Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies.

BACKGROUND/AIMS: Previous studies have shown that secretory losses in patients with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be suppressed by the somatostatin analogue, octreotide, thus facilitating fluid balance. However, the hormone also has antianabolic actions that may interfere with the use of infused amino acids. METHODS: Amino acid metabolism, pancreatic enzyme synthesis and secretion, and mucosal protein turnover were measured by primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation with pentagastrin and cholecystokinin 8. RESULTS: In comparison with normal healthy controls, baseline measurements of amino acid metabolism were normal in patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were elevated. Octreotide therapy improved fluid balance but suppressed gut hormone (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses. CONCLUSIONS: Octreotide improves fluid balance in patients who have undergone jejunostomy but reduces the use of amino acids for splanchnic protein synthesis. This may interfere with the physiological process of adaptation to intestinal resection.

Histamine leukocytosis. II. Source of histamine leukocytosis.

Leukocytes were labelled by intravenous injection of tritiated thymidine (3H-thymidine) in dogs to discover the source of the increased number of neutrophils in the circulating blood after injection of histamine in beeswax. Dogs with normal hemograms were given 1.0 mCi/kg of 3H-thymidine alone, and in different sequences, with histamine in beeswax. When 3H-thymidine was given during maintained histamine leukocytosis, labelled granulocytes appeared in and disappeared from the blood earlier than in control tests and the number of labelled cells was greater in the histamine-treated animals. Administration of histamine in beeswax 3 days after injection of 3H-thymidine also induced the premature appearance and disappearance of labelled neutrophils in the circulating blood. It was concluded that leukocytosis induced by the chronic action of histamine is due to 1) stimulated proliferation and differentiation of neutrophil precursor cells in the bone marrow and 2) the release of mature leukocytes from the bone marrow.

Radical resection for carcinoma of the ampulla of Vater.

One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients. The 5- and 10-year survival rates were 34% and 25%, respectively. Eight patients died of tumor recurrence more than 5 years after resection. Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin. In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival. Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma.

Prevalence of Helicobacter pylori in specific forms of gastritis. Further evidence supporting a pathogenic role for H. pylori in chronic nonspecific gastritis.

Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest that H. pylori may cause this form of gastritis. However, there is little or no information on the prevalence of H. pylori in specific forms of gastritis. Our hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates of H. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence of H. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence that H. pylori is a primary pathogenic factor in chronic nonspecific gastritis.

Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic gastritis and gastric acid secretion.

Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.

[14C]urea breath test for diagnosis of Helicobacter pylori.

H. pylori is a potent urease producer, a characteristic that has been exploited in the development of the [14C]- and [13C]urea breath tests. The prevalence of H. pylori infection also is known to increase with advancing age; however, the individual patient's age has not routinely been considered when interpreting urea breath test results. The aim of this study was to validate a short, age-adjusted [14C]urea breath test for use in diagnosing H. pylori infections. Forty-one subjects (28 volunteers, 13 patients) underwent esophagogastroduodenoscopy with biopsies. Subjects were defined as being H. pylori-positive if histology or culture was positive. In addition, all subjects completed a 120-min [14C]urea breath test. A logistic regression analysis adjusting for age was used to estimate the probability of H. pylori positivity as a function of the 14C values generated. Sixteen subjects were H. pylori-positive, and 25 were H. pylori-negative. The 14C values generated between 15 and 80 min were found to be equally predictive in identifying H. pylori-positive subjects. Advancing age was associated with a higher probability of H. pylori-positivity. By taking advantage of the statistical probabilities, older patients could be accurately diagnosed with H. pylori at lower 14C values. We found that [14C]urea breath test to be both a sensitive and specific test that can be abbreviated to a 30-min examination (total test time). Moreover, our mathematical model indicates that a patient's age should be considered in order to optimize interpretation of the [14C]urea breath test, although further observations are needed to confirm this model.

Does Helicobacter pylori colonize the gastric mucosa of Meckel's diverticulum?

Helicobacter pylori (formerly, Campylobacter pylori) is a highly adapted organism that seems to infect only gastric-type mucosa. In this study, we attempted to determine whether gastric epithelium at a site distant from the stomach, the heterotopic gastric mucosa of Meckel's diverticulum, was susceptible to colonization by H. pylori. Retrospectively, we examined biopsy specimens from 23 patients who had undergone resection of Meckel's diverticulum that contained heterotopic gastric mucosa. As a methodologic control, we also reviewed antral biopsy specimens from 18 patients with chronic duodenal ulcer who had undergone antrectomy. Heterotopic gastric mucosa in Meckel's diverticulum was of antral type in 13 patients and fundic type in 10 patients. Six patients had an ulcer in the diverticulum. No evidence of chronic or active chronic gastritis was detected in the heterotopic gastric mucosa. H. pylori was not found in any Meckel's diverticula but was present in the antrum of 89% of patients with duodenal ulcer. These results suggest that H. pylori may not colonize the heterotopic gastric mucosa of Meckel's diverticulum and has no role in the development of ulceration at this site.

Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues.

