High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

Gastroenterological aspects of primary aorto-enteric fistulae (PAEF).

BACKGROUND: Gastrointestinal haemorrhage associated with a primary aorto-enteric fistula (PAEF) is potentially lethal. The aims of this study were to discuss the gastrointestinal characteristics of PAEF, to identify associated laboratory findings and to discuss pitfalls in pre-operative diagnostics. METHODS: Medical and surgical charts of patients with PAEF. RESULTS: Individuals with PAEF (n = 7, 68 +/- 5 years) presented with multiple episodes of haematemesis (n = 5) and/or melaena (n = 6), all in the presence of aneurysmatic aortas (5.4 +/- 1.0 cm). Laboratory testing reflected a state of acute (C-reactive protein, CRP, 94 +/- 12 mg/ml; leucocyte counts, 12.0 +/- 1.0.10(9)/L) and chronic inflammation (erythrocyte sedimentation rate, ESR 52 +/- 5 mm/hr). Prior to operation, a gastroduodenoscopy correctly diagnosed only one PAEF patient and CT scans identified 3. Two patients exsanguinated in a two-week waiting period prior to corrective surgery. CONCLUSIONS: Recurrent gastrointestinal blood loss in the presence of an aneurysm requires urgent gastroduodenoscopic evaluation. Computer tomography is sensitive in providing direct or circumstantial evidence of a fistula. A combined acute and chronic inflammatory state associated with PAEF is reflected by elevations of CRP and ESR. A PAEF is a unique form of ruptured aneurysm, and this entity mandates imminent radiological and surgical consultation aimed at instituting aggressive treatment within hours.

Bacterial fermentation of fructooligosaccharides and resistant starch in patients with an ileal pouch-anal anastomosis.

Patients with large bowel disease may undergo ileal pouch-anal anastomosis, in which the colon is removed and part of the distal ileum is used to construct a pelvic reservoir. Competence of the ileal pouch to ferment carbohydrates is associated with the absence of pouchitis. However, the extent to which bacterial fermentation takes place and whether it is affected by diet are unclear. We investigated fermentation of two nondigestible carbohydrates, fructooligosaccharides and resistant starch, in 15 healthy patients with an ileal pouch by using a placebo-controlled crossover design (with glucose as the placebo). Apparent fermentability of fructooligosaccharides was 83%; that of resistant starch was 46%. Resistant starch increased fecal excretion of butyrate by 69% whereas fructooligosaccharides reduced excretion of amino acid-derived isobutyrate by 94% and of isovalerate by 77%. Fructooligosaccharides also significantly increased fecal weight (651 compared with 541 g/d) and breath-hydrogen excretion (286 compared with 85 ppm x h). Bacterial fermentation of nondigestible carbohydrates in pouches takes place to an appreciable extent and in a substrate-specific manner. The relation between such fermentation and inflammation of the pouch (pouchitis) deserves study.

Plasma cholecystokinin levels and gallbladder volumes after proctocolectomy with ileal pouch-anal anastomosis.

BACKGROUND: The colon and rectum contain regulatory peptides in mucosal endocrine cells, which suggests a hormonal role. In animal studies colectomy leads to increased plasma levels of cholecystokinin. Little is known about the effects of proctocolectomy with ileal pouch-anal anastomosis on the release of cholecystokinin in human beings. Therefore we studied the effects of this procedure on fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels and gallbladder volumes. METHODS: Ten patients who had undergone proctocolectomy with ileal pouch-anal anastomosis and 12 healthy volunteers participated in the study. Fasting and postprandial plasma cholecystokinin levels and gallbladder volumes were studied for 3 hours at 15-minute intervals. In a second experiment plasma cholecystokinin levels were measured before and during intravenous administration of bombesin in six patients with ileal pouch and five healthy volunteers. RESULTS: Fasting plasma cholecystokinin levels were higher (p < 0.05) in patients with ileal pouch-anal anastomosis (2.6 +/- 0.3 pmol/L) compared with controls (1.7 +/- 0.2 pmol/L). Integrated postprandial plasma cholecystokinin levels were also distinctly higher (p < 0.01) in patients (978 +/- 126 pmol/L.180 min) than in controls (588 +/- 60 pmol/L.180 min). Mean fasting gallbladder volume was significantly (p < 0.01) decreased in patients with ileal pouch-anal anastomosis (18 +/- 2 ml) compared with controls (28 +/- 2 ml). Postprandial gallbladder emptying as measured by percentage change was similar in both groups. After infusion of bombesin, integrated plasma cholecystokinin responses were higher (p < 0.05) in patients (161 +/- 20 pmol/L.20 min) than in controls (90 +/- 12 pmol/L.20 min). CONCLUSIONS: Fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels are elevated in patients with ileal pouch-anal anastomosis compared with controls. Fasting gallbladder volume is decreased after ileal pouch-anal anastomosis. These findings suggest that the colon contains a factor that inhibits the release of cholecystokinin.

Clinical and physiological aspects of ileal pouch-anal anastomosis.

Proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for severe chronic ulcerative colitis and familial polyposis coli because the entire colonic mucosa is removed while anal function can be preserved and the necessity for permanent ileostomy is eliminated. Long-term functional results are generally gratifying, as defecation frequency and degree of incontinence are acceptable in most patients. Pouchitis, however, a non-specific inflammation of the ileal reservoir, is a major long-term complication occurring in a considerable number of patients. The etiology of pouchitis is unknown. Since pouchitis occurs more frequently or even exclusively in ulcerative colitis patients it is assumed that pouchitis is a novel manifestation of inflammatory bowel disease. However, bacterial overgrowth in the ileal pouch may also play a pathogenetic role. Chronic inflammation and villous atrophy of varying severity is found in virtually all pouches. Acute inflammatory changes and ulceration are associated with pouchitis.

Subcutaneous emphysema of the lower extremity secondary to a perforated esophageal carcinoma.

The psoas muscle is a potential pathway of disease from the mediastinum to the leg. We describe a case of subcutaneous emphysema of the lower extremity due to a perforated esophageal carcinoma in a 58-year-old man.

Spontaneous regression of hepatocellular carcinoma.

A 72-year-old Caucasian woman suffered from histologically-proven advanced hepatic cancer, for which she received no treatment. She had been a regular drinker for a long time. Serologic markers for hepatitis B and C were negative. In spite of her poor prognosis, she remained in good clinical condition and at 14 months of follow up the hepatocellular carcinoma could not be visualised any more radiologically. At that time the serum alpha foetoprotein concentration was normal. At present, 28 months after diagnosis, the patient is doing well and her tumour still appears to be in complete spontaneous remission.

Postoperative and long-term results of ileal pouch-anal anastomosis for ulcerative colitis and familial polyposis coli.

The immediate postoperative and long-term functional results of 51 ulcerative colitis patients and 21 familial polyposis patients who underwent ileal J-pouch-anal anastomosis were compared in this study. The incidence of postoperative complications requiring reoperation was not statistically different in both groups. The mean daily stool frequency was significantly higher in colitis patients. Pouchitis occurred in 44% of colitis patients but not in polyposis patients (P < 0.005). Symptoms of pouchitis included bloody diarrhea, urgency, abdominal pain, weight loss, fever, and arthritis. Six colitis patients required pouch excision because of intractable pouchitis. The overall pouch excision rate was 22% in ulcerative colitis patients and 5% in familial polyposis patients. Patient satisfaction was good in 46% of ulcerative colitis patients and 76% of polyposis patients (P < 0.05). Our data demonstrate that the long-term outcome of ileal pouch-anal anastomosis is more favorable in polyposis patients than in colitis patients. Pouchitis is a major long-term complication occurring exclusively in colitis patients.

Postprandial conjugated and unconjugated serum bile acid levels after proctocolectomy with ileal pouch-anal anastomosis.

In patients with ileal pouch-anal anastomosis (IPAA) bile acid reabsorption may be impaired, and stasis may lead to deconjugation and dehydroxylation of bile acids as a result of bacterial overgrowth. We therefore studied fasting and postprandial conjugated and unconjugated serum levels of cholic (CA), chenodeoxycholic (CDCA), and deoxycholic acid (DCA) in 11 patients who underwent proctocolectomy with IPAA and in 11 healthy controls. Fasting levels of conjugated DCA but not CA and CDCA were significantly lower in IPAA patients. Postprandially, conjugated bile acid levels were significantly lower in IPAA patients. Postprandial unconjugated CA levels were significantly higher and CDCA levels tended to be higher in IPAA patients, whereas unconjugated DCA levels were lower in IPAA patients. These data suggest that reabsorption of conjugated bile acids is impaired after IPAA; deconjugation of bile acids may result from bacterial overgrowth secondary to stasis in the pouch; and dehydroxylation of bile acids is decreased after proctocolectomy with IPAA.

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects.

Colorectal cancer is a disease of elderly subjects. A decreased ileal absorption of bile acids in elderly subjects may lead to an increased exposure of the colonic mucosa to secondary bile acids. This may contribute to an enhanced risk of colorectal cancer. In this study fasting and postprandial conjugated and unconjugated serum levels of cholic, chenodeoxycholic, and deoxycholic acid in 12 elderly and 12 younger subjects were investigated. Intestinal transit time, gallbladder emptying and jejunal bacterial flora were also studied in both age groups. Fasting levels of conjugated and unconjugated serum bile acids were similar in both age groups. Postprandial levels of all individual conjugated bile acids increased to a significantly higher extent in the younger subjects. Postprandial unconjugated serum bile acid levels did not differ significantly between both age groups, although unconjugated deoxycholic levels tended to increase to higher levels in the elderly. Results of jejunal bacterial counts, gallbladder emptying and intestinal transit time were similar in both groups. These data suggest that conjugated bile acids are reabsorbed less effectively in elderly subjects.

Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. METHODS: Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. RESULTS: Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). CONCLUSION: PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY.

Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance. AIM: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated. METHODS: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between. RESULTS: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens. CONCLUSION: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.

Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses.

BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis. RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups. CONCLUSIONS: Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.