Abstract: OBJECTIVE: Recurrence of Helicobacter pylori infection after eradication is rare in developed countries and more frequent in developing countries. Most recurrent cases are attributed to recrudescence (recolonization of the same strain within 12 months) rather than to reinfection (colonization with a new strain after more than 12 months). The aim of the study was to analyze recurrence rates in developed and developing countries and to deduce the relative roles of recrudescence and reinfection. METHODS: The PubMed database was searched up to January 31, 2007 using the keywords "Helicobacter pylori" or "H. pylori" and "recurrence" or "recrudescence," or "reinfection." Only prospective case studies in adults that used the (13)C-urea breath test ((13)CUBT) were included. Meta-analyses were performed with statdirect Statistical software, version 2.6.1, StatsDirect Ltd, Chesire, UK. RESULTS: The literature search yielded 10 studies of H. pylori recurrence in developed countries (3014 patients followed for 24-60 months) and 7 studies in developing countries (2071 patients followed for 12-60 months). The calculated annual recurrence rates were 2.67% and 13.00%, respectively. Nested meta-analysis of cases with a longer follow-up after eradication revealed an annual recurrence rate of 1.45% (RR 0.54) in developed countries and 12.00% (RR 0.92) in developing countries. CONCLUSIONS: The similarity of the annual recurrence rates during the first year after eradication and the annual recurrence rates in the second year after successful eradication in developing countries supports reinfection as the main cause in the second period. Therefore, a different approach for follow-up of H. pylori eradication may be needed between developed and developing countries.

Abstract: Background The guaiac fecal occult blood test (G-FOBT), HemoccultSENSA(TM), is sensitive for significant neoplasms (colorectal cancer (CRC), advanced adenomatous polyps (AAP)), but faulted by non-specificity for human hemoglobin (Hb). Quantified, Hb- specific, immunochemical fecal occult blood tests (I-FOBT) are now used. Aims (1) Compare I-FOBT and G-FOBT efficacy in identifying significant neoplasms and colonoscopy needs for positive tests; (2) Examine number of I-FOBTs needed and test threshold to use for equivalent or better sensitivity than G-FOBT, and fewest colonoscopies for positive tests. Methods Three daily G-FOBTs and I-FOBTs were collected and analyzed in 330 patients scheduled for colonoscopy. Results Colonoscopy found significant neoplasms in 32 patients, 6 CRC, 26 AAP. G-FOBT, sensitivity and specificity were 53.1% (17 neoplasms) and 59.4%, resulting in 8.1 colonoscopies/neoplasm. One I-FOBT having >/=50ngHb/mL of buffer provided equivalent sensitivity but 94.0% specificity, resulting in 2.1 colonoscopies/neoplasm. By analyzing the higher of two I-FOBTs at 50ngHb/mL threshold, sensitivity increased to 68.8% (22 neoplasms, P=0.063), specificity fell to 91.9% (P<0.001), but still required 2.1 colonoscopies/neoplasm. Conclusions In this population quantified I-FOBT had significantly better specificity than G-FOBT for significant neoplasms, reducing the number of colonoscopies needed/neoplasm detected. Results depend on number of I-FOBTs performed and development threshold chosen.

Abstract: Good preparation before endoscopic procedures is essential for successful visualization. The small bowel is difficult to evaluate because of its length and complex configuration. A meta-analysis was conducted of studies comparing small bowel visualization by capsule endoscopy with and without preparation. Medical data bases were searched for all studies investigating the preparation for capsule endoscopy of the small bowel up to July 31, 2007. Studies that scored bowel cleanness and measured gastric and small bowel transit time and rate of cecum visualization were included. The primary endpoint was the quality of bowel visualization. The secondary endpoints were transit times and proportion of examinations that demonstrated the cecum, with and without preparation. Meta-analysis was performed with StatDirect Statistical software, version 2.6.1 (http://statsdirect.com). Eight studies met the inclusion criteria. Bowel visualization was scored as "good" in 78% of the examinations performed with preparation and 49% performed without (P<0.0001). There were no significant differences in transit times or in the proportion of examinations that demonstrated the cecum with and without preparation. Capsule endoscopy preparation improves the quality of small bowel visualization, but has no effect on transit times, or demonstration of the cecum.

Abstract: BACKGROUND: Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. AIM: To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. MATERIALS AND METHODS: Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. RESULTS: Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. CONCLUSIONS: In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.

Abstract: Ethical and legal implications arise both when seeking a second medical opinion and when providing one. There has been debate as to whether a second opinion for a patient is a right or a concession and whilst today most would consider it to be a patient's right, there are nevertheless some disadvantages associated with seeking a second opinion. This article addresses the reasons why patients seek second opinions, it considers when physicians themselves should refer patients and it covers the issues involved in providing a second opinion particularly in cases where there is the potential for an allegation of malpractice. Finally, the arguments for and against treating patients who are referred for a second opinion are addressed. This paper has been prepared following a round table discussion on this subject, which was addressed during a symposium on Ethics in Gastroenterology and Digestive Endoscopy held in Kos in 2006.

Abstract: INTRODUCTION: In developing countries the recurrence rate of Helicobacter pylori after successful eradication therapy is as high as 42%, while in developed countries it is estimated to be less than 3%. Such figures are very important in terms of determining clinical strategy and outcome. AIM: To estimate the recurrence rate of H. pylori in Israel using the database of the "Central H. Pylori Laboratory of Clalit Health Services". METHODS: The database was searched for patients who had undergone the [(13)C]-urea breath test ([(13)C]-UBT) for validation of the successful eradication of H. pylori or for evaluation of dyspepsia 7 years previously and for whom the result had been negative. These patients were invited to participate in the trial, fill a symptom questionnaire and undergo another [(13)C]-UBT. RESULTS: A In total, 65 patients participated; of these, 26 patients had tested negative in the first( 13)CUBT, indicating the successful eradication of H. pylori (Group A), and 39 had been tested for dyspepsia (Group B). One patient in each group had a positive [(13)C]-UBT - 3.84% in Group A and 2.56% in Group B (non-significant difference, NS). The mean annual H. pylori recurrence rate was calculated to be 0.55% and 0.37% in Group A and Group B patients, respectively (NS). CONCLUSION: Our results shown a very low re-infection or new infection rates in Israeli adults and are in line with other trials in developed countries; they do not support the a retesting program for patients after a successful eradication therapy.

Abstract: BACKGROUND: Capsule endoscopy is a relatively new imaging tool for the detection of small bowel pathology. The assessment of the severity of Crohn's disease by capsule endoscopy is not standardized and is limited by interobserver variations in interpreting the findings. AIM: To develop, assess and validate a new, simple capsule endoscopy Crohn's disease activity index (CECDAI) in order to grade the severity of small bowel capsule endoscopy findings. METHODS: The system involves dividing the small bowel into proximal and distal segments according to transit time and then rating each segment on the basis of three parameters: inflammation (A), extent of disease (B) and presence of strictures (C). The segmental score is calculated by multiplying the inflammation subscore by the disease-subextent score and adding the stricture subscore (A x B + C); the final score is calculated by adding the two segmental scores: CECDAI = (A1 x B1 + C1) + (A2 x B2 + C2). In the present study, four senior endoscopists (two with experience in capsule endoscopy interpretation) independently reviewed coded capsule endoscopy videos of 20 patients with Crohn's disease and rated them according to the CECDAI. Interobserver variability was analyzed by Spearman's correlation test. RESULTS: The CECDAI total scores for the 20 patients ranged from 0 to 26. The correlation for the total score assigned between every two observers was 0.867 (0.700-1.000 = strong degree association; WHO classification; P < 0.0001). The Kappa statistics for agreement among all observers for the subscores and total scores were as follows: A1, 0.31 +/- 0.05; B1, 0.25 +/- 0.05; C1 (no cases); A2, 0.51 +/- 0.05; B2, 0.57 +/- 0.05; C2, 0.27 +/- 0.07. All examiners reported that the system was simple to learn and apply. CONCLUSIONS: The CECDAI score may serve as a convenient, reliable and reproducible diagnostic and follow-up tool for use by experienced endoscopists in the evaluation of patients with Crohn's disease of the small bowel.

Abstract: Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative (13)CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent.

Abstract: BACKGROUND: The C-caffeine breath test (CBT) is a noninvasive tool for the evaluation of the cytochrome P450 system, implicated in the development of nonalcoholic steatohepatitis. GOAL: To apply the CBT to assess the extent of hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Twenty-six consecutive patients (mean age 56.1+/-6.85 y, 69.2% women) with NAFLD underwent the CBT, in addition to the clinical and laboratory evaluations and liver biopsy. Ten healthy individuals matched for age served as controls. RESULTS: Mean delta over baseline values differed significantly between patients and controls (1.51+/-0.9 vs. 2.37+/-0.8 Delta per thousand/mg, respectively) (P=0.01) and were significantly higher in patients with fibrosis stage <2 (Brunt's system) (2.0+/-0.77 vs. 1.3+/-0.9 for stage > or =2, P=0.05). Mean delta over baseline values correlated highly with fibrosis stage (P=0.01), albumin (P=0.007), international normalized ratio (P=0.04), bilirubin (P=0.0008), and platelet count (P=0.0001). On multivariate stepwise logistic regression analysis, CBT was the best predictor of severe fibrosis (stage > or =2) (odds ratio 0.274, 95% confidence interval 0.086-0.872, P=0.028), with an area under the curve of 0.788. CONCLUSIONS: The CBT is safe and easy to perform. It can reliably predict severe hepatic fibrosis in patients with NAFLD. Further large-scale studies are still needed.

Abstract: CONTEXT: Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE: To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS: Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS: Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE: Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS: For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION: In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

Abstract: In 2007 Helicobacter pylori research continued to deal with some controversies raised in the last decade. The main problems remain unsolved: peptic ulcer disease negative for H. pylori, synergism of H. pylori infection and aspirin and other nonsteroidal anti-inflammatory drugs or cyclooxygenase 2 specific inhibitors, the role of H. pylori eradication in uninvestigated and nonulcer dyspepsia, and the possible protective effect of H. pylori infection against gastroesophageal reflux disease and its complications such as Barrett's esophagus and adenocarcinoma. The incidence and prevalence of peptic ulcer disease as well as ulcer-related mortality are continuing to decline all over the world. The increasing consumption of anti-inflammatory and antisecretory drugs was not found to change the trend over the last period and therefore H. pylori was considered the key factor in causing ulcer-related mortality. Some progress has been achieved in understanding H. pylori-induced immunological processes, and attack mechanisms, as well as specific pathogenesis in uremic and cirrhotic patients. There is still a lot to learn about the bacterium and host factors related to H. pylori infection and its complications.

Abstract: BACKGROUND: Dedicated, organ-specific screening clinics have been shown to significantly reduce cancer morbidity and mortality. OBJECTIVES: To establish a dedicated clinic for Clalit Health Service patients at high risk for hereditary gastrointestinal cancer and to provide them with clinical and genetic counseling, diagnostic screening and follow-up. RESULTS: During the 3 years of the clinic's activity, 634 high risk families, including 3804 at-risk relatives, were evaluated. The most common conditions were hereditary colorectal syndromes, Lynch syndrome (n=259), undefined young-onset or familial colorectal cancer (n=214), familial adenomatous polyposis (n=55), and others (n=106). They entered follow-up protocols and 52 underwent surgical procedures. CONCLUSIONS: Consistent public and professional education is needed to increase awareness of hereditary colorectal cancer and the possibility of family screening, early diagnosis and therapy. The public health services--i.e., the four health management organizations--should provide genetic testing for these patients who, at present, are required to pay for almost all of these available but costly tests. Dedicated colorectal surgical units are needed to provide the specialized therapeutic procedures needed by patients with familial colorectal cancer. Our future plans include adding psychosocial support for these at-risk patients and their families as well as preventive lifestyle and dietary intervention.

Abstract: OBJECTIVE: The objectives of this study were to describe gastrointestinal (GI) disease prevalence in Israeli adolescents, and possible associations between prevalence and body mass index (BMI), sex and Jewish ethnicity. DESIGN: A retrospective analysis of screening for GI disease performed by the Israeli Defense Forces recruiting office between 1998 and 2003. SETTING: Screening was performed at the recruiting office, and included detailed history and physical examination performed by a general practitioner. Further testing was performed as needed and the final diagnosis was established by a gastroenterologist at the recruiting office. PATIENTS: Seventeen-year-old Israeli nationals. RESULTS: During the study period, 466,855 (58.5% male) adolescents were screened for GI disease. Peptic ulcer disease, irritable bowel syndrome, and nonulcer dyspepsia were the most prevalent disorders affecting 466/10, 460/10, and 296/10, respectively. There was an increase in the prevalence of lactose intolerance during the study period and also an increase in the prevalence of peptic ulcer disease in females. The prevalence of inflammatory bowel disease has also increased from 100/10 to 149/10, although this trend failed to reach statistical significance (P=0.097). Higher BMI was associated with statistically significant higher prevalence rates of gastroesophageal reflux disease (P<0.05). A stronger association in females was found in gallbladder disease (P<0.001). Lower BMI was associated with higher prevalence rates of irritable bowel syndrome (P<0.001), and higher rates of inflammatory bowel disease and lactose intolerance in males (P<0.01 and <0.001, respectively). CONCLUSIONS: GI diseases are not uncommon among adolescents, and for some disorders prevalence is rising. The association between BMI and prevalence has been further clarified.

Abstract: Objectives This is the third survey that we have performed in the kibbutz population in Israel. The previous two surveys were 10 years apart, in 1987 and 1997, demonstrating an increase in Crohn's disease prevalence. The aim of the present study was to confirm the trend for increasing Crohn's disease prevalence in Israel. Methods There are 269 kibbutz settlements in Israel, with a total of 117,700 people, accounting for 2.4% of the Jewish Israeli population. The local physician for each kibbutz was contacted by mail, e-mail, telephone, and fax in order to obtain information on Crohn's disease patients. Data was retrieved and updated to 31st December 2007, the point prevalence date. Details of gender, age, origin, clinical spectrum of the disease, therapy, and complications were recorded. Results There were 133 confirmed cases of Crohn's disease. The prevalence rate rose from 25.53/100,000 in 1987 to 65.11/100,000 in 1997, and then to 112.99 in 2007 (P < 0.0001). The prevalence rate was higher in women than men, and Israeli- or European/American-born than Asian/African-born individuals. The rise in prevalence was steady from 1987 to 1997 and then to 2007 in all subgroups, except for Asian/African-born kibbutz members. In the last group, a decrease in prevalence was demonstrated between 1987 and 1997, and then a sharp increase between 1997 and 2007. Conclusions We conclude that the incidence and prevalence of Crohn's disease increased in the three ethnic groups of Israeli Jews. Differences still exist but become smaller, maybe due to the strong environmental influence that overcame genetic preponderance.

