Am J Gastroenterol

Adding once-daily omeprazole 20 mg to metronidazole/amoxicillin treatment for Helicobacter pylori gastritis: a randomized, double-blind trial showing the importance of metronidazole resistance.

Veldhuyzen van Zanten S. Hunt RH. Cockeram A. Schep G. Malatjalian D. Sidorov J. Matisko A. Jewell D.
Department of Anatomic Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
OBJECTIVE: We compared the Helicobacter pylori eradication rate after a 14-day treatment with amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. with or without omeprazole 20 mg once daily. METHODS: This was a randomized, controlled trial in which omeprazole was given in double-blind fashion. Patients with H. pylori-associated gastritis were enrolled in four centers in Canada from July 1991 to January 1994. Eradication of H. pylori was assessed by histological evaluation and culture of endoscopic biopsies obtained from the antrum and corpus of the stomach. RESULTS: The H. pylori eradication rate was 73% (33 of 45) in the omeprazole-amoxicillin-metronidazole group, compared with 66% (31 of 47) in the amoxicillin-metronidazole group. This 7% difference was not statistically significant (p = 0.43, 95% confidence interval for difference -11% to 26%). Metronidazole primary resistance in the prestudy cultures was found more frequently in the omeprazole-amoxicillin-metronidazole group than in the amoxicillin-metronidazole group. Resistance to metronidazole was an important predictor of treatment failure. The H. pylori eradication rate was 61% (19 of 31) for patients infected with metronidazole-resistant H. pylori strains, compared with 91% (30 of 33) eradication for those infected with metronidazole-sensitive strains (p < 0.01). Vaginal candidiasis was reported in four patients. CONCLUSIONS: The H. pylori eradication rate was higher (73%) for omeprazole-amoxicillin-metronidazole than for the dual antibiotic therapy given without omeprazole (66%); however, this difference was not statistically significant. Metronidazole resistance significantly reduces H. pylori eradication rates.

Gastroesophageal reflux after distal gastrectomy: possible significance of the angle of His.

Fujiwara Y. Nakagawa K. Kusunoki M. Tanaka T. Yamamura T. Utsunomiya J.
Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
OBJECTIVE: We investigated whether the angle of His influences gastroesophageal reflux after distal gastrectomy. METHODS: Thirty-eight patients having distal gastrectomy and 10 controls underwent upper gastroesophageal fluoroscopy to measure the angle of His, and gastroesophageal reflux was assessed by scintigraphy. The association between scintigraphic reflux and the angle of His was then evaluated. RESULTS: In distal gastrectomy patients with and without reflux symptoms, the angle was 108.82 +/- 21.88 degrees and 96.07 +/- 13.25 degrees, respectively; it was 74.14 +/- 10.85 degrees in the controls. The angle was significantly larger in the patients than in the controls (p < 0.01). In addition, the angle in the symptomatic gastrectomy group tended to be larger than in the asymptomatic group. The angle was also significantly larger in patients with a scintigraphic reflux index > or =6% than in those with an index

Comparison of helisal rapid blood test and 14C-urea breath test in determining Helicobacter pylori status and predicting ulcer disease in dyspeptic patients.

Mowat C. Murray L. Hilditch TE. Kelman A. Oien K. McColl KE.
University Department of Medicine & Therapeutics, Western Infirmary, Glasgow, United Kingdom.
OBJECTIVE: Noninvasive tests for Helicobacter pylori are used increasingly. Our aim was to compare the Helisal Rapid Blood (HRB) test and 14C-urea breath test (UBT) for determining H. pylori status and predicting ulcer disease. METHODS: Three hundred fifty-one consecutive patients with dyspepsia (mean age 40 yr; range 16-77 yr) had an HRB test and UBT followed by endoscopy with biopsies of the antrum and body for histology and antral urease slide test (CLO test). Patients were excluded if they had previously confirmed ulcer disease, gastric surgery, or anti-H. pylori therapy or were taking nonsteroidal anti-inflammatory drugs. RESULTS: Sixty-three percent of the patients were "gold standard" H. pylori positive (positive CLO test, positive staining), 34% were gold standard negative (negative CLO test, negative staining), and 3% had conflicting CLO test and histology. The UBT was superior to HRB for determining H. pylori status (sensitivity 98% vs 92%, p = 0.04; specificity 100% vs 69%, p < 0.001). The specificity of the HRB decreased with increasing patient age (74% for age or =46 yr). A negative UBT was superior to a negative HRB test for predicting the absence of ulcer disease (47% vs 36 %; p < 0.01). A positive UBT was similar to a positive HRB in predicting the presence of ulcer disease (92% vs 84%; p = 0.23). CONCLUSIONS: The HRB test is inferior to the UBT for determining H. pylori status. The tests have a similar ability to predict the presence of ulcer disease when positive, but a negative UBT is a better predictor of the absence of ulcer disease.

Semiquantitative evaluation for diagnosis of Helicobacter pylori infection in relation to histological changes.

Tokunaga Y. Shirahase H. Yamamoto E. Gouda Y. Kanaji K. Ohsumi K.
Department of Surgery, Maizuru Municipal Hospital, Kyoto, Japan.
OBJECTIVES: Several methods are used to detect Helicobacter pylori (HP) infection. However, few reports have evaluated the accuracy of each method and compared the grade of HP infection with the severity of histological changes. HP infection was evaluated semiquantitatively in relation to the severity of gastritis, and the sensitivity, specificity, and accuracy of several methods to detect HP infection were compared. METHODS: Biopsy specimens, obtained from a total of 64 patients who underwent endoscopy for evaluation of gastroduodenal diseases, were studied using a rapid urease test, culture, and histological assessment. An immunohistochemical method was used as the gold standard and graded according to the number of individual bacteria seen, as follows: 0 = 0; 1+ = 100. The severity of gastritis was evaluated histologically in each specimen and compared with the grade of HP infection. RESULTS: The rapid urease test had a sensitivity of 53%, specificity of 100%, and accuracy of 73%. The culture method had a sensitivity of 75%, specificity of 100%, and accuracy of 86%. Sensitivities of the rapid urease test and the culture method decreased in a positive correlation with the decrease in total number of HP bacteria counted. Using the rapid urease test, sensitivity was or =2+. The severity of gastritis determined with Rauws scores increased in a positive correlation with the grade of HP infection as evaluated by immunohistochemical stain. CONCLUSIONS: The rapid urease test and culture of HP may result in false-negative tests for a mild infection, although they had high sensitivity and specificity for moderate to severe infection. Immunohistochemical stain provides a reliable semiquantitative diagnosis of HP infection and a positive correlation with histological changes. Clinicians should be aware of the characteristics of each method to detect HP infection and select the appropriate one(s) for their purposes.

Analysis of the expression of CagA and VacA and the vacuolating activity in 167 isolates from patients with either peptic ulcers or non-ulcer dyspepsia.

Takata T. Fujimoto S. Anzai K. Shirotani T. Okada M. Sawae Y. Ono J.
Department of Laboratory Medicine, Faculty of Medicine, Fukuoka University, Japan.
OBJECTIVES: The goals of this study were: 1) to examine the prevalence of cytotoxin-associated protein (CagA), vacuolating cytotoxin (VacA), and the vacuolating cytotoxin activity (VCA) in vitro of infecting Helicobacter pylori isolates and 2) to clarify the relation between the expression of these virulence factors and the occurrence of peptic ulceration. METHODS: One hundred sixty-seven clinical isolates of H. pylori from patients with peptic ulcer disease (gastric ulcer, 62 cases; duodenal ulcer, 48 cases) and nonulcer dyspepsia (57 cases) were studied regarding their genetic and phenotypic properties. RESULTS: Type 1 bacteria, which had both CagA and VCA, and type 2 bacteria, which did not express either CagA or VCA, represented 62.9% and 7.8%, respectively; the remaining 29.4% had an intermediate phenotype, expressing either CagA independent of the presence of VCA (CagA+VCA-) or vice versa (CagA-VCA+). CagA+VCA- and CagA-VCA+ bacteria represented 17.4 % and 12.0%, respectively, both of which were more numerous than the type 2 category. The proportion of the CagA-positive isolates was significantly higher in both the duodenal ulcer (97.9%) and gastric ulcer (83.9%) patients than in the non-ulcer dyspepsia patients (61.4%) (p < 0.01). On the other hand, the proportion of VacA/VCA-positive isolates was not significantly different between peptic ulcer disease and non-ulcer dyspepsia. CONCLUSIONS: The currently used classification of this bacterium based on the concomitant expression of CagA and VacA/VCA into the two major types is not adequate. The CagA-positive phenotype thus may be important as a virulence marker for peptic ulcer disease independent of the presence of VacA/VCA.

Randomized clinical trial comparing two one-week triple-therapy regimens for the eradication of Helicobacter pylori infection and duodenal ulcer healing.

Forne M. Viver JM. Esteve M. Fernandez-Banares F. Lite J. Espinos JC. Quintana S. Salas A. Garau J.
Department of Gastroenterology, Hospital Mutua de Terrassa, University of Barcelona, Spain.
OBJECTIVE: One-week triple therapy has been shown to be effective in Helicobacter pylori eradication and duodenal ulcer healing. However, the optimal therapeutic combination has not yet been identified. Bismuth-containing regimens have the advantage of requiring only one antibiotic. It has been suggested that high doses of omeprazole improve the bactericidal efficacy of antimicrobial regimens against H. pylori. We evaluated the efficacy of two 1-wk triple-therapy regimens for H. pylori eradication and duodenal ulcer healing. METHODS: On an intention-to-treat basis, 182 patients with H. pylori-associated duodenal ulcer were randomized. Group OCB patients (n = 91) were given omeprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d., and colloidal bismuth subcitrate 120 mg q.i.d. for 7 days. Group OCA patients (n = 91) were treated with omeprazole and clarithromycin at the same doses plus amoxicillin 1 g b.i.d., also for 7 days. Endoscopies were performed at entry and at 4 wk after the end of treatment. The presence of H. pylori was assessed by urease test, histology, Gram stain, and culture. No patient received follow-up treatment. RESULTS: H. pylori eradication rates achieved in the OCB and OCA groups were similar whether by intention-to-treat (82.4% vs 88.9% ;p = 0.21) or per protocol analysis (83.3% vs 89.9%; p = 0.19). Duodenal ulcer healing rates also were the same for OCB and OCA in intention-to treat (91.2% vs 91.1%) and per protocol analysis (92.2% vs 92.1%), respectively (p = 0.98). CONCLUSIONS: High rates of H. pylori eradication and duodenal ulcer healing were obtained with both short-treatment regimens, which were safe and well-tolerated. Colloidal bismuth subcitrate seems to be a good alternative to amoxicillin in the triple-therapy combination with omeprazole and clarithromycin. The omeprazole dose does not seem to play a major role in H. pylori eradication in these therapeutic combinations.

Durability of serological remission in chronic hepatitis C treated with interferon-alpha-2B.

Sim H. Yim C. Krajden M. Heathcote J.
Department of Medicine, University of Toronto, Ontario, Canada.
OBJECTIVE: We assessed the long-term effect of a course of interferon therapy on the biochemical and virological markers of Canadian patients with chronic hepatitis C. METHODS: Thirty-six patients with chronic hepatitis C were treated with a median total dose of interferon-alpha-2B of 181.0 million U (range 109.0-384.0 million U) and were followed for a median of 37.2 months (range 12.0-94.2 months) after completing treatment. All patients received an initial 16 wk of interferon at a dose of 3 million U three times weekly; this was followed by either no further interferon or by 8 wk more at doses ranging from 1.5 to 10.0 million U three times weekly. Serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were measured before interferon therapy, 6 months after treatment, and at the end of follow-up for each patient. HCV RNA was analyzed by branched DNA 1.0 assay and, if undetectable, by polymerase chain reaction. HCV genotyping was performed on serum samples. RESULTS: Five (13.6%) of the 36 patients had a sustained treatment response, defined as normal ALT and undetectable viremia 6 months after treatment. All five patients remained in serological remission to the end of their follow-up, a median of 48.2 months (range 23.0-66.2 months) after interferon therapy. Responders were similar to nonresponders in age, gender, initial ALT and serum HCV RNA levels, pretreatment histology, and total dose of interferon received. CONCLUSIONS: In patients with chronic hepatitis C, 13.6% had normal ALT and undetectable serum HCV RNA 6 months after finishing interferon therapy. These patients remained in serological remission to the end of their follow-up, 48.2 months after interferon therapy.

AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection.

Sheth SG. Flamm SL. Gordon FD. Chopra S.
Department of Medicine, Beth Israel Deaconess Medical Center Hospital, Boston, Massachusetts 02215, USA.
OBJECTIVE: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio >1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. METHODS: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. RESULTS: The mean AST/ALT ratio in the cirrhotic patients (n = 47) was higher than in the noncirrhotic patients (n = 92) (1.06 +/- 0.06 vs 0.60 +/- 0.09; p < 0.001). A ratio > or =1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio > or =1. CONCLUSION: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.

Hepatitis B and C virus sexual transmission among homosexual men.

Osella AR. Massa MA. Joekes S. Blanch N. Yacci MR. Centonze S. Sileoni S.
Laboratory of Epidemiology and Biostatistics, Research Institute for Digestive Diseases Saverio De Bellis, Castellana G., Italy.
OBJECTIVE: We estimated hepatitis B virus (HBV) and hepatitis C virus (HCV) sexual transmission among homosexual men. METHODS: Two hundred twenty-eight homosexually active men attending two clinical centers and presenting no risk factors except for sexual exposure were interviewed, and a blood sample was drawn. HBV marker test was performed using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, and HCV was tested using ELISA-2 and recombinant immunoblot assay-2. RESULTS: HBV and HCV infection prevalence rates were 34.4% and 12.7%, respectively. Using logistic regression analysis including sexual exposure and controlling for confounders, we found that anal receptive intercourse (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.34-11.94), duration of homosexuality (OR = 3.43; 95% CI = 1.29-9.12), insertive anilingus (OR = 2.02; 95% CI = 1.06-3.87), and sexually transmitted diseases (OR = 1.87; 95% CI = 1.00-3.47) were independently associated with the risk of HBV sexual transmission. We did not find any association between sexual behavior and HCV transmission. CONCLUSIONS: Sexual behavior is a plausible explanatory factor of HBV sexual transmission among homosexual men. Further evidence is needed to elucidate the occurrence and the efficiency of HCV sexual transmission in the absence of other risk factors.

The prevalence of intestinal metaplasia in patients with and without peptic strictures.

Kim SL. Wo JM. Hunter JG. Davis LP. Waring JP.
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
OBJECTIVE: Several studies suggest that patients with esophageal peptic strictures have a high prevalence of Barrett's esophagus. However, these studies did not include appropriate control groups, were retrospective in nature, or did not strictly define Barrett's esophagus. Our aim was to compare the prevalence of Barrett's esophagus in patients with and without gastroesophageal reflux disease strictures in a prospective study. METHODS: Seventy-nine patients referred for endoscopy for gastroesophageal reflux disease symptoms were evaluated. We collected demographic information and an esophageal symptom assessment. Biopsy specimens were obtained from peptic strictures, Schatzki rings, or from any areas of columnar-lined esophagus or mucosal injury. Barrett's esophagus was strictly defined as the presence of intestinal metaplasia from tubular esophagus. RESULTS: There were 46 patients without strictures and 28 patients with peptic strictures. Five patients had Schatzki's rings. The prevalence of intestinal metaplasia was 23.9% in patients without strictures, and 25% in patients with peptic strictures (p = NS). There was no difference in prevalence of short- or long-segment Barrett's esophagus between the groups. Patients with strictures were older than patients without strictures (mean age 58.9 vs 48.6 yr), and more likely to have mucosal injury (50% vs 26.1%). Otherwise, there were no significant differences with regards to gender, race, heartburn duration or frequency. CONCLUSIONS: Barrett's esophagus, as defined by the presence of intestinal metaplasia in the tubular esophagus, is equally common in patients with and without peptic strictures. There does not appear to be an association between Barrett's esophagus and peptic strictures.

Endoscopic evaluation of chronic human immunodeficiency virus-related diarrhea: is colonoscopy superior to flexible sigmoidoscopy?

Bini EJ. Weinshel EH.
Division of Gastroenterology, New York University Medical Center, New York, USA.
OBJECTIVES: In patients with chronic human immunodeficiency virus (HIV)-related diarrhea undergoing lower endoscopy, the decision to perform flexible sigmoidoscopy or colonoscopy is controversial. The purpose of this study is twofold: 1) to evaluate the diagnostic yield of colonoscopy in a large group of patients with chronic HIV-related diarrhea and negative stool studies, and 2) to determine whether colonoscopy is superior to flexible sigmoidoscopy in this setting. METHODS: All HIV-infected patients with chronic diarrhea who were referred for diagnostic colonoscopy at Bellevue Hospital Center between January 1992 and December 1996 were identified. Patient charts, pathology reports, and endoscopy records were reviewed. RESULTS: During the 5-yr study period, 317 consecutive patients with chronic unexplained diarrhea undergoing colonoscopy were identified. A potential cause of diarrhea was found in 116 patients (36.6%). Cytomegalovirus was the most common pathogen detected (24%). The yield of colonoscopy was significantly higher in patients with a CD4 count of

Pretreatment with methylprednisolone to prevent ERCP-induced pancreatitis: a randomized, multicenter, placebo-controlled clinical trial.

Dumot JA. Conwell DL. O'Connor JB. Ferguson DR. Vargo JJ. Barnes DS. Shay SS. Sterling MJ. Horth KS. Issa K. Ponsky JL. Zuccaro G.
Department of Gastroenterology, Cleveland Clinic Foundation, Ohio 44195, USA.
OBJECTIVE: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP). Uncontrolled data suggest a lower incidence of pancreatitis in patients with a history of iodine sensitivity when given pretreatment with corticosteroids. We conducted a clinical trial to assess the efficacy of a commonly prescribed corticosteroid, methylprednisolone, to prevent ERCP-induced pancreatitis. METHODS: Patients were entered into a randomized, multicenter, double-blind, placebo-controlled study of intravenous methylprednisolone (125 mg) versus a saline placebo immediately before the ERCP. All patients were evaluated for early and late complications. RESULTS: Two hundred eighty-six patients were randomized. Thirty-one randomized patients were excluded for technical reasons at the time of ERCP. Overall, the incidence of pancreatitis was 16 of 129 (12.4%, 95% CI: 6.7-18.1%) in the methylprednisolone group and 11 of 126 (8.7%, 95% CI: 4.4-15.1%) in the placebo group, which was not significantly different (p = 0.34). Although there was a higher rate of sphincterotomy performed in the methylprednisolone group compared to the control group (31.8% vs 16.8%, p = 0.005), the incidence of pancreatitis was not different when patients undergoing sphincterotomy were analyzed separately (13.6% in the methylprednisolone group and 9.6% in the placebo group,p = 0.50). There was no significant difference between the two groups for those with ERCP-induced pancreatitis in hospital length of stay (p = 0.22), days of parenteral analgesia (p = 0.09), or days of parenteral nutrition (p = 0.15). CONCLUSION: Intravenous methylprednisolone is not beneficial in preventing ERCP-induced pancreatitis.

Somatostatin-receptor scintigraphy in the management of gastroenteropancreatic tumors.

Krausz Y. Bar-Ziv J. de Jong RB. Ish-Shalom S. Chisin R. Shibley N. Glaser B.
Department of Nuclear Medicine, Hadassah University Hospital, Jerusalem, Israel.
OBJECTIVE: This study evaluates the diagnostic and therapeutic implications of somatostatin-receptor scintigraphy in the management of patients with proven or high clinical suspicion of gastroenteropancreatic endocrine tumors. METHODS: Forty-one patients were studied by planar and tomographic imaging at 4 h and 24 h after 111In-pentetreotide injection. Scintigraphic findings were compared with computed tomography, and in several patients also with ultrasound, angiography, biopsy, and/or surgery, when performed. RESULTS: Among 23 patients with carcinoid tumor, three of nine primary tumors were initially identified by scintigraphy. Unsuspected mesenteric metastases found on scintigraphy in three patients led to octreotide treatment. Scintigraphic detection of multiple metastases in a patient with thyroid metastasis of bronchial carcinoid spared her an unnecessary total thyroidectomy. Among 18 patients with 19 islet-cell tumors, scintigraphy detected three of five insulinomas, whereas computed tomography identified only one. Receptor positivity in an islet-cell tumor (vipoma?) with no metastases on the scan led to surgical removal of the primary tumor. Receptor-positive metastases of gastrinoma (two of three patients), glucagonoma (two of three patients), and parathyroid hormone-related peptide-producing tumor (one patient) led to octreotide treatment. Nonvisualization of metastases of a glucovipoma led to chemotherapy. CONCLUSIONS: Somatostatin-receptor scintigraphy contributes to the management of patients with gastroenteropancreatic tumors in the following ways: 1) localization of a primary occult tumor, allowing surgical removal; 2) staging of the disease for optimal therapy-surgical excision or systemic treatment; and 3) identification of receptor status of the metastases for octreotide treatment or chemotherapy.

Effects of endoscopic variceal ligation on portal hypertensive gastropathy and gastric mucosal blood flow.

Yoshikawa I. Murata I. Nakano S. Otsuki M.
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu.
OBJECTIVE: Portal hypertensive gastropathy (PHG) has been recognized recently as a potential cause of upper gastrointestinal tract bleeding and is associated with a change in gastric hemodynamic indices in cirrhotic patients with portal hypertension. Endoscopic variceal ligation (EVL) is the treatment of choice for esophageal varices. We investigated the early effect of EVL on PHG and gastric mucosal blood flow (GMBF). METHODS: We examined 35 cirrhotic patients who were treated by EVL. PHG was evaluated endoscopically and GMBF was measured by laser Doppler flowmetry before and 1 or 2 wk after EVL. RESULTS: After EVL, only two patients (5.7%) developed severe PHG, 6 (17.1%) developed mild PHG, and 27 (77.1%) showed no change in endoscopic appearance of PHG. In those patients who developed PHG, EVL significantly decreased GMBF at the corpus (p < .05). However, no significant changes of GMBF at the corpus were noted after EVL in those patients who had no worsening of endoscopic features. EVL had no effect on GMBF at the antrum in any patients. CONCLUSIONS: Endoscopic variceal ligation is safe and does not lead, at least within 1-2 wk, to worsening of gastropathy in most cases. Our finding that gastropathy developed in the presence of reduced GMBF may suggest that PHG develops as a result of congestion caused by blockade of gastric blood drainage rather than by hyperemia.

Urgent transjugular intrahepatic portosystemic shunt for control of acute variceal bleeding.

Banares R. Casado M. Rodriguez-Laiz JM. Camunez F. Matilla A. Echenagusia A. Simo G. Piqueras B. Clemente G. Cos E.
Department of Gastroenterology, Hospital General Universitario Gregorio Maranon, Madrid, Spain.
OBJECTIVE: Endoscopic sclerotherapy and pharmacological therapy are widely used in the treatment of acute variceal hemorrhage. However, they fail at arresting acute bleeding in 20-30% of bleeding episodes. The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the prevention of recurrent variceal bleeding has been proved recently, but the effectiveness and safety of urgent TIPS in the treatment of acute variceal bleeding refractory to conventional therapy are still under evaluation. METHODS: Over 4.5 yr, 358 variceal hemorrhage episodes were treated in our hospital. Pharmacological and endoscopic therapy failed to control hemorrhage in 93 episodes. Thirty-two patients died because of uncontrolled massive bleeding. In 56 patients, TIPS (Strecker stent) was performed after temporary control of the episode with balloon tamponade. RESULTS: Eleven of 56 patients with urgent TIPS belonged to Child-Pugh class A, 22 to class B, and 23 to class C. The mean time between indication and insertion was 17 +/- 10 h (range 4-24 h). Control of bleeding was achieved in 53 patients (95 %). Eight patients had recurrent bleeding at 1 month after TIPS, seven of them during the first week after the procedure. The 1-month actuarial probability of rebleeding was 22%. The main complications of the procedure were massive hemoperitoneum (n = 1), cardiorespiratory arrest (n = 2), cardiac failure (n = 1), acute renal failure (n = 2), and bacteremia (n = 7). Operative mortality (30 days) was 28%. The actuarial probability of survival at 30 days was significantly lower in Child-Pugh class C than in class A or B (48% vs 90%; p < 0.001). The presence of ascites, hepatic encephalopathy, and serum albumin level before TIPS were independent prognostic factors associated with the risk of operative mortality. CONCLUSIONS: Urgent TIPS is an effective alternative for the treatment of acute variceal bleeding refractory to endoscopic and pharmacological therapy, but sometimes is associated with major complications. Because of the high operative mortality rate in patients with severe liver failure, careful selection of patients is required before TIPS.

Regulation of hepatic thrombopoietin production by portal hemodynamics in liver cirrhosis.

Sezai S. Kamisaka K. Ikegami F. Usuki K. Urabe A. Tahara T. Kato T. Miyazaki H.
Division of Gastroenterology, Kanto NTT Hospital, Tokyo, Japan.
OBJECTIVE: This study was designed to clarify how thrombopoietin (TPO) functions in and, to some extent, causes thrombocytopenia complicating liver cirrhosis and portal hypertension. METHODS: Our study population consisted of 19 cirrhotic and six noncirrhotic patients who underwent percutaneous transhepatic portography (PTP) and hepatic venography. RESULTS: The platelet counts of the cirrhotic patients were significantly lower than those of the noncirrhotic patients (8.7 +/- 4.1 vs 17.4 +/- 7 x 10(4)/microl; p < 0.01). The flow direction in the splenic vein was confirmed by PTP. Ten hepatofugal and nine hepatopetal flow directions in the splenic vein were noted among the cirrhotics. The hepatofugal group showed lower portal venous pressure (20 +/- 10 vs 32 +/- 4 cm H2O; p < 0.01) than the hepatopetal group and had a higher incidence of hepatic encephalopathy (six of 10 vs zero of nine; p < 0.01). The hepatic vein-portal difference in TPO did not differ substantially between the cirrhotics and noncirrhotics (0.12 +/- 0.04 vs 0.24 +/- 0.07 fmol/ml). Comparisons of this value among the three groups showed the TPO difference to be lowest in the hepatofugal group (hepatofugal: 0.04 +/- 0.03, hepatopetal: 0.21 +/- 0.07, noncirrhotic: 0.24 +/- 0.07; p < 0.05). CONCLUSIONS: Our findings suggest that TPO production in the cirrhotic liver is regulated by the portal blood supply to the liver. Thus, portal hemodynamics may play a critical role in the development of thrombocytopenia.

Fecal hydrogen sulfide production in ulcerative colitis.

Levine J. Ellis CJ. Furne JK. Springfield J. Levitt MD.
Department of Medicine, Minneapolis VA Medical Center and University of Minnesota Medical School, 55417, USA.
OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.

Diagnosis of Crohns ileitis and monitoring of disease activity: value of Doppler ultrasound of superior mesenteric artery flow.

van Oostayen JA. Wasser MN. Griffioen G. van Hogezand RA. Lamers CB. de Roos A.
Department of Diagnostic Radiology, Leiden University Medical Center, The Netherlands.
OBJECTIVE: To assess the value of measurements of superior mesenteric artery flow using Doppler ultrasound for detecting disease activity in patients with proven or suspected Crohn's disease. METHODS: Superior mesenteric artery flow was measured prospectively in 31 patients with known or suspected small-bowel disease. Sixteen patients were known to suffer from Crohn's disease and were suspected of having active disease. Fifteen patients had abdominal complaints without a specific diagnosis. Enteroclysis was used as the standard of reference to detect Crohn's disease, to define the location of small-bowel Crohn's disease, and to assess disease activity by demonstrating cobblestoning. Disease activity was further substantiated by clinical signs, laboratory values, and clinical follow-up. RESULTS: Ten patients with active disease on enteroclysis made up group 1. Group 2 comprised nine patients known to have Crohn's disease but without active disease (inactive small-bowel disease). The remaining 12 patients made up group 3. In group 1, the flow volume values were significantly higher than those in group 2 and group 3: 738 +/- 411 (mean +/- SD) versus 364 +/- 101 and 300 +/- 91, respectively (p < 0.05). CONCLUSIONS: Whereas the initial diagnosis of small-bowel involvement in Crohn's disease may rely on enteroclysis, Doppler measurements of superior mesenteric artery flow are useful to monitor the activity of Crohn's disease.

Multiple pancreatic masses associated with autoimmunity.

Ohana M. Okazaki K. Hajiro K. Kobashi Y.
Department of Gastroenterology, Tenri Hospital, Nara, Japan.
A 59-year-old woman was detected to have a high titer of serum gamma-globulin, positive antinuclear antibody and multiple pancreatic masses. In the course of 1 yr, Sjogren's syndrome developed, and her pancreatic masses spread diffusely and compressed the main pancreatic duct. A pancreatic biopsy by an exploration of the abdomen showed that many CD4 positive T-lymphocytes had infiltrated to the ducts and acinar cells expressing HLA-DR antigens. This suggested a diagnosis of autoimmune-related pancreatitis. She was treated with oral prednisolone, and a marked improvement of the above abnormal findings followed. In this report, a case of autoimmune-related multiple pancreatic masses associated with Sjogren's syndrome is presented, and a possible mechanism is discussed.

Pancreatic pseudocyst mimicking idiopathic achalasia.

Colarian JH. Sekkarie M. Rao R.
Department of Medicine, Bluefield Regional Medical Center, West Virgina, USA.
Pseudoachalasia or secondary achalasia is commonly recognized and sought for in the context of an elderly patient presenting with weight loss and brief duration of symptoms. The majority of cases are caused by adenocarcinomas of the fundus or the cardia. It is accepted by gastroenterologists that endoscopy with "routine retroflexion" and biopsy are necessary in any newly diagnosed case of achalasia. Benign causes of pseudoachalasia are extremely rare in this country. In developing countries and South America, Chagas' Disease may mimic achalasia. Herein, we present a case of secondary achalasia linked to an unrecognized mediastinal pancreatic pseudocyst that resolved with appropriate treatment of the underlying cause.

Systemic mastocytosis: a rare cause of noncirrhotic portal hypertension simulating autoimmune cholangitis--report of four cases.

Kyriakou D. Kouroumalis E. Konsolas J. Oekonomaki H. Tzardi M. Kanavaros P. Manoussos O. Eliopoulos GD.
Department of Pathology, University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Four patients with systemic mastocytosis, two men and two women, are presented. Three of them (patients 1, 2, and 4) developed portal hypertension and ascites without histological evidence of cirrhosis in liver biopsy. The remaining patient (patient 3) had severe bone lesions with multiple vertebral fractures. None of the patients had skin or lymph node involvement. Two patients (patients 1 and 2) died 12 and 9 months after diagnosis with acute nonlymphocytic leukemia and overt mastocytic leukemia, respectively, while the other two (patients 3 and 4) are alive 58 and 14 months after diagnosis. Treatment with hydroxyurea or cytosine arabinoside had not any beneficial effect in two patients, while a substantial amelioration of back pain had been obtained by local irradiation and recombinant human interferon-alpha-2b administration in one patient (patient 3). All patients had laboratory findings compatible with autoimmune cholangitis. We concluded that systemic mastocytosis is a rare cause of noncirrhotic portal hypertension often simulating autoimmune cholangitis and leading to the erroneous diagnosis of liver cirrhosis. Diagnosis is based on the presence of mast cells in Giemsa-stained liver histological sections, and it may be confirmed by immunohistochemical detection of tryptase in the cytoplasm of these abnormally proliferating cells.

Carolis disease: a magnetic resonance cholangiopancreatography diagnosis.

Asselah T. Ernst O. Sergent G. L'hermine C. Paris JC.
Department of Hepatogastroenterology, Hopital Huriez, Centre Hospitalier Universitaire de Lille, France.
Magnetic resonance cholangiopancreatography (MRCP) has received much attention in the recent literature as a noninvasive alternative to endoscopic retrograde cholangiography, primarily for biliary calculus disease, but also for the less common indication of evaluation of biliary anomalies. We present a case of Caroli's disease in which the diagnosis can be clearly inferred by MRCP. The findings of MRCP and endoscopic retrograde cholangiopancreatography are similar. This new procedure could be a noninvasive alternative to direct cholangiography and perhaps will become the first-choice imaging technique for diagnosing Caroli's disease.

Metastatic breast cancer masquerading as gastrointestinal primary.

Schwarz RE. Klimstra DS. Turnbull AD.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Seven patients with metastatic breast cancer presenting as gastrointestinal primary are described. These included six gastric and one colonic lesions. None of the patients had known systemic metastases at the time of diagnosis. The mean age at presentation was 66.7 yr (range 55-78). Median interval between breast cancer and gastrointestinal metastasis diagnosis was 6 yr (range 0.25-12.5). Original breast cancer histology included infiltrating lobular cancer (n = 4), infiltrating ductal cancer (n = 1), and a mixed type (n = 2). All patients with gastric involvement presented with epigastric pain and early satiety; the patient with colonic involvement had heme-positive stool. In three cases of gastric tumor and the one case of colonic tumor presentation, a definitive diagnosis of metastatic breast cancer was only confirmed after surgical resection of a presumed primary gastric or colonic malignancy. In the other three cases, pathological diagnostic confirmation was obtained through endoscopic biopsies and comparison to breast biopsy material, and operative treatment was avoided in favor of systemic cytotoxic therapy. The diagnosis was confirmed through similarities between mammary and gastric histopathology with regard to growth pattern, hormone receptor status, or gross cystic disease fluid protein. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis will help avoid unnecessary surgical treatment in patients with a history of mammary carcinoma presenting with a newly diagnosed gastrointestinal neoplasm.

An autopsy case of Ki-1 lymphoma associated with hepatic failure.

Suzuki N. Tsuji H. Nakamura S. Asabe H. Sueishi K. Fujishima M.
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
A 62-year-old man was admitted to our hospital because of severe jaundice and fever. Physical examination demonstrated hepatosplenomegaly. The laboratory data revealed elevated serum bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase, and the reduced hepaplastin test (Normotest). Computed tomography showed hepatosplenomegaly and swelling of the paraaortic lymph nodes. Although he was treated with antibiotics and steroids, he died of hepatic failure 22 days after admission. At autopsy, his liver weighed 1910 grams, and a histological examination of the liver revealed marked infiltration of CD30 (Ki-1) positive lymphoma cells. He was diagnosed as having non-Hodgkin lymphoma, large cell anaplastic type, Ki-1 lymphoma. We herein report our findings of this very rare case of Ki-1 lymphoma associated with hepatic failure.

A new variant of food poisoning: enteroinvasive Klebsiella pneumoniae and Escherichia coli sepsis from a contaminated hamburger.

Sabota JM. Hoppes WL. Ziegler JR. DuPont H. Mathewson J. Rutecki GW.
Northeastern Ohio Universities College of Medicine, Affiliated Hospitals at Canton, 44708, USA.
For the first time, we report Klebsiella pneumoniae as an enteroinvasive food-borne pathogen transmitted from a hamburger. A 28-year-old previously healthy African-American male ingested a portion of a hamburger from a fast food chain. Symptoms of gastroenteritis rapidly deteriorated to multiorgan failure. Blood and hamburger cultures grew Escherichia coli and Klebsiella pneumoniae. Since Klebsiella had not previously been reported as enteroinvasive, the isolates were compared. Full biochemical profiles, antimicrobial sensitivity, plasmid profile, and toxin assay by DNA hybridization probe were completely concordant. The patient survived the episode of food-borne sepsis. Deliberate or inadvertent employee contamination of food products with feces may be a potential source of life-threatening food-borne illness.

Gastrointestinal infarction as a manifestation of rheumatoid vasculitis.

Babian M. Nasef S. Soloway G.
Department of Gastroenterology, Bridgeport Hospital, Connecticut 06610-3175, USA.
We report a case of combined small and large intestinal infarction caused by rheumatoid vasculitis in a 60-yr-old man who had a long history of rheumatoid arthritis and presented with abdominal pain and constipation. Eventually, he developed signs of peritonitis and underwent exploratory laparotomy and was found to have sigmoid and ileal infarction secondary to rheumatoid vasculitis.

Nonsteroidal-induced benign strictures of the colon: a case report and review of the literature.

Eis MJ. Watkins BM. Philip A. Welling RE.
University of Cincinnati College of Medicine, and Department of Surgery, Good Samaritan Hospital, Ohio 45220, USA.
Colonic strictures are a rare complication reported to result from chronic use of sustained release formulations of indomethacin and diclofenac. Such strictures often present with associated mucosal ulceration and are thought to result from nonsteroidal antiinflammatory drug-induced alterations in enterocyte homeostasis. Strictures generally occur in the cecum, ascending, and proximal transverse colon with symptoms of occult blood loss, obstruction, changes in bowel habits, and rarely, perforation. The first reported case of a 69-year-old woman who developed recurrent colonic strictures with inflammatory changes and mucosal ulceration while taking Lodine (etodolac) is presented. A brief review of the relevant literature and suggested preventative therapies are discussed.

Interferon-induced anosmia in a patient with chronic hepatitis C.

Maruyama S. Hirayama C. Kadowaki Y. Sagayama A. Omura H. Nakamoto M.
Department of Medicine, Saiseikai Gotsu General Hospital, Gotsu-City, Shimane, Japan.
We report a patient with chronic active hepatitis C developing acute anosmia during interferon (IFN) therapy. On July 31, he began receiving 6 MU of IFN-alpha daily. On September 26, he failed to smell gas leaking from a gas cooker, so IFN therapy was discontinued. He showed no reaction on a standard olfactory acuity test. As the patient had borderline diabetes, the association of anosmia with impaired glucose tolerance cannot completely be excluded, but his anosmia was probably induced by IFN therapy, since anosmia developed 10 days after the initiation of the IFN therapy, without any deterioration of his glucose intolerance.

A rare case of hepatic injury associated with ovarian hyperstimulation syndrome.

Shimono J. Tsuji H. Azuma K. Hashiguchi M. Fujishima M.
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
A 26-year-old married woman was admitted to our hospital because of massive ascites and hepatic injury. The patient had been treated with human menopausal gonadotropin and clomiphene citrate to prevent recurrence of spontaneous abortions. About 1 month later, she developed upper abdominal pain and noticed dark urine. On admission, she had elevated concentrations of serum transaminases with an asparate aminotransferase of 127 IU/L and alanine aminotransferase of 194 IU/L. An abdominal ultrasound showed massive ascites. Her serum concentration of estradiol was high at 12,100 pg/mL, which was much greater than the value of early stage of pregnancy (2,279-7,353 pg/mL). She was thus diagnosed as having ovarian hyperstimulation syndrome. Following a period of bed rest, her liver function normalized and the ascites disappeared. Based on the above findings, the patient was considered to have suffered from ovarian hyperstimulation syndrome, complicated by hepatic injury.

A case of ischemic colitis associated with pheochromocytoma.

Sohn CI. Kim JJ. Lim YH. Rhee PL. Koh KC. Paik SW. Rhee JC. Chung JH. Lee MS. Yang JH.
Department of General Surgery, Samsung Medical Center, Seoul, Korea.
A 40-year-old woman was admitted because of abdominal pain and diarrhea. She sometimes experienced paroxysmal hypertension, sweating, headache, and palpitation. Sigmoidoscopic findings showed well-demarcated diffuse mucosal edema, hyperemia, and easy touch bleeding from distal descending colon up to the splenic flexure area. Barium x-ray showed loss of haustral marking, thumb printing appearance, and diffuse luminal stenosis in the transverse, descending, and sigmoid colon. On the abdominal computed tomogram, a 3.8-cm sized well-enhanced right adrenal mass was incidentally found. Twenty-four hour urinary excretion of vanillyl mandelic acid, norepinephrine, and normetanephrine were increased. Iodine131 metaiodobenzylguanidine scan showed hot uptake on the right adrenal gland compatible with pheochromocytoma. Exploratory laparotomy was done under the impression of ischemic colitis associated with pheochromocytoma. Adrenalectomy and resection of the stenotic left colon were performed. After surgery, pain subsided, blood pressure fell gradually, blood sugar and catecholamine level became normal, and bowel habit returned to normal.

Milk thistle (Silybum marianum) for the therapy of liver disease.

Flora K. Hahn M. Rosen H. Benner K.
Division of Gastroenterology, Oregon Health Sciences University, Portland 97201-3098, USA.
Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.

Inflammatory bowel disease and smoking--a review.

Thomas GA. Rhodes J. Green JT.
Department of Gastroenterology, University Hospital of Wales, Cardiff, United Kingdom.
The relationship between smoking and inflammatory bowel disease is a curious but well-established one. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. It also has opposite influences on the clinical course of the two conditions with possible beneficial effect in ulcerative colitis and detrimental effect in Crohn's disease. The diametrically "opposite" relationship of smoking status with the two conditions has been the subject of much interest in the hope that it may reveal pathogenic mechanisms responsible for the two conditions and possibly offer the key to alternative therapeutic options. Nicotine may be the principal agent in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role and possible mechanisms of action. In this article, we review the historical, clinical, and therapeutic aspects of the association between smoking and inflammatory bowel disease.

A pilot study on modified endoscopic variceal ligation using endoscopic ultrasonography with color Doppler function.

Nagamine N. Ueno N. Tomiyama T. Aizawa T. Tano S. Wada S. Suzuki T. Amagai K. Ono K. Kumakura Y. Hirasawa T. Ishino Y. Ido K. Kimura K.
Department of Gastroenterology, Jichi Medical School, Yakushiji, Tochigi, Japan.
OBJECTIVE: The purpose of the study was to evaluate feasibility of modified endoscopic variceal ligation (EVL), namely the "intensive ligation" method, using endoscopic ultrasonography with color Doppler function (EUS-CD). METHODS: Forty-five patients with esophageal varices were treated by modified EVL. Variceal hemodynamics in 38 patients were examined using EUS-CD, which showed abdominal hemodynamics in detail under physiological conditions before and after the modified procedure. RESULTS: 1) The median number of treatment sessions was 3.2, and 41 O-rings on average were required per individual patient. 2) The median nonrecurrence period after treatment was 18 months (Kaplan-Meier method). 3) Nine patients with a good response to modified EVL did not have recurrences for 16.9+/-2.8 months, and five with a poor response had recurrences at 5.8+/-2.2 months. Gastric varices were related to the response to modified EVL (p < 0.05, Mann-Whitney's U test). 4) Minor complications in modified EVL as well as standard EVL were experienced; however, we had a patient with the development of meningitis, which was a major septic complication. 5) Before modified EVL, EUS-CD demonstrated that good responders had undeveloped (grade I) gastric varices in five of nine (56%); however, poor responders had developed (grade III) gastric varices in four of five (80%) (p < 0.05, Mann-Whitney's U test]. 6) After modified EVL, EUS-CD revealed that six of nine (67%) good responders and one of five (20%) poor responders showed a decrease in color signals in supplying veins; however, none of the former (0%) and three of the latter (60%) showed an increase (p < 0.05, Mann-Whitney's U test]. CONCLUSION: Modified EVL was safe and effective, at least with regard to intermediate-term outcome, especially when treating patients with undeveloped gastric varices revealed by EUS-CD. Both good and poor responders showed no exacerbation of gastric varices after the modified procedure, ultrasonographically as well as endoscopically.

Intraductal papillary tumors of the pancreas: evaluation with magnetic resonance cholangiopancreatography.

Sugiyama M. Atomi Y. Hachiya J.
The First Department of Surgery, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
OBJECTIVE: We analyzed the findings of intraductal papillary tumors of the pancreas by magnetic resonance cholangiopancreatography (MRCP). METHODS: Twelve patients with intraductal papillary tumors (main duct type, n = 3; branch duct type, n = 8; combined type, n = 1) underwent endoscopic retrograde cholangiopancreatography (ERCP) (n = 11) and MRCP, using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences (n = 12). Imaging findings were compared with operative and pathological findings in all the patients. RESULTS: Although ERCP failed to fully depict the main pancreatic duct and cystic tumors in six of 11 patients because of copious intraductal mucin, MRCP provided complete images of these structures in all 12 patients. In main duct type tumors, MRCP demonstrated moderate-marked, diffuse dilation of the main pancreatic duct. Branch duct type tumors showed "grape-like" clusters of cysts with no or only mild, diffuse dilation of the main duct. In combined type tumors, MRCP demonstrated a markedly dilated main duct with a large unilocular cyst of the collateral duct. MRCP detected more mural nodules (75%, three of four patients) than ERCP (25%, one of four). MRCP allowed more precise diagnosis of the type, size, and extent of tumors than ERCP, as confirmed by pathologic findings. CONCLUSION: MRCP demonstrates intraductal papillary tumors less invasively and more completely than ERCP.

Quality of life after proctocolectomy and ileo-anal anastomosis for severe ulcerative colitis.

Martin A. Dinca M. Leone L. Fries W. Angriman I. Tropea A. Naccarato R.
Divisione di Gastroenterologia e Clinica Chirurgica I, Universita degli Studi di Padova, Italy.
OBJECTIVE: Impaired quality of life (QOL) in patients with ulcerative colitis (UC) may be a prominent feature of the disease, and in some cases, may become an indication for surgical treatment. The objective of this study was to assess QOL in patients who underwent proctocolectomy with ileo-anal anastomosis with a J pouch for severe UC and to compare it with patients with UC of different severity who were under medical treatment. METHODS: We used a validated, disease-specific research instrument (a 29 item, self-administered questionnaire) that examines the following four functions: intestinal (score 0-24) and systemic symptoms (0-21), and emotional (0-27) and Social Function (0-15). High scores indicate an impairment of the function examined and the sum of the four scores (maximal total score = 87) reflects the patient's QOL. We studied 29 operated patients (22 men, mean age 35 yr, mean time after intervention 3.8 yr) and compared their scores with those of 57 UC patients (39 men, mean age 36 yr) with different degrees of disease activity, and with those of 72 healthy controls (38 men, mean age 31 yr). RESULTS: In UC, scores were significantly higher than in controls, increasing with the severity of the disease. Even patients in remission had higher scores than controls in the "systemic" (4.6 vs. 2.0) and emotional (5.6 vs. 2.5) functions. Patients who underwent surgical treatment had much better scores than patients with severe disease (total score 20.1 vs. 38.2), with values comparable to those of patients in remission or with mild disease activity. There was no significant gender difference, either for UC and ileo-anal anastomosis patients, or in healthy controls. CONCLUSION: In patients with UC, even in remission, there is a measurable impairment of QOL, which increases with the severity of disease. Operated patients have a QOL that is comparable to that of patients in remission or with mild disease, and proctocolectomy with ileo-anal anastomosis may restore an acceptable QOL in patients with moderate/severe UC.

Etiology and outcome of lower gastrointestinal bleeding in patients with AIDS.

Chalasani N. Wilcox CM.
Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
OBJECTIVE: The objective of the study was to investigate bleeding (LGIB) in patients with acquired immunodeficiency syndrome (AIDS). METHODS: All hospitalized AIDS patients with LGIB evaluated by the gastroenterology service at a large city-county hospital during a 6 yr period were identified by database review and by endoscopy and consultation records. RESULTS: Of the 691 AIDS patients seen during the study period, 18 (2.6%) (median age 41+/-7 years) were evaluated for LGIB. In these patients, LGIB was caused by human immunodeficiency virus type 1 (HIV)-associated disorders in 72% including cytomegalovirus colitis in seven patients, idiopathic colonic ulcers in five patients, and intestinal Kaposi's sarcoma in one patient. HIV-associated thrombocytopenia contributed to substantial bleeding from hemorrhoidal disease in two patients. Rebleeding occurred in four patients (22%), including hemorrhoids in three and idiopathic colonic ulcers in one. Surgery was not performed in any patient. Following the institution of ganciclovir therapy, no patient with CMV colitis had recurrent bleeding. The in-hospital mortality was high (28%), although bleeding was the direct cause of death in only one patient. CONCLUSIONS: LGIB is infrequent in patients with AIDS and is usually caused by opportunistic diseases specifically related to immunodeficiency. Although some of these conditions are potentially treatable medically, in-hospital mortality is high and long-term prognosis is poor because of AIDS-related comorbidity.

