Andreas Sieg

Is PillCam COLON capsule endoscopy ready for colorectal cancer screening? A prospective feasibility study in a community gastroenterology practice.

OBJECTIVES:Colorectal cancer (CRC) screening with colonoscopy was introduced into the National Cancer Prevention Program in Germany in 2002. As compliance for screening is low (around 3% per year), colon capsule endoscopy (CCE) could be an alternative approach. In this study, feasibility and performance of CCE were evaluated in comparison with colonoscopy in ambulatory patients with special attention to a short colon transit time.METHODS:CCE was prospectively tested in ambulatory patients enrolled for colonoscopy who presented for screening or with positive fecal occult blood test. Study subjects underwent colon preparation and ingested the capsule in the morning. Colonoscopy was performed after excretion of the capsule. Colonoscopy and CCE were performed by independent physicians who were blinded to the results.RESULTS:In total, 38 patients were included. One patient was excluded because the capsule remained in the stomach during the entire period of examination. Another patient had limited time and the procedure had to be stopped when the capsule was still in the transverse colon. We therefore report the results of 36 patients (30 men and 6 women; mean age 56 years, range 23–73 years) who successfully completed CCE and the conventional colonoscopy examination. The capsule was excreted within 6 h in 84% of the patients (median transit time 4.5 h). If oral sodium phosphate was excluded from the preparation, the colon transit time increased to a median of 8.25 h. In total, 7 of 11 small polyps (<6 mm) detected by colonoscopy were identified by CCE. One small polyp detected by CCE was not identified by colonoscopy. In this series, no large polyps were found. One CRC was detected by both methods. The mean rates of colon cleanliness (range from 1=excellent to 4=poor) in the cecum (2.1), transverse colon (1.6), and in the descending colon (1.5) were significantly better than in the rectosigmoid colon (2.6), and the overall mean rate during colonoscopy was significantly better than during CCE. No adverse effects occurred.CONCLUSIONS:CCE appears to be a promising new modality for colonic evaluation and may increase compliance with CRC screening. To achieve a short colon transit time, sodium phosphate seems to be a necessary adjunct during preparation. The short transit time is a prerequisite to abandon the delay mode of the capsule. With an undelayed PillCam COLON capsule, a “pan-enteric” examination of the gastrointestinal tract would be possible. Further studies are needed to improve the cleanliness, especially in the rectum and to evaluate the method as a potential screening tool.

Elevated serum levels and reduced immunohistochemical expression of thrombomodulin in active ulcerative colitis

BACKGROUND & AIMS The pathogenesis of ulcerative colitis and Crohns disease is still unclear. Vascular injury has been suggested as a potential pathogenetic mechanism. Serum thrombomodulin is a marker of endothelial cell injury. The aim of this study was to determine the relevance of increased serum thrombomodulin levels for assessing disease activity in inflammatory bowel disease. As a potential cause of serum thrombomodulin level increase, the loss of local vascular thrombomodulin expression was investigated immunohistochemically. METHODS Thrombomodulin levels were determined by enzyme-linked immunosorbent assay in sera from patients with ulcerative colitis, Crohns disease, Schistosoma mansoni infection, and infectious diarrhea and controls. The vascular expression of thrombomodulin was investigated immunohistochemically in fresh frozen transmural specimens of normal, Crohns, and ulcerative colitis bowel samples. RESULTS Significantly elevated serum thrombomodulin levels were only detected in active ulcerative colitis and infectious diarrhea complicated by septicemia. A marked and general loss of vascular endothelial cell thrombomodulin expression was found immunohistochemically in inflamed bowel tissues. Graded by a newly established thrombomodulin staining index, this was significantly more marked in ulcerative colitis than Crohns disease. CONCLUSIONS Serum thrombomodulin proved to be a novel marker of disease activity in ulcerative colitis closely related to local vascular endothelial cell damage, which might be a relevant pathophysiological feature of ulcerative colitis.

Adverse events requiring hospitalization within 30 days after outpatient screening and nonscreening colonoscopies.

