[Colonoscopy. In investigation, treatment and control of gastrointestinal diseases]. / Kolodkopi. I utredning, behandling og kontroll av gastrointestinale sykdommer.

Colonoscopy is the initial examination for patients with manifest or occult rectal bleeding, inflammatory bowel disease and colorectal polyps. In addition to polypectomy, colonoscopy is useful in decompression of adynamic colonileus and laser palliation of intractable tumours. In adenoma patients controls should be limited to high risk patients, i.e. those with large and multiple tubular adenomas, villous adenomas, multiple hyperplastic polyps (> 30), and first degree relatives of patients with colorectal carcinomas. Control after radical surgical treatment of colorectal cancer is offered during the first two years after the operation and to persons younger than 40 years. The efficacy of control programmes for hereditary nonpolyposis colorectal cancer families have to be evaluated in controlled series. Rectosigmoidoscopies could probably replace some total colonoscopies to examine ulcerative colitis patients for cancer, since cancer usually occurs in the distal colon. Complications are rare after diagnostic and therapeutic colonoscopies, but perforation, bleeding and injury to surrounding organs can be experienced.

[Gastrointestinal diseases--the place of endoscopy in examination, treatment and control]. / Gastrointestinale sykdommer--endoskopiens plass i utredning, behandling og kontroll.

Dyspepsia, defined as discomfort in the upper abdomen after a meal, is the most frequent indication for gastroscopy. Such dyspepsia was earlier considered to be an element of the ulcer disease, Moynihan's disease. Whether examination showed an ulcer or not was of minor importance as long as the treatment was the same. Similar opinions still contribute to a negative attitude towards the need to obtain a more specific diagnosis, especially in young patients where risk of cancer is low. We are of the opinion that dyspepsia is a non-specific symptom of several different diseases, and that curative therapy is often available today provided the diagnosis is correct. It is therefore necessary to make an active effort to diagnose the cause of the dyspepsia, also in younger persons. In practice, this means that there are many different indications for gastroscopy. We try, however, to practice a restrictive policy with respect to control gastroscopy.

Effect of wheat fibre supplements on duodenal ulcer recurrence.

In the present study the prophylactic effect of concentrated wheat fibre on duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or placebo was added to an ordinary Norwegian diet for 1 year after endoscopic healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37 patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side effects were infrequently seen. A concentrated wheat fibre supplement seems to have no preventive effect when given to duodenal ulcer patients living on a traditional Norwegian diet.

Increased fecal eosinophil cationic protein in inflammatory bowel disease.

Eosinophil cationic protein (ECP) is a cytotoxic substance released by eosinophilic granulocytes. Serum and body-fluid levels may be elevated in some allergic and inflammatory conditions characterized by heavy infiltration of eosinophils. ECP has not previously been measured in feces. Because pronounced infiltration with eosinophils is often seen in ulcerative colitis, we examined fecal excretion of ECP in 29 patients with active inflammatory bowel disease (IBD) and in 10 healthy persons. Mean fecal ECP levels were more than 14 times higher in the patients than in the healthy persons (p < 0.001). Fecal ECP was similarly elevated in ulcerative colitis and Crohn's disease. During storage, ECP in feces was relatively stable. Steroid treatment may suppress fecal ECP excretion. The possible value of fecal ECP as an IBD activity parameter warrants further studies. ECP may also be involved in the pathogenesis of IBD.

Effectiveness and acceptability of three bowel cleansing regimens.

The effectiveness and acceptability of three colon cleansing regimens for colonoscopy were compared in a prospective study in 271 patients stratified as in- and out-patients and randomly assigned to either I) a diet and Senna laxative (X-prep), combined with a saline enema (n = 88); II) 41 of a polyethylene glycol electrolyte lavage solution (Golytely) (n = 90); or III) a combined regimen of Cascara-Salax laxative (PicoSalax) and 1.51 Golytely (n = 93). Patients and colonoscopists indicated independently their overall impression of palatability and convenience and the completeness of the preparation, respectively, on 0- to 10-cm visual analogue scales. No differences were found between the regimens, either for the patients' impression of palatability or for the convenience of the preparation. A significantly cleaner colon was obtained with regimen II in outpatients than with regimen I (p = 0.02), whereas no differences were found either between regimens I and III or between regimens II and III. With regimen I, II, and III, 14%, 8%, and 12% of the patients, respectively, had scores indicating inadequate preparation. Outpatients (n = 175) had significantly cleaner colon than inpatients (n = 96) (p less than 0.001). In conclusion, no clinically important differences were found between the three bowel preparation regimens. An oral irrigation regimen is acceptable to the patients and may be preferable because it provides more flexibility to the endoscopic laboratory.