Abstract: Capsule endoscopy is the most recent innovation in gastrointestinal endoscopy. The capsule contains a video camera that photographs the bowel for 8 h after the capsule has been orally ingested and transmits the images for interpretation to a computerized workstation. Ethical considerations of the use of capsule endoscopy should cover the following main issues: justification of the procedure, its potential benefits and harm, and patient autonomy. Capsule endoscopy has several advantages over traditional endoscopy. The procedure is painless, does not require sedation, is easy to perform and for the first time enables exploration of the entire small bowel at high magnification. However, the clinician cannot control its passive advance along the bowel. In addition, the examination may be incomplete, as the capsule reaches the cecum in only 80% of cases. This paper discusses the problems related to the new endoscopic procedure, the diagnostic yield in comparison with other procedures, proper indications for the procedure, outcome and complications.

Abstract: Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and co-investigators showed recently that MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through beta-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-beta-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.

Abstract: Objective The preferred method for screening asymptomatic people for colorectal cancer (CRC) is colonoscopy, according to the new American guidelines. The aim of our study was to perform a meta-analysis of the prospective cohorts using total colonoscopy for screening this population for CRC. We looked for the diagnostic yield of the procedure as well as for its safety in a screening setting. Methods We included papers with more than 500 participants and only those reporting diagnostic yield of adenoma (and/or advanced adenoma) and CRC. Nested analysis were performed for secondary endpoints of complications and CRC stages when this information was available. All analyses were performed with StatDirect Statistical software, version 2.6.1 ( http://www.statsdirect.com ). Results Our search yielded ten studies of screening colonoscopy conducted in asymptomatic people that met our inclusion criteria, with a total of 68,324 participants. Colonoscopy was complete and reached the cecum in 97% of the procedures. Colorectal cancer was found in 0.78% of the participants (95% confidence interval 0.13-2.97%). Stage I or II were found in 77% of the patients with CRC. Advanced adenoma was found in 5% of the cases (95% confidence interval 4-6%). Complications were rare and described in five cohorts. Perforation developed in 0.01% of the cases (95% confidence interval 0.006-0.02%) and bleeding in 0.05% (95% confidence interval 0.02-0.09%). Conclusions Our findings support the notion that colonoscopy is feasible and a suitable method for screening for CRC in asymptomatic people.

Abstract: BACKGROUND: Guaiac-based fecal occult blood tests (FOBTs) for colorectal cancer screening are not specific for human hemoglobin and have low sensitivity. Automated-development, immunochemical FOBT is quality-controlled, is specific for human hemoglobin, and does not require diet restriction. OBJECTIVES: To measure the sensitivity and specificity of quantitative immunochemical fecal hemoglobin measurements for detection of cancer and advanced adenoma in patients undergoing colonoscopy, to determine fecal hemoglobin thresholds that give the highest posttest probability for neoplasia, and to determine the number of immunochemical FOBTs needed. DESIGN: Prospective, cross-sectional study. SETTING: Ambulatory endoscopy services of the main health medical organization in Tel Aviv, Israel. PARTICIPANTS: 1000 consecutive ambulatory patients--some asymptomatic but at increased risk for colorectal neoplasia and some symptomatic--who were undergoing elective colonoscopy and volunteered to prepare immunochemical FOBTs. INTERVENTION: The hemoglobin content of 3 bowel movements was measured, and the highest value was compared with colonoscopy findings. MEASUREMENTS: Sensitivity, specificity, predictive values, likelihood ratios, and 95% CIs of fecal hemoglobin measurements for clinically significant neoplasia, their relationship to the amount of fecal hemoglobin measured, and the number of immunochemical FOBTs performed. RESULTS: Colonoscopy identified clinically significant neoplasia in 91 patients (cancer in 17 patients and advanced adenomas in 74 patients). Using 3 immunochemical FOBTs and a hemoglobin threshold of 75 ng/mL of buffer, sensitivity and specificity were 94.1% (95% CI, 82.9% to 100.0%) and 87.5% (CI, 85.4% to 89.6%), respectively, for cancer and 67% (CI, 57.4% to 76.7%) and 91.4% (CI, 89.6% to 93.2%), respectively, for any clinically significant neoplasia. LIMITATIONS: The fecal sampling method is standardized, but the sample size depends on fecal consistency. Some patients were tested while discontinuing aspirin and anticoagulant therapies. Study patients were at increased risk, and results might not apply to average-risk populations. CONCLUSIONS: Quantitative immunochemical FOBT has good sensitivity and specificity for detection of clinically significant neoplasia. Test performance in screening average-risk populations is not known.

Abstract: The colorectal cancer (CRC) screening program in Israel offers the average-risk population fecal occult blood tests from the age of 50 years. Compliance, however, is very low, reaching only 6% of eligible persons in 2005. Our aim in this study was to describe the results of an improved CRC screening program directed at the in-house staff of Beilinson Hospital. All employees of Beilinson Hospital over age 50 years were sent a letter explaining the new CRC screening program and an accompanying questionnaire. Responders who reported a family history of CRC or related cancers or symptoms were offered colonoscopy; the remainder were offered sigmoidoscopy or, if they preferred, colonoscopy. Two hundred twenty of the 888 candidates (24.7%) completed the questionnaire, of whom 144 (16.2%) agreed to further investigation. These included 90 of 105 patients with a positive questionnaire and 20 of 115 with a negative questionnaire who underwent colonoscopy and 34 of 115 with a negative questionnaire who underwent sigmoidoscopy. The colonoscopy group included 26 of the 30 patients (86.6%) with a positive family history. Early-stage CRC was diagnosed in three patients (1.36%), all with a positive questionnaire. There were no pathologic findings on sigmoidoscopy. The sensitivity, specificity, and positive and negative predictive values of the questionnaire for identifying subjects with CRC or advanced adenoma were 100.00%, 18.86%, 2.27%, and 100.00%, respectively. In conclusion, using hospital facilities, we initiated a unique CRC screening program for employees. Our method may be applicable in other medical centers for the detection of adenomas and CRCs in the early, curative stages.

Abstract: BACKGROUND & AIMS: Our aim was to establish the incidence of symptomatic upper gastrointestinal ulcers, ulcer perforation, ulcer obstruction, or bleeding episodes (PUBs) associated with the use of selective cyclooxygenase-2 inhibitors at standard clinical doses compared with placebo. We report here on the PUB outcomes associated with the use of rofecoxib 25 mg in a 3-year, multicenter, double-blind, placebo-controlled trial designed to determine the effect of rofecoxib on the risk of recurrent neoplastic polyps of the colon. METHODS: A total of 2587 patients with a history of colorectal adenomas underwent randomization to 25 mg/day of rofecoxib or to placebo. Investigator-reported PUBs were adjudicated by an external blinded committee. Kaplan-Meier and Cox proportional hazards techniques were used to estimate incidence and relative risks of PUBs in an intention-to-treat analysis. RESULTS: Patients assigned to rofecoxib had a higher incidence of confirmed PUBs than those randomized to placebo (.88 vs .18 events per 100 patient-years; relative risk, 4.9; 95% confidence interval, 1.98-14.54). The incidence of confirmed complicated PUBs (ulcer perforation, obstruction, or bleeds) was low, but was numerically higher in the rofecoxib than in the placebo group (.23 vs .06 events per 100 patient-years; relative risk, 3.8; 95% confidence interval, .72-37.46; P = .14). Rofecoxib increased the incidence of confirmed PUBs vs placebo in both low-dose aspirin users and nonusers. CONCLUSIONS: Among patients with a history of colorectal adenomas, the long-term use of 25 mg/day of rofecoxib was associated with an increased risk of clinically relevant upper gastrointestinal events when compared with placebo.

Abstract: Successful colonoscopy depends on good preparation of the colon before the procedure. Inadequate preparation may lead to cancelled or repeat procedures and compromise patient safety, quality of care, and cost effectiveness. The primary aim of this study was to isolate factors that affect preparation success, especially in older, more severely ill, bedridden patients. The secondary aim was to examine the possible differences in preparation quality between ambulatory and hospitalized patients and the impact of a staff educational program on the preparation of hospitalized patients for colonoscopy. The study group included 303 consecutive ambulatory patients and 104 hospitalized patients referred for colonoscopy between January and March 2002, before the department introduced an educational program on colonoscopy preparation, and 310 ambulatory patients and 105 hospitalized patients referred for colonoscopy between January and March 2003. All patients completed an ad hoc questionnaire, and the findings were compared between ambulatory and hospitalized patients and between patients treated before and after the educational program. Polyethylene glycol was used significantly more often for colonoscopy preparation in hospitalized patients than in ambulatory patients (53.1% versus 8.8%; P=.0001). The hospitalized group was characterized by more incomplete or repeated colonoscopies and poorer preparation quality. On multivariate analysis, the variables found to be independent predictors of good preparation were successful patient completion of the preparatory procedure according to instructions, colonoscopy performed for follow-up after polypectomy, and preparation with sodium phosphate. The educational intervention had no impact on the quality of preparation. In conclusion, sodium phosphate preparation and complete adherence to preparation instructions are the most important factors for successful colonoscopy preparation. Current preparatory methods for hospitalized and severely ill patients need to be revised.

Abstract: Mucin is a high molecular weight glycoprotein that plays an important role in protecting the gallbladder epithelium from the detergent effect of bile. However, it also participates in gallstone formation. There is little information about a possible relationship between gallbladder inflammation and mucin expression or gallbladder stones' characteristics. The aims of this study were to investigate stone characteristics and patterns of mucin expression in the gallbladder epithelium and bile of gallstone patients, in relation to inflammation. Gallbladder bile and tissue samples from 21 patients were obtained at surgery. Mucin content was evaluated by gel filtration on a Sepharose CL-4B column. Dot blot for bile mucin apoproteins and immunohistochemistry staining for gallbladder mucosal mucin apoproteins were performed with antibodies to MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score (0-3) was used for assessment of antigen expression and the level of inflammation. Gallstone cholesterol content was determined in 16 patients. MUC 5AC and MUC 5B were demonstrated in 95.4 and 100% of gallbladder bile samples, respectively. Immunohistochemistry staining with antibodies to MUC 2, MUC 3, MUC 5AC, MUC 5B and MUC 6 were positive in 0, 100, 85.7, 100 and 95.4% of the gallbladder mucosal samples, respectively. Pigmented brown stones were associated with a higher level of gallbladder inflammation. Mucin species expressed in gallbladder epithelium are MUC3, MUC5AC, MUC5B and MUC6. MUC5AC and MUC5B are secreted into bile. Inflammation of the gallbladder is accompanied by a higher level of MUC5AC expression and is associated with pigmented brown stones.

Abstract: Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Abstract: Follicular lymphoma with gastrointestinal tract involvement is rare. We describe the case of a young woman with follicular lymphoma with multiple nodular lesions involving segments of the proximal jejunum and terminal ileum. The presenting symptom was chronic diarrhea. The diagnosis was made by endoscopy with histologic examination of the mucosal lesions of the proximal and distal small intestine, immunohistochemical staining, and molecular analysis. The initial spread and pattern of the small bowel involvement, as well as treatment response, were evaluated by videocapsule endoscopy. The application of molecular analysis along with immunophenotypic evaluation has made it possible to precisely diagnose follicular lymphoma. In the present case, the use of capsule endoscopy improved the evaluation of the extent of small bowel involvement prior to and following treatment.

Abstract: BACKGROUND: Upper gastrointestinal (UGI) bleeding is associated with a mortality rate of up to 14% in emergency hospital admissions (primary bleeding), and up to 28% in hospitalized patients (secondary bleeding). AIM: To characterize and compare the clinical pictures and outcome of primary and secondary nonvariceal UGI bleeding. STUDY: A retrospective, case-control design was used. The files of all consecutive patients admitted to our tertiary academic center between January 1, 2001 and December 31, 2002 for UGI bleeding were reviewed for demographic and clinical data, treatment details, number of blood transfusions, endoscopic procedures, surgical procedures, and mortality. RESULTS: Compared to primary UGI bleeding, secondary bleeding was associated with female sex, older age, more chronic diseases, intake of more drugs, hospitalization in internal medicine departments, longer hospital stay, fewer endoscopic procedures, and less Helicobacter pylori-related peptic ulcer disease. Total mortality rate in the secondary bleeders was 30.3% versus 4.6% in the primary bleeders (P<0.0001). There was no significant difference between primary and secondary bleeders in treatment with nonsteroidal anti-inflammatory agents or aspirin, severity of bleeding, or death related to gastrointestinal bleeding. CONCLUSIONS: Despite the significant differences in the clinical picture of primary and secondary bleeders, the severity of bleeding appear to be similar in both groups. Although there was a trend towards a higher gastrointestinal-related mortality in secondary bleeders, it was not statistically significant.

Abstract: The role of dopamine in decision making has received much attention from both the experimental and computational communities. However, because reinforcement learning models concentrate on discrete action selection and on phasic dopamine signals, they are silent as to how animals decide upon the rate of their actions, and they fail to account for the prominent effects of dopamine on response rates. We suggest an extension to reinforcement learning models in which response rates are optimally determined by balancing the tradeoff between the cost of fast responding and the benefit of rapid reward acquisition. The resulting behavior conforms well with numerous characteristics of free-operant responding. More importantly, this framework highlights a role for a tonic signal corresponding to the net rate of rewards, in determining the optimal rate of responding. We hypothesize that this critical quantity is conveyed by tonic levels of dopamine, explaining why dopaminergic manipulations exert a global affect on response rates. We further suggest that the effects of motivation on instrumental rates of responding are mediated through its influence on the net reward rate, implying a tight coupling between motivational states and tonic dopamine. The relationships between phasic and tonic dopamine signaling, and between directing and energizing effects of motivation, as well as the implications for motivational control of habitual and goal-directed instrumental action selection, are discussed.

Abstract: Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.

Abstract: BACKGROUND: Open access gastroscopy allows physicians to refer patients for endoscopic procedures without a prior consultation. OBJECTIVES: To compare the safety and efficacy of OAG with gastroscopy performed after a gastroenterological consultation. METHODS: Patients referred for gastroscopy directly (open access) or after consultation with a gastroenterologist, by physicians in the departments of internal medicine and surgery at a major tertiary center, were compared for indications, background disease, outcome and diagnostic yield. The data were collected prospectively over a 5 month period following the introduction of OAG at the center. Physicians in both departments participated in an education program on the indications and procedure of gastroscopy. For each patient referred for OAG the attending physician completed a specially designed questionnaire that had to be signed by a senior physician. Data were managed and analyzed with Excel and SPSS software. RESULTS: The study sample comprised 494 patients, of whom 236 were referred for OAG and 258 after prior consultation. On multivariate analysis, hospitalization in the department of internal medicine was the only independent factor for OAG. Severe background disease and aspirin treatment had no effect on physician use of OAG, although they served as a "red light" for the gastroenterology consultants. There was no difference in the diagnostic yield of the procedures (26.4% normal findings for OAG and 28.3% for consultations) or in mortality rates. The main indications for referral to gastroscopy in the surgery department were melena, hematemesis and "coffee grounds," and anemia and vomiting in the internal medicine department. CONCLUSIONS: OAG is feasible and beneficial in an academic medical center setting, with no bias in appropriateness of indications or decrease in the diagnostic yield compared to the traditional approach. More attention should be directed to safety issues by the referring physicians.

