EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma.

BACKGROUND: Preoperative diagnosis of pancreatic adenocarcinoma can be difficult. Computed tomography (CT) is the standard, noninvasive imaging method for evaluation of suspected pancreatic adenocarcinoma, but it has limited sensitivity for diagnosis, local staging, and metastases. Endoscopic ultrasound (EUS) and fluoro-deoxyglucose/positron emission tomography (FDG-PET) are imaging methods that may improve diagnostic accuracy. METHODS: Thirty-five patients with presumed resectable pancreatic adenocarcinoma were prospectively evaluated with helical CT, EUS, and FDG-PET. RESULTS: Sensitivity for the detection of pancreatic cancer was higher for EUS (93%) and FDG-PET (87%) than for CT (53%). EUS was more sensitive than CT for local vascular invasion of the portal and superior mesenteric veins. EUS diagnosis of vascular invasion was associated with poor outcome after surgery. EUS-guided, fine-needle aspiration allowed tissue diagnosis in 14 of 21 attempts (67%). FDG-PET diagnosed 7 of 9 cases of proven metastatic disease, 4 of which were missed by CT. Two of three metastatic liver lesions suspected by CT were indeterminate for metastases. FDG-PET confirmed metastases. CONCLUSIONS: EUS and PET improve diagnostic capability in pancreatic adenocarcinoma. EUS is useful in determining local vascular invasion and obtaining tissue diagnosis. FDG-PET is useful in identifying metastatic disease. Both techniques are more sensitive than helical CT for identification of the primary tumor. (Gastrointest Endosc 2000;52:367-71).

"Familial hyperpepsinogenemia" and Helicobacter pylori infection.

OBJECTIVE: Pepsinogen 1 (PG1) is a proenzyme precursor to pepsin, a protease secreted by the gastric chief cell. PG1 levels correlate with maximal gastric acid output. In 1979, Rotter et al. reported two pedigrees in which elevated PG1 levels and duodenal ulcers were prevalent. They proposed autosomal dominant inheritance of elevated PG1 and suggested that it was a risk factor for duodenal ulcer disease. In 1982, Helicobacter pylori (Hp) was discovered and was shown to be an important factor in peptic ulcer disease. Hp infection is also associated with increased PGI levels. We tested serum from one of the original pedigrees for Hp antibodies to determine whether Hp infection could explain the ulcers and elevated PG1 levels. METHODS: ELISA tests were performed using the urease fraction of a crushed Hp extract. Banked serum from one of the original families was thawed and tested. RESULTS: Of the subjects, 90% (nine of 10) with elevated PG1 were seropositive for Hp, compared to only 31% (17 of 55) of those with normal PG1 levels (p < 0.001). The mean PG1 level was higher in the seropositive (94.1+/-13.3 ng/ml) than the seronegative subjects (54.8+/-3.6, p < 0.05). Three of the four subjects with ulcers were Hp-seropositive. The prevalence of Hp-seropositivity and elevated PG1 declined in parallel in each successive generation. When neither parent was seropositive, children were seronegative. CONCLUSIONS: The etiology of elevated PG1 levels in this pedigree is more likely due to Helicobacter pylori infection than to a genetic predisposition.

New concepts of irritable bowel syndrome.

Significant recent advances in basic and clinical science have improved our understanding of irritable bowel syndrome (IBS). Sensory abnormalities, particularly visceral hypersensitivity after sensitizing stimulation, indicate neural dysfunction in patients with IBS. This dysfunction could be mediated by N-methyl-D-aspartate or calcium gene-related peptide receptors in the spinal cord. The stress response in the gut is augmented in IBS, which may be related to hypothalamic release of corticotropin-releasing factor. Postinfectious IBS may be related to psychologic factors that allow persistent inflammation. Finally, functional brain imaging has shown augmented central nervous system responses to visceral pain in IBS, particularly in the prefrontal cortex. Low-dose tricyclic antidepressants are useful to control symptoms, and the new serotonin type 3 (5-HT3) receptor antagonists show promise for symptom control.

Optimal screening and diagnosis of microsporida in tissue sections: a comparison of polarization, special stains, and molecular techniques.

With improving therapeutic protocols, confirmation of microsporidiosis has become increasingly important. We designed a study to determine the best screening method(s) for microsporidian detection in biopsy specimens. Forty-two small intestinal biopsy specimens from 31 immunocompromised patients (68% AIDS) were stained (hematoxylin-eosin [H & E], modified trichrome, Warthin-Starry, and Brown-Brenn) and polarized. Polymerase chain reaction and Southern blot assays were performed on all positive cases. Microsporida were detected in nine cases (21%) by modified trichrome (all patients with AIDS). Of these, seven were Brown-Brenn positive, and five Warthin-Starry positive. Two cases polarized on H & E and three on special stains. Four of nine positive cases were confirmed by molecular studies. We found polarization to be the least sensitive screening method. The modified trichrome was the most sensitive when screening for microsporidiosis in paraffin-embedded biopsy specimens. Furthermore, combining Brown-Brenn or Warthin-Starry with the trichrome stain helps exclude false-positive results due to granular artifacts (eg, eosinophils, Paneth cells).

Validation of a new measure of diarrhea.

Adequate measures of diarrheal disease are important to assess severity for clinical use and outcomes research. We developed a questionnaire to assess diarrhea severity and complications, and administered it to 205 HIV positive patients with diarrhea, fever, or weight loss. Noteworthy variations in stool form were reported by individuals and across subjects. Self-reported diarrhea correlated with the occurrence of any stool pictured without form. However, verbal descriptors "loose" and "semiformed" had little value in assessment of diarrheal disease. Both verbal and pictorial stool descriptors correlated well with diarrhea complications (pain, urgency, tenesmus, incontinence, and nocturnal diarrhea). By factor analysis, discomfort and nondiscomfort diarrhea complications loaded on different factors, consistent with clinical experience that discomfort is a distinct problem in diarrheal disease. In summary we have developed an instrument to precisely characterize diarrhea severity that correlates well with clinically important events such as incontinence and abdominal pain.

Peptic ulcer pathophysiology.

Despite extensive research, the etiology of peptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process. It is clear that the majority of gastric ulcers and a substantial number of duodenal ulcers do not have increased gastric acid secretion. Recent research has focused more on protection and repair of the stomach and duodenum. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protective effects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Evidence is mounting in support of H. pylori as a necessary ingredient in the ulcerative process, similar to acid and pepsin. It is not known whether the bacteria or the accompanying inflammation is the more important factor in the pathophysiology. Although the pathophysiology of gastric ulcer and duodenal ulcer is similar, there are clearly differences between the two groups. Duodenal ulcer is typified by H. pylori infection and duodenitis and in many cases impaired duodenal bicarbonate secretion in the face of moderate increases in acid and peptic activity. These facts suggest the following process: increased peptic activity coupled with decreased duodenal buffering capacity may lead to increased mucosal injury and result in gastric metaplasia. In the presence of antral H. pylori, the gastric metaplasia can become colonized and inflamed. The inflammation or the infection itself then disrupts the process of mucosal defense or regeneration resulting in ulceration. A cycle of further injury and increased inflammation with loss of the framework for regeneration may then cause a chronic ulcer. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosal defensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation.