/or blood replacement) or major [necessitating blood transfusion (> or = 1 unit red blood cells). Of the 52 procedures 29 (in 24 patients) were performed while the patient was receiving aspirin at the time of operation (aspirin group). The remaining 23 were without aspirin and constituted the control group. ASA dose was 100 mg/day in all but three who were on buffered ASA (325 mg/day). The groups were well matched with regard to age; sex; mean residual renal function; and preoperative international normalized ratio, activated partial thromboplastin time, and platelet count. In no case was there significant intraoperative bleeding. There were five (17.2%) and three (13.0%) minor bleeds in the aspirin group and control group, respectively. One major bleed occurred in the control group ending in an exploratory laparotomy. Of the nine bleeding complications six were observed after catheter removal. From these data we conclude that PD catheter insertion/removal can be safely performed under conventional low-dose aspirin therapy.