Peter J. McDonald

Double-blind randomised controlled trial of effect of metronidazole on pain after day-case haemorrhoidectomy

BACKGROUND Haemorrhoidectomy is commonly an inpatient procedure because patients and doctors worry about postoperative pain. Day-case haemorrhoidectomy (DCH) is possible if patient anxiety is addressed and postoperative pain and bowel function are managed. Pain sometimes increases a few days after haemorrhoidectomy, possibly because of secondary infection. We studied the effect of metronidazole on pain after DCH. METHODS We randomly assigned 40 consecutive patients admitted for DCH metronidazole 400 mg (n = 20) or placebo (n = 20) three times daily, both for 7 days. All patients received lactulose from 2 days before surgery for 2 weeks. Diathermy DCH was performed without pedicle ligature or anal-canal dressing, and a diclofenac suppository was administered at the end of the procedure. Patients were discharged on the same day with diclofenac, 0.2% glyceryl-trinitrate ointment, lactulose, a telephone number to call for queries in emergencies, and an outpatient appointment. Patients took paracetamol or Co-dydramol (dihydrocodeine and paracetamol) as required; they completed linear analogue charts every day and completed questionnaires on satisfaction at 1 and 6 weeks. FINDINGS 34 patients had all three major piles excised, of whom seven had additional division and reconstruction of the posterior skin bridge. Overall, both groups of patients experienced less pain than expected, except on days 3 and 4. Patients in the metronidazole group had significantly less pain than those in the placebo group on days 5, 6, and 7 (p = 0.004, p = 0.02, and p = 0.006). Median time to return to work or normal activity was 15 days (range 12-28) in the metronidazole group and 18 days (7-34) in the placebo group (p = 0.009). The patient satisfaction score was higher in the metronidazole group than in the placebo group at 1 week (p = 0.005). INTERPRETATION Prophylactic metronidazole in diathermy DCH suppressed secondary pain around days 5-7 and increased patient satisfaction and earlier return to work.

Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate

BACKGROUND Topical application of glyceryl trinitrate (GTN) ointment heals chronic anal fissures, providing an alternative to the traditional first line treatment of surgical sphincterotomy. AIMS To determine the most effective dose of topical GTN for treatment of chronic anal fissures and to assess long term results. METHODS Seventy consecutive patients with chronic anal fissure, were randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%, in a double blind study. RESULTS After eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). No significant difference was seen between the two active treatments. Headaches were reported by 72% of patients on GTN compared with 27% on placebo (p<0.001). Maximum anal sphincter pressure reduced significantly from baseline by GTN treatment (p=0.02), but not placebo (p=0.8). Mean pain scores were lower after treatment with GTN compared with placebo (NS). Of fissures healed with placebo 43% recurred, compared with 33% of those healed with 0.2% GTN and 25% healed with escalating dose GTN (p=0.7). CONCLUSIONS GTN is a good first line treatment for two thirds of patients with anal fissure. An escalating dose of GTN does not result in earlier healing. Significant recurrence of symptomatic fissures and a high incidence of headaches are limitations of the treatment.

Up-Regulation of Collagen and Tissue Inhibitors of Matrix Metalloproteinase in Colonic Diverticular Disease

PURPOSEThickening of the muscularis propria is a key pathologic feature of colonic diverticulosis but its cause is unknown. This study was designed to investigate the role of collagens, matrix metalloproteinases, and tissue inhibitor of metalloproteinases in colonic diverticulosis.METHODSCollagen content was determined by Sircol Collagen Assay and standard van Gieson staining. Messenger-RNA expression for matrix metalloproteinases and tissue inhibitor of metalloproteinase was analyzed by quantitative competitive reverse transcription polymerase chain reaction. Immunohistochemical staining was performed to localize tissue inhibitor of metalloproteinases in sections.RESULTSIn mucosa and submucosal layer, complicated diverticular disease samples had a higher collagen content than uncomplicated disease, which in turn had higher levels than controls. There was an 18-fold increase in tissue inhibitor of metalloproteinase-1 mRNA, and a threefold increase in tissue inhibitor of metalloproteinase-2 mRNA in complicated diverticulosis compared with controls. In the muscularis propria, the amount of total soluble collagen also was higher in both uncomplicated and complicated diverticulosis samples than in the controls. Tissue inhibitor of metalloproteinase-1 and metalloproteinase-2 mRNA was significantly increased in diverticulosis compared with controls. Macrophage-like and fibroblast-like cells stained strongly positive for tissue inhibitor of metalloproteinases in the submucosa, serosa, and muscularis propria and in areas around the blood vessels.CONCLUSIONSColonic diverticulosis is associated with altered collagen content and tissue inhibitor of metalloproteinases expression. These factors may play a role in remodeling the gut wall in this condition.

Perforating and nonperforating Crohn's disease

Four hundred eighty-six patients who have had resections for Crohns disease at the Cleveland Clinic were reviewed. The patients were categorized by indication for surgery into three groups: perforating (P) (135 patients), nonperforating (NP) (278 patients), and miscellaneous (M) (77) patients. One hundred ninety-four patients had two or more resections and 56 underwent a third resection. Patients were no more likely to have the same indication for surgery at the time of the second resection (P=25 percent; NP=44 percent; M=57 percent) or the third resection (P=11 percent; NP=65 percent; M=55 percent). There was also no difference in the interval between resections for the P and NP groups. The lack of agreement between resections suggests that the categorization of patients into P and NP groups does not facilitate prediction of the nature of recurrent disease. The concept of aggressive perforating and indolent nonperforating Crohns is not substantiated by this study.

Angiogenesis and hypoxic factors in colorectal cancer

Colorectal cancer is a common cause of cancer death in the developed world. Angiogenesis is a key factor in the growth and dissemination of malignant disease, including colorectal cancer, with significant implications for its clinical management. Over the past few years, significant inroads have been made into understanding the mechanisms and processes of angiogenesis in various malignancies. It is postulated that, with a greater understanding of the angiogenic mechanisms that govern tumor growth, anti-angiogenic compounds may be introduced to combine with conventional means to combat the growth and spread of malignant disease. This review discusses the mechanisms involved in tumor angiogenesis, highlighting its influence in colorectal cancer.