BACKGROUND The incidence of adverse events (AEs) is a crucial factor when colonoscopy is considered for mass screening, but few studies have addressed delayed and non-GI AEs. OBJECTIVES To investigate the risk of AEs requiring hospitalization after screening and nonscreening colonoscopies compared with control subjects who did not undergo colonoscopy. DESIGN Retrospective matched cohort. SETTING Statutory health insurance fund in Germany. PATIENTS A total of 33,086 individuals who underwent colonoscopy as an outpatient (8658 screening, 24,428 nonscreening) and 33,086 matched controls who did not undergo colonoscopy. INTERVENTIONS Outpatient screening and nonscreening colonoscopies. MAIN OUTCOMES MEASUREMENTS Risk of AEs (perforation, bleeding, myocardial infarction, stroke, splenic injury, and others) requiring hospitalization within 30 days after colonoscopy/index date and risk differences between the group that underwent colonoscopy and the group that did not. RESULTS The incidence of perforation was 0.8 (95% confidence interval [CI], 0.3-1.7) and 0.7 (95% CI, 0.4-1.1) per 1000 screening and nonscreening colonoscopies, respectively. Hospitalizations because of bleeding occurred in 0.5 (95% CI, 0.1-1.2) and 1.1 (95% CI, 0.8-1.7) per 1000 screening and nonscreening colonoscopies, respectively. The incidence of myocardial infarction, stroke, and other non-GI AEs was similar in colonoscopy and control groups. No splenic injury was observed. Those with AEs generally had a higher mean age and comorbidity rate than the overall study population. LIMITATIONS The analysis relies on health insurance claims data. CONCLUSIONS This study provides further evidence of the safety of colonoscopy in routine practice with regard to delayed and non-GI AEs. Hospitalizations because of the investigated AEs were uncommon or rare for both screening and nonscreening colonoscopies.

Alcohol dehydrogenase in the human colon and rectum.

Alcohol dehydrogenase (ADH) activities were measured in rectal biopsies from 55 patients (28 males, 27 females aged 22-81 years), in colonic biopsies from 19 patients (10 males, 9 females aged 21-81 years) and in three surgical specimens. All patients had normal mucosa as determined by light microscopy. The activity of rectal ADH was comparable to gastric ADH activity and did not exhibit any significant gender effect (5.5 +/- 1.1 vs. 6.7 +/- 1.0 nmol/mg protein x min; nonsignificant). No significant correlation was found between age and rectal ADH activity. Compared to ADH activities in other colonic segments, rectal ADH activity was found to be significantly increased (ascending colon: 3.9 +/- 0.7 nmol/mg protein x min; p < 0.05; transversal colon: 3.4 +/- 1.1 nmol/mg protein x min; p < 0.05; descending colon 2.3 +/- 0.4 nmol/mg protein x min; p < 0.001; rectum 6.1 +/- 0.8 nmol/mg protein x min). This higher activity of ADH in the rectum could result in increased acetaldehyde levels after alcohol administration and could therefore play a role, at least in part, in the ethanol-associated rectal cocarcinogenesis.

First clinical trial of a newly developed capsule endoscope with panoramic side view for small bowel: A pilot study

Capsule endoscopy is the first‐line diagnostic technique for the small bowel. However, the inability to visualize the duodenal papilla is an inherent limitation of this method. In the present study, we evaluated feasibility of a newly developed CapsoCam SV1 capsule.

Biliary Excretion of Procollagen Type III Peptide in Healthy Humans and in Patients With Alcoholic Cirrhosis of the Liver

Serum concentrations of procollagen type III peptide are found to be elevated in liver disease and to correlate with fibrosis activity in liver tissue. These elevated serum levels may be due to enhanced synthesis, decreased excretion, or release from deposits of the propeptide in connective tissue. To quantitatively investigate the excretion of procollagen type III peptide, we studied its presence in the bile and urine of 10 healthy controls and 11 patients with alcoholic cirrhosis of the liver. Biliary excretion rates of procollagen propeptide were determined by the duodenal perfusion method. The serum concentrations of procollagen type III peptide were 2.5 +/- 0.5 ng/ml in the healthy controls and 33.6 +/- 6.8 ng/ml in the patients with cirrhosis. Procollagen type III peptide was found in the bile; the healthy controls excreted 0.4 +/- 0.07 nmol/h and the cirrhotics excreted 0.98 +/- 0.27 nmol/h. A fragment of the procollagen propeptide, Col 1, was excreted in urine; the healthy controls excreted 0.25 +/- 0.04 nmol/h, and the cirrhotics excreted 0.11 +/- 0.03 nmol/h. These data demonstrate that the biliary excretion of procollagen type III peptide represents a quantitatively important pathway.

