Robert L. MacCarty

Natural history of untreated colonic polyps

The natural history of untreated colonic polyps is uncertain. A retrospective review of Mayo Clinic records from a 6-yr period just before the advent of colonoscopy identified 226 patients with colonic polyps greater than or equal to 10 mm in diameter in whom periodic radiographic examination of the colon was elected over excisional therapy. In all patients, follow-up of polyps spanned at least 12 mo (mean, 68 mo; range, 12-229 mo) and included at least two barium enema examinations (mean, 5.2; range, 2-17). During the follow-up period, 83 polyps (37%) enlarged. Twenty-one invasive carcinomas were identified at the site of the index polyp at a mean follow-up of 108 mo (range, 24-225 mo). Actuarial analysis revealed that the cumulative risk of diagnosis of cancer at the polyp site at 5, 10, and 20 yr was 2.5%, 8%, and 24%, respectively. In addition, 11 invasive cancers were found at a site remote from the index polyp during the same follow-up period. These data further support the recommendation for excision of all colonic polyps greater than or equal to 10 mm in diameter. Periodic examination of the entire colon is recommended in this group of patients to identify neoplasms arising at a site remote from the index polyp. Although this study has limitations inherent to any retrospective analysis, comparable prospective data are unlikely to be available in the future because of the current widespread availability of colonoscopy.

Simplified assessment of segmental colonic transit.

Transit times of radiopaque markers through the human gut were measured by published techniques and compared with a simplified method. Three sets of distinctive markers were ingested by 24 healthy persons on 3 successive days. In the first part of the study, daily abdominal x-rays were taken and individual stools were collected for radiography. Mouth-to-anus transits were assessed from the fecal output of markers and mean colonic and segmental colonic transits were calculated from the daily radiographs. These established methods were then compared with estimates of total colonic and segmental transits based on a single abdominal film, taken on the fourth day. The single-film technique correlated well with values obtained from the previous, but more inconvenient, methods. Using the simpler approach, colonic transit was assessed in 49 additional healthy subjects, for a total group of 73. Total colonic transit was 35.0 +/- 2.1 h (mean +/- SE); segmental transits was 11.3 +/- 1.1 h for the right colon, 11.4 +/- 1.4 h for the left colon, and 12.4 +/- 1.1 h for the rectosigmoid. Men had significantly shorter transits for the whole colon than did women (p less than 0.05), and this difference was apparent to some extent in the right (p = 0.06) and left colon (p = 0.07) but not in the rectosigmoid. Age did not influence transit significantly nor did a small dose of supplemental fiber. The technique is simple, convenient for clinical usage, and reduces the exposure to radiation to acceptable levels. There should be a role for this approach in the evaluation of colonic transit in selected patients.

Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps.

BACKGROUND & AIMS This study used a low lesion prevalence population reflective of the screening setting to estimate the sensitivity and specificity of computerized tomographic (CT) colonography for detection of colorectal polyps. METHODS This prospective, blinded study comprised 703 asymptomatic persons at higher-than-average risk for colorectal cancer who underwent CT colonography followed by same-day colonoscopy. Two of 3 experienced readers interpreted each CT colonography examination. RESULTS Overall lesion prevalence for adenomas >/=1 cm in diameter was 5%. Seventy percent of all lesions were proximal to the descending colon. With colonoscopy serving as the gold standard, CT colonography detected 34%, 32%, 73%, and 63% of the 59 polyps >/=1 cm for readers 1, 2, 3, and double-reading, respectively; and 35%, 29%, 57%, and 54% of the 94 polyps 5-9 mm for readers 1, 2, 3, and double-reading, respectively. Specificity for CT colonography ranged from 95% to 98% and 86% to 95% for >1 cm and 5-9-mm polyps, respectively. Interobserver variability was high for CT colonography with kappa statistic values ranging from -0.67 to 0.89. CONCLUSIONS In a low prevalence setting, polyp detection rates at CT colonography are well below those at colonoscopy. These rates are less than previous reports based largely on high lesion prevalence cohorts. High interobserver variability warrants further investigation but may be due to the low prevalence of polyps in this cohort and the high impact on total sensitivity of each missed polyp. Specificity, based on large numbers, is high and exhibits excellent agreement among observers.

Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease☆☆☆

BACKGROUND & AIMS Recurrence of Crohns disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohns disease after surgical resection is performed. METHODS One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months. RESULTS The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group. CONCLUSIONS Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohns disease after surgical resection is performed.

GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man

The newly recognized class of 5-hydroxytryptamine receptors (5HT3) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT3 antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P<0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT3 receptors may be involved in the regulation of colonic transit in healthy man.