[Crohn disease. Diagnosis and treatment]. / Crohns sykdom. Diagnostikk og behandling.

Crohn's disease was the topic of a meeting of gastroenterologists in Bergen last year with the purpose of working out consensus guidelines for diagnosis and treatment of this chronic disease. The most important diagnostic procedures are radiology, gastrointestinal endoscopy and histopathology. Transmural, segmental involvement is characteristic, whereas granulomas are found in only 25% of biopsy specimens. Corticosteroids are effective in active Crohn's disease located to all parts of the intestine, whereas sulfasalazine and metronidazole are most effective in Crohn's colitis. Azathioprine and 6-mercaptopurine should be reserved for patients with chronic active disease that is unresponsive to steroids or requires higher doses. Azathioprine also has a prophylactic effect. Surgery is indicated in patients whose quality of life is diminished in spite of adequate medical treatment, in patients with bowel or ureter stenosis, fistula or abscess, and in patients with acute perforation or toxic dilatation. Limited resection is recommended, and stricture plasty can be alternative to extensive resection.

Endoscopic ultrasonographic findings in benign and malignant diseases of the stomach.

Endoscopic ultrasonographic (EUS) imaging was performed to examine the depth, extent and tissue character of gastric lesions in nine patients. Two patients with linitis plastica had endoscopically normal gastric mucosa, but a thickened gastric wall showing loss of normal layer structure on examination with EUS. In four patients the internal structure of gastric polyps could be imaged, showing the relationship to the gastric wall layers. EUS demonstrated the depth of gastric ulcers in three patients. Abnormalities in the echogenicity of the gastric wall adjacent to the ulcers were observed. EUS provides a three-dimensional endoscopic and ultrasonographic picture of the gastric mucosal surface and underlying wall, providing structural information not otherwise obtainable without examining the resected tissue.

Enzyme activities in the gastric mucosa in duodenal ulcer patients.

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.

[Endoscopic hemostasis in hemorrhagic peptic ulcer. A review and pilot study of local thrombin injection combined with systemic fibrinolysis inhibition (with tranexamic acid)]. / Endoskopisk hemostase ved blødende ulcus pepticum. En oversikt og en pilotstudie med lokal injeksjon av trombin kombinert med systemisk fibrinolysehemning (med tranexamsyre).

Today, most upper GI-haemorrhages can be handled without surgery. We discuss the available endoscopic haemostatic methods. Injection therapy seems to be as effective as laser-, heater probe- and bipolar electrocoagulation, and is often preferred because the equipment is inexpensive. In a pilot study of 37 patients with haemorrhage from peptic ulcer (13 with active bleeding and 24 with stigmata of recent hemorrhage) we injected thrombin in the ulcer base and treated the patients systemically with an antifibrinolytic drug (tranexamic acid) for five days. Endoscopic follow-up revealed stigmata of recent haemorrhage in 23 patients on day 1 and in eight patients on day 5. "Blood in stomach" was seen in eight patients on day 1 and in two patients on day 5. Four patients had clinical signs of rebleeding, but only one of them needed operation (definite hemostasis 97%). There were no obvious side effects of the treatment. Contrary to other endoscopic methods, local injection of thrombin does not damage the normal mucosa. However, the method has not been sufficiently explored as yet, and cannot be recommended without strict control and follow-up measures. Early control endoscopy seems to be a sensitive way of monitoring haemostasis.

Enzyme activities in the duodenal mucosa in duodenal ulcer patients.

The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU.

Whipple's disease. Demonstration of a persisting monocyte and macrophage dysfunction.