The outpatient evaluation of hematochezia.

Segal WN. Greenberg PD. Rockey DC. Cello JP. McQuaid KR.
San Francisco Veterans Affairs Hospital, University of California San Francisco, USA.
OBJECTIVE: The objective of this study was to determine whether specific clinical symptoms associated with hematochezia are predictive of important GI pathology and whether full colonoscopic examination is necessary. METHODS: A total of 103 outpatients (> or = 45 yr) with hematochezia, defined as the passage of bright red blood per rectum, underwent anoscopy and colonoscopy. Before endoscopy, patients completed a detailed interview, quantitating the amount and frequency of bleeding, weight loss, use of aspirin/NSAIDs, change in bowel habits, family history, and prior GI illnesses. Based on this information, physicians were asked to predict whether the bleeding was from a perianal or more proximal site. At colonoscopy, pathology was stratified as either proximal or distal to the sigmoid/descending junction. Substantial pathology was defined as one or more adenomas > 8 mm, carcinoma, or colitis. RESULTS: Anoscopy demonstrated internal and external hemorrhoids in 78 and 29 patients, respectively. On colonoscopy, 36 patients had 43 substantial lesions. Thirty-seven of these lesions were distal to the junction of the descending and sigmoid colons and six were proximal lesions. Four patients had cancer; all were distal lesions. Patients with substantial lesions were more likely to give a history of blood mixed within their stool (p = 0.03), to have more episodes of hematochezia per month (p = 0.008), and to have a significantly shorter duration of bleeding before medical evaluation (p = 0.02) than did patients without such lesions. However, the physician's clinical assessment did not predict reliably which patients were likely to have substantial pathology. CONCLUSIONS: In patients with hematochezia, clinicians were unable to distinguish between those patients with and those without significant colonic lesions by history alone. Flexible sigmoidoscopy would have demonstrated most (95%) substantial lesions. The lesions that flexible sigmoidoscopy missed were an unlikely cause of bleeding in this small group of patients.

Geographic distribution of constipation in the United States.

Johanson JF.
University of Illinois College of Medicine, Rockford 61107-5078, USA.
OBJECTIVE: Despite its frequent occurrence, the etiology of constipation has remained poorly understood. The influence of widely accepted risk factors such as inadequate dietary fiber intake, immobility, insufficient fluid intake, and poor muscle tone is unclear. This study examined the geographic distribution of constipation among Medicare beneficiaries to identify potential environmental risk factors. METHODS: All Medicare beneficiaries with a diagnosis of constipation were extracted from the total Health Care Financing Administration data file of 1987 and stratified by sex, race, and state of residence. The population of each state by sex, race, and age >65 yr served as the denominator to calculate sex- and race-specific morbidity rates. RESULTS: A distinct geographic distribution was observed. When stratified by individual states, hospital discharges for constipation were more common in rural as compared with urban states. Constipation also appeared to be more common in northern and in poorer states. CONCLUSION: The distinct geographic pattern of constipation suggests the influence of three global environmental factors: rural living, colder temperature, and lower socioeconomic status.

Comparison of two interferon alfa treatment regimens characterized by an early virological response in patients with chronic hepatitis C.

Kagawa T. Hosoi K. Takashimizu S. Kawazoe K. Mochizuki K. Wasada M. Nagata N. Uchiyama J. Nakano A. Nishizaki Y. Watanabe N. Matsuzaki S.
Department of Internal Medicine (III), Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan.
OBJECTIVE: We investigated the efficacy of an interferon regimen characterized by an early virological response in patients with chronic hepatitis C and evaluated whether the patient's virological status during therapy would be useful for predicting a complete response. METHODS: We treated 62 patients with chronic hepatitis C with 6 million units (MU) of human lymphoblastoid interferon daily for 4 wk. The serum HCV RNA was assayed at week 2 by the reverse transcription-polymerase chain reaction. HCV RNA-negative patients (group A) received 6 MU of interferon three times weekly for an additional 22 wk (total dose, 564 MU). HCV RNA-positive patients were randomly assigned to group B-1, which received the same regimen as group A, or to group B-2, which received 6 MU of interferon daily for 4 wk followed by 6 MU three times weekly for 18 wk (total dose, 660 MU). RESULTS: Complete responses were achieved by 19 (63.3%) of 30 group A patients, compared with one (6.3%) of 16 group B-1 patients and none of 16 group B-2 patients. The virological response at week 2 and the pretreatment serum HCV RNA level were independent significant predictors of a complete response. CONCLUSION: Patients who were still HCV RNA-positive at week 2 were unlikely to achieve a complete response after interferon therapy. An increase in the total dose of interferon failed to yield further benefit in these patients.

Do parotid duct abnormalities occur in patients with chronic alcoholic pancreatitis?

Sagatelian MA. Fravel J. Gallo SH. Makk LJ. Looney SW. Wright RA.
Department of Medicine, University of Louisville, Kentucky 40292, USA.
OBJECTIVE: Several studies have suggested that ethanol affects the pancreas and parotid gland. We performed a prospective study to determine whether ductal lesions of ethanol-induced chronic pancreatitis occur in the parotid. METHODS: Parotid sialograms were performed in 11 alcoholic patients who had endoscopic retrograde pancreatograms. Sialograms and pancreatograms were examined in all subjects for ductal abnormalities. RESULTS: Seven of nine patients (77.8%) with ductal lesions of the pancreas had coexistent ductal abnormalities of the parotid gland (Kendall's tau = 0.578, p = 0.035). CONCLUSIONS: Chronic ethanol intake induces ductal alterations in the parotid gland similar to those seen in the pancreas. These results suggest a common histopathological effect of alcohol in the ductal system of the parotid gland and pancreas and raise the possibility that the parotid sialogram could be useful as an adjunct in the diagnosis of ethanol-induced chronic pancreatitis.

Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease?

Geboes K. Ectors N. D'Haens G. Rutgeerts P.
Department of Pathology, University Hospitals, Leuven, Belgium.
OBJECTIVE: To assess the value of adding ileoscopy with biopsy to colonoscopy, hence increasing the indications for ileoscopy in patients presenting with symptoms of inflammatory bowel disease. METHODS: Two hundred fifty-seven patients with persistent diarrhea and 43 patients with sporadic colonic polyps were studied prospectively. The final diagnosis based on clinical and follow-up data, the histology of multiple ileal biopsies, and endoscopic findings were analyzed. RESULTS: Endoscopic lesions of the terminal ileum were found in 123 of 300 patients. In the 43 patients with colonic polyps, no ileal lesions were seen. Ileal disease without colonic involvement was present in 44 of 123 patients. Microscopic lesions of the ileum were present in 125 of 300, or in 125 of 257 (49%) with symptoms of diarrhea. Two of these had a normal endoscopy. Thirteen patients had a diffuse colitis and 11 had a predominantly left-sided colitis, both originally suggestive of ulcerative colitis. Crohn's disease was diagnosed in 88 patients and infectious disease in 17. Ileal biopsies were essential for the diagnosis in 15 patients and were contributive in 53. Granulomas, solitary giant cells, pseudopyloric gland metaplasia, eosinophils, and a disturbed villous architecture were the most important lesions observed in Crohn's disease and were contributive for this diagnosis. CONCLUSIONS: Ileoscopy with biopsy is useful in carefully selected patients presenting with symptoms of inflammatory bowel disease. The main indications are diagnosis of isolated ileal disease in the presence of a normal colon and differential diagnosis in patients with pancolitis and predominantly left-sided colitis. Multiple biopsy specimens show definite pathology in almost half of the patients.

Simplified 10-day bismuth triple therapy for cure of Helicobacter pylori infection: experience from clinical practice in a population with a high frequency of metronidazole resistance.

Lerang F. Moum B. Ragnhildstveit E. Sandvei PK. Tolas P. Whist JE. Henriksen M. Haug JB. Berge T.
Department of Internal Medicine, Ostfold Central Hospital, Fredrikstad, Norway.
OBJECTIVE: To evaluate the cure rate of Helicobacter pylori infection, including the impact of in vitro metronidazole resistance (M-R), and the side effects of a simplified 10-day bismuth triple therapy in routine clinical practice. METHODS: From September 1995 to March 1996, 248 consecutive H. pylori-positive patients received 10 days of bismuth subnitrate 150 mg, oxytetracycline 500 mg, and metronidazole 400 mg, all t.id. Before treatment, upper endoscopy, including biopsy specimens for microbiological analysis and IgG serology were performed. M-R was found in 45% of females and 36% of males. At least 2 months after treatment, H. pylori status was assessed by the 14C urea breath test (n = 131), endoscopy (n = 37), urea breath test and endoscopy (n = 63), or solely by IgG serology (n = 7). Ten patients withdrew. IgG serology was performed again after 1 yr. RESULTS: H. pylori infection was cured in 205 patients: 86% by all-patients-treated analysis and 83% by intention-to-treat analysis. When patients were classified according to pretreatment metronidazole susceptibility, cure of infection was achieved in 76% of females harboring M-R strains versus 96% of those with sensitive strains (p = 0.002) and in 81% versus 88% (p = 0.34) of males with M-R versus sensitive strains, respectively. Twelve patients (5 %) had to stop treatment prematurely because of severe side effects, but eight of them were treated successfully. One case of H. pylori infection (0.6 %) was detected at 1-yr follow-up. CONCLUSIONS: Ten-day bismuth triple therapy t.i.d. was effective in curing H. pylori infection in the context of routine clinical practice. The efficacy was reduced in females harboring M-R strains.

Prospective comparison of rapid urease tests (PyloriTek, CLO test) for the diagnosis of Helicobacter pylori infection in symptomatic children: a pediatric multicenter study.

Elitsur Y. Hill I. Lichtman SN. Rosenberg AJ.
Pediatric Gastrointestinal Divisions of Marshall University, Huntington, West Virginia 25701-0195, USA.
OBJECTIVE: Rapid urease tests are reliable methods to diagnose Helicobacter pylori (HP) infection in the endoscopy suite. The PyloriTek test kit is a new rapid urease test that has the advantage of a 1-h final reading. The aim of this study was to compare the accuracy of PyloriTek and the test in the diagnosis of H. pylori infection in children. METHODS: Children from four different pediatric gastroenterology centers were recruited prospectively into the study. These children were >5 yr old and had an upper endoscopy procedure. Antral biopsies were examined for both rapid urease tests in the endoscopy suite, and others were sent for routine histological examination. RESULTS: A total of 242 children were recruited into the study over approximately 1 yr. The concordance between PyloriTek and CLO test was 98% (238 of 242). Twenty-five children were positive for HP organisms by PyloriTek and CLO test, whereas four children were positive by PyloriTek but negative by CLO test. PyloriTek was comparable to CLO test for the diagnosis of HP organisms and HP-associated gastritis. Moreover, in 48% of the positive results, PyloriTek gave significantly faster results than CLO test. CONCLUSIONS: We conclude that PyloriTek is an appropriate rapid urease test to use in children and may have an advantage over the CLO test because of its shorter reading time.

A study of the prevalence of Helicobacter pylori infection and other markers of upper gastrointestinal tract disease in patients with rosacea.

Sharma VK. Lynn A. Kaminski M. Vasudeva R. Howden CW.
Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, USA.
OBJECTIVE: Recent reports have suggested that patients with rosacea, a chronic inflammatory skin disorder of unknown etiology, have an increased prevalence of Helicobacter pylori infection. However, no causal relation has been identified. This study was designed to determine the prevalence of H. pylori infection and upper gastrointestinal symptoms in rosacea patients and in subjects without chronic skin disorders. METHODS: Forty-five patients with rosacea and 43 healthy subjects underwent serological testing for H. pylori infection. Demographics, gastrointestinal symptoms, and medication use were recorded using a structured questionnaire. RESULTS: There was no significant difference in the seroprevalence of H. pylori infection between rosacea patients and healthy subjects (26.7% vs 34.9%; p = 0.40). Significantly more patients with rosacea complained of indigestion (66.7% vs 32.6%; p = 0.001) and used antacids (60% vs 32.6; p = 0.01). There was no significant difference in the prevalence of H. pylori infection between symptomatic and asymptomatic rosacea patients, or in those using antacids. There were no differences in the frequency of heartburn, history of peptic ulcer disease, family history of peptic ulcer disease, use of H2-receptor antagonists, or use of nonsteroidal antiinflammatory drugs. CONCLUSIONS: Patients with rosacea have similar rates of H. pylori infection as healthy subjects. Rosacea patients complain significantly more frequently of "indigestion" and use more antacids unrelated to H. pylori infection.

Anti-Helicobacter pylori specific antibody immunohistochemistry improves the diagnostic accuracy of Helicobacter pylori in biopsy specimen from patients treated with triple therapy.

Marzio L. Angelucci D. Grossi L. Diodoro MG. Di Campli E. Cellini L.
Institute of Fisiopatologia Medica, Universita G. D'Annunzio, Chieti, Italy.
OBJECTIVE: To investigate the effectiveness of immunohistochemical technique to detect Helicobacter pylori (H. pylori) in patients treated with triple therapy. METHODS: Forty patients (18 men, 22 women, mean age 43 years) with active antral gastritis, H. pylori positive at urease test, culture, and histology, were treated for 1 wk with omeprazole, amoxicillin, and metronidazole. Gastritis was scored according to Sydney criteria. Two months after the end of therapy, endoscopy, urease test, culture, and histology were repeated. RESULTS: Culture and histology were negative in 32 (80%) of treated cases. Biopsy specimens of the eradicated group were stained with immunohistochemical technique using an anti-H. pylori specific polyclonal antibody. In 12 of 32 (37.5%) patients, clusters of round or vibrio-shaped bacteria, unidentified at histology, were stained by the specific anti-H. pylori antibody. After triple therapy, at histology all patients were found with improved gastritis. In six patients however, mucosal-associated lymphoid tissue (MALT) appearance, present before therapy, persisted after therapy. In five of six patients with MALT, immunostaining with anti-H. pylori antibody was positive. CONCLUSIONS: The immunohistochemical technique is more accurate than classical methods in identifying H. pylori after specific therapy. This method should, therefore, be used in all studies that aim to achieve eradication. Whether the H. pylori identified at immunohistochemistry is able to reactivate and induce recrudescence of infection remains to be clarified.

Helicobacter pylori cytotoxic genotype is associated with peptic ulcer and influences serology.

Navaglia F. Basso D. Piva MG. Brigato L. Stefani A. Dal Bo N. Di Mario F. Rugge M. Plebani M.
Department of Laboratory Medicine, University Hospital of Padova, Italy.
OBJECTIVE: We studied 146 patients with peptic ulcer disease (n = 72), antral gastritis (n = 58), or duodenitis (n = 16) to ascertain whether the cytotoxic genotype of Helicobacter pylori (Hp) is associated with peptic ulcer disease and/or antral gastritis and whether it influences the circulating levels of total anti-Hp antibodies, anti-cagA antibodies, and pepsinogens. METHODS: A gastric juice sample was obtained from each patient. After DNA extraction, polymerase chain reaction was used to amplify the genes urease A (ureA), cagA, and vacA of Hp. RESULTS: A significant association was found between peptic ulcer disease and the cytotoxic genotypes, characterized by the presence of s1 and m1 alleles of vacA and by cagA. Patients with a cagA-positive genotype showed a significant increase in anti-cagA antibodies and also had significantly increased circulating levels of pepsinogen C. CONCLUSIONS: Cytotoxic Hp strains are mainly involved in determining peptic ulcer disease, but not antral gastritis. The higher levels of circulating pepsinogen C found in patients infected with cytotoxic genotypes may reflect the higher degree of inflammation sustained by these strains.

Risk of breast cancer in men with liver cirrhosis.

Sorensen HT. Friis S. Olsen JH. Thulstrup AM. Mellemkjaer L. Linet M. Trichopoulos D. Vilstrup H. Olsen J.
The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, Aarhus University, Denmark.
OBJECTIVE: Liver cirrhosis is associated with increased levels of estrogens, which may be causally related to breast cancer. Because background estrogen levels are lower in men than in women, an estrogen-mediated link between liver cirrhosis and breast cancer would be easier to detect in men. METHODS: Men hospitalized with liver cirrhosis in Denmark from January 1, 1977, to December 31, 1989, were followed up, through record linkage, until the end of December 1993 for the possible occurrence of breast cancer. RESULTS: A total of 11,642 men with liver cirrhosis were identified and were followed for a mean period of 4.3 yr, for a total of 49,687 person-years. Three cases of male breast cancer were observed whereas 0.75 was expected, for a standardized incidence ratio of 4.0 (95% confidence interval, 0.8-11.7). CONCLUSIONS: Cirrhosis, possibly via high levels of endogenous estrogens, increases the risk of breast cancer in men.

Liver damage in human small intestinal bacterial overgrowth.

Riordan SM. McIver CJ. Williams R.
Institute of Hepatology, University College London Medical School, England.
OBJECTIVE: Some rodent strains with experimental small intestinal bacterial overgrowth (SIBO) unrelated to jejunoileal bypass are susceptible to hepatic damage, possibly because of increased small intestinal permeability to proinflammatory bacterial polymers. However, data on the prevalence of hepatic damage in human subjects with SIBO in this setting are lacking. This study addressed this issue. METHODS: Seventy adult subjects were investigated for possible SIBO and hepatic damage with bacteriological analysis of small intestinal aspirates and measurement of serum concentrations of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, and alanine aminotransferase. Nutritional indices (serum albumin and anthropometry) and the urinary lactulose/mannitol ratio, an index of small intestinal permeability, were measured in all subjects with SIBO and liver damage. RESULTS: SIBO was present in 40 of 70 subjects (57.1%). Overgrowth flora included salivary-type bacteria alone in 11 subjects and colonic-type bacteria in 29 subjects (facultative anaerobes [Enterobacteriaceae] alone in 21 subjects and both facultative and obligate anaerobes [Enterobacteriaceae and Bacteroides spp] in eight subjects). Biochemical evidence of liver damage was found in zero of 30 subjects without SIBO, zero of 11 subjects with SIBO with salivary-type bacteria alone, zero of 21 subjects with SIBO with facultative but not obligate anaerobic colonic-type bacteria, and in one of eight subjects (12.5%) with SIBO with obligate anaerobic colonic-type bacteria, in whom serum alkaline phosphatase and gamma-glutamyl transpeptidase levels were elevated. Nutritional indices were normal in this patient. Small intestinal permeability was increased and, along with liver enzyme abnormalities, normalized after eradication of SIBO. Small intestinal permeability was also increased in three of six patients (50.0%) with SIBO with obligate anaerobic colonic-type bacteria who had no evidence of liver damage. CONCLUSIONS: SIBO per se is not a major risk factor for liver damage in humans, even when the overgrowth flora includes obligate anaerobes. Liver damage is not a necessary consequence of increased small intestinal permeability in this setting.

A placebo-controlled dose-ranging study of lansoprazole in the management of reflux esophagitis.

Earnest DL. Dorsch E. Jones J. Jennings DE. Greski-Rose PA.
University of Arizona Health Sciences Center, Tucson, USA.
OBJECTIVE: We compared the efficacy of three different doses of the proton pump inhibitor lansoprazole in the management of reflux esophagitis. METHODS: Two hundred ninety-two patients with endoscopically confirmed reflux esophagitis were enrolled in a double-blind, multicenter study and were randomized to lansoprazole 15, 30, or 60 mg or placebo administered once daily for 8 wk. RESULTS: Healing rates after 4 wk of lansoprazole 15, 30, and 60 mg/d were 67.6%, 81.3%, and 80.6%, respectively. These were all significantly superior (p < 0.001) to placebo, which produced endoscopic healing in only 32.8% of the patients after 4 wk. The 4-wk healing rates with lansoprazole 30 or 60 mg were significantly higher than that with lansoprazole 15 mg (p < 0.05), confirming a dose-response effect. Cumulative healing rates after 8 wk of treatment were 52.5% with placebo and 90.0%, 95.4%, and 94.4% with lansoprazole 15, 30, and 60 mg, respectively (p < 0.001 for all doses of lansoprazole vs placebo). Lansoprazole was also significantly superior to placebo in relieving symptoms in patients with reflux esophagitis. Lansoprazole was well tolerated, and no serious treatment-related adverse events were encountered. Up to 3 months after discontinuation of treatment, all lansoprazole-treated groups had more patients free of endoscopic evidence of esophagitis than the group treated with placebo. CONCLUSIONS: Lansoprazole was safe and effective for the treatment of reflux esophagitis in this trial. This study indicates that the optimum daily dose of lansoprazole for reflux esophagitis is 30 mg.

Circulating vascular endothelial growth factor in patients with colorectal cancer.

Fujisaki K. Mitsuyama K. Toyonaga A. Matsuo K. Tanikawa K.
Second Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
OBJECTIVE: The expression of vascular endothelial growth factor (VEGF), a glycoprotein that selectively promotes proliferation of endothelial cells, has been associated with cancer development. The aim of the present study was to determine whether serum levels of VEGF correlate with disease progression in patients with colorectal cancer. METHODS: VEGF levels were measured by a highly sensitive enzyme-linked immunosorbent assay in sera from 67 patients with colorectal cancer, 14 patients with colorectal adenomas, and 72 healthy volunteers, and in tissue homogenates from 10 patients with colorectal cancer. RESULTS: Serum VEGF levels were significantly higher in patients with colorectal cancer than in patients with colorectal adenomas or in normal controls (p < 0.01). In patients with colorectal cancer, serum VEGF levels were significantly associated with Dukes stage (p < 0.01) and with carcinoembryonic antigen levels (r = 0.725, p < 0.001). Patients with hepatic and/or lymph node metastasis had higher serum VEGF levels than those without. Surgical resection of the colorectal tumor led to a decrease in serum VEGF levels whether or not metastasis was present (p < 0.05). The tumor-bearing tissue contained significantly more VEGF than normal-appearing mucosa (p < 0.05). CONCLUSIONS: VEGF is involved in the development of colorectal cancer. Measurement of VEGF in the serum may be a useful noninvasive clinical marker for evaluating the disease status.

Cholangiocarcinoma presenting as pyogenic liver abscess: is its outcome influenced by concomitant hepatolithiasis?

Jan YY. Yeh TS. Chen MF.
Department of Surgery, Chang-Gung Memorial Hospital, Chang-Gung University, Taipei, Taiwan.
OBJECTIVE: The etiology of pyogenic liver abscess is changing. Malignant biliary obstruction has emerged as one of the most important causes. We explored the clinical course of pyogenic liver abscess caused by cholangiocarcinoma. METHODS: The medical records of 19 patients with cholangiocarcinoma presenting as pyogenic liver abscess were reviewed. Of them, 57.8% (11 of 19) had concomitant hepatolithiasis. Escherichia coli and Klebsiella pneumoniae were the most common pathogens isolated from aspirates of the abscesses. Eight patients received percutaneous drainage, whereas 11 patients initially underwent surgical drainage because of the presence of ascites or coagulopathy or lack of awareness of the underlying cholangiocarcinoma. RESULTS: Overall, the hospital mortality rate was 36.8% (seven of 19). Patients with hepatolithiasis had a hospital mortality rate of 54.5% (six of 11), compared with 12.5% (one of eight) in those without (p < 0.01). Notably, 84.2% (16 of 19) of the patients died within 6 months after the diagnosis was made. CONCLUSIONS: Cholangiocarcinoma presenting as liver abscess has a dismal prognosis. Concomitant hepatolithiasis worsened the infectious process and adversely affected the survival.

Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: a case report and review of the Japanese literature.

Horiuchi A. Kawa S. Akamatsu T. Aoki Y. Mukawa K. Furuya N. Ochi Y. Kiyosawa K.
Second Department of Internal Medicine, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
We report a case demonstrating the progressive narrowing of the pancreatic duct, which is presumed to be characteristic of autoimmune pancreatitis, and we review the 37 cases of chronic pancreatitis in which autoimmunity was suggested as an etiological factor in the Japanese literature. A 55-year-old man presented with abdominal discomfort, jaundice, and diffuse swelling of the pancreas on ultrasonography. Serial endoscopic retrograde pancreatography demonstrated the progression of an irregular narrowing of the main pancreatic duct forming diffusely over the course of 2 months. Because the patient had hyperglobulinemia and tested positive for autoantibodies, he was diagnosed as a case of autoimmune chronic pancreatitis. Steroid therapy was carried out with excellent success.

Pouchitis associated with primary cytomegalovirus infection.

Moonka D. Furth EE. MacDermott RP. Lichtenstein GR.
Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
We report a patient with a history of ulcerative colitis status after total proctocolectomy with an ileoanal J pouch who presented with marked, refractory pouchitis associated with a primary cytomegalovirus (CMV) infection. The patient had atypical lymphocytosis in the blood and serology consistent with primary CMV infection. Biopsies of the pouch revealed CMV inclusion bodies and yielded positive CMV cultures. The patient improved clinically with resolution of pouchitis after a 10-day course of therapy with gancyclovir and has remained in remission for over 5 yr. This is the first report of pouchitis associated with a primary CMV infection. This case demonstrates that CMV infection is in the differential diagnosis for causes of pouchitis, and it suggests that the pouch, like the colon, is a potential site for a primary CMV infection in an immunocompetent host.

Strictureplasty with a pedunculated jejunal patch in Crohns disease of the duodenum.

Eisenberger CF. Izbicki JR. Broering DC. Bloechle C. Steffen M. Hosch SB. Broelsch CE.
Department of Surgery, University Hospital-Eppendorf, Hamburg, Germany.
Surgical treatment for duodenal stenosis caused by Crohn's disease is only indicated in symptomatic duodenal obstruction when conservative treatment has failed. Previously described operative procedures include strictureplasty for short stenoses and bypass or resectional procedures, if duodenal stenosis is extensive. In this case of an extensive duodenal Crohn's stenosis, we performed a strictureplasty of the duodenum with a pedunculated jejunal patch. Thus, duodenal passage could be well preserved, and the patient has remained asyptomatic during a follow-up of more than 9 months.

Oral budesonide for lymphocytic colitis.

Van Gossum A. Schmit A. Peny MO.
Department of Gastroenterology, Erasme Hospital, Free University of Brussels, Belgium.
Lymphocytic colitis is a rare inflammatory colonic disease of unknown etiology accompanied by watery diarrhea. Diagnosis is based upon pathological examination of colonic biopsies. Treatment essentially involves antiinflammatory agents such as sulfasalazine/5-ASA or corticosteroids if necessary. We report the case of a female patient suffering from severe lymphocytic colitis who remained unresponsive after 5-ASA therapy but who improved dramatically after oral budesonide administration.

Recurring encephalopathy abolished by gastrorenal shunt ligation in a diabetic hemodialysis patient.

Shimono J. Tsuji H. Azuma K. Hashiguchi M. Fujishima M.
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
A 57-year-old man was admitted to our hospital for hepatic encephalopathy. He previously had undergone a partial gastrectomy for gastric ulcer, and also had been on maintenance hemodialysis because of diabetic nephropathy. Despite treatment with branched-chain amino acids and lactulose, encephalopathy occurred repeatedly. The findings of his laboratory examinations, computed tomography, and liver biopsy were not suggestive of chronic liver damage. Angiography revealed a portal-systemic shunt from the superior mesenteric vein via the left gastric vein to the left renal vein. A ligation of the gastrorenal shunt was performed. After the shunt ligation, hepatic encephalopathy no longer recurred, and no medication was required to prevent it. The insulin requirements also decreased, the plasma ammonia concentration then decreased, and serum concentration of several amino acids related to the ammonia metabolism also decreased. The molar ratio of branched-chain amino acids to aromatic amino acids increased. The ligation of the portal-systemic shunt was thus considered to be the key to the successful treatment of hepatic encephalopathy in this unusual case.

Successful therapy of bleeding duodenal varices by TIPS after failure of sclerotherapy.

Jonnalagadda SS. Quiason S. Smith OJ.
Gastroenterology and Liver Disease, Truman Medical Center, UMKC School of Medicine, Kansas City, Missouri 64104, USA.
Hemorrhage from duodenal varices may be severe and life threatening. We report a patient with portal hypertension and bleeding duodenal varices caused by cirrhosis of the liver. Endoscopic sclerotherapy and intravenous vasopressin failed to control bleeding in this patient. Hemorrhage was subsequently controlled by placement of a transjugular intrahepatic portosystemic shunt. We recommend that in patients with life-threatening hemorrhage from duodenal varices caused by cirrhosis of the liver, transjugular intrahepatic portosystemic shunt be considered in the management.

Primary large cell lymphoma presenting as hilar mass and obstructive jaundice.

Al-Fadda M. Fashir BM.
Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
We report the case of a 65-year-old patient who was diagnosed with large-cell lymphoma arising and remaining localized in the porta hepatis, causing obstructive jaundice, and resulting into ascending cholangitis, septicemia, and acute renal failure. We discuss how jaundice can be a manifestation of both Hodgkins and non-Hodgkins lymphoma.

Esophageal variceal bleeding caused by hypoplasia of the portal vein in a patient with the Klippel-Trenaunay syndrome.

Bataller R. Sans M. Escorsell A. Elizalde JI. Bosch J. Rodes J.
Liver Unit, Hospital Clinic i Provincial, University of Barcelona, Spain.
The case of a patient affected by Klippel-Trenaunay syndrome presenting with esophageal variceal bleeding caused by hypoplasia of the vena porta is reported. Hemostasis was achieved by performing a proximal spleno-renal shunt. We discuss the likely association of this mesodermal development abnormality and vascular disorders of the portal vein.

Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers.

Year 1998
Aoyama N. Kinoshita Y. Fujimoto S. Himeno S. Todo A. Kasuga M. Chiba T.
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospectively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent upper gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly.

Treatment of cytomegalovirus esophagitis in patients with acquired immune deficiency syndrome: a randomized controlled study of foscarnet versus ganciclovir. The Italian Cytomegalovirus Study Group.

Year 1998
Parente F. Bianchi Porro G.
Department of Gastroenterology, L. Sacco University Hospital, Milan, Italy.
OBJECTIVE: Although several uncontrolled studies have shown that the response rate to ganciclovir and foscarnet for all forms of cytomegalovirus (CMV) infection in immunocompromised patients is almost similar, to date, no controlled clinical trial has been specifically designed to compare these two agents in the treatment of CMV esophagitis. The aim of this study was, therefore, to compare the efficacy and safety of these two drugs in the induction therapy of CMV esophagitis in patients with acquired immunodeficiency syndrome (AIDS). METHODS: Thirty-nine of 211 (18%) consecutive AIDS patients undergoing endoscopy for esophageal symptoms had macroscopic esophagitis that proved to be sustained by CMV based on the documentation of typical intranuclear inclusions at histology; 23 were considered eligible for this study and were randomized to receive foscarnet 90 mg/kg b.i.d. or ganciclovir 5 mg/kg b.i.d. for 21 days. Twelve patients received foscarnet, whereas 11 were treated with ganciclovir. Clinical and laboratory evaluation was performed weekly, and endoscopy was repeated at the end of therapy. The two treatment groups were well balanced as to the following characteristics at entry: age, sex, absolute number of CD4 cells, duration of AIDS, Karnofsky score, frequency of concomitant Candida esophagitis (grade I or II), and severity of esophageal symptoms. RESULTS: Marked endoscopic improvement (complete disappearance of macroscopic lesions or significant reduction of the endoscopic score) was observed in eight of 11 (73%) of foscarnet and seven of 10 (70%) of ganciclovir-treated patients, and inclusion bodies disappeared from follow-up biopsies in 55% and 50% of patients, respectively. The symptomatic response was also similar for both treatments: 82% of patients who received foscarnet and 80% of those treated with ganciclovir had a complete or at least a good clinical response. Frequency of adverse events was comparable with both drugs: only one patient in each group suspended treatment because of severe side effects. CONCLUSIONS: Foscarnet and ganciclovir appear to be similarly effective and safe in the induction therapy of AIDS-related CMV esophagitis. Consequently, the choice of the anti-CMV agent should be tailored to the individual patient according to the different toxicity profiles of the two drugs.

The circulating common gamma chain (CD132) in inflammatory bowel disease.

Year 1998
Nielsen OH. Kirman I. Johnson K. Giedlin M. Ciardelli T.
Department of Gastroenterology F, Glostrup Hospital, University of Copenhagen, Denmark.
OBJECTIVE: Inflammatory bowel disease (IBD) is characterized by T cell activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2Ralpha (CD25) and disease activity is well documented in IBD, whereas IL-2Rgamma (CD132) has not been investigated in this respect. Sera from 42 patients with ulcerative colitis (UC), 34 with Crohn's disease (CD), 31 healthy volunteers, and 12 patients with infectious enterocolitis were obtained. METHODS: Disease activity was scored according to a semiquantitative score for UC and CD. sIL-2R alpha chain and gamma chain were assessed by sandwich ELISA techniques using monoclonal antibodies specific for CD25 and CD132, respectively. RESULTS: The concentration of IL-2Ralpha chain (CD25) was found to be median 3.8 ng/ml in healthy volunteers versus 7.0 ng/ml in UC patients (p < 0.001), and 9.6 ng/ml in CD patients (p < 0.001). With respect to IL-2Rgamma (CD132), significantly higher amounts were found in CD patients: 6.6 ng/ml as compared with healthy controls 0.05). A difference of gamma chain levels were found between CD and UC in moderate and severe disease activity (p < 0.05). Further analyses revealed that mesalazine did not influence the IL-2Ralpha or -gamma concentration either in UC or in CD patients. CONCLUSION: An increased circulating level of the soluble common gamma chain (CD132) seems to be found in CD, and an overlap exists between CD and UC.

Squamous islands in Barretts esophagus: what lies underneath?

Year 1998
Sharma P. Morales TG. Bhattacharyya A. Garewal HS. Sampliner RE.
Section of Gastroenterology, Tucson VA Medical Center and Arizona Health Sciences Center, 85723, USA.
OBJECTIVE: Squamous islands are frequently visualized at the time of upper endoscopy in patients with Barrett's esophagus, especially those on proton pump inhibitor therapy (PPI). The significance of these islands is not clearly understood. The aim of this study was to systematically biopsy macroscopic squamous islands and to examine their histologic characteristics. METHODS: Patients with Barrett's esophagus undergoing surveillance had squamous islands documented and biopsied at the time of endoscopy. Barrett's esophagus was defined as the presence of a columnar lined esophagus on endoscopy with intestinal metaplasia on biopsy. All biopsies were obtained by a single senior endoscopist and were stained with alcian blue at pH 2.5. Biopsy samples with inadequate tissue quantity were not included in the study. RESULTS: A total of 39 biopsies were obtained from 22 patients. Twenty of the 22 patients were male, with a mean age of 65.4 yr (range 47-80 yr). The mean length of Barrett's mucosa was 5.6 cm (range 1-11 cm). Eleven of 22 patients were on omeprazole (mean dose 29.1 mg/day), whereas seven patients were on lansoprazole (60 mg/day). The mean duration of PPI therapy was 2.3 yr (range 9-71 months) at the time of biopsy of the squamous islands. Three patients were on H2-blocker therapy whereas the remaining patient had not been started on acid suppression therapy. On histology, 24 biopsy specimens (61.5%) revealed only squamous epithelium, whereas 15 (38.5%) showed the presence of intestinal metaplasia underlying the squamous epithelium. There was no significant difference between the patients with and without underlying intestinal metaplasia in regard to age, Barrett's length, dose, and duration of PPI therapy. CONCLUSION: In more than one-third of biopsies of macroscopic squamous islands within Barrett's esophagus, microscopic intestinal metaplasia is detected. The presence of squamous islands should not be equated with regression of Barrett's esophagus or with decreased cancer risk.

Early indicators of prognosis in upper gastrointestinal hemorrhage.

Year 1998
Corley DA. Stefan AM. Wolf M. Cook EF. Lee TH.
Department of Medicine, Brigham & Women's Hospital and the Harvard Medical School, Boston, Massachusetts, USA.
OBJECTIVE: Endoscopy allows accurate risk stratification of patients presenting with gastrointestinal bleeding; frequently, however, it is not immediately available. Initial management and triage of patients thus depends on nonendoscopic information. We sought to risk stratify patients with upper gastrointestinal bleeding using variables available on initial presentation (ie., before endoscopy). METHODS: A retrospective observational study was performed using data from 335 admissions with an initial diagnosis of upper gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated for an adverse outcome during their hospitalization. An adverse outcome was defined as death, the need for any operation, recurrent hematemesis, recurrent melena after initial clearing, or a hematocrit falling despite transfusion. RESULTS: Univariate analysis identified 17 distinct variables associated (p < 0.05) with an adverse outcome. A stepwise logistic regression identified five variables as independent predictors (p < 0.05) of an adverse outcome: an initial hematocrit

Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis.

Year 1998
Lock G. Pfeifer M. Straub RH. Zeuner M. Lang B. Scholmerich J. Holstege A.
University of Regensburg, Department of Internal Medicine I, Germany.
OBJECTIVE: The aim of this study was to investigate the relationship between esophageal dysfunction and pulmonary involvement in patients with systemic sclerosis (SSc). METHODS: Pulmonary function parameters were compared between groups of patients with and without manometric evidence for SSc-induced esophageal dysmotility. RESULTS: Twenty-six of 43 patients (60.5%) exhibited a marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total lung capacity, inspiratory vital capacity, and forced vital capacity were significantly lower in patients with esophageal dysfunction compared with those with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of SSc (n = 20) had significantly lower values for total lung capacity and inspiratory vital capacity compared with patients with the limited type of SSc (n = 23; p < 0.05). CONCLUSION: There is a significant association of esophageal dysmotility with reduced lung volumes in SSc. Possible explanations for these findings are pulmonary damage due to increased gastroesophageal reflux and, more likely, simultaneous involvement of the lungs and the esophagus in the disease process.

Laparoscopic antireflux surgery in the elderly.

Year 1998
Trus TL. Laycock WS. Wo JM. Waring JP. Branum GD. Mauren SJ. Katz EM. Hunter JG.
Department of Digestive Diseases, Emory University, Atlanta, Georgia 30322, USA.
OBJECTIVE: Laparoscopic antireflux surgery is indicated in young patients with medication-dependent gastroesophageal reflux disease (GERD), both because of their need for lifelong medical treatment and the need to prevent the complications of GERD. Many elderly patients with GERD have similar concerns. We compared the safety and efficacy of laparoscopic antireflux surgery in the elderly with the results achieved in patients or = 65 yr of age. Symptoms were scored from 0 (none) to 4 (severe) before and after surgery. Ambulatory pH monitoring was also performed before and after surgery. Results were compared between age groups with the Mann-Whitney U test. RESULTS: Elderly patients had significantly higher preoperative American Society of Anesthesiologists (ASA) scores (mean 2.4 vs 2.0) (p = 0.0024), but otherwise there were no significant differences in preoperative symptom scores or pH results. Both groups demonstrated equivalent postoperative improvement in symptoms and 24-h pH study. There was no mortality in either group, and there was no significant difference in morbidity or hospital stay between the two groups. CONCLUSION: Laparoscopic antireflux surgery is a safe and effective treatment of GERD in the elderly and should not be refused solely on the basis of age.

Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers.

Year 1998
Liaw YF. Tsai SL. Sheen IS. Chao M. Yeh CT. Hsieh SY. Chu CM.
Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei, Taiwan.
OBJECTIVE: Hepatitis B, C, and delta virus (HBV, HCV, HDV) share similar transmission routes; thus, dual or triple infections may occur and even persist in the same patient. However, little is known about the presentations and course of chronic HBV infection with HCV and HDV markers, which this study examined. METHODS: Antibodies against HCV (anti-HCV) and HDV (anti-HDV) were assayed as appropriate in patients with HBV infection. The clinical, pathological, and virological presentations as well as the course of the disease in patients with HBV/HDV/HCV triple infection markers were then reviewed. RESULTS: A total of 60 patients, 51 men and nine women, age 19-67 yr (mean 45.9+/-1.6 yr) were identified. Of these 60 patients, five (8.3%) were HBeAg positive and 10 (16.7%) cirrhotic at entry, 30 (50%) presented with acute superinfection (HCV or HDV, or both) and the remaining 30 presented with chronic liver disease. On presentation, 16 (53.3%) of the 30 patients with acute superinfection showed hepatic decompensation and eight (26.7%) died. In contrast, only one of the patients with "chronic liver disease" presented with hepatic decompensation. Of the 42 patients followed up for 1-15 (mean, 4.7+/-0.6) yr, 45.2% showed remission and 19% showed HBsAg seroclearance, whereas 12.5% of the 32 noncirrhotics developed cirrhosis and three of the nine cirrhotics became decompensated. At the end of follow-up, 29 patients (69.9%) were still seropositive for HCV-RNA but only nine (22.5%) were seropositive for HDV-RNA and five (12.5%) were seropositive for HBV-DNA. CONCLUSIONS: These results suggest that infection with HBV, HCV, and HDV triple markers is a severe disease in acute superinfection stage but that the course is relatively benign, slowly progressive, and usually dominated by HCV.

Bilirubinate granules: main pathologic bile component in patients with idiopathic acute pancreatitis.

Year 1998
Perez-Martin G. Gomez-Cerezo J. Codoceo R. Olveira A. Conde P. Garces MC. Barbado FJ. Vazquez JJ.
Department of Internal Medicine, La Paz Hospital, Autonoma University, Madrid, Spain.
OBJECTIVE: The aim of this study was to evaluate the main pathologic component of bile obtained by biliary drainage in patients with acute idiopathic pancreatitis and therapeutic implications. METHOD: Eighteen patients diagnosed with idiopathic acute pancreatitis underwent biliary drainage. Microscopic evaluation of bile was performed and pathologic components were classified in cholesterol microcrystals, bilirubinate granules, and calcium microspherolites. RESULTS: Five patients showed no abnormalities. In 11 patients, bilirubinate granules were found, cholesterol microcrystals in two, and Giardia lamblia in two. CONCLUSION: Bilirubinate granules are the main pathologic component of bile in patients with acute idiopathic pancreatitis. Cholecystectomy is the preferred therapeutic approach.

LDH to AST ratio in biliary pancreatitis--a possible indicator of pancreatic necrosis: preliminary results.

Year 1998
Isogai M. Yamaguchi A. Hori A. Kaneoka Y.
Department of Surgery, Ogaki Municipal Hospital, Japan.
OBJECTIVE: Lactate dehydrogenase (LDH) has been reported to be a sensitive indicator of pancreatic necrosis (PN). In patients with biliary pancreatitis (BP), however, liver enzymes are generally elevated early in the course of the disease because of acute inflammatory liver cell injury caused by ampullary stones impacted during their transpapillary passage. Accordingly, the identification of PN using the initial high LDH activity as an indicator of PN in BP may not be accurate. In patients with ongoing PN, LDH would be expected to increase thereafter. We hypothesized that an elevation of the ratio of LDH to aspartate aminotransferase (AST) (LDH/AST) would better reflect PN in BP. METHODS: The plasma concentrations of the LDH/AST ratio over a 3-wk postadmission period were evaluated and compared with serial computed tomograpy (CT) scans of the abdomen in two groups of patients with BP, consisting of 5 PN patients and 17 non-PN patients. A group of 50 healthy adults served as controls for the LDH/AST ratio measurement. RESULTS: On postadmission days 1 and 2, the LDH/AST ratios in both groups of patients were low, with no significant difference. In the PN patients, the LDH/AST ratio increased thereafter, reached peak values, and decreased. In the non-PN patients, the LDH/AST ratio increased gradually, but remained within the control range. In the PN patients, the LDH/AST ratios on postadmission days 3, 5, and 7 were significantly higher than those of the non-PN patients. The CT scans of the abdomen of the PN patients showed an initial edematous pancreas with the development of late PN. The peak values of the LDH/AST ratio correlated well with the extent of PN. CONCLUSION: An elevated LDH/AST ratio identifies patients who develop PN. The LDH/AST ratio could be used as an indicator of PN in BP patients.

Atrophic gastritis and intestinal metaplasia in Helicobacter pylori infection: the role of CagA status.

Year 1998
Sozzi M. Valentini M. Figura N. De Paoli P. Tedeschi RM. Gloghini A. Serraino D. Poletti M. Carbone A.
Division of Gastroenterology and Digestive Endoscopy, C.R.O. Istituto Nazionale Tumori Centroeuropeo, Aviano, Italy.
OBJECTIVE: Helicobacter pylori (H. pylori) is a major factor in determining the risk for development of gastric adenocarcinoma through the intermediate steps of atrophic gastritis and intestinal metaplasia. Because H. pylori infection is highly prevalent in asymptomatic populations and only a few people develop cancer, additional factors may influence the risk for development of cancer, once infection is established. Some factors may pertain to differences among bacterial strains. Because infection by H. pylori strains possessing cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen (CagA), is associated with enhanced induction of gastritis, the aim of our study was to evaluate potential differences in the prevalence and intensity of atrophy and intestinal metaplasia between CagA-positive and CagA-negative H. pylori-infected patients. METHODS: Eighty H. pylori-infected patients among 120 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were studied. Six bioptic specimens were taken from the gastric antrum: five for histological examination, and one for urease test. The H. pylori status was determined by histology, CLO test, and serology (in a standardized ELISA) for serum IgG and IgA directed to H. pylori. The CagA status was determined by Western blotting to detect serum IgG antibodies to CagA. Gastritis was classified according to the Sydney System. A score from 0 to 3 was assigned to each of the following morphological variables: atrophy, intestinal metaplasia, and mononuclear and neutrophilic cell infiltration. The association between CagA status and histological features was assessed by means of the chi2 test for trend. RESULTS: Among the 80 H. pylori-infected patients 53 (66%) were CagA seropositive and 27 (34%) were CagA seronegative. The mean age of the two groups was similar. CagA-positive patients had significantly higher scores for atrophy (p = 0.006), intestinal metaplasia (p = 0.01), and mononuclear (p < 0.001) and polymorphonuclear (p = 0.002) cell infiltration than did CagA-negative patients. No differences in contrast, were found for H. pylori density. CONCLUSION: Infection with CagA-positive H. pylori strains is associated with an increased prevalence and intensity of antral atrophy and intestinal metaplasia, in addition to higher degrees of gastritis. Our results seem to suggest that the CagA status could be a helpful parameter to define a subgroup of H. pylori-infected patients at increased risk of developing gastric adenocarcinoma.

Ranitidine bismuth citrate with clarithromycin given twice daily effectively eradicates Helicobacter pylori and heals duodenal ulcers.