The aim of this study was to evaluate the clinicopathological spectrum of eosinophilic gastroenteritis and identify possible difficulties in establishing the diagnosis. All patients with a diagnosis of eosinophilic gastroenteritis, defined by the presence of gastrointestinal symptoms and eosinophilic infiltration of the gut (38), or a radiological diagnosis with peripheral eosinophilia (two), were identified from the Mayo Clinic records; in none was there evidence of extraintestinal disease. Patients were divided into three groups according to the Klein classification: predominant mucosal (23), muscular (12), or subserosal disease (five). A fourth group of patients (10) for comparison had abdominal symptoms and unexplained peripheral eosinophilia but no proven eosinophilic infiltration of the gut. It was found that a history of allergy was reported by 20 of 40 patients with eosinophilic gastroenteritis. Peripheral eosinophilia was absent in nine of 40. The patients with subserosal disease were distinct from the other groups in presentation (abdominal bloating, ascites), higher eosinophil counts and in their dramatic responses to steroid therapy. Otherwise the patients were similar regarding demographic factors, presenting symptoms (abdominal pain, nausea, weight loss, diarrhoea), and laboratory parameters. The ESR was moderately raised in 10 of 40 patients. The disease may affect any area of the gastrointestinal tract; eosinophilic infiltration was documented in the oesophagus in one patient and in the colon in two cases. Endoscopic biopsies missed the diagnosis in five of 40 presumably because of patchy disease. Eosinophilic gastroenteritis should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia.

Campylobacter pylori and Barrett's esophagus.

Campylobacter pylori is thought to be confined to gastric mucosa; when detected in the duodenum in association with duodenal ulceration, the organism infects only areas of gastric metaplasia. Barrett's esophagus is a metaplastic condition of the esophagus, in which areas or islands of "gastric-type" epithelium are found. To determine whether C. pylori colonized the esophagus of patients with Barrett's esophagus, we studied retrospectively 23 unselected patients who had endoscopic and biopsy evidence of Barrett's esophagus. Mucosal biopsy specimens were stained by the Warthin-Starry silver technique and reviewed by an experienced, "blinded" histopathologist. Of the 23 patients, 12 (52%) had C. pylori in the esophagus. Patients with and those without C. pylori were of similar age and gender, had similar scores for acute and chronic inflammation, and had similar lengths of tubular esophagus with metaplastic gastric mucosa. These observations suggest that C. pylori commonly infects Barrett's esophagus. The clinical importance of this finding is unknown.

Primary sclerosing cholangitis and celiac disease. A novel association.

The association of primary sclerosing cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with chronic cholestatic liver disease at ages 32, 46, and 62 years, respectively. In each patient, endoscopic retrograde cholangiography showed the typical findings of primary sclerosing cholangitis. Histologic features of liver biopsy were compatible with the diagnosis. Two patients had associated chronic ulcerative colitis. All three patients complained of frequent loose stools and weight loss; subsequent testing showed severe steatorrhea (204 to 323 mmol/d of fecal fat on a 100 g fat diet). Total villous atrophy was found in all three patients on histologic examination of the small bowel. Celiac disease was diagnosed at the time of presentation in two patients who had primary sclerosing cholangitis and was diagnosed three years after the onset of primary sclerosing cholangitis in the third patient. The celiac disease responded to a gluten-free diet in each patient whereas the primary sclerosing cholangitis was not affected by dietary treatment. The possibility of a chance association of primary sclerosing cholangitis and celiac disease cannot be accurately assessed but seems unlikely given the rarity of both diseases. The relationship between the two diseases remains unknown, although an immunologic connection is suspected. Celiac disease should be considered in the differential diagnosis of severe steatorrhea in patients with primary sclerosing cholangitis.

Whipple's disease: clinical, biochemical, and histopathologic features and assessment of treatment in 29 patients.

Whipple's disease is a chronic systemic illness, the optimal treatment of which remains poorly defined. In our analysis of a 30-year, 29-patient experience with Whipple's disease at the Mayo Clinic, the frequent initial manifestations of diarrhea, weight loss, arthritis, and lymphadenopathy correlated with findings reported previously by other investigators. Antibiotic therapy yielded rapid symptomatic and biochemical improvement, and histologic changes in the small bowel occurred subsequently. Despite antimicrobial therapy, relapses in patients with Whipple's disease are common, and the central nervous system is considered the most serious site of involvement for recurrence. Administration of an antibiotic agent that is able to cross the blood-brain barrier may be more important in preventing relapse than prolonged duration of initial antimicrobial therapy.

Interrelationships among gastric mucosal morphology, secretion, and motility in peptic ulcer disease.