Safety analysis of endoscopist‐directed propofol sedation: A prospective, national multicenter study of 24 441 patients in German outpatient practices

Since 2008, there exists a German S3‐guideline allowing non‐anesthesiological administration of propofol for gastrointestinal endoscopy. In this prospective, national, multicenter study, we evaluated the safety of endoscopist‐administered propofol sedation (EDP) in German outpatient practices of Gastroenterology.

Detection of colorectal neoplasms by the highly sensitive hemoglobin-haptoglobin complex in feces.

Abstract Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity, but hemoglobin is degraded during its transport through the gastrointestinal tract. We compared the hemoglobin test to a newly developed immuno-chemiluminometric (ILMA) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation. From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml samples from a single stool; there were no dietary restrictions. The sensitivity for detecting colorectal carcinomas proved 87% with hemoglobin. With the hemoglobin-haptoglobin complex it was 87% at a cutoff level of 1.5 µg/g feces, 83% at 2.0 µg/g feces, and 78% at 2.5 and 3.0 µg/g feces. The sensitivity for detecting large adenomatous polyps was 54% with hemoglobin, 76% with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 µg/g feces, 73% with the hemoglobin-haptoglobin complex at 2.0 and 2.5 µg/g feces, and 65% with the hemoglobin-haptoglobin complex at 3.0 µg/g feces. The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 µg/g stool. The specificity for hemoglobin (99%) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 µg/g feces (96%). Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity. Its use for colorectal cancer prevention is currently being evaluated in a screening study.

Hepatic Secretion of Bilirubin and Biliary Lipids in Patients with Alcoholic Cirrhosis of the Liver

In patients with cirrhosis of the liver elevated bilirubin concentrations in the plasma could be the result of decreased bilirubin excretion or an overproduction of bilirubin with insufficient excretion of the increased amounts of bilirubin. Under steady state conditions with constant serum bilirubin concentrations bilirubin synthesis equals biliary and urinary bilirubin excretion. In the present study in 10 healthy volunteers and 11 patients with alcoholic cirrhosis of the liver and serum bilirubin concentrations of 7.0 +/- 1.9 mg/dl the biliary excretion of bilirubin was studied by the intestinal perfusion method and compared with the excretion of bile lipids. Biliary excretion of bilirubin in the cirrhotics was 38.7 +/- 8.8 mumol/h, the 10 healthy controls excreted 17.9 +/- 0.9 mumol/h bilirubin. Only minor amounts of bilirubin were excreted in urine. In 4 of the 11 cirrhotics 51Cr-red blood cell half-lives were studied revealing ongoing hemolysis. Bilirubin production calculated from red cell life span was identical to biliary excretion of bilirubin with an error less than 5%. The data indicate that in patients with alcoholic cirrhosis of the liver serum concentrations of bilirubin may be elevated due to overproduction of bilirubin and a concomitant decrease of the biliary transport capacity of bilirubin.

Gilbert's syndrome: diagnosis by typical serum bilirubin pattern

Analysis of serum unconjugated and conjugated bilirubin fractions by routine diazo procedures does not allow a definite diagnosis of Gilberts syndrome. By the alkaline methanolysis procedure of Blanckaert followed by thin-layer chromatography we were able to discriminate Gilberts syndrome even in the presence of normal serum bilirubin concentrations from healthy subjects, patients with chronic persistant hepatitis and patients with chronic hemolysis. The relative proportion of unconjugated bilirubin in serum was 95 +/- 2% in patients with Gilberts syndrome (n = 28), 84 +/- 5% in healthy subjects (n = 29), 75 +/- 6% in patients with chronic persistant hepatitis (n = 7) and 85 +/- 3% in patients with chronic hemolysis (n = 9). The difference between Gilberts syndrome and the control groups with normal or elevated serum bilirubin was highly significant (p less than 0.001). In Gilberts syndrome, unconjugated bilirubin ranged between 90 and 99%, in healthy subjects between 72 and 90%, in patients with chronic persistant hepatitis between 68 and 85% and in patients with chronic hemolysis between 81 and 89% of total. An overlap was only seen in one patient with Gilberts syndrome and in 2 healthy subjects at the 90% level. We conclude that in most patients with Gilberts syndrome provocation tests are no longer necessary.