Year 1998
Bardhan KD. Wurzer H. Marcelino M. Jahnsen J. Lotay N. Roberts PM.
Rotherham General Hospitals National Health Service Trust, UK.
OBJECTIVE: Ranitidine bismuth citrate (RBC) b.i.d. with clarithromycin q.i.d. eradicates Helicobacter pylori (H. pylori) in 82-94% of patients, and heals duodenal ulcers in 88-90% of patients. This double blind, placebo-controlled study examines the efficacy of a simpler b.i.d. treatment regimen, and examines the potential benefit of including a second antibiotic, metronidazole, to the b.i.d. treatment regimen. METHODS: A total of 648 patients with active duodenal ulcer received RBC 400 mg b.i.d. for 4 wk, coprescribed with clarithromycin 250 mg q.i.d., clarithromycin 500 mg b.i.d., or clarithromycin 500 mg b.i.d. with metronidazole 400 mg b.i.d. for the first 2 wk of treatment. Endoscopies were performed prestudy, after 4 wk of treatment, and at least 4 wk posttreatment. H. pylori status was assessed by CLOtest, 13C-urea breath test (UBT), and histology prestudy, and by UBT and histology at least 4 wk posttreatment. Adverse events were recorded at each visit. RESULTS: All three regimens were highly effective and well tolerated. H. pylori eradication rates were 84-94% and duodenal ulcer healing rates were 92-96% (observed data). Highest H. pylori eradication and ulcer healing rates were achieved with RBC 400 mg b.i.d. with clarithromycin 500 mg b.i.d. CONCLUSION: Ranitidine bismuth citrate with clarithromycin 500 mg b.i.d. provides an effective, simple and well tolerated regimen for the eradication of H. pylori and healing of duodenal ulcers.

Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis: an unexplored triangle.

Year 1998
Xia HH. Talley NJ.
Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia.
OBJECTIVE: H. pylori causes chronic gastritis, which may progress to peptic ulcer, gastric atrophy, or gastric cancer. However, little is known about the role of H. pylori infection in reflux esophagitis and the relationship between reflux esophagitis and atrophic gastritis needs to be clarified. We sought to identify the possible interrelationships among Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis, to signal areas in which researchers should consider focusing their attention. METHODS: A broad-based Medline search was performed to identify all related publications addressing H. pylori infection, atrophic gastritis, gastroesophageal reflux disease (GERD), secretion of gastric acid, and gastric motility published between 1966 and July 1997. RESULTS: Whereas some studies have shown no significant association between H. pylori infection and reflux esophagitis, others have observed that the prevalence of H. pylori infection was lower in patients with GERD, implying a protective role. Eradication of H. pylori leads to occurrence of reflux esophagitis in some cases, but the mechanisms inducing posteradication reflux esophagitis are unknown. H. pylori infection may lead to atrophic gastritis (and hence hypochlorhydia) through both bacterial and host factors, although gastric atrophy and subsequent intestinal metaplasia are hostile to H. pylori because of hypochlorhydria. Although it has been reported that long-term proton pump inhibitor therapy for refractory reflux esophagitis may induce or enhance the development of gastric atrophy in H. pylori-infected patients, this relationship has been disputed. CONCLUSIONS: H. pylori infection may be negatively associated with reflux esophagitis, but this requires confirmation. Research then needs to focus on whether this is explained through motility- or acid-related mechanisms. The potential costs of maintenance antireflux therapy may need to be taken into account when evaluating the cost effectiveness of anti-H. pylori therapy.

Direct determination of colonic nitric oxide level--a sensitive marker of disease activity in ulcerative colitis.

Year 1998
Rachmilewitz D. Eliakim R. Ackerman Z. Karmeli F.
Department of Medicine, Hadassah University Hospital, Mount Scopus, Hebrew University Hadassah Medical School, Jerusalem, Israel.
OBJECTIVE: In active ulcerative colitis, colonic nitric oxide (NO) generation is enhanced and probably has an important role in its pathogenesis. We tested the reliability of an NO electrode in monitoring colonic NO levels in ulcerative colitis patients and control subjects and its possible usage as a marker of disease activity. METHODS: Colonic NO level was determined by the NO detection system model NO-501 (InterMedical, Nagoya, Japan). The working electrode was inserted into a 7-mm diameter polyvinyl tube and introduced at a distance 6 cm from the anus. In each subject sigmoidoscopy was performed and mucosal biopsies were obtained. NO synthase (NOS) activity was determined by monitoring the conversion of 3H-arginine to citrulline. RESULTS: Colonic NO level is significantly increased in patients with active ulcerative or Crohn's colitis--more than 2-fold higher than in control subjects. There was good correlation between colonic NO level and NOS activity and the clinical and endoscopic indices of disease activity. CONCLUSION: Direct determination of colonic NO level is convenient, and reliable, and may help to monitor disease activity in ulcerative colitis.

A retrospective analysis of 1570 appendiceal carcinoids.

Year 1998
Sandor A. Modlin IM.
Gastric Surgical Pathobiology Research Group, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
OBJECTIVE: Information about the management and outcome of appendiceal carcinoids is sparse, because few series comprise more than 100 cases. In this study we have analyzed the epidemiology of 1570 appendiceal carcinoids, to compare outcome with other gastrointestinal carcinoid tumors. METHODS: We evaluated 1570 appendiceal carcinoids in a series of 8305 carcinoid tumors from the SEER, the End Results Group, and the Third National Cancer Survey programs of the National Cancer Institute over the time period 1950-1991. RESULTS: Appendiceal carcinoids comprised 18.9% of all carcinoid tumors and exhibited a marked female predominance (M/F ratio: 0.47). Age-adjusted incidence rates were 1.7-fold higher in women compared to men. Appendiceal carcinoids present earlier (average age: 42.2 yr) than other gastrointestinal carcinoids (62.9 yr) or noncarcinoid appendiceal tumors (61.9 yr). At the time of diagnosis 35.4% were nonlocalized. The overall 5-yr survival for localized lesions was 94%, for regional invasion 84.6%, and for distant metastases 33.7%. The 5-yr survival of appendiceal carcinoids (85.9%) was the highest among all types of carcinoid tumors. In 14.6% noncarcinoid tumors at other sites were also evident. CONCLUSION: The high relative incidence of carcinoid tumors in the appendix is still poorly understood. The good overall 5-yr survival rates of appendiceal carcinoids as opposed to other carcinoids represents either a different biological behavior, earlier diagnosis, or expeditious management (appendectomy). However, the increased likelihood of coexisting neoplasms and the not uncommon presentation of metastatic disease should warrant careful evaluation and postoperative follow-up of such lesions.

Beneficial hemodynamic effects of dipyridamole on portal circulation in cirrhosis.

Year 1998
Sansoe G. Ferrari A. D'Alimonte P. Trenti T. Zoboli P. Romagnoli R. Villa E. Manenti F.
Department of Internal Medicine, University of Modena, Italy.
OBJECTIVE: Dipyridamole is a vasodilator that inhibits the cellular uptake of adenosine, which physiologically reduces the resistance to hepatic arterial flow inside the liver. This study aims at assessing the acute effect of dipyridamole on functional liver plasma flow (measured as the extrarenal sorbitol clearance) and on the Doppler US Congestion Index of the portal vein (the ratio between the cross-sectional area of this vein and the mean velocity of portal flow), which correlates with the severity of portal hypertension. METHODS: We have determined the extrarenal sorbitol clearance (14 cases) and the Congestion Index (seven cases) before and at 30, 60, and 90 min after the oral administration of 25 mg dipyridamole in patients with liver cirrhosis. We also measured the effect of dipyridamole on functional liver plasma flow in six healthy subjects. RESULTS: Dipyridamole increased the extrarenal sorbitol clearance in controls (+17%, p < 0.01) and in cirrhotic patients (+15%, p < 0.01). The drug decreased the portal Congestion Index in all patients, averaging -24% (p < 0.05) 90 min after its oral administration. CONCLUSIONS: This result was due both to a mean decrease of the portal sectional area and to a mean increase in portal flow velocity. In conclusion, these data suggest that dipyridamole should decrease the vascular resistance to portal flow in cirrhosis; this effect may be mediated by an adenosine-dependent vasodilation in the intrahepatic site or along the portosystemic collaterals.

Abnormal duodenal bile composition in patients with acalculous chronic cholecystitis.

Year 1998
Venkataramani A. Strong RM. Anderson DS. Gilmore IT. Stokes K. Hofmann AF.
Department of Medicine, University of California, San Diego 92103-0813, USA.
OBJECTIVE: Our goal was to characterize biliary lipid composition in patients with the syndrome of chronic biliary pain, absence of gallstones, and inflammation of the gallbladder mucosa (acalculous chronic cholecystitis). METHODS: Duodenal bile, obtained from 27 patients with a history of right upper quadrant pain and with negative imaging studies of the biliary tract, was analyzed enzymatically for bile acids, phospholipids, and cholesterol. Fifteen patients were found to have inflammation and/or fibrosis of the gallbladder at cholecystectomy. RESULTS: The 15 patients with abnormal gallbladder histology had more dilute duodenal bile, as indicated by a low bile acid concentration and a lower proportion of phospholipids (p < 0.01) when values were compared with those of duodenal bile samples from postmenopausal women without gallbladder disease or from radiolucent gallstone subjects participating in the National Cooperative Gallstone Study. Cholecystectomy relieved pain in 9 of 14 patients. CONCLUSIONS: Some patients with acalculous chronic cholecystitis have duodenal bile samples characterized by a decreased bile acid concentration and a decreased proportion of biliary phospholipids. The low biliary bile acid concentration may result from impaired gallbladder contraction and/or secretion by the biliary tract epithelium. The low proportion of phospholipid may result from posthepatic hydrolysis of luminal phosphatidylcholine followed by absorption of the hydrolysis products. The latter process could be caused by and/or contribute to mucosal inflammation and would also elevate the cholesterol saturation of bile, increasing the risk for cholesterol gallstone formation.

Clinical outcome following treatment of refractory inflammatory and fistulizing Crohns disease with intravenous cyclosporine.

Year 1998
Egan LJ. Sandborn WJ. Tremaine WJ.
Inflammatory Bowel Disease Clinic, Division of Gastroenterology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
OBJECTIVE: To determine outcome following treatment of refractory Crohn's disease with intravenous (i.v.) cyclosporine (CYA). METHODS: The medical records of 18 patients with refractory Crohn's disease treated with i.v. CYA were reviewed. Nine patients had refractory inflammatory Crohn's disease and nine patients had complex fistulizing Crohn's disease. All patients were initially treated with i.v. CYA (4 mg/kg/day). Patients who responded were converted to standard oral CYA. Patient outcomes were classified as complete response, partial response, or nonresponse. RESULTS: Four of nine patients with severe inflammatory Crohn's disease and seven of nine patients with fistulizing Crohn's disease had a partial response to i.v. CYA. Four of four responding patients in the inflammatory group and four of six responding patients in the fistulizing group (plus one initial nonresponder) maintained or improved their response during oral CYA therapy. After discontinuing oral CYA, all four patients in the inflammatory group and five of seven patients in the fistulizing group relapsed despite 1-17 wk of concomitant treatment with azathioprine or 6-mercaptopurine (AZA/6MP). Two patients who received overlapping CYA and AZA/6MP for 17 and 23 wk maintained long-term responses. CYA toxicity was minimal: reversible nephrotoxicity (n = 2), headache (n = 2), oral candidiasis (n = 1), paresthesia (n = 2). CONCLUSIONS: I.v. CYA appears to benefit both refractory inflammatory and fistulizing Crohn's disease. Most patients who respond to i.v. CYA will maintain their response during oral CYA therapy. However, the majority of these patients relapse when oral CYA is discontinued, probably because of inadequate duration of overlap with the slow acting maintenance drugs, AZA/6MP.

Carcinoma of the stomach with hyperkeratosis palmaris et plantaris and acanthosis of the esophagus.

Year 1998
Murata I. Ogami Y. Nagai Y. Furumi K. Yoshikawa I. Otsuki M.
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu.
A 59-yr-old man with carcinoma of the stomach, concurrent acquired hyperkeratosis (tylosis) of the palms and soles, and acanthosis of the esophageal mucosa is reported. He presented the tylosis and esophageal lesions when the carcinoma was evident. Resection of the stomach resulted in diminution of the skin and esophageal lesions. The association of sporadic tylosis and carcinoma of the stomach is extremely rare. This is the first case report documenting the association of gastric cancer, tylosis, and acanthosis of the esophageal mucosa.

Acute ileal diverticulitis.

Year 1998
Prakash C. Clouse RE.
Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.
Four cases of acute ileal diverticulitis are presented wherein early diagnosis helped avoid emergent surgery. All patients did well initially with conservative medical management. Acute ileal diverticulitis, although uncommon, should be suspected when the clinical presentation indicates an inflammatory condition of the lower right abdomen. Surgery, when required for recurrent disease, can be reserved for the interval between acute episodes.

Transjugular intrahepatic portosystemic shunt: a successful treatment for hepatopulmonary syndrome.

Year 1998
Selim KM. Akriviadis EA. Zuckerman E. Chen D. Reynolds TB.
The University of Southern California Liver Unit and Department of Nuclear Medicine, Rancho Los Amigos Medical Center, Downey, California, USA.
Hepatopulmonary syndrome is a well described complication of chronic liver disease. Though uncommon, it carries a high morbidity and mortality. The pathogenesis of the syndrome has not been clearly defined. Portal hypertension seems to play a crucial role in the pathogenesis of the syndrome, probably by enhancing nitric oxide production. As yet, no pharmacological therapy has been proven effective. Many reports of successful reversal of the syndrome after liver transplantation have been published. We report a patient with hepatopulmonary syndrome who showed a significant and durable (4 months') improvement in his symptoms, arterial oxygenation, and intrapulmonary shunts, as calculated by radionuclide studies after transjugular intrahepatic portosystemic shunt placement. Transjugular intrahepatic portosystemic shunt may represent a durable treatment option for patients with hepatopulmonary syndrome.

Terbinafine hepatotoxicity: case report and review of the literature.

Year 1998
Fernandes NF. Geller SA. Fong TL.
Center for Liver Diseases and Transplantation and Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
We report a patient who developed significant liver dysfunction following therapy with terbinafine. At the end of a 3 1/2-wk course of terbinafine, he developed progressive jaundice and pruritus. His serum bilirubin peaked at 30.9 mg/dl 3 wk after discontinuing terbinafine. A liver biopsy revealed mild to moderate mixed cellular infiltrate in the portal tracts, and hepatocellular and canicular cholestasis. His liver tests normalized 100 days after stopping terbinafine.

Sialadenoma papilliferum of the esophagus.

Year 1998
Su JM. Hsu HK. Hsu PI. Wang CY. Chang HC.
Department of Surgery and Internal Medicine, Veterans General Hospital-Kaohsiung, Taiwan.
Sialadenoma papilliferum is an extremely rare benign tumor of the esophagus. We report a 70-yr-old woman who was first thought to have adenocarcinoma in the distal esophagus. Transhiatal esophagectomy and left colon interposition were performed. The pathological diagnosis of sialadenoma papilliferum of the esophagus arising in the submucosal gland ducts was confirmed after surgery.

Cutaneous necrosis associated with interferon alpha-2b.

Year 1998
Sickler JB. Simmons RA. Cobb DK. Sherman KE.
University of Cincinnati Medical Center, Ohio 45267, USA.
Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.

Esophagopericardial fistula arising from Barretts esophagus.

Year 1998
Shah S. Saum K. Greenwald BD. Krasna MJ. Sonett JR.
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Esophagopericardial fistula is a rare complication of numerous benign, malignant, and traumatic conditions of the esophagus. Approximately 100 cases of fistulae between the esophagus and heart have been reported. We describe the second reported case of an esophagopericardial fistula secondary to a benign esophageal ulcer within Barrett's mucosa without prior surgery. The radiologic, endoscopic, and surgical management of this case are discussed.

Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature.

Year 1998
Pardi DS. Romero Y. Mertz LE. Douglas DD.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Hepatitis-associated aplastic anemia is rare in general, but occurs in up to 28% of patients receiving liver transplantation for fulminant non-A, non-B hepatitis. Cases are commonly young men with mild hepatitis but severe aplastic anemia. Although cases have been reported in association with hepatitis A, B, and C, most appear to be due to a non-A-B-C virus. We report two cases of acute hepatitis subsequently complicated by marrow hypoplasia in patients with acute parvovirus B19 infection. Hepatic manifestations of parvovirus B19 infection range from liver chemistry abnormalities to fulminant hepatic failure and aplastic anemia. Our cases demonstrate a less severe form of hepatitis-associated aplastic anemia, and together with other data, suggest that parvovirus B19 is at least one cause of hepatitis-associated aplastic anemia, and may be a heretofore underrecognized hepatotrophic virus.

Severe symptomatic sinus bradycardia associated with mesalamine use.

Year 1998
Asirvatham S. Sebastian C. Thadani U.
Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
A 29-yr-old white woman was hospitalized with bloody diarrhea secondary to ulcerative colitis. Within 24 h of receiving intravenous steroids, loperamide, and mesalamine, she developed symptomatic hypotension, severe sinus bradycardia, sinus pauses, and junctional escape beats. The hypotension and sinus bradycardia resolved after discontinuing mesalamine. She had a family history of conduction tissue disease but her exercise ECG and Holter studies were normal. She was rehospitalized 6 wk later with an exacerbation of ulcerative colitis and, within 8 h of receiving mesalamine, developed hypotension and severe sinus bradycardia, which resolved after stopping mesalamine. Thus mesalamine should be used with caution, especially in patients predisposed to cardiac conduction tissue disease.

Liver failure caused by hepatic angiodysplasia in hereditary hemorrhagic telangiectasia.

Year 1998
Mukasa C. Nakamura K. Chijiiwa Y. Sakai H. Nawata H.
The Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hereditary hemorrhagic telangiectasia is a systemic vascular disease with autosomal dominant inheritance that results in telangiectasia, arteriovenous malformations, and hemangiomas. The liver is one of the organs commonly affected in hereditary hemorrhagic telangiectasia, and hepatic lesions consist of angiodysplasia and fibrosis. A patient with hereditary hemorrhagic telangiectasia and significant impairment of synthetic liver function is reported. Dynamic computed tomography revealed marked enlargement of the common hepatic and intrahepatic arteries, heterogeneous parenchymography, and early opacification of the hepatic veins consistent with telangiectasias and arteriovenous shunting. Overall, the liver was predominantly occupied by vascular structures and scarce residual hepatic parenchyma. Other causes of liver dysfunction, such as viral hepatitis and alcohol abuse, were excluded. In general, hepatic fibrovascular dysplasia seen in hereditary hemorrhagic telangiectasia usually results in only mild liver dysfunction; however, this case shows that hepatic involvement may rarely result in hepatic failure.

Cholestatic liver diseases in adults.

Year 1998
McGill JM. Kwiatkowski AP.
Department of Medicine, Indiana University School of Medicine and the Roudebush VA Medical Center, Indianapolis, USA.
Cholestatic liver diseases are a diverse group of disorders that are recognized by either increases in laboratory studies or the appearance of jaundice, fatigue, pruritus, and/or complications of cirrhosis. The etiologies for most forms of these diseases are unknown. In this paper, diagnostic and therapeutic strategies are reviewed for select forms of cholestatic disorders and for the management of shared complications of cholestatic illness.

Intestinal tuberculosis: return of an old disease.

Year 1998
Horvath KD. Whelan RL.
Department of Surgery, College of Physicians and Surgeons, Columbia University and Presbyterian Hospital, New York, New York, USA.
OBJECTIVE: Tuberculosis (TB) can no longer be considered a rare disease in the United States due, in part, to the AIDS epidemic. Because the signs and symptoms of intestinal TB are nonspecific, a high index of suspicion must be maintained to ensure a timely diagnosis. The aim of this article is to review the history, epidemiology, pathophysiology, and treatment of TB. METHODS: This review is based on an examination of the world literature. RESULTS: In only 20% of TB patients is there associated active pulmonary TB. Areas most commonly affected are the jejunoileum and ileocecum, which comprise >75% of gastrointestinal TB sites. Diagnosis requires colonoscopy with multiple biopsies at the ulcer margins and tissue sent for routine histology, smear, and culture. If intestinal TB is suspected, empiric treatment is warranted despite negative histology, smear, and culture results. Treatment is medical, and all patients should receive a full course of antituberculous chemotherapy. Exploratory laparotomy is necessary if the diagnosis is in doubt, in cases in which there is concern about a neoplasm, or for complications that include perforation, obstruction, hemorrhage, or fistulization. CONCLUSIONS: This review draws attention to the resurgence of tuberculosis in the United States. An increased awareness of intestinal tuberculosis, coupled with knowledge of the pathophysiology, diagnostic methods, and treatment should increase the number of cases diagnosed, thus improving the outcome for patients with this disease.

Complementary medicine use by patients with inflammatory bowel disease.

Year 1998
Hilsden RJ. Scott CM. Verhoef MJ.
Department of Community Health Sciences, University of Calgary, Alberta, Canada.
OBJECTIVE: The purpose of this study was to establish the degree and determinants of the use of complementary therapies by patients with inflammatory bowel disease (IBD) and their reasons for seeking them. METHODS: The first phase was a cross-sectional survey of 134 patients with IBD (98 with Crohn's disease, 34 with ulcerative colitis, and two indeterminate) using a mailed, structured questionnaire (response rate 70%). Determinants of complementary medicine use were examined using logistic regression. The second phase was an in-depth exploration using personal interviews of the beliefs and perceptions of 14 complementary medicine users about the management of their disease. Analysis was performed using standard qualitative techniques and the identification of important, patient-identified themes about the management of IBD. RESULTS: Complementary therapies had been used by 51% of patients in the previous 2 yr. Current use was reported by 33%, of whom one-half were using it for their IBD. Vitamins and herbal products were the most commonly reported therapies. In multivariate analysis, duration of disease > 10 yr and a history of hospitalization were independent predictors of complementary medicine use. The side effects and lack of effectiveness of standard therapies were the most commonly cited reasons for seeking complementary medicine. Sixty-two percent had told their doctor about their use of complementary medicine. CONCLUSION: Complementary medicine use is common in patients with IBD, especially among those with a longer duration of disease or a history of hospitalization.

Changing trends in esophageal cancer: a 15-year experience in a single center.

Year 1998
Sharma VK. Chockalingam H. Hornung CA. Vasudeva R. Howden CW.
Department of Internal Medicine, University of South Carolina, Columbia 29203-6808, USA.
OBJECTIVE: Esophageal adenocarcinoma is increasing in white men. We sought to identify trends in esophageal cancer in different patient groups in our region. METHODS: We reviewed the records of all patients with esophageal cancer seen at two hospitals in Columbia, SC between 1981 and 1995. Patients were divided into three cohorts (1981-1985, 1986-1990, and 1991-1995). Demographic data, histological type, tumor stage, grade, and survival were recorded. RESULTS: Histology was available in 371 of 386 patients (cohort 1, 113 patients; cohort 2, 144; and cohort 3, 114). Adenocarcinoma accounted for 24%, 27%, and 49% of esophageal cancer in white men in cohorts 1, 2, and 3, respectively (p = 0.03). Corresponding figures for African-Americans were 10%, 7%, and 3% (p = 0.22). Women comprised 8%, 14%, and 22% of patients with squamous carcinoma in the three cohorts (p = 0.03). Median survival for esophageal cancer was 6.0, 6.8, and 10.4 mo in cohorts 1, 2, and 3 (p = 0.0002). CONCLUSION: Adenocarcinoma is increasing in whites. Squamous carcinoma remains the predominant type in this region, seen mainly in African-Americans. Esophageal squamous carcinoma is increasing in women. The mean age at diagnosis of squamous carcinoma has decreased in whites. There is a trend toward improved survival in patients with esophageal cancer.

Esophageal manometry: a comparison of findings in younger and older patients.