Abstract: Colorectal cancer (CRC) is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsatellite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracil-based chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.

Abstract: BACKGROUND: Colonoscopy is the gold standard procedure for screening for colorectal cancer and surveillance after polypectomy or colorectal cancer surgery, for diagnosis in symptomatic patients and patients with fecal occult blood, and for screening in the high risk population. The adherence of referring physicians to the accepted recommendations can prevent long waiting lists for colonoscopy and save lives, costs and resources. OBJECTIVES: To evaluate the knowledge of primary care physicians and gastroenterologists in Israel about current guidelines for colonoscopy screening and surveillance. METHODS: A 10-item questionnaire on proper follow-up colonoscopy for surveillance after polypectomy and screening for colorectal cancer in various clinical and epidemiological situations was administered to 100 expert gastroenterologists and 100 primary care physicians at a professional meeting. Answers were evaluated for each group of physicians and compared using the chi-square test. RESULTS: The compliance rate was 45% for the gastroenterologists and 80% for the primary care physicians. The rate of correct answers to the specific items ranged from 18.7% to 93.75% for the gastroenterologists and from 6.2% to 58.5% for the primary care physicians (P< 0.001 for almost every item). CONCLUSIONS: The knowledge of physicians regarding the screening and surveillance of colorectal cancer needs to be improved.

Abstract: We tested the in vitro activity of levofloxacin (LEV), amoxicillin (AMP), clarithromycin (CLA), metronidazole (MET), and tetracycline (TET) against 70 clinical isolates of Helicobacter pylori recovered from 70 dyspeptic patients. All patients had previously failed 2 treatment regimens: first-line triple therapy with omeprazole, AMP, and CLA, and second-line quadruple therapy with omeprazole, MET, TET, and bismuth. Resistance to CLA, MET, and LEV was found in 65.7%, 57.1%, and 18.6% of isolates, respectively. Resistance to both CLA and MET was found in 32.8%, and to CLA, MET, and LEV in 12.8%. Only 4 of the isolates were resistant to both CLA and LEV, and none was resistant to LEV alone or to MET and LEV. Physicians should consider triple therapy with omeprazole, LEV, and AMP in patients unsuccessfully treated with first- and second-line regimens.

Abstract: BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.

Abstract: UC (ulcerative colitis) patients have an increased risk of developing colorectal cancer compared with the normal population. The cause underlying this higher risk is not fully defined but includes nutritional and environmental factors concomitant with genetic alterations. We aimed to evaluate genetic stability in the colonic tissue of UC patients in clinical remission compared with the healthy population, and to establish a possible correlation between nutritional habits and these molecular assessments. UC patients (n 42) and healthy controls (n 37) participated in the study. All participants were histopathologically and medically diagnosed. Participants completed five separate 7 d dietary records, food-frequency questionnaires and validated 24 h recalls for nutritional assessment. The extent of chromosome 17 loss and the calculated chromosome index was determined in colon tissue biopsies by fluorescence in situ hybridisation. Correlations between the molecular and nutritional assessments were performed using Pearson's correlation coefficients. Significant differences in the nutritional intake of total fat (65 (SD 15) v. 89 (SD 25) g), cholesterol (330 (SD 168) v. 464 (SD 177) mg), dietary fibre (32 (SD 4.7) v. 9 (SD 4) g), vitamin A (1009 (SD 209) v. 506 (SD 204) microg), vitamin C (308 (SD 108) v. 72 (SD 53) mg) and folic acid (412 (SD 89 microg) v. 187 (SD 107)) were recorded for UC patients compared with controls. Significant correlations were found for the consumption of different food groups and the chromosome index for chromosome 17. The results of our study suggest that the nutritional habits adopted by UC patients during clinical remission may affect key cellular components of the colonic tissue, inducing a high degree of aneuploidy and genetic instability, and probably affecting the development of colon cancer.

Abstract: AIM: To review the experience of a major medical teaching center with diagnostic and therapeutic colonoscopies and to assess the incidence and management of related colonic perforations. METHODS: All colonoscopies performed between January 1994 and December 2001 were studied. Data on patients, colonoscopic reports and procedure-related complications were collected from the departmental computerized database. The medical records of the patients with post procedural colonic perforation were reviewed. RESULTS: A total of 120067 colonoscopies were performed during the 8 years of the study. Seven colonoscopic perforations (4 females, 3 males) were diagnosed (0.058%). Five occurred during diagnostic and two during therapeutic colonoscopy. Six were suspected during or immediately after colonoscopy. All except one had signs of diffuse tenderness and underwent immediate operation with primary repair done in 4 patients. No deaths were reported. CONCLUSION: Perforation rate during colonoscopy is low. Nevertheless, it is a serious complication and its early recognition and treatment are essential to optimize outcome. In patients with diffuse peritonitis early operative intervention makes primary repair a safe option.

Abstract: OBJECTIVE: Colorectal cancer (CRC) is the most common of the gastrointestinal cancers in Israel. The low rate of patient compliance to a recent CRC screening program of Clalit Health Services, a major health management organization in Israel, prompted the present survey of primary care physicians' knowledge and practices regarding CRC screening. METHODS: A 23-item questionnaire, formulated according to the policy of the Israel Ministry of Health and the recommendations of the American Gastroenterological Association, was distributed to 150 primary physicians of Clalit Health Services. The relative ratio of correct to incorrect answers was calculated for every question and by professional group. RESULTS: The response rate was 89%. Total score (out of a maximum 23) was 20.68 for family physicians (experts in family medicine), 17.79 for experts in other fields, and 17.82 for general practitioners (average, 0.90, 0.77, and 0.77, respectively). The score for the family physicians was significantly higher than for the other two groups (P=0.0070). Clustering items by specific issues yielded significantly better scores for the family physicians in four areas: screening (P=0.0164), appropriate test for high-risk population in Israel (P=0.0012), definition of average-risk population (P=0.0012), and CRC symptoms (P=0.0108). A low level of knowledge on the definition of the high-risk population was noted in all three groups. CONCLUSIONS: Experts in family medicine in Israel have significantly greater knowledge of most issues of CRC than primary care experts in other fields and general practitioners, although all three groups lack knowledge on the definition of the high-risk population. Continuing physician education should focus on these areas.

Abstract: BACKGROUND: The guaiac fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is user dependent and not specific for human hemoglobin (Hb). The automated-developed, quantitative, immunochemical human Hb FOBT (I-FOBT) is specific, allows for quality control and selection of a suitable Hb level, with optimal sensitivity and specificity, for colonoscopy. MATERIAL/METHODS: We evaluated a desktop instrument, OC-MICRO (Eiken, Japan), which automatically develops and quantifies 50 fecal tests/hr for Hb; for ease of use, test reproducibility and stability and intra-patient daily I-FOBT variation; clinical evaluation included sensitivity and specificity for neoplasia in patients undergoing colonoscopy. RESULTS: Five hundred patients prepared 3 fecal tests which were quantified for Hb, I-FOBT samples were: (1) repeatedly re-examined; (2) stored at 4 degrees C or 20 degrees C or 28 degrees C and re-examined; (3) I-FOBT levels correlated with colonoscopic findings. Five I-FOBTs re-examined 6 times had no significant changes; 30 tests stored > or = 21 days had a decay/day of: 0.3%+/-0.4 at 4 degrees C (NS), 2.2%+/-1.7 at 20 degrees C (NS) and 3.7%+/-1.8 at 28 degrees C (P<0.05). Receiver operator characteristic curve analysis showed that at the 100 ng Hb/mL I-FOBT level 76.5% of CRCs and advanced adenomas were detected with a specificity of 95.3%. CONCLUSIONS: The instrument provided reproducible results and refrigerated I-FOBT samples were stable 21 days. An I-FOBT level can be chosen to provide optimal sensitivity and specificity for significant neoplasia.

Abstract:

Abstract: A high retention rate of patients and control subjects is an important criterion for the credibility and accuracy of prospective, randomized, controlled clinical trials. Retention and adherence depend on a combination of patient-, physician- and coordinator-related factors, and these need to be carefully evaluated to ensure success. The aim of the study was to evaluate predictive factors for patient retention in a clinical trial. Questionnaires containing items on demographic and clinical data and specific questions related to patient motivation were distributed to 31 patients participating in a clinical study comparing rofecoxib (Vioxx) and placebo for the prevention of colonic polyp recurrence. Adherence of the group with the rofecoxib study and the questionnaire was 100%. The sample included 24 men (77%) and 7 women of mean age 66+/-9 years; 90% were married, 42% were employed. A family history of colorectal cancer (CRC) was reported by 29%. The main reasons for adherence reported by the patients (on an analog scale of 0-10) were 24-hour availability of a nurse (9.2+/-1.9), the chance to prevent CRC (9.1+/-1.9), and participation in a multicenter study (9.1+/-2.2). The least important factor was support of the family physician (5.8+/-4.1). In conclusion, retention in a clinical trial mainly depends on the subject of the trial and the scientific/professional setting where it takes place, and less on the support of the family physician.

Abstract: Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.

Abstract:

Abstract: BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.

Abstract:

Abstract: General practitioners base their clinical strategy on evidence-based medicine and experience. When prospective randomized controlled studies have not provided an answer to a specific clinical question, or when common practice in a certain area is not well established, guidelines formulated by specialists with in-depth knowledge of the field are needed. Studies have shown that gastroenterology guidelines have improved the approach to Helicobacter pylori infection and the management of gastroesophageal reflux disease. Failure to use these guidelines by general practitioners can lead to diagnostic inconsistencies and faulty patient care. This is particularly important in Israel, where the heterogeneous patient and physician populations are characterized by differences in the interpretation of symptoms, disease prevalence, and education.

Abstract: Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin is widely accepted in Israel for Helicobacter pylori eradication. Recently, a generic drug for omeprazole was introduced to the market, but its efficacy as a PPI was questioned. The aim of the study was to compare eradication efficacy of triple therapy-based regimens with Losec (Astra-Zeneca, Sweden) and the generic form, Omepradex (Dexxon, Israel). People belonging to Clalit Health Services (CHS), the biggest health insurance provider in Israel, and receiving omeprazole (Losec or Omepradex) for 7 days (assumed to be Helicobacter pylori eradication purposes), between 1.1.2001 and 31.12.2001, were retrieved from the CHS central computer. Of 450 patients (287 in the Losec group and 163 in the Omepradex group), 97 (21.6%) underwent 13C-urea breath test (13CUBT) for validation of Helicobacter pylori successful eradication and participated in the study. They were all treated with triple therapy with omeprazole, amoxicillin, and clarithromycin, and were stratified according to the PPI used: Group A, Losec; and Group B, Omepradex. Positivity of 13CUBT was computed. Sixty-one (21.25%) and 36 (22.08%) patients in Groups A and B, respectively, underwent 13 CUBT for validation of successful Helicobacter pylori eradication (NS). In Group A 41 of 61 patients (67.21%) had a negative 13CUBT, in comparison with 26 of 36 (72.22%) in Group B (NS). Using logistic regression analysis all confounding factors were found to be noncontributory to the discrimination between negative (successful eradication) and positive (failed eradication) 13CUBT. There is no statistically significant difference between Losec and the generic drug Omepradex as part of a PPI-based triple therapy for eradication efficacy of Helicobacter pylori.

Abstract: Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin is widely accepted for Helicobacter pylori eradication. The choice of PPI for triple therapy in Israel is arbitrary, with no preference for any one PPI except for economic considerations. Direct comparison between omeprazole and lansoprazole for efficacy of H. pylori eradication has never been performed in an Israeli poplulation. Based on the pharmacokinetic data, lansoprazole-based therapy may be a better alternative than omeprazole-based therapy. The aim of this study was to compare the effectiveness of triple therapy regimens with omeprazole (Losec, AstraZeneca; or Omeradex, Dexxon) or lansoprazole (TAP Pharmaceuticals) in eradicating H. pylori infection. The database of the biggest health insurance provider in Israel was reviewed for all patients who received 1 week of treatment with omeprazole (n = 1293) or lansoprazole (n = 85) with additional amoxicillin and clarithromycin for H. pylori eradication in 2002. All patients underwent the 13C-urea breath test (13CUBT) for validation of eradication. A negative 13CUBT result was noted in 1026 of the patients treated with omeprazole (79.4%) and 61 treated with lansoprazole (71.8%). On logistic regression analysis, none of the confounding factors (sex, age, indication, chronic use of PPI, eradication protocol) were found to contribute to the discrimination between a negative (successful eradication) and a positive (failed eradication) 13CUBT. There is no statistically significant difference between omeprazole and lansoprazole as part of a PPI-based triple therapy for eradication of H. pylori.

Abstract: The athymic nude mouse provides a powerful tool in the study of human tumors, as it enables growth of human tumors due to deficiencies in T cell functions. However, deficiencies in T cell functions might limit research on efficacy of immune modulators in cancer immunotherapy. BAT mAb mediates its anti-cancer activity through modulation of the immune system that involves both NK and T cells. We analyzed lymphocyte populations in blood 5 and 14 days following the injection of BAT antibody alone or following engraftment of human colon carcinoma cells. Our results demonstrate that BAT injection induced lymphopoiesis in the nude mouse. Percentage of CD3 cells increased up to 24%, CD4 cells up to 20% but no increase was found in CD8 T cells in BAT-injected nude mice. Injection of BAT 12 days post-tumor engraftment propagated CD3, CD4 and CD8 cells seen in the blood 5 days later but not seen in the blood 14 days post-BAT injection. It is possible that this decrease is associated with migration of the lymphocytes from the blood to the tumor sites in the livers. The percentage of CD56-positive NK cells increased (up to 18%) by BAT administration alone or post-tumor injection. The presence of tumors alone did not induce lymphopoiesis in the nude mice. Propagation and lymphopoiesis by BAT mAb might have future clinical implications.

Abstract: PURPOSE OF REVIEW: Most colorectal cancers (CRCs) have deletions, duplications, and rearrangements of their chromosomes that reflect a destabilizing process called chromosomal instability (CIN). The cause of CIN is controversial, but no intrinsic mutation in cancer cells has been reported that can reasonably account for this in CRC. This review explores the new hypothesis that JC virus (JCV) may be the cause of CIN. RECENT FINDINGS: A polyomavirus has been found in most colon cancers that encodes a T-antigen gene, which can induce CIN in several laboratory models. This virus, JCV, infects virtually every human population that has been investigated, and evidence for the virus has been found in the gastrointestinal tracts of most healthy adults. It is hypothesized that the virus infects the gut in childhood and remains there in a latent form for most people. In people who develop colorectal neoplasia, it is proposed that the virus is activated, and expression of the oncogene-T-antigen-leads to CIN. This form of genomic instability is necessary to explain the losses of tumor suppressor genes that occur in the context of the multistep carcinogenesis pathway. Furthermore, it is proposed that once neoplastic colonic epithelial cells have experienced biallelic inactivation of a critical number of tissue-specific tumor suppressor genes-including APC and p53-the ongoing effect of the transforming virus may be relatively deleterious to a neoplastic cell, and selective pressure may lead to loss of viral infection. SUMMARY: This review summarizes the experimental data that have led to the hypothesis that JCV is a common cause of CIN in CRC.