A patient with Whipple's disease has been followed up for 4 years. Primary involvement was limited to the small intestines, and accumulation of periodic acid-Schiff-positive material, containing typical more or less intact bacillary bodies, was demonstrated within macrophages of affected tissue. After initial oxytetracycline treatment and clinical remission, the patient relapsed, with multiorgan affections. The antibiotic regimen was changed to chloramphenicol, followed by continuous trimethoprim-sulfamethoxazole. Flow cytometric studies showed persisting impairment of monocyte and macrophage intracellular degradation of bacteria during all the 4 years tested. After relapse, reduced activity of several brush border enzymes was demonstrated in distal duodenal biopsy specimens. After 17 months of continuous trimethoprim-sulfamethoxazole therapy complete clinical remission, regression of histopathologic abnormalities, and restoration of duodenal enzyme activities had occurred. The results demonstrate a persisting dysfunction of mononuclear phagocytes from a patient with Whipple's disease, suggesting a primary abnormality of cell-mediated immunity which may promote the susceptibility to the causative bacillus.

Flow cytometry of biopsy specimens from ulcerative colitis, colorectal adenomas, and carcinomas.

The cellular DNA distribution pattern in biopsy specimens from all main segments and neoplastic lesions of the large bowel, obtained from 16 patients with ulcerative colitis, 22 with adenomas, 17 with carcinoma, and 20 controls, has been studied by the flow cytometry technique. Aneuploid cell populations were demonstrated in three patients with ulcerative colitis (19%), in six with tubular adenomas (27%), and in nine with carcinoma (53%). Aneuploid cells were found in all cases of poorly differentiated adenocarcinomas. The fractional number of cells with a DNA content corresponding to the DNA synthetic and G2M phases of the cell cycle was defined as the 'proliferative index' (PI). In controls PI and its complementary G1 cell fraction varied significantly (p less than 0.005) between the segments, on the basis of analysis of variance. When compared two by two, PI was significantly higher in the sigmoid colon (p less than 0.01) and rectum (p less than 0.05) than in the ascending part. The PI of uninvolved mucosa from adenoma patients with diploid histograms was significantly higher than that in controls (p less than 0.01), ulcerative colitis (p less than 0.05), and cancer patients (p less than 0.05), when dependence on segment was taken into account.

Enzyme activities in biopsy specimens from large-bowel mucosa in colorectal adenomas and carcinomas.

Biopsy specimens from 29 adenomas, 17 adenocarcinomas, and 6 synchronous adenomas in cancer patients and from uninvolved mucosa of all main segments of the large bowel were examined histologically and assayed for a series of organelle marker enzymes. Six enzymes--lactase, sucrase, alkaline phosphatase, 5'-nucleotidase, acid phosphatase, and N-acetyl-beta-D-glucosaminidase--showed less activity in adenomas than in adjacent uninvolved mucosa and in specimens from controls. Cancer tissue had higher gamma-glutamyltransferase and lower lactase, alkaline and acid phosphatases, and N-acetyl-beta-D-glucosaminidase activities than specimens from uninvolved mucosa in cancer patients and control patients. Enhanced alkaline phosphatase and N-acetyl-beta-D-glucosaminidase activities were seen in uninvolved mucosa of cancer patients as compared with those of adenoma and control patients. Evidence has been found for multienzyme analysis to identify adenomas with signs of malignant transformation and carcinomas with poor prognosis.

Enzyme activities in biopsy specimens from large-bowel mucosa in ulcerative colitis.

Biopsy specimens from all main segments of the large bowel, obtained from 16 patients with ulcerative colitis, were examined histologically and assayed for a series of organelle marker enzymes. Compared with a control group of 20 subjects, significant dependence on diagnosis was demonstrated for N-acetyl-beta-D-glucosaminidase (p less than 0.01) and monoamine oxidase (p less than 0.05), when dependence on segment was taken into account. Significant correlation with degree of inflammatory cell infiltration was seen in the gamma-glutamyltransferase (p less than 0.0001), 5'-nucleotidase (p less than 0.05), and monoamine oxidase (p less than 0.0001) activities. Patients with dysplasia had lower activity of N-acetyl-beta-D-glucosaminidase (p less than 0.05) than those without dysplasia when evaluated by two-way analysis of variance modified for repeated measurements. Multienzyme analysis could distinguish between specimens with dysplasia and aneuploidy and those without when discriminant analyses were used.

Enzyme activities in human gastric cancer and polyps.