Year 1998
Ribeiro AC. Klingler PJ. Hinder RA. DeVault K.
Department of Medicine, Mayo Clinic, Jacksonville, Florida 32224, USA.
OBJECTIVE: We sought to determine the utility of esophageal manometry in an older patient population. METHODS: Consecutively performed manometry studies (470) were reviewed and two groups were chosen for the study, those > or = 75 yr of age (66 patients) and those < or = 50 years (122 patients). Symptoms, manometric findings (lower esophageal sphincter [LES], esophageal body, upper esophageal sphincter [UES]) and diagnoses were compared between the groups. RESULTS: Dysphagia was more common (60.6% vs 25.4%), and chest pain was less common (17.9 vs 26.2%) in older patients. In the entire group, there were no differences in LES parameters. Older patients with achalasia had lower LES residual pressures after deglutition (2.7 vs 12.0 mm Hg), but had similar resting pressures (31.4 vs 35.2 mm Hg) compared with younger achalasia patients. Duration and amplitude of peristalsis were similar in both groups, whereas peristaltic sequences were more likely to be simultaneous in the older group (15% vs 4%). The UES had a lower resting pressure in the older patients (49.6 vs 77.6 mm Hg) and a higher residual pressure (2.0 vs -2.7 mm Hg). The older patients were less likely to have normal motility (30.3% vs 44.3%) and were more likely to have achalasia (15.2% vs 4.1%) or diffuse esophageal spasm (16.6% vs 5.0%). When only patients with dysphagia were analyzed, achalasia was still more likely in the older group (20.0% vs 12.9%). CONCLUSION: When older patients present with dysphagia, esophageal manometry frequently yields a diagnosis to help explain their symptoms.

Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal acid reflux in patients with Barretts esophagus.

Year 1998
Ouatu-Lascar R. Triadafilopoulos G.
Gastroenterology Section, Palo Alto Veterans Affairs Health Care System, California 94304, USA.
OBJECTIVE: Normalization of intraesophageal acid exposure is increasingly recognized as a desired goal in the management of Barrett's esophagus. In this prospective trial, we studied patients with Barrett's esophagus by 24-h intraesophageal pH monitoring after having completely eliminated their reflux symptoms with lansoprazole, to determine whether they had achieved normalization of intraesophageal pH. METHODS: Thirty patients with Barrett's esophagus, all of whom had presented with reflux symptoms, were treated with lansoprazole (15-30 mg/day) until they were asymptomatic. Twenty-four-hour ambulatory pH monitoring was performed while they were receiving lansoprazole and were asymptomatic. RESULTS: Twelve patients (40%) showed persistent bipositional, pathologic acid reflux while on therapy, with a mean DeMeester score of 52.8 (95% CI: 33.8-71.8); the remaining 18 (60%) exhibited normalization of intraesophageal acid exposure with a score of 4.4 (95% CI: 2.3-6.6,p < 0.001). This inadequate control of intraesophageal pH is most likely due to incomplete gastric acid suppression induced by the drug and is associated with a variable acid (distal > proximal) exposure within the esophagus. The two groups were not different in regard to their symptom frequency and severity before therapy, amount of lansoprazole dosage required to eliminate symptoms, length of Barrett's metaplasia, presence of hiatal hernia, lower esophageal sphincter resting tone and length, or esophageal peristaltic function. CONCLUSION: Complete symptom eradication with lansoprazole (15-30 mg daily) in patients with Barrett's esophagus does not guarantee normalization of intraesophageal pH profile. If the goal of therapy in such patients is to achieve complete intraesophageal acid suppression, 24-h ambulatory esophageal pH monitoring should be performed to titrate therapy.

Clinical aspects of upper gastrointestinal bleeding associated with the use of nonsteroidal antiinflammatory drugs.

Year 1998
Laszlo A. Kelly JP. Kaufman DE. Sheehan JE. Retsagi G. Wiholm BE. Koff RS. Sundstrom A. Shapiro S.
National Institute of Rheumatology and Physiotherapy, Budapest, Hungary.
OBJECTIVE: The aim of this study was to compare the clinical features of major upper gastrointestinal bleeding among patients exposed to nonsteroidal antiinflammatory drugs (NSAID) and those not taking these drugs. METHODS: Using data from a multicenter international case-control study designed to evaluate the role of drugs in the etiology of major upper gastrointestinal bleeding (UGIB), patients with a confirmed first episode of major UGIB were divided into two groups: those exposed to NSAIDs during the week before the onset of bleeding, and those not exposed. The groups were compared according to age and sex, clinical appearance and site of the bleeding, preceding symptoms, and requirement for transfusion and acute surgery. RESULTS: The median age was significantly higher and the proportion of women was slightly higher among the NSAID users. There was no significant difference between users and nonusers according to the clinical presentation, the site of the bleeding, or the frequency of preceding symptoms. Forty percent in each group had no symptoms before the onset of bleeding. Slightly more NSAID users received blood transfusions, although the same median amount of blood per transfusion was given in both groups. There was no difference in the frequency of surgical intervention. CONCLUSIONS: There are no important differences in the clinical presentation of major UGIB according to whether or not an individual is an NSAID user. An important finding is the frequent absence of preceding symptoms in patients with major UGIB, regardless of NSAID use.

Analysis of risk factors for chronic hepatic encephalopathy: the role of Helicobacter pylori infection.

Year 1998
Dasani BM. Sigal SH. Lieber CS.
Section of Liver Diseases and Nutrition, Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, Mount Sinai School of Medicine, New York, USA.
OBJECTIVE: Elevated blood ammonia is an important pathogenic factor of hepatic encephalopathy. Although colonic bacteria are considered the main source of ammonia, the stomach in subjects with urease-producing Helicobacter pylori (H. pylori) is an alternative site. The objective of this study was to determine whether H. pylori is associated with this complication. METHODS: After assessing liver function and portal hypertension, 55 cirrhotics were evaluated for encephalopathy and H. pylori infection. Response to 2 weeks of amoxicillin (2 g/day) and omeprazole (40 mg/day) was then assessed in 17 (13 H. pylori-positive, four H. pylori-negative) encephalopathic subjects. RESULTS: H. pylori infection was more common (67 % vs 33%, p = 0.004) among encephalopathic patients. Additional factors associated with encephalopathy included older age (60.1 +/- 1.5 vs 49.8 +/- 2.4 yr, p = 0.001), lower albumin (3.17 +/- 0.08 vs 3.69 +/- 0.12 g/dl, p = 0.001), higher total bilirubin (2.24 +/- 0.20 vs 1.53 +/- 0.23 mg/dl, p = 0.034), greater ascites score (0.8 +/- 0.1 vs 0.3 +/- 0.1, p = 0.01), greater diuretic score (1.1 +/- 0.1 vs 0.3 +/- 0.1, p = 0.002), and greater modified Child score (6.7 +/- 0.3 vs 5.1 +/- 0.3, p = 0.001). When adjusted for severity of cirrhosis and age, H. pylori continued to demonstrate a statistical association (p = 0.039). After anti-H. pylori therapy, symptomatology in infected encephalopathic patients appeared to improve, whereas noninfected subjects were unaffected. CONCLUSION: In cirrhotic patients, H. pylori infection is associated with hepatic encephalopathy, especially in younger patients with decompensated liver disease.

Treatment of gastric MALT lymphoma by Helicobacter pylori eradication: a study controlled by endoscopic ultrasonography.

Year 1998
Nobre-Leitao C. Lage P. Cravo M. Cabecadas J. Chaves P. Alberto-Santos A. Correia J. Soares J. Costa-Mira F.
Servico de Gastrenterologia, Centro de Investigacao em Patobiologia Molecular, Departamento de Patologia Morfologica, Instituto Portugues de Oncologia Francisco Gentil, Lisboa.
OBJECTIVE: Previous studies have demonstrated a link between Helicobacter pylori infection and low grade B-cell gastric MALT lymphoma. The aim of this study was to evaluate the effect of Helicobacter pylori eradication in 17 patients with low grade B-cell gastric MALT lymphoma stage EI. METHODS: For disease staging EUS and CT scan were systematically performed. Eight patients were excluded from the present series because stage EII disease was diagnosed. To demonstrate B-cell monoclonality, immunohistochemistry and polymerase chain reaction were used. H. pylori eradication was performed with triple therapy. RESULTS: H. pylori was eradicated in all patients after first (n = 15) or second line (n = 2) treatment. Histologic regression of lymphoma was observed in all patients after a median period of 2 mo. Disappearance of monoclonality according to polymerase chain reaction took significantly longer (7 mo). At the end of the study, four of 16 patients still exhibited persistent monoclonal bands. Relapse of lymphoma occurred in two patients associated with H. pylori reinfection/recrudescence. CONCLUSION: Eradication of H. pylori seems to be an effective therapy in patients with stage EI gastric MALT lymphoma, although long-term results are still uncertain. Endoscopic ultrasonography is useful for a more accurate staging of the disease. The clinical significance of detecting monoclonality by polymerase chain reaction remains to be determined.

Weekend therapy for the treatment of Helicobacter pylori infection.

Year 1998
Tucci A. Poli L. Paparo GF. Bocus P. Togliani T. Mazzoni C. Orcioni GF. Agosti R. Grigioni WF. Sottili S. Caletti G.
The Institute of Medical Clinic and Gastroenterology, Department of Pathology, Hospital S. Orsola-Malpighi, University of Bologna, Italy.
OBJECTIVES: The aim of the present study was to evaluate the efficacy and the safety of a short-term regimen (weekend therapy) in the cure of Helicobacter pylori infection and to analyze the factors that may influence the success of the treatment. METHODS: Seventy-one patients with gastric colonization by a tinidazole sensitive H. pylori strain (34 duodenal ulcer and 37 nonulcer dyspepsia) received omeprazole 40 mg o.m. for 7 days (from Monday to Sunday) and bismuth 240 mg q.i.d. + amoxicillin 1000 mg/q.i.d. + tinidazole 500 mg q.i.d. for only 2 days (Saturday and Sunday). Endoscopy, histology, culture, urease test, and susceptibility studies were done at entry and 30 days after treatment. RESULTS: Successful eradication was obtained in 84% of patients. The percentage of eradication was higher in duodenal ulcer patients (94%) than in those with nonulcer dyspepsia (74%; p < 0.05), and in patients who received the treatment during hot weather (94%) than in those who received the treatment during cold weather (74%; p < 0.05). Side-effects were induced by the treatment in 17% of patients, and these were all not severe, self-limiting, short-lasting, and did not require specific treatment. CONCLUSIONS: These data suggested that weekend therapy with high doses of drugs represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection, particularly in patients with duodenal ulcer. Furthermore, they also confirm the relevant role that short-term treatments may play in the therapeutic approach to H. pylori infection, and highlight some important aspects influencing short-term schedules.

A cost analysis of a Helicobacter pylori eradication strategy in a large health maintenance organization.

Year 1998
Levin TR. Schmittdiel JA. Henning JM. Kunz K. Henke CJ. Colby CJ. Selby JV.
Division of Gastroenterology, University of California, San Francisco, USA.
OBJECTIVES: We sought to describe the effect of a Helicobacter pylori eradication strategy on health care costs among a cohort of health maintenance organization (HMO) members with peptic ulcer disease (PUD). METHODS: Patients were identified from an outpatient diagnosis database and verified at chart review to have new-onset PUD by upper endoscopy or upper gastrointestinal radiographic series. Health plan registration and accounting databases were used to track costs over 12 months after initial diagnosis. Costs were analyzed separately for an initial 2-month interval and a 10-month follow-up period. Inpatient and pharmacy costs are those directly attributable to PUD (either a PUD-related discharge diagnosis or an antiulcer medication prescription). Outpatient costs are total costs. All cost differences were adjusted for age and gender. RESULTS: Twenty-seven of 93 patients meeting selection criteria received H. pylori treatment. During the 2-month treatment window, adjusted PUD-related inpatient costs were higher for the H. pylori treated group (difference, $234.00/person), whereas total outpatient costs and PUD-related pharmacy costs were similar. During the 10-month follow-up period, PUD-related inpatient and pharmacy adjusted costs were similar, but adjusted outpatient costs in the H. pylori treated group were lower than in the untreated group (difference, $508.00/person). Total adjusted follow-up period costs were $555.00/person less in the H. pylori treated group (p = 0.05). Total 12-month costs in the H. pylori treated group were $285.00/per person less than in untreated patients, (p > 0.2); 30% of H. pylori treated patients were still receiving antisecretory therapy 1 yr after diagnosis, compared to 41.9% of untreated patients. CONCLUSIONS: H. pylori treatment is associated with a decreased cost of follow-up care for patients with PUD, primarily due to decreased outpatient utilization.

The association between antral G and D cells and mucosal inflammation, atrophy, and Helicobacter pylori infection in subjects with normal mucosa, chronic gastritis, and duodenal ulcer.

Year 1998
Kamada T. Haruma K. Kawaguchi H. Yoshihara M. Sumii K. Kajiyama G.
The First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
OBJECTIVE: The aim of this study was to clarify the mechanism of inappropriate hypergastrinemia in Helicobacter pylori (H. pylori)-infected subjects. METHODS: We measured fasting serum gastrin (SG) concentrations, and investigated immunohistochemically G and D cell numbers in 47 subjects with normal mucosa, 24 subjects with chronic gastritis, and 24 subjects with duodenal ulcer (DU). The degree of inflammation and atrophy were classified into four categories based on criteria established in the Sydney System: none, mild, moderate, and severe. Avidin-biotin complex methods were used to identify G and D cells, which were counted per unit square (0.25 mm2) in five random fields from each of two well-oriented antral and fundic biopsies. SG concentrations were measured by radioimmunoassay. RESULTS: The G cell number was not significantly different between 24 subjects with H. pylori-associated gastritis and those with DU. However, the number of antral D cells was significantly lower and the G/D cell ratio was significantly higher in subjects with DU than in those with H. pylori-associated gastritis (p < 0.01), although the degree of inflammation and atrophy in the antrum and H. pylori status were similar between the two groups. The mean fasting SG concentration was higher in subjects with DU than in those with H. pylori-associated gastritis, but the difference was not statistically significant. CONCLUSIONS: Our results demonstrate that a marked decrease in antral D cell number with a high G/D cell ratio may contribute to hypergastrinemia and the pathogenesis of DU.

Synchronous gastric tumors associated with esophageal cancer: a retrospective study of twenty-four patients.

Year 1998
Koide N. Adachi W. Koike S. Watanabe H. Yazawa K. Amano J.
Second Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
OBJECTIVES: Synchronous gastric tumors (including benign and secondary tumors) associated with esophageal cancer present diagnostic and therapeutic issues. We investigated this synchronous association, and retrospectively determined the frequency of the gastric tumors and the clinical characteristics. METHODS: In a series of 208 patients with esophageal cancer, we investigated the synchronous gastric tumors, as well as the frequency of association, clinicopathological characteristics, diagnosis, treatment, and the clinical outcome after surgery. RESULTS: Twenty-eight gastric tumors were found in 24 patients. Adenocarcinoma was most frequent. Most of these tumors were located at the upper or middle third of the stomach. Eight gastric tumors in six patients could not be detected preoperatively. Six of these tumors including a gastric remnant cancer were detected in the resected stomach, and two leiomyomas were detected during the operation. In one patient in which an endoscope could not pass through the esophagus, a leiomyoma was detected in the resected stomach. For the gastric cancers, total gastrectomy or proximal gastrectomy with lymph node dissections was performed. For the benign tumors, partial resection of the stomach was performed, and endoscopic resection was performed preoperatively for an adenoma. In both the postoperative hospital mortality rate and the survival rate after surgery, there were no significant differences between the patients with and without gastric tumors. CONCLUSIONS: Synchronous gastric tumors associated with esophageal cancer are not rare. When an endoscope cannot pass through the esophagus before surgery, other techniques must be performed to explore the stomach. For these patients, surgical treatment should be adapted positively.

Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors.

Year 1998
Peghini PL. Katz PO. Bracy NA. Castell DO.
The Esophageal Research Laboratory, Allegheny University Hospitals, Graduate, Philadelphia, Pennsylvania 19146, USA.
OBJECTIVES: It is our experience that many patients treated with proton pump inhibitors (PPI) b.i.d. recover acid secretion during the night. Our aim was to assess the efficacy of omeprazole and lansoprazole b.i.d. on nocturnal gastric acidity. METHODS: Three groups were studied with intragastric pH monitoring. Group 1 consisted of 17 patients with gastroesophageal reflux disease (GERD) taking omeprazole 20 mg b.i.d. Group 2 was 16 male volunteers taking omeprazole 20 mg b.i.d. and Group 3 comprised 12 volunteers taking lansoprazole 30 mg b.i.d. RESULTS: The percentages of time that subjects had pH < 4 were lower during supine than upright periods in Groups 1 and 3 (P < 0.01). Recovery of nocturnal acid secretion lasting > 1 h, termed acid breakthrough, occurred in three-fourths of all individuals within 12 h from intake of the evening dose of PPI. Median time to acid breakthrough for the whole group was 7.5 h. CONCLUSION: Nocturnal acid breakthrough occurs in a majority of patients and normal volunteers taking PPI b.i.d.

Appendicitis: the impact of computed tomography imaging on negative appendectomy and perforation rates.

Year 1998
Balthazar EJ. Rofsky NM. Zucker R.
Department of Radiology, New York University--Tisch Medical Center, New York 10016, USA.
OBJECTIVES: The purposes of this study were to investigate the use of computed tomography (CT) imaging in patients with suspected acute appendicitis and to evaluate the impact of CT on negative appendectomy and perforation rates. In patients clinically diagnosed of acute appendicitis the reported overall negative appendectomy rate is about 15-20%; 10% in men and 25-45% in women of childbearing age. This is associated with a perforation rate of 21-23%. METHODS: This is a retrospective analysis of 146 consecutive patients presenting with clinical symptoms suspicious of appendicitis over a 2-yr period in whom CT examinations were performed before therapy was instituted. The overall negative appendectomy and perforation rates were calculated for the entire group, as well as for the 54 women aged 15-50 yr in the childbearing cohort. RESULTS: The negative appendectomy rate was 4% in 122 patients operated on and the perforation rate was 22%. Among 36 women 15-50 yr of age operated on, the negative appendectomy rate was 8.3% and the perforation rate was 19%. Surgery was avoided in 24 patients, 18 of whom were women of childbearing age. CONCLUSIONS: The judicious use of CT imaging in patients with equivocal clinical presentation suspected of having appendicitis led to a significant improvement in the preoperative diagnosis. It resulted in a substantial decrease in the negative appendectomy rate compared to previously published reports, without incurring an increase in the perforation rate.

Serious gastrointestinal pathology found in patients with serum ferritin values < or = 50 ng/ml.

Year 1998
Lee JG. Sahagun G. Oehlke MA. Lieberman DA.
Division of Gastroenterology, Portland VAMC, Oregon, USA.
OBJECTIVE: Our aim was to evaluate the gastrointestinal tract in patients with serum ferritin values < or = 50 ng/ml for the presence of serious gastrointestinal pathology, including neoplasia and acid peptic disease. METHODS: In this prospective observational study, patients with serum ferritin values < or = 50 ng/ml who did not have an obvious cause of iron deficiency underwent colonoscopy and/or esophagogastroduodenoscopy. RESULTS: Between October 1, 1994, and February 29, 1996, 725 of 3015 patients who had serum ferritin determinations were found to have values < or = 50 ng/ml. To date, 143 patients have been fully evaluated and 77 were found to have serious gastrointestinal pathology including acid peptic disease (N = 46), cancer (N = 15), and large adenomas (N = 6). Colon cancer was discovered in five asymptomatic patients. The prevalences of serious gastrointestinal pathology did not differ between patients with serum ferritin values < or = 20 ng/ml and those with values between 21-50 ng/ml (63% vs 48%, p = 0.07). However, multivariate analysis showed that the presence of upper or lower gastrointestinal symptoms and serum ferritin value < or = 20 ng/ml is predictive of finding serious pathology (p = 0.0002 for the whole model), with odds ratios of 3.8 (95% confidence interval of 1.84-7.70) for presence of gastrointestinal symptoms and 2.2 (95% confidence interval of 1.09-4.57) for serum ferritin value < or = 20 ng/ml. CONCLUSIONS: Endoscopic examination is warranted in patients with serum ferritin values < or = 50 ng/ml to detect serious gastrointestinal pathology, present in 54% of such patients.

Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases.

Year 1998
McNair AN. Moloney M. Portmann BC. Williams R. McFarlane IG.
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
OBJECTIVE: We report five cases (four male; median age 20 yr, range 14-38 yr) of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. The patients presented with jaundice, elevated serum aminotransferase and alkaline phosphatase activities, hyperglobulinemia with high immunoglobulin G (IgG) levels, circulating antinuclear and/or smooth muscle autoantibodies (> or = 1:40), and moderate to severe interface hepatitis on liver biopsy (with biliary features in four). METHODS: All five fulfilled criteria for diagnosis of "definite" autoimmune hepatitis and showed marked responses to prednisolone and azathioprine therapy, with relapses occurring during reduction or withdrawal of treatment. Cholangiographic features of primary sclerosing cholangitis were found in three patients at presentation and after intervals of 7 and 14 yr in the other two. Only two had evidence of inflammatory bowel disease. Diagnostic criteria for identifying those patients who may benefit from immunosuppressive therapy were reviewed. RESULTS: Review of the literature revealed only 11 similar cases that were sufficiently well described for comparison. However, in contrast to these and the present cases, preliminary data from other studies have suggested a marked association with ulcerative colitis and a poor response to immunosuppressive therapy. CONCLUSIONS: It is recommended that the possibility of an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome responsive to immunosuppressive therapy should be considered in any patient presenting with a hepatitic illness with hyperglobulinemia, antinuclear or smooth muscle autoantibodies, and biliary changes on liver biopsy. Cholangiography should be considered in such patients.

Hepatitis C virus and depression in drug users.

Year 1998
Johnson ME. Fisher DG. Fenaughty A. Theno SA.
IVDU Project, Department of Psychology, University of Alaska Anchorage 99508, USA.
OBJECTIVES: Clinical case studies have implicated depression as a possible side-effect of interferon treatment for the Hepatitis C virus (HCV). However, because these studies generally did not include a pretreatment assessment of depression, it cannot be definitively stated whether depression is a side-effect of interferon treatment, a syndrome coexisting with HCV, or a common characteristic of individuals who are vulnerable to HCV infection. To gather more information about this issue, self-reported depressive symptomatology of drug users with HCV who have not received interferon treatment was compared to that of uninfected drug users. METHODS: Subjects were 309 drug users not currently in substance abuse treatment who were participating in a National Institute on Drug Abuse project. Subjects completed the Center for Epidemiological Studies-Depression (CES-D) instrument and provided a blood sample for HCV testing. RESULTS: Serological findings revealed that 52.4% of the subjects tested positive for HCV antibodies. Of the HCV-positive subjects, 57.2% had significant depressive symptomatology, whereas only 48.2% of the HCV-negative subjects did, for an overall rate of 52.6%. The two groups also differed on two specific dimensions of depression, with the HCV-positive group scoring lower on the Positive Affect scale and higher on the Somatic/Retarded Activity scale. CONCLUSIONS: These findings reveal high levels of depressive symptomatology among drug users, as well as the possibility of a coexisting depressive syndrome with HCV infection. These findings raise the possibility that depression associated with interferon treatment may, at least partially, be accounted for by preexisting depression. Further research is needed to determine the nature and origins of depression in individuals in treatment with interferon for HCV with specific focus placed on determining the dimensions of depression associated with HCV infection and interferon treatment.

Soluble CD44 and CD44v6 serum levels in patients with colorectal cancer are independent of tumor stage and tissue expression of CD44v6.