Abstract:

Abstract: Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 +/- 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 +/- 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.

Abstract: BACKGROUND: To investigate possible association between infection with CagA(+) strains of Helicobacter pylori and aortic atheroma diagnosed by transesophageal echocardiography. METHODS AND RESULTS: One hundred and eighty-eight consecutive subjects prospectively examined for presence of aortic atheroma (localized intimal thickening of >/=3mm) by transesophageal echocardiography were tested for serum IgG antibodies against H. pylori (enzyme-linked immunosorbent assay) and CagA protein (Western blot assay). The association between infection with H. pylori, CagA status of the infecting H. pylori strains, and aortic atherosclerosis was evaluated after adjusting for coronary artery disease risk factors. There was a linear trend for presence of atheroma in subjects with CagA-positive H. pylori infection (51/81, 63%) compared to subjects with CagA-negative H. pylori infection (21/45, 46.7%) and uninfected subjects (18/62, 29%) (p=0.003). H. pylori seropositivity was not associated with aortic atheroma (OR 2.9; 95% CI, 0.8-10.3; p=0.11) when CagA status is not taken into account. On multivariate analysis, parameters associated with risk of aortic atheroma were CagA-positive H. pylori seropositivity (OR 4.4; 95% CI, 1.4-14.7; p=0.01), older age (OR 1.2; 95% CI, 0.9-14.7; p=0.01), having ever smoked cigarettes (OR 3.6; 95% CI, 1.3-10.0; p<0.001), and elevated serum triglyceride level (OR 3.4; 95% CI, 1.3-9.4; p=0.02). CONCLUSIONS: After controlling for H. pylori infection and coronary artery disease risk factors, infection with a CagA-positive strain of H. pylori was independently associated with aortic atherosclerosis. This study suggests a gradient of atherosclerosis between uninfected individuals and patients with CagA-positive H. pylori infection and should prompt research into the role of CagA-positive H. pylori infection in the inflammatory atherosclerotic process.

Abstract: BAT is an immune-activating monoclonal antibody produced against Daudi cell membranes and selected for stimulating lymphocyte proliferation. The anti-tumor activity of BAT is related to its immunostimulatory properties. Both T and NK cells mediate the anti-tumor activity of BAT. CD4-positive T cells respond to BAT activation by proliferation and INF-gamma production. The aim of the study was to assess the probability that the BAT monoclonal antibody binding capacity to T cells is a marker for different cancers. Human peripheral blood T cells from colon, breast and prostate cancer patients, as well as healthy volunteer donors, were tested for the percentage of binding to BAT mAb (BAT/CD3 cells) by FACS analysis. All patients were tested before undergoing surgery or treatment, and their diagnosis was confirmed by histology. The results showed that the percentage of BAT monoclonal antibody binding to CD3-positive T cells in the peripheral blood was different in cancer patients with diverse tumor types. We found that lymphocytes from the blood of healthy donors contained 25% BAT/CD3 cells. In colon and breast cancer patients, a significant decrease to 13 and 11% of BAT/CD3 cells was found. In contrast, these cells increased ><50% in patients with prostate cancer. These findings may have a potential diagnostic significance and also assist in the evaluation of strategies for the therapeutic use of BAT for different cancer patients.

Abstract: OBJECTIVES: Guaiac fecal occult blood colorectal cancer (CRC) screening tests (FOBT) are faulted for low sensitivity and nonspecificity for human hemoglobin (Hb). Automated-developed, immunochemical, human Hb FOBT (I-FOBT) is specific, eliminates diet restrictions, and Hb quantification allows selection of a threshold for colonoscopy. Aims were to determine 1) test reproducibility; 2) test stability; 3) intrapatient daily I-FOBT variation; 4) test sensitivity and specificity for neoplasia in 500 symptomatic/high-risk patients undergoing colonoscopy; and 5) to correlate fecal Hb measurements with findings. METHODS: The desktop instrument OC-Sensor (Eiken, Japan) automatically develops and quantitates 50 tests/h for Hb. Patients prepared three tests, which were quantified and then 1) repeatedly re-examined; 2) stored at 4 degrees C or 20 degrees C or 28 degrees C and repeatedly examined; and 3) fecal Hb levels were correlated with colonoscopic findings. RESULTS: Five I-FOBTs re-examined five times in 1 day had no significant measurement changes. Thirty tests stored for 21 or more days had a decay/day of 0.3%+/- 0.4 at 4 degrees C (NS), 2.2%+/- 1.7 at 20 degrees C (NS), and 3.7%+/- 1.8 at 28 degrees C (p < 0.05). There were intrapatient variations between the three daily I-FOBTs (NS). At the recommended 100 ng Hb/mL threshold, all six cases of CRCs and 20 out of 28 cases of advanced adenomas were detected; evaluated together their sensitivity and specificity were 76.5% and 95.3%. CONCLUSIONS: Desktop, automated-developed, quantitative I-FOBT is now available. Refrigerated OC-Sensor samples are stable for 21 days, easy to prepare and develop and, at the 100 ng Hb/mL threshold, have high sensitivity, specificity, and negative predictive values for significant neoplasia. Suitability for population CRC screening awaits further evaluation.

Abstract: Capsule endoscopy (CE) has been recommended as the method of choice for diagnostic endoscopy of the small bowel. An experienced nurse, after proper training, may contribute to the endoscopy procedures as previously described for sigmoidoscopy. The aim of this study was to evaluate the ability of an experienced gastroenterology nurse to prepare CE records for physician interpretation, by detecting abnormal thumbnails. A prospective, observational design was used. Fifty CE videos were pre-read by a specially trained gastroenterology nurse who thumbnailed the abnormalities detected for interpretation by the gastroenterologist. The nurse's description of the lesions and the calculated gastric and bowel transit times were compared to the interpretation of the videos made directly by the gastroenterologist (gold standard). The primary end point of the study was the quality of the nurse's pathology findings; the secondary end point was the cost effectiveness of this practice. There was complete agreement between the nurse and gastroenterologist for all 12 cases interpreted as normal by the gastroenterologist. In the remaining 38 cases, the nurse created 130 thumbnail selections and the physician, 99. Complete interobserver agreement was achieved for 93 of the 96 lesions categorized as "significant" by the physician (96.9%). After all relevant variables were taken into account, this approach saved dollar 324 per CE examination. The use of nurse practitioner to pre-read CE videos and prepare thumbnail selections for further assessment by the gastroenterologist appears to be safe, reliable, and cost effective.

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Abstract: BACKGROUND: The present study was prompted by our previous successful experience with the compression anastomosis clip (CAC) on animals followed by a study on 20 patients scheduled for colonic resection. METHODS: Sixty patients with colonic cancer were assigned randomly to undergo an anastomosis either with the CAC or a stapler. To perform anastomosis with CAC, the 2 edges of the resected colon are aligned. Two 5-mm incisions are made close to the edges, through which (using a special applier) the CAC, after being cooled in ice water, is introduced in an open position. In response to the body temperature, the clip resumes its original (closed) position, thereby clamping the 2 bowel segments together. At the same time, a small scalpel incorporated in the applier makes a small incision through the clamped walls for the passage of gas and feces. The clip is detached from the applier to be left inside the intestine. The 2 5-mm incisions are sutured. The clip is expelled with the stool within 5 to 7 days, creating a perfect uniform compression anastomosis. RESULTS: Neither group had anastomotic complications such as leakage or obstruction. All the other parameters were better in the study group than in the control patients. CONCLUSIONS: The use of the CAC for colonic surgery is safe, simple, efficient, shortens operation time, and is almost what we call the "no-touch concept" in surgery and may decrease infection.

Abstract: Low or minimal doses of aspirin are widely used for prevention of cardiovascular diseases. Aspirin is known to produce severe adverse gastrointestinal effects, such as bleeding and perforation. Less is known about the risk associated with minidose aspirin. Our aim was to assess the possible association of upper gastrointestinal tract bleeding with minidose aspirin therapy. A retrospective controlled design was used. Patients hospitalized for melena or hematemesis between January 1, 2000, and December 31, 2001, were identified by ICD-9 codes, and their clinical findings were compared to these of patients without upper gastrointestinal bleeding hospitalized during the same period and matched for age and sex. Bleeding was attributed to therapy if patients used a nonsteroidal anti-inflammatory drug or aspirin therapy within 30 days before hospitalization. The study group included 318 patients (59% male), and the control group 141 (65% male). Mean ages were 67 +/- 19 and 64 +/- 19 years, respectively. Study patients had more accompanying diseases, used more medications, and required more blood transfusions than controls (37%, vs. 2% of controls; P < 0.001). Minidose aspirin was used by 28% of the study group and 18% of the controls (P = 0.03). The average dose was 40 +/- 86 and 21 +/- 55 mg/day, respectively (P = 0.012). Only 26% of the study patients received a gastric protective agent. On multivariate analysis, aspirin consumption was the only independent risk factor for upper gastrointestinal tract bleeding. There appears to be an association between minidose aspirin treatment and hospitalization for upper gastrointestinal tract bleeding. Despite the advanced age of the patients, only one-quarter were treated with gastric protective agent.

Abstract: BACKGROUND: Capsule endoscopy can identify lesions of the small bowel that cannot be detected by other techniques. In addition to patient safety, quality of care and cost-efficiency, good preparation is an important factor for good visualization. AIM: To evaluate the efficacy of oral sodium phosphate preparation. METHODS: Forty-six consecutive patients scheduled for capsule endoscopy in two medical centres. The patients treated in Dallas were prepared by 12 h fasting (group A), and those treated in Israel were also asked to drink 45 mL of sodium phosphate with water (group B). An experienced endoscopist, blinded to the method used, graded the quality of preparation according to visual capability, and to relative durations of each grade. RESULTS: The quality of the preparation was poor in 35% of group A compared with 4% of group B (P = 0.023). The mean duration of good preparation with excellent visualization was 122 +/- 110 min in group A and 180 +/- 96 min in group B (P = 0.006). Preparation with sodium phosphate and lower patient weight were significant predictive factors for good visualization. CONCLUSIONS: Bowel preparation offers better visualization than overnight fasting alone and is associated with fewer disturbances by intraluminal turbid fluid.

Abstract: BAT monoclonal antibody exhibited anti-tumor activity mediated by T and NK cells. We have evaluated the efficacy of murine and humanized BAT for the treatment of human colorectal carcinoma liver metastases in nude mice. HM7, a human colorectal carcinoma was injected into the spleen to colonize the liver. A single intravenous administration of both BAT antibodies significantly reduced the number of metastases and liver weights. Histological examinations demonstrated lymphocyte accumulation near remnant tumors and in tumor-free tissues of BAT treated mice. The efficacy of humanized BAT in the regression of hepatic metastases in human colorectal carcinoma has potential clinical use.

Abstract: Colorectal cancers develop as a consequence of genomic instability. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and in most hereditary non-polyposis cancers. High frequency MSI has been associated with a favorable prognosis, however it is not clear whether this is because MSI-H tumors are inherently less aggressive or because they are more sensitive to chemotherapy. Chemotherapy with a combination of 5-fluorouracil and leukovorin or levamizole has been the standard of care for high risk stage II and stage III CRC; it is also used in stage IV CRC. Several in vitro studies have shown that colon cancer cell lines displaying MSI-H are less responsive to fluorouracil than microsatellite-stable cell lines. Human studies, all of them retrospective, yielded conflicting results. The selection of patients with CRC for 5-FU treatment has been based so far on the stage of the tumor rather than the biology of the tumor. Although surgical staging is highly predictive of survival, there are indications that the form of genomic instability within a patient's colorectal tumor has clinical implications, with and without 5-FU treatment. This review suggests that patients with MSI-H colorectal tumors may not benefit from 5-FU-based chemotherapy and can avoid its potential side effects (nausea, diarrhea, stomatitis, dermatitis, alopecia, and neurologic symptoms) that occur in half the treated patients. If confirmed by future prospective randomized controlled studies, these findings would indicate that microsatellite-instability testing should be conducted routinely and the results used to direct rational adjuvant chemotherapy in colon cancer.

Abstract: Helicobacter pylori (Hp) infection is highly prevalent in many countries and may cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful eradication depends on the specific treatment used, patient compliance, and Hp antibiotic resistance. The primary aim was to characterize groups of patients with one or more failures of Hp eradication treatment. The secondary aim was to evaluate the factors that influence eradication failure. Between April 1, 1998, and December 31, 2001, 5885 patients were studied for the success of Hp eradication with the 13C-urea breath test (13C-UBT): 5442 after one course of treatment (Group I), 380 after two courses (Group II), and 63 after three courses (Group III). The 13C-UBT was positive in 27.8%, 37.4%, and 47.6% of patients in Groups I, II, and III, respectively (P(I-II) = 0.000, P(II-III) = 0.126). A combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in 31.3%, 27.4%, and 7.9% of Groups I, II, and III, respectively, and a combination of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2%, 28.9%, and 28.6%, respectively. Regimens that contained clarithromycin were used in decreasing order in Groups I, II, and III, and regimens containing metronidazole, bismuth, or tetracycline, in increasing order. The only good prognostic factor for successful eradication was Israeli origin, while European-American and Asian-African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic proton pump inhibitor (PPI) use did not favor successful eradication. Our results suggest that origin, history of peptic disease, and chronic PPI use are predictors of eradication failure.

Abstract: BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

Abstract: We prospectively evaluated a (13)C urea breath test (UBT) that involves passive continuous sampling for diagnosis of Helicobacter pylori in 72 children. Results were obtained within 10 minutes in 96% of patients. The test is rapid, user-friendly, and has 100% concordance with conventional diagnostic methods.

Abstract: BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the technique of choice for long-term enteral nutrition. Though safe and technically simple, PEG has been associated with significant morbidity and mortality. AIM: We compared the outcome of strategies applied in two different periods; the original approach of PEG insertion during hospitalization (upon request), and PEG insertion 30 days after hospital discharge. METHODS: A cohort of 127 patients scheduled for PEG insertion from 1.1.1997 to 31.12.2000, was evaluated. In 61 consecutive patients admitted from 1.1.1997 to 31.12.1998 the PEG insertion was planned during hospitalization, as close to the time of the physician's request (period 1). Sixty-six consecutive patients admitted from 1.1.1999 to 31.12.2000 were scheduled for the PEG insertion 30 days after discharge (period 2). The 30-day mortality rate was calculated from the time of the request. Univariate and multivariate analyses were used to find predictive factors for 30-day mortality. RESULTS: There were 61 patients with a mean age of 78+/-13 in period 1, and 66 patients with a mean age of 77.8+/-15.5 in period 2. There was no significant difference between patients of the two periods in regard to age, sex, underlying disease, nutritional and mental status. Patients received PEG 30 days after hospital discharge had a 40% lower 30-day mortality rate than patients who received PEG during hospitalization from the time of request for PEG (P=0.01) and a 87.5% lower rate when calculated from the time of insertion (P<0.0001). In-hospital PEG insertion, bed-ridden and disorientation were found to be independent factors predictive of 30-day mortality after PEG insertion (P=0.016,P=0.001, and P=0.0005, respectively). CONCLUSION: PEG insertion during hospitalization increases mortality and should be avoided. A grace period of 30 days with nasogastric tube feeding before PEG insertion may prevent mortality and achieve a long-term enteral nutrition.