Enzyme activities and the protein to DNA ratio in gastric biopsy specimens from patients with gastric cancer and polyps have been measured and compared with values from controls. In uninvolved mucosa in antral gastric cancer increased activities were found for several membrane and lysosomal enzymes, whereas the monoamine oxidase (MAO) activity was decreased (p less than 0.0005). In cancer tissue the MAO was also decreased (p less than 0.0003). In uninvolved mucosa in gastric cancer of the body, most membrane and lysosomal enzyme activities were increased. In the cancer tissue itself an increase in membrane enzyme activities was found for several enzymes, whereas the MAO activity was decreased (p less than 0.0001). Differences between activities in specimens from the gastric mucosa in patients with gastric polyps and those in controls were less pronounced than between gastric cancer and controls. A discriminant analysis, using the enzymes most sensitive to establish correct diagnosis, could identify normal gastric mucosa in 85-95%, atrophic gastritis in 56-63%, and uninvolved mucosa in gastric cancer in 66-78%.

Enzyme activities in human gastric mucosa in gastritis and resected stomachs.

Biopsy specimens from the antral and body part of the stomach were studied for a range of marker enzymes in 11 patients with superficial gastritis, 9 patients with atrophic gastritis, and 31 Billroth-II-resected patients and compared with activities found in controls with normal gastric mucosa. In the antral part of the stomach increased gamma-glutamyltransferase activity was found in superficial (p less than 0.01) and atrophic gastritis (p less than 0.05), whereas monoamine oxidase activity was decreased in superficial (p less than 0.01) and atrophic gastritis (p less than 0.05). In the body part, increased activity of gamma-glutamyltransferase (p less than 0.01) and acid-beta-glucuronidase (p less than 0.01) was found in superficial gastritis. In atrophic gastritis increased activities for lactase (p less than 0.01), alkaline phosphatase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), gamma-glutamyltransferase (p less than 0.05), 5'-nucleotidase (p less than 0.01), N-acetyl-beta-D-glucosaminidase (p less than 0.05), and acid-beta-glucuronidase (p less than 0.01) were found. Specimens from the gastric remnant showed an enzyme activity pattern similar to that seen in the body in atrophic gastritis, apart from a significantly decreased monoamine oxidase activity (p less than 0.004). Specimens with dysplasia in the gastric remnant showed decreased monoamine oxidase activity when compared with specimens without dysplasia (p less than 0.01).

Enzyme activities in biopsy specimens from human gastric mucosa.

The distribution of a series of marker enzymes in the gastric mucosa was studied by analysis of homogenized biopsy specimens from the lesser and greater curvature of the body and antrum, respectively, obtained from 11 control patients. The activities varied significantly between the regions for the membrane enzymes lactase (p less than 0.0001), neutral-alpha-glucosidase (p less than 0.005), alkaline phosphatase (p less than 0.01), leucyl-beta-naphthylamidase (p less than 0.005), and 5'-nucleotidase (p less than 0.0001) and the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (p less than 0.0001) and acid beta-glucuronidase (p less than 0.0001), using analysis of variance modified for repeated measurements. When paired comparisons between regions were evaluated, the enzyme activities of the antral regions were significantly higher than those of the body stomach. The activities of gamma-glutamyltransferase, acid phosphatase, and the mitochondrial enzyme monoamine oxidase did not alter between regions, nor did the protein to DNA ratio. The demonstrated biochemical distinction between antrum and body of the stomach may be explained by different physiological and histological properties of the two parts.

Longitudinal distribution of mucosal enzymes in the human large bowel.

The distribution of a series of mucosal enzymes along the large bowel was studied by analysis of homogenized biopsy specimens from five different segments, obtained from 20 control patients. The activities varied significantly between the segments for the membrane enzymes lactase (p less than 0.005), alkaline phosphatase (p less than 0.0005), leucyl-beta-naphthylamidase (p less than 0.0001), and 5'-nucleotidase (p less than 0.001) and the mitochondrial enzyme monoamine oxidase (p less than 0.0005) when tested by analysis of variance modified for repeated measurements. When paired comparisons between segments were evaluated, the enzyme activities of the proximal large bowel were significantly higher than those of distal segments. The levels of sucrase, neutral-alpha-glucosidase, gamma-glutamyltransferase, and lysosomal enzymes remained unchanged throughout the large intestine, as did the protein to DNA ratio. The results are compatible with the theory that different segments of the large bowel have different functions.