Year 1998
Weg-Remers S. Hildebrandt U. Feifel G. Moser C. Zeitz M. Stallmach A.
Department of Internal Medicine II, University of the Saarland, Homburg, Germany.
OBJECTIVES: Tissue overexpression of CD44 variants, especially CD44v6, and elevated serum concentrations of soluble CD44 variants (sCD44) have been demonstrated in patients with colorectal cancer and several other tumors. Our aim was to evaluate the clinical value of their measurement in colorectal cancer. METHODS: To examine the suitability of sCD44 and sCD44v6 as tumor markers in colorectal cancer these parameters were analyzed in serum of patients with colorectal cancer, inflammatory bowel disease, chronic renal failure, and controls. Tissue expression of CD44v6 in colorectal carcinomas was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: sCD44 and sCD44v6 levels were significantly elevated in most of the patient groups (medians, sCD44: 330-709 ng/ml; sCD44v6: 125-160 ng/ml) compared to controls (sCD44: 346 ng/ml; sCD44v6: 106.5 ng/ml). No difference was seen between colorectal cancer patients of different UICC (Union Internationale Contre le Cancer) stages and between patients with CD44v6-positive or -negative primary tumors. CONCLUSIONS: sCD44 and sCD44v6 concentrations showed no correlation to tumor burden or CD44v6 tissue expression. Sensitivity and specificity were low, compared to CEA. Therefore, in our view sCD44 and sCD44v6 measurement in screening or follow-up of patients with colorectal cancer is of very little clinical value.

Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population.

Year 1998
Gupta SK. Fitzgerald JF. Chong SK. Croffie JM. Garcia JG.
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA.
OBJECTIVE: Increasing evidence suggests that nitric oxide participates in the pathophysiology of intestinal barrier function/dysfunction and inflammation. Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression have been observed in colonic mucosal biopsies of adults with inflammatory bowel disease (IBD). It is unclear whether iNOS induction is specific for IBD or a reflection of nonspecific mucosal inflammation. Furthermore, the characteristics of iNOS mRNA expression in pediatric patients with gastrointestinal disorders remains ill-defined. Our objective was to examine the relationship between iNOS mRNA expression and gastrointestinal mucosal inflammation in a pediatric population. METHODS: Esophageal and colonic mucosal biopsies were obtained during endoscopy. Total RNA was isolated from these biopsies and reverse transcription-polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp primers that amplified a predicted 372-bp conserved iNOS mRNA fragment. RESULTS: Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7-16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR amplification in six of 10 patients with ulcerative colitis and in two of four patients with Crohn disease. However, iNOS mRNA was not amplified in any esophageal biopsy or in rectal mucosa biopsies with normal histology. CONCLUSIONS: These data indicate that upregulation of iNOS mRNA expression in colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not upregulated in esophageal mucosa or in the absence of colonic inflammation. Further studies designed to determine the site- and cell-specificity of iNOS mRNA upregulation in mucosal biopsies from children with IBD may further illuminate the pathophysiology of these disorders.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.

Year 1998
d'Albasio G. Paoluzi P. Campieri M. Porro GB. Pera A. Prantera C. Sturniolo GC. Miglioli M.
Unita Operativa di Gastroenterologia, Ospedale Careggi, Firenze, Italy.
OBJECTIVES: A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. METHODS: From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurrence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. RESULTS: The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. CONCLUSIONS: The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.

Distal procto-colitis, natural cytotoxicity, and essential fatty acids.

Year 1998
Almallah YZ. Richardson S. O'Hanrahan T. Mowat NA. Brunt PW. Sinclair TS. Ewen S. Heys SD. Eremin O.
Department of Surgery, University of Aberdeen, United Kingdom.
OBJECTIVES: Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis. METHODS: In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored. RESULTS: After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group. CONCLUSIONS: This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease.

Benefit of uncooked cornstarch in the management of children with dumping syndrome fed exclusively by gastrostomy.

Year 1998
Borovoy J. Furuta L. Nurko S.
Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, Boston, Massachusetts 02115, USA.
OBJECTIVES: Children with dumping syndrome fed exclusively by gastrostomy are difficult to manage because liquid diets are given directly into the antrum. The gastric contents are emptied rapidly into the small intestine, with consequent hyperglycemia followed by a delayed hypoglycemia and multiple, often debilitating, symptoms. Uncooked cornstarch is a complex carbohydrate that provides a slow and continuous glucose source and may delay gastric emptying. The objective of this study was to determine the efficacy of uncooked cornstarch in the treatment of these children. METHODS: The medical records of eight children with dumping syndrome fed exclusively by gastrostomy were reviewed. Dumping syndrome was diagnosed if there was consistent symptomatology, rapid gastric emptying, and abnormal glucose measurements after a glucose tolerance test. Enough uncooked cornstarch to match hepatic glucose production for 4 h was added to control hypoglycemia, and the feeding formula was modified to control hyperglycemia. RESULTS: All patients had debilitating symptoms. Weight z-score on admission was -2.31 +/- 0.29. Glucose shifts were controlled in all. There was a significant difference between the maximum (221.3 +/- 19.3 mg/dl vs 121.3 +/- 6.9 mg/dl; p < 0.008) and minimum serum glucose (47 +/- 7.8 mg/dl vs 65.6 +/- 4 mg/dl; p < 0.04) before and after uncooked cornstarch. Weight increased from 11.87 +/- 1.4 kg to 15.10 +/- 2.3 kg (p = 0.06). In seven patients, bolus feedings were successfully administered, and symptoms improved or resolved. CONCLUSIONS: Uncooked cornstarch controlled the glucose shifts, resolved most of the symptoms, allowed bolus feedings, and enhanced weight gain in these children.

Possible cholestatic injury from ranitidine with a review of the literature.

Year 1998
Ramrakhiani S. Brunt EM. Bacon BR.
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63110-0250, USA.
Although one of the histamine-2 (H2) receptor antagonists, oxmetidine, has been shown to be intrinsically hepatotoxic, overt liver injury attributable to the commonly used analogues such as ranitidine is rare, given the millions of patients who have received this medication. However, isolated cases of hepatitis associated with ranitidine have been reported in the literature since the early 1980s when this drug was first introduced. We report a case of cholestatic hepatitis associated with ranitidine use. Liver biopsy showed diffuse panacinar canalicular cholestasis and cholestatic rosettes in zone 3. The clinical syndrome and the laboratory abnormalities resolved completely after discontinuation of the drug. There have been a few other published reports of ranitidine associated acute cholestatic hepatitis, and in this case ranitidine was temporally related to the onset of symptoms and liver enzyme abnormalities. With recent over-the-counter (OTC) availability of the H2 receptor antagonists and the increasing use of these drugs in the general population, physicians need to be aware of this rare but potentially serious side effect of ranitidine.

Hepatic cystadenoma: an unusual presentation.

Year 1998
Catinis GE. Frey DJ. Skinner JW. Balart LA.
Department of Gastroenterology, Louisiana State University Medical Center, New Orleans, USA.
A 53-yr-old woman with a history of hepatic cystadenoma 25 yr before presented with a simple hepatic cyst, which evolved over 9 yr into a complex cystadenoma with septations and internal bleeding. She was treated with a left hepatectomy. Review of the literature shows that hepatic cystadenomas, although rare, frequently can recur years later and have potential for malignant transformation. Histologic similarities of one variant with ovarian stroma raises interesting possibilities regarding the origin of these lesions. The best treatment results are obtained with radical excision.

Liver transplantation for disulfiram-induced hepatic failure.

Year 1998
Rabkin JM. Corless CL. Orloff SL. Benner KG. Flora KD. Rosen HR. Olyaei AJ.
Department of Surgery, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, USA.
Fulminant hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram. A patient without a known history of liver disease was transplanted for fulminant hepatic failure secondary to disulfiram. A high index of suspicion and aggressive therapeutic approaches are essential for the prompt diagnosis and treatment of disulfiram-induced hepatic failure. The clinical presentation, histopathology, treatment, and all cases of disulfiram-induced hepatic failure reported in the English literature are reviewed. The role of orthotopic liver transplantation in a case of disulfiram-induced hepatic failure is discussed.

Duodenal hemangioendothelioma: a case report.

Year 1998
Panzini L. Homer RJ.
Department of Medicine and Pathology, Connecticut Healthcare Department of Veterans Affairs, West Haven, USA.
Epithelioid hemangioendothelioma is extremely rare. A patient with an epithelioid hemangioendothelioma presenting as an annular mass encircling the second portion of the duodenum is described. We believe this to be the first such lesion in this location reported.

Familial occurrence of gastric carcinoid tumors associated with type A chronic atrophic gastritis.

Year 1998
Yoshikane H. Nishimura K. Hidano H. Sakakibara A. Takahashi Y. Niwa Y. Goto H.
Department of Internal Medicine, Handa City Hospital, Handa, Japan.
We present here familial occurrence of two patients with gastric carcinoid. Both patients, a sister and older sister, had type A chronic atrophic gastritis with hypergastrinemia. This is the first case report of familial occurrence of gastric carcinoid associated with type A chronic atrophic gastritis in the world literature. The possible mechanism of familial occurrence in the patients is discussed.

Hodgkins disease diagnosed by endoscopic ultrasound-guided fine needle aspiration of a periduodenal lymph node.

Year 1998
Lewis JD. Faigel DO. Dowdy Y. Sack MJ. Salhany KE. Haynes B. Fox KR. Ginsberg GG.
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Hodgkin's disease rarely presents as obstructive jaundice. We report a case of Hodgkin's disease arising in periduodenallymph nodes, presenting with biliary obstruction, definitively diagnosed on cytologic material obtained by endosonographically-guided real-time fine needle aspiration biopsy and confirmed at laparotomy. The medical literature pertaining to the use of endosonography and fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is reviewed. Currently available data support the use of fine needle aspiration biopsy in establishing the diagnosis of lymphoma. This case highlights the utility of endoscopic ultrasonography with endosonographically guided real-time fine needle aspiration biopsy in diagnosing and managing patients with extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing endosonographically guided real-time fine needle aspiration biopsy with on-site cytologic assessment and immediate specimen triage can lead to definitive diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.

Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.

Year 1998
Longo F. Hastier P. Buckley MJ. Chichmanian RM. Delmont JP.
Department of Hepato-Gastroenterology, Archet Hospital, Nice, France.
An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.

Idiopathic pulmonary fibrosis associated with rectal carcinoma--a paraneoplastic syndrome or coincidence?

Year 1998
Haviv YS. Kramer MR. Safadi R.
Division of Medicine and Institute of Pulmonology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is well documented, complicating > or = 10% of cases involving IPF. This association is considered to be a result of neoplastic degeneration, rather than a paraneoplastic phenomenon. However, rectal carcinoma has only rarely been linked to paraneoplastic manifestations. We describe a young patient with IPF that preceded the appearance of rectal carcinoma by 6 mo. The possible association between the two disorders is discussed.

Renal and urologic complications of inflammatory bowel disease.

Year 1998
Pardi DS. Tremaine WJ. Sandborn WJ. McCarthy JT.
Inflammatory Bowel Disease Clinic, Division of Gastroenterology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
Renal and urologic complications are not uncommon in patients with inflammatory bowel disease, and can be directly or indirectly related to the underlying disease process or its treatment. Many of these patients have asymptomatic disease, or the urinary symptoms are nonspecific or overshadowed by bowel symptoms. By the time a urinary complication is considered, significant disease progression or renal damage may have occurred. These risks necessitate a high degree of diligence and periodic urologic evaluation as part of the long-term management of patients with inflammatory bowel disease.

Primary sclerosing cholangitis: a clinical review.

Year 1998
Ponsioen CI. Tytgat GN.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by fibro-obliterative inflammation of the entire biliary tree. It is a slowly progressive disease with an undulating course, resulting in terminal biliary cirrhosis after a median period of about 12 years after diagnosis. The etiology of the disease is unknown and there is no effective therapy that can halt disease progression. Around 8% of PSC patients develop cholangiocarcinoma, which, by the time it is diagnosed, cannot be treated curatively. The purpose of this article is to review the current knowledge about primary sclerosing cholangitis and to speculate on future strategies to address the issues of etiology and therapy.

Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones.

Year 1998
Chang L. Lo SK. Stabile BE. Lewis RJ. de Virgilio C.
Department of Medicine, University of California Los Angeles School of Medicine, Harbor-UCLA Medical Center 90509, USA.
OBJECTIVE: The aim of this study was to define the incidence of cholangitis in gallstone pancreatitis, in the absence of cholangitis, to identify the clinical predictors of persistent common bile duct (CBD) stones at endoscopic retrograde cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A total of 122 consecutive patients with acute gallstone pancreatitis were prospectively evaluated for the presence of CBD stones as determined by elective ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis. APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%) patients had cholangitis and all underwent urgent ERCP successfully. Eighteen (15%) patients without cholangiogram were excluded. The remaining 100 patients underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%) patients had persistent CBD stones. Univariate analysis detected significant differences in serum total bilirubin, ALT, and alkaline phosphatase levels between patients with and without persistent CBD stones. On multivariate analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best clinical predictor of persistent CBD stones is serum total bilirubin on hospital day 2.

Palliative treatment of malignant esophagorespiratory fistulas with Gianturco-Z stents. A prospective clinical trial and review of the literature on covered metal stents.

Year 1998
May A. Ell C.
Department of Medicine II, Horst-Schmidt-Kliniken Wiesbaden, Germany.
OBJECTIVE: Esophagorespiratory fistulas, especially in the upper third of the esophagus, are a complication of malignant esophageal tumors, which are difficult to manage. The efficacy of polyurethane-covered, self-expanding metal stents for palliation of malignant esophagorespiratory fistulas was investigated prospectively. METHODS: Eleven patients with malignant esophagorespiratory fistulas resp. perforations were treated with Gianturco-Z stents. In five patients the lesion was located in the proximal part of the esophagus. Because of the fistula all patients suffered from dysphagia even for liquids. RESULTS: No technical problems during the implantation procedure of the stents occurred. In the control radiography with water-soluble contrast media, the fistulas were completely sealed in 10 of 11 patients. Therefore the dysphagia score improved from 3.0 to 0.6. Nearly all Gianturco-Z stents (10/11) showed a sufficient expansion within 24 h after placement. Severe early or late complications were not encountered, with the exception of tumor overgrowth in one patient about 9 months after stent placement. In five patients, short term (3-6 days) retrosternal pain was observed, and one patient complained of slight foreign body sensation. By August 1997 all 11 patients had died of advanced disease, with a median survival time of 121 days (range, 22-300 days). CONCLUSIONS: Gianturco-Z stents are highly effective for palliative treatment of esophagorespiratory fistula resp. perforations and have a low complication rate. Due to the fact that this stent shows no retraction during the release, a precise positioning is possible, especially in the case of tumors and fistulas in the upper third of the esophagus. It seems that use of the Gianturco-Z stent can be considered a good therapeutic method for palliative endoscopic treatment of this high risk patient group.

The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barretts esophagus.

Year 1998
Katz D. Rothstein R. Schned A. Dunn J. Seaver K. Antonioli D.
Department of Medicine, Veterans Administration Medical Center, White River Junction, Vermont, USA.
OBJECTIVE: Periodic endoscopic surveillance is generally recommended for patients with Barrett's esophagus. The optimal follow-up strategy for uncomplicated Barrett's esophagus is controversial, in part because of limited data on the rate of neoplastic progression (through the sequence of metaplasia-dysplasia-carcinoma) during endoscopic surveillance. This study aims to quantify the development of dysplasia in patients with uncomplicated Barrett's esophagus and to explore clinical risk factors associated with the development of dysplastic lesions. METHODS: We identified 102 patients with endoscopic evidence of Barrett's esophagus and the presence of specialized columnar epithelium who had received endoscopic surveillance for adenocarcinoma at our medical center between 1970 and 1994. We abstracted endoscopic and histologic data from the medical record. All specimens that showed any degree of atypia (per report) were reexamined in blinded fashion by a team of study pathologists who indicated the grade of dysplasia. Time to first diagnosis of dysplasia was plotted using Kaplan-Meier survival curves, and risk factors for development of dysplasia were assessed using Cox regression. RESULTS: During 563 patient-yr of endoscopic follow-up, three patients developed adenocarcinoma at least 4 yr after initial diagnosis (one developed adenocarcinoma of the cardia, which was incidentally detected during surveillance for Barrett's esophagus). At some point during follow-up, 19 patients developed new onset, low grade dysplasia and four developed high grade dysplasia. None of the patients who had received antireflux surgery developed dysplasia. CONCLUSION: If confirmed by larger follow-up studies, our results suggest that surveillance endoscopy can be safely deferred for at least 2 yr following an initial biopsy that is negative or indeterminate for dysplasia. Adoption of this approach would substantially reduce the cost of surveillance for adenocarcinoma. Future trials should explore the role of antireflux surgery in protecting against neoplastic transformation of Barrett's esophagus.

Barretts esophagus and the presence of Helicobacter pylori.

Year 1998
Henihan RD. Stuart RC. Nolan N. Gorey TF. Hennessy TP. O'Morain CA.
Department of Surgery, Trinity College, St. James's Hospital, Dublin, Ireland.
OBJECTIVE: Although the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease and antral gastritis has been well documented, the role of H. pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 141 patients with histologically confirmed esophageal disease. METHODS: The study group consisted of 82 patients with Barrett's esophagus, 19 with adenocarcinoma of the esophagus arising in columnar epithelium and 40 patients with reflux esophagitis without columnar metaplasia of the esophagus. In each of these cases the presence or absence of H. pylori was assessed histologically. RESULTS: H. pylori was present in 19 of 82 patients (23%) with Barrett's esophagus, but was absent in all patients with adenocarcinoma of the esophagus and in patients with reflux esophagitis without Barrett's metaplasia. H. pylori was found only in areas of gastric type metaplasia in the patients with Barrett's esophagus. All of the 19 Barrett's esophagus group with H. pylori had chronic inflammation, and in 16 the inflammation was severe. H. pylori was significantly associated with severity of inflammation in patients with Barrett's esophagus (p < 0.001). Members of the Barrett's group with evidence of moderate to severe dysplasia were negative for H. pylori. CONCLUSION: These data confirm that the presence of gastric type mucosa within the esophagus is a prerequisite for H. pylori colonization, and that H. pylori may contribute to the severity of inflammation in Barrett's epithelium.

Cisapride 20 mg b.i.d. provides symptomatic relief of heartburn and related symptoms of chronic mild to moderate gastroesophageal reflux disease. CIS-USA-52 Investigator Group.

Year 1998
Castell DO. Sigmund C Jr. Patterson D. Lambert R. Hasner D. Clyde C. Zeldis JB.
Allegheny University Hospitals, Philadelphia, Pennsylvania 19146, USA.
OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.

Biopsy sites suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis.

Year 1998
Satoh K. Kimura K. Taniguchi Y. Kihira K. Takimoto T. Saifuku K. Kawata H. Tokumaru K. Kojima T. Seki M. Ido K. Fujioka T.
Department of Gastroenterology, Jichi Medical School, Yakushiji, Tochigi, Japan.
OBJECTIVES: We performed this study to determine which biopsy sites in the stomach are suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis. METHODS: Endoscopy was performed in 76 H. pylori-positive patients with histologically confirmed chronic gastritis. Biopsies were taken from the following six sites: the lesser curvatures of the mid-antrum (site 1), the angulus (site 2), the middle body (site 3), and the greater curvatures of the mid-antrum (site 4), the angulus (site 5), and the middle body (site 6) of the stomach. The extent of atrophic gastritis was assessed endoscopically as well as histologically, and patients were classified into five groups according to its extent. H. pylori status was assessed histologically. The histological severity of inflammation, activity, atrophy, and intestinal metaplasia was assessed according to the Updated Sydney System. The grades of these items were compared among the six biopsy sites in each group of patients. RESULTS: Site 6 was most reliable for the diagnosis of H. pylori infection, and site 4 was suitable for examining the status of H. pylori colonization in the antrum. Site 1, site 3, and site 6 were suitable for the assessment of the extent of atrophic gastritis. CONCLUSIONS: Our results indicate that for an accurate diagnosis and assessment, biopsies should be taken from the following four sites: the lesser curvatures of the mid-antrum (site 1) and middle body (site 3), and the greater curvatures of the mid-antrum (site 4) and middle body (site 6) of the stomach.

Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY: is empirical triple therapy justified?

Year 1998
Jyotheeswaran S. Shah AN. Jin HO. Potter GD. Ona FV. Chey WY.
The Konar Center for Digestive and Liver Diseases, University of Rochester Medical Center, New York 14642, USA.
OBJECTIVES: Among patients with peptic ulcer disease, the prevalence of Helicobacter pylori has been reported to range from 80% to 90%. Thus empirical cost-effective therapy has been suggested. We surveyed patients with peptic ulcer disease in Rochester, NY. METHODS: From two teaching hospitals all patients who had duodenal ulcers (DU) and/or gastric ulcers (GU) on esophagogastroduodenoscopy (EGD) with antral biopsy for histology for H. pylori and for rapid urease (CLO) test were included in the study. We examined a total of 160 patients with DU and 145 patients with GU, age range 18-92 yr, obtaining clinical data, race, medication profile, and history of use of nonsteroidal antiinflammatory drugs (NSAIDs). An ulcer was defined if the lesion with loss of mucosal integrity was > or = 0.5 cm, with apparent depth. H. pylori was considered present if CLO test and/or histology were positive for H. pylori. To confirm the reliability of nonuse of NSAIDs, we randomly checked blood samples of 90 such patients from the ambulatory clinic for the presence of salicylates. To identify the sensitivity of the CLO test, we performed a serology test for H. pylori antibody in 100 subjects to compare the CLO test results. Also, 500 CLO test results were compared to the histology results for H. pylori. RESULTS: Among 160 DU patients, 16 were NSAID users with negative H. pylori and excluded from the prevalence study. Of the remaining 144 patients with DU, H. pylori was present in 88 patients (61%). When these data were analyzed according to race, H. pylori was present in 54 (52%) of 104 whites compared to 34 of 40 (85%) nonwhites (blacks, Hispanics, Asians) (p < 0.01). Among 145 GU patients 18 were NSAID users with negative H. pylori and excluded from the prevalence analysis. Of the remaining 127 patients with GU, H. pylori was present in 87 patients (61%). Among them, H. pylori was present in 46 of 87 (53%) whites, whereas 31 of 40 nonwhites (78%) were H. pylori-positive (p < 0.01). Antral histology and CLO test for H. pylori were in agreement in 92% of cases. Serology and CLO test for H. pylori were in agreement in 87% of cases. None of the randomly screened patients, including 16 ulcer patients with negative H. pylori, showed presence of salicylate in blood. CONCLUSION: In greater Rochester, NY, where the majority of our patients with EGD were whites, the prevalence of H. pylori among ulcer patients was lower compared to other regions, particularly among whites. This suggests that an additional causative factor or factors for peptic ulcers may be present. Hence, empirical antibiotic therapy of ulcer patients without confirming the presence of H. pylori may not be justified.

Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens.