Abstract: PURPOSE: The causes for the increased risk of colorectal cancer associated with ulcerative colitis have not been fully defined. Colonic tissue of ulcerative colitis patients was examined for changes in chromosome-17-centromere copy number, loss of the p53 gene, and alterations in serum levels of the 53-kDa protein. This study was performed under the assumption that these molecular events correlate with ulcerative colitis status and duration. METHODS: Ulcerative colitis patients (n = 42) and healthy controls (n = 37) participated in the study. All participants were histopathologically and medically diagnosed. The stage of ulcerative colitis patients was stratified according to increasing risk factors for the development of colorectal cancer: left-sided colitis, pancolitis, sclerosing cholangitis, and dysplasia-associated lesions or masses. Changes in centromere number of chromosome 17 alone or in association with changes in copy number of the p53 gene were analyzed in colon tissue biopsies by fluorescence in situ hybridization. Serum p53 level was determined in blood samples by immunoprecipitation followed by separation using high-pressure liquid chromatography. RESULTS: Changes in chromosome 17 and p53 copy number and lower levels of serum p53 protein in ulcerative colitis patients directly correlated with colorectal cancer risk factors. All values significantly differed from controls. Significant direct correlations were obtained for ulcerative colitis disease duration, levels of p53 in the serum, and extent of aneuploidy. CONCLUSIONS: We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.

Abstract: BACKGROUND & AIMS: Helicobacter pylori (Hp) infection clusters within families, is usually acquired early in life, and is strongly associated with lower socioeconomic status during childhood. Transmission in adulthood is relatively rare, and reports on the prevalence of Hp infection among health personnel, especially endoscopists, are controversial. The present prospective study evaluated the prevalence of Hp infection in health-care workers in primary-care clinics and in gastroenterology units. METHODS: Health care personnel from gastrointestinal units (n = 191) and primary care-clinics (n = 98) of the Clalit Health Services (CHS) in Israel underwent the carbon 13 breath test (13C-UBT) and completed a 21-item demographic and socioeconomic questionnaire. The control group consisted of 4633 symptomatic patients with no evidence of previous Hp infection. RESULTS: The 13C-UBT was positive in 108 gastrointestinal unit personnel (73%) and 70 primary-care workers (71%); both rates were statistically higher significantly than the 53% positivity in the controls. Comparison of the 13C-UBT Hp-positive and Hp-negative health-care personnel yielded a significantly higher index of crowded living conditions in the Hp-positive group. In the gastrointestinal unit workers, Hp positivity was also associated with several years in practice, and in the primary-care workers, with Sephardic (Asian and African origin) versus Ashkenazi (Europe and American) origin. Profession (physician, nurse, technician, secretary, or maintenance worker), history of duodenal ulcer, smoking, marital status, and blood group did not have predictive value for Hp colonization. CONCLUSIONS: The prevalence of Hp infection in Israel is higher in health-care staff of primary-care clinics and gastrointestinal units than in the general population. This may be related to socioeconomic facts and professional hazard. Further studies are needed to clarify this issue.

Abstract: BACKGROUND: The Maastricht 2-2000 guidelines on the current management of Helicobacter pylori infection were recently adopted by the Israeli Gastroenterological Association. GOAL: To determine the impact of these clinical guidelines on the current knowledge, attitudes, and management of H. pylori among primary care physicians, hospital internists, and gastroenterologists in Israel. STUDY: Self-administered, voluntary, anonymous questionnaires were given personally to 229 physicians, 73 primary care physicians, 71 internists, and 85 gastroenterologists. The questions evaluated 4 main issues in the management of H. pylori: (1). the optimal diagnostic test, (2). indications for eradication, (3). combination and duration of triple therapy, and (4). the need for confirmation following eradication. RESULTS: There were significant variations in the adherence of those recommendations among gastroenterologists, internists, and primary care physicians. Specifically, 94.1% of gastroenterologists and 88.9% of internists consider the urea breath test the test of choice for H. pylori diagnosis compared with 60.0% of the primary care physicians. Significant differences in the eradication indications for mucosa-associated lymphoid tissue (MALT) lymphoma, first-degree relatives of gastric cancer patients, atrophic gastritis, functional dyspepsia, and concomitant use of nonsteroidal antiinflammatory drugs were demonstrated among gastroenterologists and the other groups. CONCLUSIONS: Primary care physicians may not be aware of important indications for diagnosis and eradication of H. pylori related to the risk of gastric malignancy or concomitant use of nonsteroidal antiinflammatory drugs. Public health agencies may need to increase penetration of the Maastricht 2000 recommendations to primary care physicians.

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Abstract: Mucin is a high-molecular-weight glycoprotein that is synthesized, stored, and secreted by epithelial mucosal cells, especially goblet cells. Mucin proteins are derived from many different genes, termed MUC genes. Several lines of evidence point to a biological role for mucin in cholesterol gallstone formation. Mucin serves as a pronucleating agent in experimental and human gallstone disease, and the hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. Mucin hypersecretion is prominent in many animal models of gallstone formation, thus contributing by its pronucleating quality to gallstone formation. According to some research, mucin hypersecretion may also contribute to the formation of brown pigment stones. This may be explained in part by the findings that lipopolysaccharides derived from certain bacteria are effective stimulants of mucin secretion. Aspirin and nonsteroidal anti-inflammatory drugs inhibit gallbladder mucin secretion and prevent gallstone formation in animal models. Expanding our knowledge on mucin research may improve our understanding of the natural history of gallstone formation and enable the development of new treatment strategies.

Abstract: The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.

Abstract: BACKGROUND AND AIM: Correa described a stepwise model of changes in the gastric mucosa after Helicobacter pylori infection, from the normal gastric epithelium to chronic gastritis, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. The aim of this study is to assess the reversibility of these mucosal changes after H. pylori eradication. METHODS: The study sample consisted of 89 patients who underwent at least two gastric biopsies from 1990 to 2000, with a positive finding for H. pylori in the first and a negative finding in the second. Specimens were evaluated for acute and chronic inflammation, lymphoid aggregates, proliferation, mucosal atrophy, intestinal metaplasia, dysplasia, and MUC5AC and MUC6 expression using histochemical and immunohistochemical methods. RESULTS: The average time between biopsies was 23.15 +/- 26.30 months. There was a significant decrease in acute and chronic inflammation scores, from 1.48 +/- 1.10 to 0.23 +/- 0.63 and from 2.67 +/- 0.68 to 1.44 +/- 1.04, respectively (P < 0.001), and in a number of lymphoid follicles, from 42.68% to 21.95% of cases (P < 0.008). The number of glands increased from 39.08 +/- 16.67/mm to 48.86 +/- 17.93/mm after eradication (P = 0.062). Intestinal metaplasia was found in 17.07% of the cases, with no change over time. Dysplasia appeared in one case 2 years after eradication. In 27 patients, the Ki67 labeling index decreased significantly after eradication, while MUC5AC and MUC6 expression increased. CONCLUSION: Our findings, although not conclusive for arrest of the malignant potential, support the importance of H. pylori eradication in the prevention of gastric cancer.

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Abstract: Helicobacter pylori infection has a high prevalence in the elderly, but its characteristics and treatment in the geriatric population are not well defined. The aims of the study were to characterize geriatric patients according to referral patterns and results of the 13C-urea breath test (13C-UBT) and to investigate the results of treatment combinations for H. pylori eradiction. The 13C-UBT was performed with 75 mg urea labeled with 13C. Physicians who ordered the test completed a questionnaire covering demographic data, indication for the test, chronic use of a proton pump inhibitor, or nonsteroidal anti-inflammatory drug, and type of eradiction therapy. The study sample consisted of 2128 patients, aged 70-102 years, 958 (45%) men, referred for 13C-UBT. The test was positive on 697 (33%). History of peptic disease was the main indication for referral, following by validation of successful eradication, Israeli origin screening for gastric cancer, treatment with regimen containing metronidazole, history of peptic disease, and recurrence of symptoms were predictive factors for a positive 13C-UBT. Multivariate logistic regression analysis revealed a significant influence of eradication therapy on negative results. History of peptic disease and validation of successful eradication are the main indications for referral of the elderly for 13C-UBT. Our results are in accordance with the increase in metronidazole resistance of H. pylori stains and the cohort effect of H. pylori infection on the elderly Israeli-born population.

Abstract: BACKGROUND: Colorectal cancer (CRC) is the most common of the gastrointestinal cancers in Israel, with an incidence of 50 cases per 100,000 for men and 45 per 100,000 for women in 2000. AIM: The low rate of patient compliance noted in CRC screening program conducted in our center, prompted the present survey of the knowledge and practices regarding CRC screening recommendations. METHODS: A 23-item questionnaire formulated according to the Israeli Ministry of Health policy and recommendation of the American Gastroenterological Association was distributed among the physicians of the six departments of internal medicine, and the department of surgery of the Rabin Medical Center. The relative ratio of correct answers was calculated for every question and by subgroups: internists and surgeons, experts and residents in internal medicine and in surgery. RESULTS: Fifty-five of 80 physicians (69%) completed the questionnaire. The total score for all participants was 15.82 (average 0.68), significantly lower than the optimal correct score of 23 (average 1.00). The internists had a similar total score to the surgeons, 15.61 and 15.28. When the questions were clustered according to specific issues and only the correct answers for each cluster scored, the success rate decreased with a range of 19-69%. Only 22% of responders did not advise fecal occult blood test (FOBT) for the high-risk population; 57% thought the screening age range was 40-65 years, and only 37% knew that the high-risk criteria include a family history of ovarian cancer. CONCLUSION: Both internists and surgeons' knowledge about screening recommendations of CRC can be improved. Health authorities should invest greater efforts in continuing physician education. We believe that this strategy will increase the participation rate in CRC preventive programs.

Abstract: BACKGROUND: Lesions of the small bowel that cannot be detected by other techniques can be indentified by capsule endoscopy. Good preparation before any endoscopic procedure is the most important factor for patient safety, quality of care and cost effectiveness. This should also apply to capsule endoscopy. The aim of this study was to evaluate the quality and efficacy of preparation with oral sodium phosphate for capsule endoscopy. METHODS: A retrospective cohort study design was used. The study sample consisted of 32 consecutive patients scheduled for capsule endoscopy in two periods; the first 10 patients were prepared with overnight fasting only, and the next 22 with oral sodium phosphate. An experienced endoscopist and gastroenterology nurse, who were blinded to the method used, graded the quality of preparation. RESULTS: Small-bowel cleansing was significantly better in patients given sodium phosphate. Five patients (50%) received a poor preparation rating in the first period compared with only 1 (4.5%) of the 22 patients given oral sodium phosphate (P = 0.01). Intraluminal fluid was noted in 9 patients (90%) in the first group after a mean of 53 +/- 60 min, and in 17 patients (77%) in the second group after a mean of 158 +/- 71 min (P < 0.001). The proportion of non-ideal preparation was significantly higher in group 1 than in group 2, significant visualization disturbances being more prevalent in the first period. CONCLUSIONS: Bowel preparation with sodium phosphate before capsule endoscopy offers better visualization than overnight fasting alone and induces fewer disturbances by intraluminal turbid fluid.

Abstract: Demented patients may refuse to eat at the end of life. Many caregivers believe that food is as essential as air, and hence, tube feeding is as important as mechanical ventilation. Many believe that demented patients should be fed in any event, even against their will. The aim of this study was to assess the opinions of the elderly about tube feeding and advanced medical procedures in dementia. Inhabitants of protected homes, over 70 years of age, were asked to complete a questionnaire with demographic details, self-estimation, and self grading according to mobility, quality of life, function, pain, family and environmental support. They were asked what they consider to be a situation worse than death, and then, to grade their consent to life support procedures in the different stages of dementia: percutaneous endoscopic gastrostomy, nasogastric tube, resuscitation, artificial respiration or surgery. They were also asked whether they want a living will for medical interventions in dementia for future guardian consideration. One hundred and twenty questionnaires were distributed and 61 were completed (compliance of 50.8%) including responses from 47 women (77%). The average age was 83 years. Most of the participants were women of European origin, not religious, executives with an average of 12 years of education. More than 70% of participants opposed life-supporting procedures in lower stages of dementia, and more than 80% in higher stages. Ninety-five percent of the participants believed in a living will that denied tube feeding and advanced therapies in dementia.

Abstract: BACKGROUND: The 13C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibody titer. OBJECTIVES: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by 13C-UBT in our central laboratory, to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success. METHODS: 13C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy. RESULTS: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01). CONCLUSION: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as reported in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Abstract: BACKGROUND: Histopathologic examination (HP) is the primary method of monitoring intestinal graft rejection. Alterations in mucin levels have been demonstrated in bowel diseases. The aim of this study was to detect early markers of intestinal graft rejection based on mucin and cytokine levels. METHODS: Allogeneic and syngeneic orthotopic intestinal transplantations were performed in untreated Lewis strain recipient rats from Dark Agouti and Lewis strain donors, respectively (unmodified rejection and nonrejection groups). Similarly, allogeneic and syngeneic orthotopic intestinal transplantations were performed in tacrolimus (immunosuppression)-treated groups. HP was performed on hematoxylin-eosin and periodic acid Schiff-stained sections. Expression of MUC2 and MUC4 proteins and of mRNA was detected by immunohistochemistry and Northern analysis, respectively. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and transforming growth factor-beta(1) were measured by reverse transcription-polymerase chain reaction. RESULTS: HP revealed early or mild rejection on day 3, moderate rejection on day 5, and severe rejection on day 7 posttransplantation (posttx) in the unmodified rejection group. A significant (P<0.01) increase in MUC2 and MUC4 expression was observed on day 3 posttx in the allogeneic rejection group compared with syngeneic controls; the levels decreased by day 7. Goblet cells were significantly more frequent on day 3 compared with days 5 and 7 posttx (P<0.01). IFN-gamma and TNF-alpha expression were also higher in the rejection group. CONCLUSIONS: Early transplant rejection is associated with increased MUC2, MUC4, IFN-gamma, and TNF-alpha expression. These markers combined with HP may assist in the diagnosis of early intestinal graft rejection.