Pathophysiologic abnormalities associated with ulcer disease include gastritis (particularly of the antral mucosa), excessive duodenogastric reflux, and altered motor activity of the stomach. It is not known whether these abnormalities are interrelated and whether they occur during periods of ulcer inactivity. We have tested the hypothesis that the morphological abnormalities of the gastric mucosa in inactive ulcer disease are proportional to an alteration of the gastric luminal milieu itself due to abnormal secretory and motor function. Thus, multiple endoscopic biopsies and 24-hr physiologic measurements were performed in 12 patients with well-documented ulcers in the past (seven type I gastric ulcer patients, five duodenal ulcer patients), now clinically and endoscopically in remission. Seven healthy individuals underwent similar studies and served as controls. Histologic quantification of inflammation and metaplasia (expressed as a gastritis index) was found to be significantly different among groups (P less than 0.01). Gastric ulcer patients exhibited a higher gastritis index than controls, while duodenal ulcer patients were intermediate. A significant inverse relationship was found between gastritis index and postprandial motility index (R2 = 0.59, P less than 0.01) and a nonsignificant trend between gastritis index and fasting motility index. There was no difference among groups or detectable associations between gastritis index and intragastric pH or bile acid concentration. We conclude that gastric mucosal disease, expressed as gastritis index, persists during inactive ulcer disease. There is an association with antral hypomotility, which is more strongly manifested postprandially. It is not associated with gastric pH or bile acid concentration. Gastric mucosal inflammation and antral hypomotility predispose to ulceration rather than simply accompanying it.

Postoperative reflux gastritis: pathophysiology and long-term outcome after Roux-en-Y diversion.

Sixteen patients with clinical features of postoperative gastritis who had been advised to have a Roux-en-Y diversion were studied prospectively. Studies were done pre- and postoperatively (mean follow-up, 4.9 years; range, 3.8 to 6.9), and the findings were compared with those in 11 control subjects with previous enterogastric anastomosis but with no symptoms. The patients had higher concentrations of bile acids and trypsin in gastric samples than did controls. Patients had greater endoscopic changes, although mucosal histologic characteristics were similar in both groups. Administration of aluminum hydroxide or cholestyramine reduced the aqueous concentrations of bile acids in gastric contents. Roux-en-Y diversion virtually eliminated duodenogastric reflux, and gastroscopic appearances returned to normal. However, Roux-en-Y diversion did not change mucosal histologic characteristics. Symptom scores were reduced in the early postoperative period, but bilious vomiting was the only symptom alleviated consistently and permanently. As a treatment for postoperative gastritis, Roux-en-Y diversion offers potential but limited benefits.

Cytotoxicity of mononuclear cells for autologous colonic epithelial cells in colonic diseases.

Macrophage-depleted isolates of mononuclear cells from the colonic mucosas of 25 patients with chronic ulcerative colitis or Crohn's colitis were cytotoxic for autologous colonic epithelial cells, as were mononuclear cells from their peripheral blood. This was markedly reduced by trypsinizing the mononuclear cells and was restored by a 1-h exposure of the trypsinized cells to 25% vol/vol heat-inactivated autologous plasma. Trypsinization of the target cells had no effect on cytotoxicity. Mononuclear cells that adhered to plates coated with heat-aggregated immunoglobulin G contained the effectors. It was suggested that this phenomenon was a form of antibody-dependent cell-mediated cytotoxicity in which the effector cells rather than the targets were "armed" by antibody. Cytotoxicity for autologous colonic epithelial cells was also shown by colonic mononuclear cells but not by mononuclear cells from the peripheral blood in a group of 40 patients with colorectal tumors, and by 1 of 4 patients with diverticulitis. This cytotoxicity was markedly reduced by trypsinizing the colonic mononuclear cells but was not restored by exposing the trypsinized cells to autologous plasma. Colonic mononuclear cells that adhered to plates coated with heat-aggregated immunoglobulin G contained the effectors. It seems likely that this cytotoxicity was spontaneous cell-mediated cytotoxicity.

Hematoporphyrin derivative: quantitative uptake in dimethylhydrazine-induced murine colorectal carcinoma.

The selective affinity of hematoporphyrin derivative (HpD) for dimethyl-hydrazine-induced colorectal malignancies in mice was evaluated both visually and by a quantitative microfluorescent photometric technique. A significant correlation was found between higher concentrations of HpD in colon biopsies determined by microfluorescence spectroscopy and the presence of carcinoma cells in these biopsies as identified by histologic examination. Visual inspection of the gross fluorescence of tumor-bearing colons in this experimental model, however, was not helpful in differentiating malignant from nonmalignant tissue. The implications of this study regarding the clinical application of HpD tumor fluorescence for the detection of colorectal carcinoma are discussed.

Risks of intestinal cancer in Crohn's disease.

This review describes the principal features of the three studies that have established clearly that patients in the U.S.A. or the U.K. who have long-standing (greater than 7 years) Crohn's colitis are at increased risk (up to 20-fold) of developing large bowel cancer. In addition, it emphasizes that there are no data on the extent of this risk in patients in other countries, and also that the magnitude of the risk of cancer of the small intestine in Crohn's disease is unknown. Despite the increased incidence of large bowel cancer in long-standing Crohn's colitis in the U.S.A. or the U.K., the total number of such patients is small, as is the number in which the colonic carcinoma will occur. However, careful supervision is advised for the small group at risk, despite the limitations of current methods for the early detection of cancer of the large intestine.