Detection of flat lesions in the colon with CT colonography

AbstractBackground:We investigated whether flat lesions of the colon could be detected on computed tomographic colonography (CTC). Methods: CTC and conventional colonoscopy were performed on 547 consecutive patients. A subset of 22 polyps was described as flat on colonoscopy (n= 16) or CTC (n= 6) and are the basis of this report. CTC was performed with a standard technique (5-mm collimation, 3-mm reconstruction intervals). Patients were scanned in supine and prone positions. Examinations were randomly assigned and reviewed in a blinded fashion by two of three radiologists. Prospective interpretations were recorded. All patients had conventional colonoscopy, which served as the gold standard. Results: Twenty-two flat lesions ranging from 0.4 to 3.5 cm were histologically classified as adenomatous (n= 8) or hyperplastic (n= 14). The sensitivities for detecting all flat lesions and flat adenomas by each reviewer were 43% and 100%, 65% and 100%, and 15% and 13%, respectively. “Double reading” resulted in detection of 68% of all lesions and 100% of adenomas. Of the seven hyperplastic polyps missed by both reviewers, four were identified retrospectively. Conclusion: Flat lesions of the colon represent an important source of false negative CTC examinations. Awareness of their morphology can assist radiologists in finding most of these challenging lesions.

Prospective trial of penicillamine in primary sclerosing cholangitis

We evaluated the therapeutic efficacy of penicillamine in primary sclerosing cholangitis. In a randomized, prospective, double-blind trial, 39 patients received penicillamine (250 mg t.i.d.) and 31 received a placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, radiologic, and hepatic histologic features. Although a predictable cupruresis and a decrease in levels of hepatic copper were achieved in patients taking penicillamine, there was no beneficial effect on disease progression within 36 mo or on overall survival. Progressive symptoms, deterioration in serial hepatic laboratory values, or histologic progression on sequential liver biopsy specimens were similar in both groups, occurring in greater than 80% of the entire study population. The development of major side effects led to the permanent discontinuation of penicillamine in 21% of the patients taking the drug. We conclude that the use of penicillamine in primary sclerosing cholangitis is not associated with a beneficial effect on disease progression or survival, and has considerable toxicity. The study also suggests that primary sclerosing cholangitis is a progressive disease in many patients.

Preoperative staging of rectal carcinoma by computed tomography and 0.15t magnetic resonance imaging: Preliminary report

A prospective study was done on 34 patients using magnetic resonance imaging (MRI) and computed tomography (CT) preoperatively to stage patients with known rectal carcinoma. The study was done to determine the accuracy and clinical usefulness of CT and MRI. The Thoeni staging method was used. Twenty-four of 30 cases were staged correctly by CT. Sixteen of 27 were staged correctly by MRI. CT detected lymph node metastases in six of 15 cases with one false-positive. MRI detected lymph node metastases in two of 15 patients with one false-positive. CT was the preferred examination, and was useful in some cases. These cases included patients with small tumors who were considered for local excision and patients with extensive disease who were candidates for preoperative or intraoperative radiation treatment. MRI demonstrated extensive disease, as did CT in our later cases.

Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis

The effect of proctocolectomy on the primary sclerosing cholangitis that frequently is associated with chronic ulcerative colitis in patients with both conditions is unknown. We have studied prospectively the progression of clinical, biochemical, cholangiographic, and hepatic histologic features in 45 patients with both primary sclerosing cholangitis and chronic ulcerative colitis to compare these variables in the 20 patients who had undergone proctocolectomy with the 25 who had not. The two groups were similar initially with regard to clinical, biochemical, cholangiographic, and hepatic histologic findings. All patients were followed for a minimum of 1 yr and overall duration of follow-up was similar in both groups (4.1 vs. 3.9 yr). Clinically, new onset of hepatomegaly, splenomegaly, esophageal varices, and ascites did not differ in patients with and without proctocolectomy. Biochemically, the serial changes in bilirubin, alkaline phosphatase, aspartate aminotransferase, prothrombin time, and albumin were similar. Histologic progression on liver biopsy did not differ between groups, nor did changes on serial cholangiograms. Proctocolectomy also had no effect on survival. We conclude that proctocolectomy for chronic ulcerative colitis has no beneficial effect on the primary sclerosing cholangitis in patients with both diseases.

Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease.

We identified and analyzed 45 patients with asymptomatic primary sclerosing cholangitis to better understand the natural history of this disease. Disease progression was monitored at regular intervals for the development of symptoms and physical signs as well as changes in liver biochemistry, cholangiography, and liver histology. During a median follow-up of 75.2 mo, 34 patients (76%) had evidence of disease progression. Fourteen patients (31%) developed liver failure which resulted in death or referral for liver transplantation. For patients with primary sclerosing cholangitis, survival curves computed using the Kaplan-Meier method were significantly worse than expected when compared to age-, sex-, and race-specific survival rates for the United States north central population (p less than 0.001). These findings indicate that primary sclerosing cholangitis is generally a progressive disease with considerable morbidity and mortality even when detected before the onset of symptoms.