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Abstract: BACKGROUND: Helicobacter pylori infection is highly prevalent and may cause disease in 10% to 15% of infected individuals: duodenal and gastric ulcer, gastric cancer and gastric lymphoma. Guidelines for a test-and-treat policy have been published by the European H. pylori working group in Maastricht. GOALS: To assess the current approach to H. pylori-related diseases, indications for testing and eradication therapy, among internists and surgeons of a University affiliated medical center. STUDY: A 15-items questionnaire was formulated according to the Maastricht II test-and-treat recommendation and distributed among the physicians of 6 internal medicine departments and the department of surgery. The questionnaires were completed anonymously at the department's staff meeting, under the supervision of the head of the department. All questions required a yes/no answer; the maximum possible score was 15. The relative ratio (RR) of correct answers was calculated for every question and by subgroups as follows: all participants, internists, surgeons, experts and residents in internal medicine and surgery. RESULTS: The response rate was 68% (55 out of 80 physicians). Total score for all participants was 10.9 (RR = 0.73), significantly lower than the maximum score of 15 (RR = 1.00). The internists had significantly higher average score than the surgeons for 2 questions: causative agent in gastric cancer (p = 0.003) or gastric lymphoma (p = 0.003), 1 question about triple therapy, PPI, penicillin and azythromycin being not recommended (p = 0.022), and for 1 question of test-and-treat policy: should this strategy apply to family members of gastric cancer patients (p = 0.045). Only 56% of the internists and 21% of surgeons knew what MALToma is, and the correlation with H. pylori infection. CONCLUSION: Knowledge of Surgeons and Internists regarding infection and correlation with diseases or test and treat policy should be improved.

Abstract: OBJECTIVE: The aim of this study was to evaluate the accuracy of a new, continuous real time (13)C-urea breath test, BreathID, for the diagnosis of Helicobacter pylori in patients taking proton pump inhibitors (PPIs). METHODS: Fifty-two consecutive patients, positive for H. pylori by BreathID, were prospectively evaluated. Patients were randomized to receive either omeprazole 20 mg/day or pantoprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 while patients received their last PPI pill. Patients were given a test drink containing 75 mg (13)C-urea and 4.0 g citric acid. Real time, continuously sampled expired (13)CO(2), obtained within 6-20 min, was compared with measurement of expired (13)CO(2) by isotope ratio mass spectrometry (IRMS). RESULTS: A full set of test data was available for 43 patients. After 14 days of treatment with PPIs, false negative detection of H. pylori occurred in only 1/43 (2.3%) patients examined by continuous real time (13)C-urea breath test compared with 2/43 (4.6%) patients examined by IRMS. With the exception of one case, complete agreement was observed between BreathID and the IRMS breath tests at both baseline and after PPI treatment. PPI treatment was associated with three different types of responses on UBT: 1) one third of the patients developed a significant decrease in the (13)CO(2)/(12)CO(2) excretion, 2) roughly one third developed a significant increase in the post-PPI breath test results, and 3) results did not change significantly in the remaining patients. Linear regression analysis of 43 H. pylori-positive subjects indicated a significant positive association between baseline and post-PPI Delta (13)CO(2)/(12)CO(2) excretion. CONCLUSIONS: The use of a single test drink containing 4.0 g citric acid in BreathID, resulted in a low number of false negative results associated with sustained PPI treatment. Although there were some differences between BreathID versus IRMS, the type of PPI and the sampling method used do not appear to play a critical role in the detection of H. pylori by BreathID. According to these results, BreathID is a reliable tool for testing H. pylori in patients taking PPIs.

Abstract: OBJECTIVES: The efficacy of colonoscopic screening and polypectomy for the prevention of colorectal cancer (CRC) is well accepted but has never been documented in a prospective, controlled study. Screening by sigmoidoscopy has been found to reduce mortality from cancer of the rectum and distal colon. Case-control studies provide an alternative method for determining the efficacy of screening methods. METHODS: Between 1998 and 2000, a total of 40 subjects were found to have CRC (study group) and 160 had a normal colon (control group) among asymptomatic individuals participating in a screening colonoscopy program for a high-risk population of first-degree relatives of CRC patients. We compared these groups for screening by fecal occult blood testing, flexible sigmoidoscopy, barium enema, and colonoscopy in the 10-yr period before the index colonoscopy. RESULTS: Screening colonoscopy was performed in only 2.5% of the case subjects and 48.7% of controls (p < 0.0001), and all screening procedures in 12.5% and 73.7%, respectively (p < 0.0001). A statistically significant difference was also found for screening with fecal occult blood test, but not for flexible sigmoidoscopy or barium enema. Significant adenomatous polyps >1 cm in diameter were detected and removed in 19% of the control group within 10 yr of the index colonoscopy. Six (15%) of the patients in the study group died of CRC. CONCLUSIONS: Screening by colonoscopy can prevent progression to CRC from adenomatous polyps and may reduce the mortality associated with this devastating disease.

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Abstract: A close link has been established between infection and gastric cancer. In this article, we suggest that using a risk stratification technique (like that for colorectal cancer), the high-risk group of first-degree relatives of patients with gastric cancer can be separated out for testing and treatment. This would be more manageable and more cost-effective than screening the whole population, in which the mortality from distal gastric cancer has declined concomitant with the eradication of infection. Support for the feasibility of this approach is derived from studies showing that the family is the core unit of transmission and that childhood colonization, especially with a virulent strain, is apparently a major risk factor for disease progression to the neoplastic stage. When there is a case of gastric cancer in the family, first-degree relatives, who might be infected by a bacterium with an identical genetic fingerprint, are at higher risk than normal for developing gastric cancer. Furthermore, genetic and epidemiologic studies based on the Correa model have shown that both primary and secondary prevention of gastric cancer is possible. Calculations done in high-risk populations, such as Japanese-Americans, confirm the savings in cost and the safety of the test-and-treat strategy. Considering that eradication should be done as early as possible, at a point in the cascade when the changes are still reversible, and that gastric cancer is associated with a high mortality rate, we suggest that this strategy be applied to this high-risk population.

Abstract: The prevalence of Helicobacter pylori infection was studied in 138 patients with dyspepsia in a hospital in Nakuru, Kenya, and in 138 asymptomatic sex- and age-matched controls from the same population. Anti-H. pylori immunoglobulin (Ig) G was more prevalent in dyspeptic than asymptomatic persons (71% vs. 51%), particularly those <30 years old (71% vs. 38%). H. pylori seropositivity was associated with dyspepsia after adjusting for age, sex, and residence (urban or rural). Among adults, the association between H. pylori infection and dyspepsia remained after adjusting for the above factors and for educational attainment, family size, and manual occupation. H. pylori infection in asymptomatic residents of Nakuru, Kenya, was more prevalent in older persons, with a rate of 68%, than in those 31-40 years of age. However, young persons with dyspepsia had an unexpectedly high prevalence of H. pylori infection. H. pylori test-and-treat strategy should be considered in Kenyan patients with dyspepsia, particularly in persons <30 years of age.

Abstract: OBJECTIVES: Recombinant human interferon has been shown to enhance the expression of histocompatibility antigens and certain tumor-associated antigens in a variety of carcinoma cell lines. Since many tumor-associated antigens are mucins, we investigated the effect of recombinant human gamma-interferon on mucin production and secretion by colon cancer cell lines. METHODS: Control and gamma-interferon-treated cells were labeled with [(3)H]glucosamine in DMEM-H16 medium with 5% FCS for 24 h. Analysis was performed by gel filtration on Sepharose CL-4B columns, and the high-molecular-weight glycoprotein eluted at the void volume from the cytosol and medium was counted (expressed as dpm/4 x 10(6) cells). In another experiment the void volume was compared to concentration curves of standard mucins (expressed as mg/10(7) cells). RESULTS: gamma-Interferon increased mucin synthesis in HT-29 and LIM-6 cells, but not in LS174T and CACO2 cells. In HT-29 and LIM-6 cells, mucin synthesis was induced by gamma-interferon in a dose-dependent manner. The percentage of mucin secreted into the medium was also increased. CONCLUSION: The heterogeneity of response of human colon cancer cell lines to gamma-interferon by mucin production may limit the specific role of gamma-interferon as a modulator of mucin-type tumor-associated antigens.

Abstract: The wide use of surgical clips in laparoscopic surgery has led to a variety of complications. We describe two cases in which a surgical clip was incorporated into a duodenal ulcer after laparoscopic cholecystectomy. The presenting symptom was acute gastrointestinal bleeding. Both patients were treated endoscopically, and the bleeding stopped after the clip was removed from the ulcer base. Although the mechanism by which a surgical clip migrates into the duodenum is unclear, we recommend meticulous Calot's triangle dissection and removal of any wandering or misplaced clips. Endoscopic removal is recommended when a surgical clip is discovered in a bleeding ulcer.

Abstract: BACKGROUND: Colon cancer is the main cause of mortality among the gastrointestinal cancers in Israel. Early detection of the average risk population is recommended from the age of 50 to 75 years. Private departments of radiology aggressively advertise virtual colonoscopy for the early detection of colon cancer, although it is not recognised as such in any country. METHODS: We collected all cases in which virtual colonoscopy was followed by endoscopic colonoscopy in the same patient from four medical centers in Israel. RESULTS: Total discrepancy between the results of the two examinations was found in 2/3 of the patients. In some cases colon cancer was missed. CONCLUSIONS: The results presented herein, raise many questions and "red lights" as to the use of virtual colonoscopy in its present form for screening purposes in Israel unless it is in the setting of clinical research.

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Abstract: BACKGROUND AND AIMS: Previous reports have suggested a possible association between hyperplastic polyposis and colorectal neoplasms. Increased gastrin may be the link between these two conditions insofar as gastrin has been reported to be a growth-promoting tumoural agent. This report describes gastric polyposis, hypergastrinaemia and colorectal neoplasms in four elderly patients. METHODS: Four male patients with no family history of cancer, who were found to have multiple gastric hyperplastic polyps, hypergastrinaemia and colorectal cancers or an adenomatous polyp, were evaluated. Assessment included clinical evaluation, biochemical and haematological profiles, fasting gastrin levels, Helicobacter pylori serology, cobalamin, parietal cell antibodies, gastroscopy with biopsies of polyps and gastric mucosa, urease tests, and colonoscopy with biopsies of colorectal neoplasms. Immunohistochemistry of specimens from gastric polyps and colonic carcinomas was performed for chromogranin A, synaptophysin, Leu 7, neuron-specific enolase and gastrin. RESULTS: The mean age at diagnosis of gastric polyps was 71.2 years and at removal of colorectal neoplasm was 70.0 years. In two patients, the gastric lesion was diagnosed before the colonic lesion and conversely in the two remaining patients. Gastrin was very high (1604 pg/ml; normal level, < 115 pg/ml) in one patient with pernicious anaemia, and the mean level for the other three was 324 pg/ml. H. pylori were found in two patients. Immunohistochemistry failed to identify neuroendocrine cells in the hyperplastic gastric polyps and three of the colonic carcinomas. CONCLUSIONS: Occurrence of sporadic colorectal neoplastic lesion in patients with diffuse hyperplastic gastric polyposis and hypergastrinaemia may represent a new syndrome. Gastrin is not secreted by the gastric polyps or colonic carcinomas and may be related to gastric mucosal changes and H. pylori colonization. In patients with hyperplastic gastric polyposis and hypergastrinaemia, colorectal neoplasms should be ruled out.

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Abstract: BACKGROUND: Colorectal cancer has the highest incidence of all malignant tumours in men and women in Israel. The public was introduced to the concept of screening in the early 1980s, and full programs began in 1983. OBJECTIVES: The study compares patients with colorectal cancer (CRC) who were diagnosed before screening and five years later, for stage differences and survival. METHODS: All patients with CRC who were diagnosed from 1981 to 1982 (period I) and 1986-87 (period II) at Soroka Medical Centre and who were residents of the Negev area were eligible for the study. Data were collected retrospectively from the Israel Cancer Registry and patient files and endoscopic, histological and surgical reports from the Departments of Pathology, Gastroenterology, Oncology and Surgery at Soroka Medical Centre. RESULTS: The study groups included 207 patients with CRC, 85-from period I and 122-from period II. The mean annual incidence of CRC for these 2 periods was 18 and 24.8 cases per 100, 000, respectively, for an increase of 37% (P < 0.001). Five-year-survival in period I was 53.3% and in period II, 39.6% (P = 0.025). Survival did not differ by origin or gender. Dukes' stage, well and moderately differentiated tumours, and left-sided tumours were associated with better prognosis (P = 0.03). Forty-two percent of the cases were less than 64-year-old-at diagnosis, compared with 27% of 2069 Israeli patients in whom CRC was diagnosed in 1991 (P < 0.001). CONCLUSIONS: Before a nation wide decision is made with regard to public screening for CRC with fecal occult blood tests or sigmoidoscopy, the available data should be thoroughly evaluated, and further in-depth investigations performed to determine trends in diagnosis and prognosis.

Abstract: BACKGROUND: The family is the core unit for Helicobacter pylori (Hp) infection. In most instances, Hp colonization occurs in early childhood, and correlates with socioeconomic parameters. Helicobacter pylori infection is highly prevalent in many countries, and may cause chronic gastritis and peptic ulcer in adults and in children. Gastritis induced by Hp may be associated with recurrent abdominal pain in children, and eradication of the bacterium may improve the clinical symptoms.AIM The primary aim of this study is to characterize the group of pediatric patients according to the referral patterns and results of 13C-urea breath test (13C -UBT) in our laboratory. The secondary aim is to investigate the result of different treatment combinations for Hp eradication. METHODS: The 13C-UBT was performed with 75 mg urea labeled with 13C in 200 mL orange juice. Breath samples were collected at 0 and 30 minutes, and the results expressed as the change in the 13C/12C ratio at T30' minus T0' The cutoff for Hp eradication was 3.5. The physicians who ordered the test completed a questionnaire covering demographic data (age, gender, and origin), indication for the test was use of a proton pump inhibitor (PPI), and type of combination eradication therapy. RESULTS: The study sample consisted of 1655 children, aged 1 to 18 years, 992 (59.9%) boys and 663 (40.1%) girls, from all parts of the country. The 13C-UBT was positive in 763 (46.1%). The prevalence of positive results was directly correlated with age. History of peptic disease was the main indication for the test, in 1346 (81.4%) cases. Details on eradication therapy were available for 435 children of whom 42.5% had a positive 13C-UBT, indicating a successful eradication rate of 57.5%. Compared with Israeli and American-European origin, children of Asian-African origin had a higher rate of referrals for reason of validation of successful Hp eradication, greater long-term PPI use, and a higher rate of 13C-UBT positivity. No significant difference was demonstrated between the triple therapy regimens used. CONCLUSION: 13C-UBT may be performed in children of all age groups. The main indication is a history of peptic ulcer disease. The prevalence of Hp infection increased with age and the only factor associated with increased Hp infection was Asian-African origin. The most frequent eradication therapy used in children is a combination of omeprazole, amoxicillin, and clarithromycin.