Year 1998
Schwartz H. Krause R. Sahba B. Haber M. Weissfeld A. Rose P. Siepman N. Freston J.
Baptist Hospital, Miami, Florida, USA.
OBJECTIVE: The efficacy and safety of dual and triple therapies with a proton pump inhibitor and antibiotic(s) for therapy of Helicobacter pylori-associated duodenal ulcer disease have been compared using results from independent studies using different methods and regimens, making interpretation difficult. In a large, double-blind, multicenter study conducted in the United States, we compared a triple therapy regimen with four dual therapy and one monotherapy regimens in the eradication of H. pylori and the prevention of ulcer recurrence. METHODS: Patients with active duodenal ulcer disease or history of duodenal ulcer disease within the past year and H. pylori infection were randomized to receive one of six 14-day treatment regimens: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 gm b.i.d.; lansoprazole 30 mg b.id. and either clarithromycin 500 mg b.i.d. or t.i.d.; lansoprazole 30 mg b.i.d. or t.i.d. with amoxicillin 1 gm t.i.d.; or lansoprazole 30 mg t.i.d. alone. No additional acid suppression therapy followed eradication therapy. Primary efficacy endpoints were eradication of H. pylori and ulcer recurrence. RESULTS: Of 396 patients enrolled in the study, 352 met the entry criteria for duodenal ulcer status and H. pylori positivity. At 4-6 wk after the end of therapy, H. pylori was eradicated from 94% (44 of 47) of patients receiving lansoprazole, clarithromycin, and amoxicillin triple therapy, 77% (39 of 51) of those receiving lansoprazole t.i.d./amoxicillin t.i.d., 75% (36 of 48) of those receiving lansoprazole b.i.d./clarithromycin t.i.d., 57% (28 of 49) of those receiving lansoprazole b.i.d./clarithromycin b.i.d., 53% (26 of 49) of those receiving lansoprazole b.i.d./amoxicillin t.i.d., and 2% (1 of 53) of those receiving lansoprazole monotherapy (p < or = 0.05, triple therapy vs each dual therapy and each dual therapy vs monotherapy). Of those patients who were documented as free of ulcer at 4-6 wk after treatment, ulcers recurred within 6 months in 7% of patients receiving triple therapy, as compared with 13-23% of patients receiving dual therapy, and 69% of patients receiving lansoprazole monotherapy. Patients who were H. pylori negative at 4-6 wk after treatment were less likely to have an ulcer recurrence than were patients who were H. pylori positive (11% [10 of 95] vs 47% [20 of 43], respectively, across treatment groups). For triple therapy and dual therapy, a similar proportion of patients reported a drug-related adverse event (23% vs 17-33%, respectively). CONCLUSIONS: In patients with active or a recent history of duodenal ulcer, a 14-day course of lansoprazole-based triple therapy without additional acid suppression therapy is highly effective in the eradication of H. pylori and in preventing ulcer recurrence. Among the dual therapies, higher eradication rates occurred when lansoprazole (with amoxicillin) or clarithromycin (with lansoprazole) was administered t.i.d. vs b.i.d., but the rates were still significantly lower than with lansoprazole triple therapy with all three drugs administered b.i.d.

Hepatitis C infection risk analysis: who should be screened? Comparison of multiple screening strategies based on the National Hepatitis Surveillance Program.

Year 1998
Lapane KL. Jakiche AF. Sugano D. Weng CS. Carey WD.
Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, USA.
OBJECTIVES: Hepatitis C, an infection of high prevalence worldwide, is insidiously progressive in many. Reduction of person-to-person spread is possible, and treatment is possible for many, particularly if offered before cirrhosis develops. Screening for hepatitis C (HCV) would be appropriate if strategies could be developed to afford adequate sensitivity and specificity at reasonable cost. We evaluated the performance characteristics of several screening strategies to determine the best balance between cost and performance. METHODS: The database of a national hepatitis screening program was used to define risk factors for HCV. Features associated with increased risk for HCV by multivariable analysis were combined in various ways to construct HCV screening models. Screening Model 1 employed a mathematical model constructed to predict the probability of hepatitis C. Using this model, testing for HCV was done if the probability of HCV was determined to be higher than 7%. Models 2 and 3 called for HCV testing if certain risk factors, stratified as socially intrusive, or nonintrusive in nature, were present. Model 4 calls for testing for HCV only when ALT values are elevated. Costs per case discovered were calculated for each model. RESULTS: Nine thousand two-hundred sixty-nine individuals from a database of 13,997 has sufficient information to be included in the modeling studies. Risk factors considered socially intrusive were intravenous (i.v.) drug use and sex with an i.v. drug user. Risk factors considered not socially intrusive were: history of blood transfusion, age 30-49 yrs, and male gender. The sensitivity of Models 1-4 were 65%, 69%, 53%, and 63%, respectively. Specificities were 84%, 74%, 77%, and 92%, respectively. The cost per case detected was lowest when Models 1 or 2 were used ($357 and $439, respectively) and higher for models 3 and 4 ($487 and $1047, respectively). CONCLUSIONS: The yield and cost of screening for HCV compares favorably with accepted current screening practices for other diseases. Models 1, 2, and 3 may be appropriate in certain clinical and epidemiological settings. Selective screening by a risk factor questionnaire (first three models) is more cost-effective than blood testing with ALT (Model 4).

Risk factors associated with chronic hepatitis C virus infection: limited frequency of an unidentified source of transmission.

Year 1998
Flamm SL. Parker RA. Chopra S.
Department of Medicine, Northwestern Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60611, USA.
OBJECTIVES: Risk factors have been studied in patients with acute non-A, non-B hepatitis, and approximately 40-50% have no known risk factor for viral acquisition. A significant undefined source of viral transmission has been suggested. We sought to clearly delineate the risk factors in a population of patients with documented chronic hepatitis C virus (HCV) infection to assess the magnitude of HCV transmission without known risk factors. METHODS: Risk factor profiles were carefully assessed in 301 consecutive patients with chronic HCV infection. Patients were classified by gender and age. Overall risk factor distributions were calculated and comparisons were made between groups to detect differences in mode of HCV acquisition. RESULTS: One hundred ninety-six men and 105 women were studied; 223 were age < or = 45 yr and 78 were > 45 yr. Overall, 25% of patients had a history of transfusion and 49% had a history of intravenous drug use (i.v.DU). Only 12% had no history of risk factor exposure. Men were more likely to have a history of i.v.DU and less likely to have a history of blood transfusion or sexual exposure/household contact. Younger patients were more likely to have a history of i.v.DU and older patients were more likely to have a history of blood transfusion and to deny all risk factor exposure. CONCLUSIONS: A careful history delineated a potential risk factor for HCV acquisition in 88% of patients with chronic HCV infection. Men and younger patients had different risk factor profiles than women and older patients, respectively. It is likely that an important unknown mode of HCV transmission occurs in a significant minority of patients.

The changes in quantitative HCV RNA titers during interferon alpha 2B therapy in patients with chronic hepatitis C infection.

Year 1998
Tong MJ. Blatt LM. Conrad A. Hur Y. Russell J. El-Farra NS. Co RL.
The Liver Center, Huntington Memorial Hospital, Pasadena, California 91105, USA.
OBJECTIVE: Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy. METHODS: Seventy anti-HCV-positive patients were treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml. RESULTS: The mean pretreatment HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p = 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p = 0.0001), while at wk 48, only. the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy. CONCLUSIONS: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.

Intestinal tuberculosis: clinicopathologic analysis and diagnosis by endoscopic biopsy.

Year 1998
Kim KM. Lee A. Choi KY. Lee KY. Kwak JJ.
Department of Gastroenterology and Clinical Pathology, Catholic University Medical College, Inchon, Korea.
OBJECTIVES: Tuberculosis is still an important cause of granulomatous colitis in developing countries. If we can diagnose tuberculosis using endoscopic biopsy material, clinicians can avoid invasive diagnostic procedures and needless operations. For this purpose, we evaluated clinical manifestations, pathological findings, and diagnostic methods in endoscopically biopsied intestinal tuberculosis patients. METHODS: From January 1991 to December 1996, 42 patients with intestinal tuberculosis were endoscopically examined and tissue culture, immunohistochemical stain, Ziehl-Neelsen stain, and polymerase chain reaction in fresh and fixed tissue were applied. The pathological findings were analyzed and compared with the results of the other diagnostic methods. RESULTS: In tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and multiple erosions were usual colonoscopic findings. The granulomas were found in 74% of the cases. The positivity ranged from 30-45%. There were no significant differences in the positivity among those diagnostic methods (p > 0.05). The positivity of Ziehl-Neelsen stain in fixed tissue was higher in the group having granulomas and it was reversed in PCR (p < 0.05). The increasing number of biopsy particles raised the positivity of Ziehl-Neelsen stain and PCR in fixed tissue (p < 0.05). CONCLUSIONS: Transverse ulcers were the most characteristic colonoscopic finding and granulomas were frequent pathological findings in intestinal tuberculosis. Higher positivity and reliable results were found in tissue culture, Ziehl-Neelsen stain, and polymerase chain reaction. To increase the diagnostic rate, the endoscopist should take enough tissue and deep biopsy material from ulcer bases and diseased mucosae.

Significance of diminished factor XIII in Crohns disease.

Year 1998
Chamouard P. Grunebaum L. Wiesel ML. Sibilia J. Coumaros G. Wittersheim C. Baumann R. Cazenave JP.
Service d'Hepato-Gastroenterologie et d'Assistance Nutritive, Hopital de Hautepierre, Strasbourg, France.
OBJECTIVE: Coagulation factor XIII is a plasma transglutaminase involved in crosslinking of fibrin, the last step of the coagulation system and a connective tissue factor contributing to the wound healing process. It circulates as a heterotetrameric molecule consisting of two identical proenzyme subunits (factor XIIIA) and two carrier protein subunits (factor XIIIS). The aim of this study was to determine the disease features associated with the diminution of factor XIII in Crohn's disease. METHODS: Factor XIIIA and factor XIIIS levels were assessed in patients presenting with Crohn's disease, ulcerative colitis, infectious colitis, or diverticulitis, in patients with rheumatoid arthritis, and in control subjects. Prothrombin fragment 1 + 2 assay, as a marker of the generation of thrombin and measurement of C-terminal telopeptide of type I collagen as an estimate of degradation of collagen type I, were performed. RESULTS: Factor XIIIA was significantly decreased in Crohn's disease, in ulcerative colitis, and in infectious colitis by comparison with subjects presenting with diverticulitis, normal, and rheumatoid subjects p = 0.0001). Factor XIIIS was unmodified in patients with Crohn's disease by comparison with controls but was reduced in those presenting with intestinal bleeding (p = 0.0002). In Crohn's disease, the lowest level of factor XIIIA was observed in patients with intestinal bleeding (p = 0.0003). Factor XIIIA was correlated with the Van Hees index (r = -0.5661; p = 0.0001) and with the C-terminal telopeptide of type I collagen (r = -0.4110; p = 0.0011) but not with prothrombin fragment 1 + 2. The multiple regression analysis showed that only Van Hees index and intestinal bleeding were independent variables for explaining the diminution of Factor XIIIA in Crohn's disease. CONCLUSIONS: Factor XIIIA subunit is an indicator of Crohn's disease activity. Our study suggests that a low factor XIIIA level is related to the presence of intestinal lesions and might be linked to intestinal repair mechanisms; loss in intestinal lumen could be also involved, especially in patients with intestinal bleeding.

Colonic polyps: experience of 236 Indian children.

Year 1998
Poddar U. Thapa BR. Vaiphei K. Singh K.
Department of Gastroenterology and Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
OBJECTIVES: We studied the clinical spectrum, histology, and malignant potential of colonic polyps in Indian children (< or =12 yr). METHODS: Two hundred thirty-six children with colonic polyps were studied from January 1991 to October 1996. They were evaluated clinically and colonoscopic polypectomy was done. Children with five or more juvenile polyps were labeled as having juvenile polyposis and serial colonoscopic polypectomies were done every 3 wk. Colectomy was performed when there were intractable symptoms or clearing of the polyps by colonoscopy was not possible. Histological examination of the polyps was done. Follow-up colonoscopy was done in children with juvenile polyposis only. RESULTS: The mean age of these children was 6.12 +/- 2.7 yr, with a male preponderance (3.5:1). Rectal bleeding of a mean duration of 14 +/- 16 months was the presenting symptom in 98.7%. Solitary polyps were seen in 76%, multiple polyps in 16.5%, and juvenile polyposis in 7% (n = 17) of the children. A majority (93%) of the polyps were juvenile and 85% were rectosigmoid in location. Adenomatous changes, seen in 11%, were more common in juvenile polyposis (59%) than in juvenile polyps (5%). Among those with juvenile polyposis, colon clearance was achieved in eight, six required colectomy for intractable symptoms, and three were still on the polypectomy program. Polyps recurred in 5% of children with juvenile polyps and 37.5% of those with juvenile polyposis. CONCLUSIONS: Juvenile polyps remain the most common colonic polyps in children. A significant number of cases of polyps are multiple and proximally located, which emphasizes the need for total colonoscopy in all. Juvenile polyps should be removed even if asymptomatic because of their neoplastic potential. Colonoscopic polypectomy is effective even in juvenile polyposis. Surveillance colonoscopy is required in juvenile polyposis only.

Colonic chicken skin mucosa: an endoscopic and histological abnormality adjacent to colonic neoplasms.

Year 1998
Shatz BA. Weinstock LB. Thyssen EP. Mujeeb I. DeSchryver K.
Department of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
OBJECTIVES: We recently described an endoscopic finding of pale yellow-speckled mucosa adjacent to colonic neoplasms. This resembled the appearance of chicken skin and was named chicken skin mucosa (CSM). CSM differs from previously reported gastrointestinal xanthelasmas in that this entity always occurs in association with colonic neoplasms. The prevalence, endoscopic characteristics, clinical significance, and possible etiology were investigated. METHODS: Eight hundred fifty-two consecutive colonoscopies were prospectively evaluated for the presence of CSM associated with either cancer or adenomas > or = 1 cm. Electron microscopy and histopathology using hemotoxylin and eosin, mucicarmine, and oil red O stains were performed. Twelve consecutive colon cancer resection specimens were prospectively examined to determine the presence of histologic CSM. RESULTS: CSM was adjacent to eight of 10 distal colorectal cancers, one of four proximal colon cancers, 16 of 42 distal adenomas, and three of 44 proximal adenomas. Four of seven resected distal cancers demonstrated histological evidence of CSM. Biopsies of the CSM revealed that lipid-filled macrophages in the lamina propria were responsible for this endoscopic appearance. Electron microscopy showed that the surface epithelial cells had small intestine-like microvilli. CSM was not seen with other colonic conditions and was not associated with the laxative preparation. In four instances, identification of the CSM alerted the endoscopist to the presence of polyps in locations difficult to visualize. CONCLUSIONS: CSM is an endoscopic entity that occurs as a result of fat accumulation in macrophages in the lamina propria of the mucosa adjacent to colonic neoplasms. Small intestine-like microvilli were present in CSM and the pathophysiological implications remain to be elucidated.

Accelerated right colonic emptying after simulated upper gut hemorrhage.

Year 1998
Hammer J. Lang K. Kletter K.
Universitatsklinik fur Innere Medizin IV, Abteilung fur Gastroenterologie und Hepatologie, Vienna, Austria.
OBJECTIVE: Upper gastrointestinal hemorrhage delays gastric emptying. Our aim was to evaluate the effect of gastrointestinal hemorrhage on small intestinal, ileocecal, and proximal colonic transit. METHODS: Healthy volunteers were randomized to receive either a duodenal infusion of heparinized autologous blood (n = 7) or egg white, acting as a control substance with similar composition; 1.5 mCi99mTc-DTPA was added to the infused substances. We infused 30 ml at an infusion rate of 1 ml/min. Gamma-camera images were taken for 4 h or until all radioactivity had entered the colon. Arrival of radiolabels in the colon and also counts in the ascending and transverse colon were quantified. RESULTS: Small intestinal and ileocecal transit were not significantly different between blood and egg white infusions. However, ascending colonic emptying was significantly faster after blood infusion compared to egg white. Four hours after the start of blood infusion a median of 30% of counts were in the transverse colon (11-50%; 25th-75th percentile) versus 0% (0-7%) after egg white infusion (p < 0.001). CONCLUSION: We concluded that simulated upper gastrointestinal bleeding hastens proximal colonic transit, but does not alter small intestinal transit and colonic filling.

Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a preliminary study.

Year 1998
Hirooka Y. Goto H. Ito A. Hayakawa S. Watanabe Y. Ishiguro Y. Kojima S. Hayakawa T. Naitoh Y.
Second Department of Internal Medicine and Clinical Laboratory Medicine, Nagoya University School of Medicine, Japan.
OBJECTIVE: The purpose of this study was to clarify the usefulness of contrast-enhanced endoscopic ultrasonography in pancreatic diseases. METHODS: The subjects comprised 37 patients with pancreatic diseases: 11 with ductal cell carcinoma, 10 with mucin-producing tumor, five with pseudo-cyst, four with islet cell tumor, four with chronic pancreatitis, and three with serous cystadenoma. After endoscopic ultrasonography, Albunex (0.22 ml/kg) was injected intravenously at a rate of 1 ml/s into the right median vein, and observation was continued for 10 min. The presence or absence of enhancement of the lesion was determined in each disease. Because all the patients with ductal cell carcinoma, islet cell tumor, chronic pancreatitis, and serous cystadenoma, as well as five with mucin-producing tumor and three with pseudo-cyst, underwent angiography, vascularity was compared between angiographic images and those of contrast-enhanced ultrasonography. RESULTS: Enhancement of the lesion was observed in all patients with islet cell tumor and serous cystadenoma, in eight with mucin-producing tumor, and in three with chronic pancreatitis. However, no enhancement effect was observed in the patients with ductal cell carcinoma and those with pseudo-cyst. Comparison between the images of contrast-enhanced endoscopic ultrasonography and angiographic images showed three patients in whom angiograms were hypovascular, but enhancement effect was observed on ultrasonographic images. CONCLUSION: The combined evaluation of plain and enhanced images of endoscopic ultrasonography may be useful for the diagnosis of pancreatic diseases.

Diffuse pancreatic fibrosis: an uncommon feature of multifocal idiopathic fibrosclerosis.

Year 1998
Levey JM. Mathai J.
Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
Multifocal idiopathic fibrosclerosis (MIF) is a rare syndrome characterized by exuberant fibrosis involving diverse organ systems. MIF is manifest by varying combinations of the following conditions: mediastinal fibrosis, retroperitoneal fibrosis, orbital pseudotumor, Riedel's thyroiditis, and sclerosing cholangitis. Less common features of MIF include Dupuytren's contractures, lymphoid hyperplasia, Peyronie's disease, vasculitis, testicular fibrosis, and pachymeningitis. Fibrosis arising from the pancreas has been previously described in two patients with MIF. We report a 58-yr-old white man with MIF manifest as orbital pseudotumor, sclerosing cholangitis, lymph node hyperplasia, and diffuse pancreatic fibrosis.

Metal stents for the palliation of inoperable upper gastrointestinal stenoses.

Year 1998
Bethge N. Breitkreutz C. Vakil N.
Krankenhaus Neukolln Berlin, Germany.
We sought to determine the efficacy of metal stents in the palliation of malignant upper gastrointestinal stenoses. Six patients with inoperable malignant obstruction of the upper gastrointestinal tract, intractable nausea and vomiting, and an inability to maintain an oral intake were studied. A metal stent was inserted under endoscopic control and deployed in the stenosis. Stents were successfully deployed in all patients, and there were no immediate complications. All patients were able to eat after the procedure and parenteral nutrition was discontinued in all. Mean survival was 23 +/- 8.6 days. We conclude that metal stents represent a promising approach to the management of selected patients with malignant upper gastrointestinal stenoses and that their use warrants further study.

Pneumatosis intestinalis and AIDS: a case report and review of the literature.

Year 1998
Gelman SF. Brandt LJ.
Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York 10467, USA.
We report five AIDS patients who developed pneumatosis intestinalis and review the pertinent literature to clarify the contributory importance of underlying infections, to suggest a management plan, and to determine whether pneumatosis intestinalis alters prognosis. Of the five patients reported, three had concurrent infections including cryptosporidiosis (one patient), presumptive CMV (one patient), and toxoplasmosis of the central nervous system (one patient). One patient also had neutropenia. Another patient was immunosuppressed during treatment for lymphoma, and the fifth patient had been taking corticosteroids before the diagnosis of CNS lymphoma. In four of five patients pneumatosis involved the right colon. Pneumatosis was linear in all five patients and also was cystic in two of the five. All patients were followed conservatively without short term adverse events, despite the known association of linear pneumatosis with bowel necrosis. We advocate conservative management and an attempt to avoid surgery whenever possible.

Budd-Chiari syndrome related to factor V Leiden mutation.

Year 1998
Delarive J. Gonvers JJ.
University Hospital (CHUV)/University Medical Outpatients Department (PMU), Lausanne, Switzerland.
We here describe a young patient who presented with chronic Budd-Chiari syndrome. An exhaustive etiological investigation to detect a procoagulable state was negative except for factor V mutation (factor V Leiden), a factor associated with resistance to activated protein C. Factor V Leiden is known to be a common, high risk factor for thrombosis. This factor should be routinely investigated in patients with Budd-Chiari syndrome, as factor V Leiden mutation is probably the procoagulable state responsible for many cases of "idiopathic" Budd-Chiari syndrome.

Immunoblastic lymphadenopathy presenting as an acute abdomen and mixed bacteremia with Eikenella corrodens and group C streptococci.

Year 1998
Monkemuller KE. Bronze MS.
Department of Medicine, The University of Tennessee, Memphis, USA.
Eikenella corrodens and group C streptococci have been noted to occur with increased frequency in patients with underlying malignancies and immunosuppressive states. We report a case where these organisms were isolated from a patient with immunoblastic lymphadenopathy and discuss the possible association between these two conditions.

Painless small bowel ischemia presenting with diarrhea and weight loss.

Year 1998
Jones DE. Barton J. Cobden I.
Department of Medicine, University of Newcastle and North Tyneside General Hospital, North Shields, Newcastle-upon-Tyne, United Kingdom.
Chronic ischemia of the small bowel is classically described as presenting with abdominal pain associated with eating (intestinal angina). Here we describe the cases of two patients with chronic small bowel ischemia who presented atypically with painless watery diarrhea and weight loss. These cases suggest that the clinical spectrum of chronic small bowel ischemia may be wider than previously appreciated. Chronic ischemia of the small bowel should be included in the differential diagnosis for painless watery diarrhea in the context of weight loss.

Fourniers gangrene: an unusual presentation for rectal carcinoma.

Year 1998
Gamagami RA. Mostafavi M. Gamagami A. Lazorthes F.
Department of Surgery, University of California, San Diego, USA.
We report a case of a large perforated adenocarcinoma of the rectum manifesting as an ischiorectal abscess progressing to Fournier's gangrene in an insulin-dependent diabetic man. Recognition and management of this rare syndrome in the setting of a common disease is discussed.

Gluten sensitivity in patients with primary biliary cirrhosis.

Year 1998
Niveloni S. Dezi R. Pedreira S. Podesta A. Cabanne A. Vazquez H. Sugai E. Smecuol E. Doldan I. Valero J. Kogan Z. Boerr L. Maurino E. Terg R. Bai JC.
Clinical Department, Hospital de Gastroenterologia Dr Carlos Bonorino Udaondo, Universidad del Salvador, Buenos Aires, Argentina.
OBJECTIVE: Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis. METHODS: Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge). RESULTS: Overall, three patients presented evidence of gluten sensitivity. All three had abnormal titers of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease. CONCLUSION: We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.

Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?

Year 1998
Fornari MC. Pedreira S. Niveloni S. Gonzalez D. Diez RA. Vazquez H. Mazure R. Sugai E. Smecuol E. Boerr L. Maurino E. Bai JC.
Departamento de Medicina, Hospital de Gastroenterologia Dr Carlos Bonorino Udaondo; Universidad del Salvador, Facultad de Medicina (UBA), Buenos Aires, Argentina.
OBJECTIVE: Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements. METHODS: We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA. RESULTS: Untreated patients had high serum levels of IL-1beta and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores). CONCLUSIONS: Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1beta and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.

Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis.

Year 1998
Esteve M. Mallolas J. Klaassen J. Abad-Lacruz A. Gonzalez-Huix F. Cabre E. Fernandez-Banares F. Menacho M. Condom E. Marti-Rague J. Gassull MA.
Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
OBJECTIVES: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. METHODS: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. RESULTS: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. CONCLUSIONS: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa.

Esophagitis dissecans superficialis (esophageal cast) complicating esophageal sclerotherapy.

Year 1998
Perez-Carreras M. Castellano G. Colina F. Rodriguez-Munoz S. Solis-Herruzo JA.
Department of Medicine, University Hospital Doce de Octubre, Madrid, Spain.
Esophagitis dissecans superficialis is a rare and benign condition that involves the formation of an esophageal cast. This disorder has been described in association with a variety of etiologic factors. We report a case of an esophageal cast in a patient included in a program of sclerotherapy of varices. We discuss the possible relationship existing between sclerotherapy and the development of esophagitis dissecans superficialis.