Abstract: INTRODUCTION: Five prospective, controlled trials of CRC screening, 4 of them randomized, using the Hemoccult test in large populations, have been reported from Europe and USA. In all the series stage shifting was documented, and mortality from CRC was reduced by 12-33%. In comparison with this large experience, the Israeli screening programs in the average risk population are very modest, started as case findings and expanded to nation-wide recommendation for FOBT in 1999. In this study the Israeli experience between 1985 and 1997 was documented. METHODS: Medline search of the last 22 years for screening programs in Israel was performed, as well as personal contact with all the Israeli investigators. Reports to the Israeli Cancer Association (ICA) were collected, reviewed and summarized. RESULTS: Since 1985 8 papers about faecal occult blood test (FOBT) and 5 papers about flexible sigmoidoscopy (SIG) screening in average risk population have been published. 35 685 people have been screened, 110 cases of CRC and 546 cases of adenoma were found. The yield of SIG was 4 times that of FOBT for CRC. In addition, since 1990 80 084 people were screened according to the reports to the ICA. Five hundred and six cases of CRC and 2714 cases of adenoma were found. In the only prospective, controlled study, CRC incidence and mortality were significantly decreased in participants of a FOBT screening program, an effect lasting 11 years. Refusers were more likely to be male, of Asian-African decent, smokers, and consumers of more coffee and less tea or dairy food. CONCLUSION: FOBT may protect against CRC for prolonged periods. Individuals who refuse FOBT have significantly higher CRC incidence and mortality rates than those who accept testing. The Israeli experience, thus small, supports a comprehensive screening campaign for early detection of CRC in Israel.

Abstract: BACKGROUND: Guidelines are important for keeping family physicians informed of the constant developments in many fields of medicine. OBJECTIVES: To compare the knowledge of gastroenterologists and family physicians regarding the diagnosis and treatment of gastroesophageal reflux disease in order to determine the need for expert guidelines. METHODS: A 25 item questionnaire on the definition, diagnosis and treatment of GERD was presented to 35 gastroenterologists and 35 family physicians. Each item was rated on a four point scale from 1 = highly recommended to 4 = not recommended. A voting system was used for each group on separate occasions. The proportions of correct answers according to the level of recommendation were compared between the groups. RESULTS: The groups' responses agreed on only 4 of the 25 items; differences between the remaining 21 were all statistically significant. For 14 items, 70% of the gastroenterologists chose the grade 1 recommendation, whereas more than 70% of the family physicians chose mostly grade 2. CONCLUSIONS: The gap in knowledge on gastroesophageal reflux disease between gastroenterologists and family physicians is significant and may have a profound impact on diagnosis and treatment. Clear and accurate guidelines may improve patient evaluation in the community.

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Abstract: BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) by faecal occult blood testing (FOBT) decreases CRC mortality by 15-33%. Compliance remains an obstacle to maximising the benefit of FOBT screening. We tested the hypothesis that individuals offered FOBT screening but refused would have an increased incidence and worse prognosis for CRC compared with those tested and with controls. METHODS: Annual screening was offered to 3548 average risk individuals, > or = 40 years of age, from a highly stable population. A total of 2538 agreed to testing (group 1) and 1010 (28%) refused (group 2). Another 1376 individuals were never offered the test and served as controls (group 3). The groups were followed for 11 years: a three year screening period (1985-1987) and an eight year follow up period at the end of the screening programme (1988-1995). Incidence, stage, and mortality were compared. Characterisation of refusers was completed in 188 and 130 subjects of groups 1 and 2, respectively. RESULTS: In the screening phase, mortality from CRC was significantly lower in group 1 than in groups 2 and 3. The cumulative incidence of CRC in the eight year follow up period was 21 (0.88%), 23 (2.28%), and 13 (0.94%) in groups 1, 2, and 3, respectively. This shows a reduction of 61.4% in group 1 compared with group 2 (relative risk 0.28 (95% confidence interval (CI) 0.19-0.32)) (p<0.001) and 6.4% compared with group 3 (relative risk 0.93 (95% CI 0.93-1.00)) (NS). During follow up, group 1 subjects also demonstrated a decrease in advanced Dukes' stage and mortality rate by 80% and 64%, and 79% and 62%, compared with groups 2 and 3, respectively. Refusers were more likely to be male, of Asian-African descent, and more likely to smoke, consume more coffee, and less tea or dairy foods. CONCLUSIONS: When accepted, FOBT may protect against CRC for prolonged periods. Individuals who refuse FOBT have a significantly higher CRC incidence and mortality rates than those who accept testing.

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Abstract: The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure.

Abstract: Percutaneous endoscopic gastrostomy (PEG) is a popular technique for long-term enteral nutrition. However it is not beneficial in all cases, and may even prolong the process of dying. The present article discusses the main indications for PEG insertion, and the ethical considerations involved. Three main questions need to be answered: (1) for what purposes should PEG be used; (2) for what type of patients, and (3) when should PEG be inserted in the natural history of the patient's illness? PEG is used in patients unable to maintain sufficient oral intake. It has been found to improve quality of life and/or to increase survival in patients with head and neck cancer, acute stroke, neurogenic and muscle dystrophy syndrome, growth failure (children) and gastric decompression. It led to no improvement in nutritional or functional status in patients with cachexia, anorexia, aspiration (and aspiration pneumonia), and cancer with a short life expectancy. Several court decisions have stipulated that PEG need be offered in patients in a persistent vegetative state or patients with senile dementia who have lost the ability for self-determination. Since the 30-day mortality after PEG insertion is very high for patients hospitalized in a general medical center, a 'cooling off' period of 30-60 days should be scheduled from the time of the PEG request to actual insertion.

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Abstract: The parietal cell is capable of secreting high concentrations of hydrochloric acid into the lumen of the stomach. The apical membrane of this cell contains K+H+ ATPase, which is responsible for proton transport into the lumen. Potassium and chloride channels are also present. The basolateral membrane of the parietal cell possesses transporters that maintain intracellular homeostasis. Specifically, large amounts of bicarbonate that are generated by carbonic anhydrase must be removed from the cell to prevent alkalinization. Efflux of bicarbonate into the blood after acid secretion can be detected and is known as the alkaline tide. Determination of the alkaline tide has been used to measure acid secretion. In this review, we summarize the published data.

Abstract: BACKGROUND AND AIMS: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. METHODS: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. RESULTS: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3-46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. CONCLUSIONS: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.

Abstract: BACKGROUND/OBJECTIVE: Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. MATERIALS AND METHODS: Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0-3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. RESULTS: There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. CONCLUSION: The change in MUC 5 synthesis may reflect H. pylori colonization.

Abstract: OBJECTIVE: Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohn's disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls. METHODS: Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed. RESULTS: Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls. CONCLUSIONS: Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

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Abstract: BACKGROUND: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HCO3- release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HCO3- production from CO2 and OH- in the parietal cell. OBJECTIVE: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon. METHODS: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 min after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1, following pretreatment with acetazolamide 60 min before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3. RESULTS: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +/- 0.2 mEq/L (mean +/- standard deviation) and the calculated alkaline tide at 45 min was 33.99 +/- 4.49 mEq. On day 2 with prior administration of acetazolamide, base excess decreased by 0.21 +/- 0.39 mEq/L, and the calculated alkaline tide was -3.28 +/- 7.57 mEq, which was significantly lower than on day 1 (P = 0.0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53 +/- 0.2 mEq/L and the alkaline tide was -10.05 +/- 3.33 mEq; there was no significant difference compared with day 2 (P = 0.44). CONCLUSION: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon.

Abstract: Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0-3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.

Abstract: The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.

Abstract: AIM: To evaluate the sensitivity and specificity of a new (13)C urea breath test, Oridion BreathID, for the diagnosis of Helicobacter pylori. METHODS: A total of 97 consecutive symptomatic patients referred for upper endoscopy were included in the 'pre-therapy' part of the study. After endoscopy the patients were analysed for H. pylori by Oridion BreathID. BreathID continuously sampled the subject's breath for 20 min, and displayed the results on the BreathID screen in real time. Results of the BreathID were compared with the 'gold standard' (rapid urease test and histology). We also prospectively tested the validity of BreathID in comparison to isotope ratio mass spectrometry, in 40 patients referred to monitor the efficacy of H. pylori eradication treatment. RESULTS: Complete agreement was observed between the 'gold standard' and the Breath ID test in 96.9% (94 out of 97) of the patients. The sensitivity and specificity of BreathID were 97.8% and 96.1%, respectively. The correlation between BreathID and isotope ratio mass spectrometry breath test was 100%. CONCLUSIONS: The Oridion BreathID has comparable sensitivity and specificity to the claims of the currently available urea breath tests. Furthermore, BreathID has the potential advantages of ease of use with minimal medical staff requirement, and real time rapid results (20 min maximum) which may make the BreathID preferable to other urea breath test assays.

Abstract: OBJECTIVES: Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status. METHODS: In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses. RESULTS: H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA- was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7-41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3-1229.2; p = 0.001). CONCLUSIONS: Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

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Abstract: OBJECTIVE: The growing use and complexity of endoscopy procedures in GI units has increased the need for good patient preparation. Earlier studies in this area have focused on the psychological benefits of patient education programs. The present study was directed at determining cost-effectiveness of a patient education program. METHODS: A prospective, randomized, controlled design was used. The patient population consisted of 142 patients aged 18-90 yr referred for an endoscopy procedure. Ninety-one (64%) participated in a targeted educational session conducted by a dedicated departmental nurse (group 1), 38 (27%) did not (group 2), and 13 (9%) received telephonic instruction (group 3). Before the endoscopy, all patients completed a questionnaire covering background data, endoscopy-related variables, anxiety level, and satisfaction. Patient cooperation and success/failure of the procedure were documented by the attending nurse. RESULTS: Male gender, previous endoscopy, and explanation from the referring physician were associated with a low level of anxiety (p < 0.05). There was a significant association between attendance in the education program and success of the endoscopy (p = 0.0009). Cancellations of procedures because of poor preparation occurred in 4.39% of group 1 in comparison with 26.31% and 15.38% of groups 2 and 3, respectively (p = 0.005). The overall cost of the procedure was reduced by 8.6%, 8.9%, and 5.5% for gastroscopy, colonoscopy, and sigmoidoscopy, respectively. All participants expressed satisfaction with the brochure. CONCLUSION: A pre-endoscopy patient education program apparently increase patient compliance, thereby decreasing both the need for repeated examinations and their attendant costs.

Abstract: Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Abstract: The association between gastric carcinoid tumors and pernicious anemia is well recognized. Such tumors occur in the presence of achlorhydria, chronic atrophic gastritis, hypergastrinemia, and enterochromaffin-like cell hyperplasia. In this case report, a 29-year-old woman with pernicious anemia and autoimmune thrombocytopenia who developed gastric carcinoid tumors of the gastric body is described. This is the second description of pernicious anemia associated with autoimmune thrombocytopenia. This association in a young woman together with the therapeutic options and decisions that were taken in the treatment of the patient are discussed.

Abstract: OBJECTIVE: The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study. METHODS: Patients with established IBD aged 18-70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject. RESULTS: A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohn's disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS).The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85-1.99) versus clinic controls, and 0.96 (0.63-1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only 12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p<0.005). The proportions of ex-smokers were higher in UC patients 29.7% versus 25.9%, and 19.5% in their respective controls (p<0.001 vs. community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p<0.05). Patients with UC were more likely to be light smokers(1-10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11-20 cigarettes/day) in comparison to their controls. CONCLUSIONS: The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Abstract: OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is a widely used method for insertion of a gastrostomy tube in patients who are unable to eat but have a normally functioning gut. Complications have been described, especially in fragile, debilitated patients, and 30-day mortality rates of 4.1-26% have been reported. We assessed the outcome of PEG tube placement for inpatients and outpatients, based on morbidity, mortality, and long-term survival. METHODS: We reviewed the medical records of all patients who underwent PEG at our institution between January 1, 1995 and December 31, 1996. Four groups of patients were compared: Group 1, patients from nursing homes; Group 2, hospitalized patients; Group 3, hospitalized patients matched to Group 2 for diseases, except mental disorder, and not treated with PEG; and Group 4, the general hospital population matched for age. RESULTS: A total of 114 PEG tubes were inserted in 114 patients, 47 from Group 1, 67 from Group 2. Eighty-seven percent of patients in Group 1 underwent PEG because of dementia, versus 46% of Group 2 (p<0.001). The mortality rate was five times higher in Group 2 than in Group 3 (p<0.001). The 30-day mortality was seven times higher in Group 2 than in Group 1, twice that in Group 3, and five times higher than in Group 4 (p = 0.002 and p<0.001, respectively). When intention-to-treat analyses were applied to the data, 19/48 patients died (39.5%) in Group 1, and 60/83 (72.0%) died in Group 2, (p<0.001). CONCLUSIONS: Patients hospitalized with acute illness are at high risk for serious adverse events after PEG insertion and this procedure should be avoided.

Abstract: OBJECTIVE: The incidence of ulcerative colitis ranges from 3 to 15 cases per 100,000 persons per year with a prevalence of 50-80 cases per 100,000, and the disease is 3-5 times more common among Jews. In Israel, Ashkenazi Jews have a higher incidence than Sephardi Jews, but a lower incidence than Ashkenazi Jews in the United States or Northern Europe. The aim of this study was to examine the prevalence, mean annual incidence, and clinical patterns of ulcerative colitis in a stable population of communal settlements (kibbutz). METHODS: We repeated a community-based survey in 124,400 kibbutz residents, 10 yr after our first study. This population represents 2.5% of the Jewish population of Israel. All ulcerative colitis patients were located by contacting the kibbutz clinics of the 269 kibbutz settlements (100% compliance). Data were updated to December 31st, 1997, which was designated the point prevalence date, and included information on gender, age, origin, education, profession, extent of the inflammatory process, clinical spectrum of the disease, therapy, complications of the disease, and treatment. The mean annual incidence for the 10 yr was calculated from the prevalence data. Only cases with a definite diagnosis of ulcerative colitis made in a recognized gastroenterology unit were accepted into the study. RESULTS: There were 208 confirmed cases of ulcerative colitis disease, 113 women and 95 men (female:male ratio = 1.19). The prevalence rate rose from 121.0/100,000 in 1987 to 167.2/100,000 in 1997 (p < 0.001). The prevalence rates were higher in women than men. Prevalence was highest in Israeli-born members in 1987 but in European/American-born members in 1997. The average annual incidence rate for the 10-yr period was 5.04/100,000/yr. In 1987, 146 cases of ulcerative colitis were collected. During 10 yr of surveillance 17 patients left the kibbutz, 12 died, and 62 new cases were added. The mean age at presentation of the disease was lower in 1987 than in 1997, 46.14 +/- 11.10 and 51.43 +/- 16.67 yr, respectively. Prevalence was highest in men with >16 yr and in women with 9-10 yr of education, 259.3 and 242.9/100,000, respectively. CONCLUSIONS: The prevalence of ulcerative colitis in this Israeli population increased and has reached the upper range for European and American populations. The mean annual incidence rate of ulcerative colitis is in the lower range of that reported for the Western countries.

Abstract: BACKGROUND: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. METHODS: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. RESULTS: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05). CONCLUSION: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

Abstract: Cellular mechanisms for Na(+) retention in portal hypertension are undefined, but epithelial Na(+) channels (ENaC) may be involved. Under high-salt diet, ENaC are absent from distal colon of rat but can be induced by mineralocorticoids such as aldosterone. Presence of rat ENaC was determined by amiloride inhibition of (22)Na(+) uptake in surface colonocytes 7 and 14 days after partial portal vein ligation (PVL) or sham surgery. At both times, uptake inhibition was significantly increased in PVL rats. Presence of mRNA transcripts, determined by RT-PCR, demonstrated that channel alpha- and gamma-subunits were similarly expressed in both groups but that beta-subunit mRNA was increased in PVL rats. This confirms that there was induction of rat ENaC and indicates that beta-subunit has a regulatory role. Urinary Na(+) was decreased for 3 days after PVL but was not different at other times, and serum aldosterone levels were elevated at 7 days, at a time when urinary Na(+) output was similar to that of sham-operated rats. We conclude that PVL leads to induction of ENaC in rat distal colon. An increase in aldosterone levels may prevent natiuresis and is probably one of several control mechanisms involved in Na(+) retention in portal hypertension.

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Abstract: The results of small bowel transplantation improved in the last 5 yr because of the development of new immunomodulating drugs and surgical techniques, as well as better candidate selection. We still need much experience until this procedure will be in routine use for terminal intestinal insufficiency.

Abstract: OBJECTIVE: The prevalence of Crohn's disease ranges from 10 to 70 cases per 100,000 population, and is 3-8 times more common among Jews. However, this excess risk is not evident in the Jewish population of Israel. Recently we have described a significant increase in the prevalence and incidence of Crohn's disease in the south of Israel. The aim of this study was to confirm this trend in a stable population found in communal (kibbutz) settlements. METHODS: We repeated a community-based survey in 124,400 kibbutz residents, 10 yr after our first study. This population represents 5% of the Jewish population of Israel. All Crohn's disease patients were located by contacting the kibbutz clinics of the 269 kibbutz settlements (100% compliance). Data was updated to December 31st, 1997, which was designated the point prevalence date, and included information on gender, age, origin, education, profession, extent of the inflammatory process, clinical spectrum of the disease, therapy, complications of the disease, and treatment. The average annual incidence for the 10 yr was calculated from the prevalence data. Only cases with a definite diagnosis of Crohn's disease made in a recognized gastroenterology unit were accepted into the study. RESULTS: There were 81 confirmed cases of Crohn's disease and the prevalence rate rose from 25.5/100,000 in 1987 to 65.1/100,000 in 1997 (p < 0.001). The mean annual incidence rate for this period (1987-1997) is 5.0/100,000/yr. Prevalence rates were higher in women than men, and in those born in Israel or Europe/America than in Asia/Africa. The mean age at presentation of the disease was lower in 1997 than in 1987, 37.4 +/- 17.0 and 45.0 +/- 17.0 yr, respectively (p = 0.041). Prevalence was highest in men with > 16 yr of education, and in women with 11-12 yr education, 119.7 and 100.3/100,000, respectively. CONCLUSIONS: During the decade 1987-1997, the prevalence of Crohn's disease has increased in Israel and is approaching the rates in Europe and America.

Abstract: BACKGROUND: Helicobacter pylori infection appears to be contracted mainly in childhood, and it is associated with disadvantaged socioeconomic conditions, overcrowding, and living in institutions. In this study we determined the seroprevalence of H. pylori among elderly patients (age > or = 70 years) admitted to a major medical center in Israel, and studied the relationship between seroprevalence of H. pylori and the duration of stay in a nursing home prior to the admission. PATIENTS AND METHODS: Whole blood from 182 consecutive patients hospitalized at the Rabin Medical Center was tested for the presence of anti-H. pylori IgG using Helisal Rapid Blood Test kit (Cortecs Diagnostics). Multivariate logistic regression analysis was used to study the relation between H. pylori seropositivity and possible predictive factors such as age, gender and duration of stay in a nursing home. RESULTS: Of the 182 patients included in the study, 80 (44%) were living in nursing homes (NH) and 102 (56%) were living in their own homes (H) prior to admission. Subjects that stayed in nursing homes for more than 15 months were significantly more likely to be seropositive than subjects with a shorter duration of stay (84% and 63% respectively, p = 0.03). Using a multivariate logistic regression analysis on both the NH group and the whole group, seropositivity was found to be significantly associated with duration of stay in a nursing home (p = 0.03 and p = 0.01 respectively). Seropositivity was not associated with age in either group. CONCLUSIONS: Living in a nursing home is associated with increased risk for H. pylori infection in the elderly. There is a strong correlation between the duration of stay in a nursing home and the prevalence of H. pylori infection.

Abstract: Effectiveness of sublingual cobalamin-replacement therapy was studied in 18 people with cobalamin deficiency. Administration was efficacious and convenient, and compliance was high.

Abstract: BACKGROUND: Epidemiologic studies have demonstrated an inverse correlation between dietary calcium and vitamin D intake and the incidence of colorectal carcinoma. Elevated serum levels of 25-hydroxyvitamin D3 (25-OH-D3) are associated with a major reduction in the incidence of this neoplasm. The reduction in tumor size and number induced by calcium supplements in an experimental carcinogenesis model was neutralized by vitamin D3 deficiency. To the authors' knowledge, vitamin D serum levels have never been determined previously in colorectal carcinoma patients. They compared serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-OH-D3, and parathyroid hormone (PTH) levels of colorectal carcinoma patients with those of healthy controls. METHODS: Serum 1,25(OH)2D3, 25-OH-D3, and PTH levels were determined in 84 colorectal carcinoma patients (10 with Stage I, 29 with Stage II, 25 with Stage III, and 20 with Stage IV) and 30 healthy controls, all of whom were normocalcemic and not taking calcium or vitamin D supplements. RESULTS: 25-OH-D3 serum levels were higher in cancer patients than controls, irrespective of stage. Serum 1,25(OH)2D3 decreased with advancing stage: 73 +/- 18, 48 +/- 16, 39 +/- 12, 34 +/- 13, and 75 +/- 20 pg/mL in Stages I, II, III, IV, and controls, respectively. There was a corresponding increase in serum PTH levels: 58.0 +/- 9.4, 73.7 +/- 14.4, 79.0 +/- 21.3, 100.4 +/- 30.9, and 51.2 +/- 3.9 pg/mL in Stages I, II, III, IV, and controls, respectively. Serum vitamin D metabolite levels did not correlate with gender, age, tumor localization, or histologic grade. CONCLUSIONS: An inverse correlation between serum levels of the active metabolite of vitamin D and colorectal carcinoma stage has been demonstrated for the first time, to the authors' knowledge, in colorectal carcinoma patients. Because 1,25(OH)2D3 has been shown to inhibit proliferation of colonic epithelial cells, decreased serum levels may facilitate the growth of colorectal carcinoma and influence its biologic behavior.

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Abstract: Intestinal transplantation, which until recently has been considered an experimental procedure, is now undergoing considerable change and becoming a standard treatment for patient with intestinal failure. The major improvement in results is due to the introduction of new immunosuppressive agents that have led to significant reduction in acute rejection. Nevertheless, reduction in severe infectious complications, which are the main cause of mortality after transplant, as well as improved techniques for early diagnosis of rejection are needed before intestinal transplantation can be widely used. We describe our experience in post-transplant follow-up of a woman, aged 32-years, who had undergone intestinal transplantation for short bowel syndrome after extensive bowel resection.

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Abstract: OBJECTIVES: Adequate preparation of the bowel is essential for accurate colonoscopic examination. We compared colonic preparation with sodium picosulphate plus magnesium citrate (SPS-Mg) with sulphate-free polyethylene glycol electrolyte lavage (PEG-EL) solution before colonoscopy, for quality of bowel cleansing, patient discomfort, and side effects. METHODS: Sixty-eight consecutive patients were randomly assigned to receive either 3 sachets of SPS-Mg (16.5 g each) (n = 39) or 3 L of PEG-EL (n = 29) on the day before colonoscopy. Shortly before the procedure each patient was interviewed to determine the degree of discomfort (1 = none or mild, 2 = moderate, 3 = severe) and side effects. The quality of bowel cleansing was graded by a gastroenterologist who was unaware of the method of preparation (from 1 = poor to 4 = excellent). RESULTS: Of the 29 PEG-EL patients, four (14%) did not complete the preparation because of side effects. The degree of discomfort was significantly greater with PEG-EL (mean score, 2.3 +/- 0.7) than with SPS-Mg (mean score, 1.4 +/- 0.5; p < 0.01). Nausea and vomiting were significantly more common in the PEG-EL group (38% vs 13%; p < 0.05). Using intention-to-treat analysis, bowel cleansing proved to be significantly better with SPS-Mg than with PEG-EL (mean score +/- SD, 3.05 +/- 0.9 and 2.57 +/- 1.0, respectively; p = 0.036). CONCLUSIONS: Colonic preparation with SPS-Mg is better tolerated, associated with significantly fewer side effects, and results in higher quality bowel cleansing than preparation with PEG-EL.

Abstract: We assessed two new rapid urease tests, the Helicobacter Urease Test (HUT, Astra, Sweden) and the Polish test, for accuracy, reaction time, and the effect of biopsy site and bacterial density on test characteristics and time to positivity. A prospective study was conducted in two groups of patients: 64 consecutive patients undergoing upper endoscopy for dyspepsia and 61 consecutive patients with duodenal ulcer on upper endoscopy. In the first group, test accuracy, time to positivity, and possible associations with biopsy site and bacterial density were assessed between the tests. In the second group, the two new tests were compared with the CLOtest for time to positivity and effect of bacterial density on test outcome. The Polish and HUT test had similar specificities (97%), but the Polish test was more sensitive (90.3% vs. 80.7%). The Polish test was positive within 10 minutes in 55% of the positive patients compared with 10% for the HUT test. There was no association between bacterial density (by histologic count) and reaction time in either test or in the CLOtest in the second group. The Polish test was more accurate and had a quicker time interval to positivity than the HUT. There was no significant association between bacterial density and reaction time in any of the urease tests assessed, and the biopsy site did not affect test accuracy in the HUT test.

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Abstract: Our objective was to determine whether colorectal cancer tissue synthesizes and secretes biologically active gastrins resulting in a rise of gastrin levels in patients with adenocarcinoma of the colon. Blood samples for gastrin determination were taken from the artery feeding, and from the vein draining colon tumors, from a vein draining an uninvolved colon segment and from a peripheral vein. Tissue gastrin levels were measured in tumor tissues and normal mucosa taken by colonoscopic biopsy from colon cancer patients and healthy controls. The setting was a university hospital research laboratory. We had seventeen patients with colorectal cancer and 23 controls. No significant difference was found in peripheral venous blood gastrin levels between the cancer and the control groups. Serum gastrin concentration was not significantly different in the arterial blood which supplied the tumor area, the venous blood draining the tumor, the "uninvolved" mucosa or the control normal epithelium. Cancer tissue gastrin levels were lower than those measured in biopsies of uninvolved mucosa from cancer patients and normal controls. The present results show no rise of gastrin blood levels in patients with colon cancer, nor any evidence of gastrin-increased synthesis by the tumors.

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Abstract: Cholinergic urticaria presents as wheals and erythroderma that develop in response to a variety of factors which stimulate muscarinic receptors, including exercise, heat, cold, sweat and emotional stress. We describe a 25-year-old man with ulcerative colitis who developed cholinergic urticaria diagnosed by a metacholine test. He had had seven previous attacks over 8 years, and the finding of elevated liver enzymes required admission to four different hospitals. The clinical picture was identical: urticaria, hepatosplenomegaly, lymphadenopathy and elevation of liver enzymes. The causative agent was never identified and recovery was complete, with or without antibiotic therapy. To the best of our knowledge, this is the first description of liver involvement in cholinergic urticaria noted in the English-language medical literature.

Abstract: Polycystic kidney disease is an autosomal dominant disease that may be associated with cystic disease of the liver. In women, the cysts may develop early and be more troublesome than in men. Cystadenocarcinoma of the pancreas is uncommon, comprising 1% of primary pancreatic malignancies. This case report is the first to describe a familial association between polycystic kidney disease and cystadenocarcinoma of the pancreas and liver in the English medical literature. A patient with autosomal dominant polycystic kidney disease (ADPKD) and multiple hepatic cysts developed cystadenocarcinoma of the pancreas with multiple malignant liver cysts. The patient's mother, sister, and niece had ADPKD, and the patient's sister also died of pancreatic cystadenocarcinoma. We believe that the development of these two disease entities in which the primary pathology is cyst formation has a genetic association.

Abstract: OBJECTIVES: Octreotide, a somatostatin analog, reduces stool and fistula outputs by a mechanism that is not completely understood. Our aim was to study its effect on gastrostomy, duodenostomy, and cholecystostomy effluents in a patient with colorectal cancer. METHODS: Effluents of gastrostomy, duodenostomy, and cholecystostomy were collected in three separate shifts over 24-h periods beginning 3 days before octreotide therapy and continuing for 15 treatment days. Fifty-four samples were tested for volume, pH, acid, and bicarbonate production, and biochemical profiles. RESULTS: A positive fluid balance was achieved immediately with octreotide therapy. Significant decreases in gastrostomy and duodenostomy outputs and in gastric acid production were observed (1433.33 +/- 33.33 ml/24 h to 535.71 +/- 55.31 ml/24 h,p < 0.0001; 2066.67 +/- 66.67 ml/24 h to 247.14 +/- 36.04 ml/24 h, p < 0.0001; and 67.50 +/- 3.20 mEq/h to 13.00 +/- 1.50 mEq/h, p < 0.0001; respectively). Gastrostomy tachyphylaxis was observed after 6 days of treatment. Remarkable dose-dependent increases were found in cholesterol and bilirubin concentrations in the cholecystostomy effluent. CONCLUSIONS: Octreotide's primary effect is a decrease in gastric and pancreatic secretions. The increased concentrations of cholesterol and bilirubin may explain the occurrence of gallstones in patients treated with octreotide.

Abstract: Glucocorticoids, such as dexamethasone, induce amiloride-sensitive Na+ conductances in rat distal colon epithelium. The activity of these conductances diminishes from the surface to the base of the crypt whereas cAMP-stimulated Cl- secretion decreases from the crypt base to the surface. These gradients are likely to be perturbed during carcinogenesis. We therefore determined the magnitude of Na+ and Cl- conductances in colonocytes isolated from normal and carcinogen-treated rats. Colon carcinogenesis was induced by injection of dimethylhydrazine (DMH) (18 mg/kg) for 5 weeks. Before sacrifice animals were treated for 3 days with dexamethasone. Colonocyte populations from the surface to the crypt base (C1-C5) were harvested from the distal colon by a Ca2+-chelating procedure. The activity of Na+ conductances was determined by uptake of 22Na+ by surface and crypt colonocyte populations and by membrane vesicles in the presence and absence of 10 microM amiloride. In control rats Na+ conductance was highest in surface colonocytes and absent in the crypt base. As early as 2 weeks after initiation of DMH treatment amiloride-inhibited Na+ uptake was virtually absent in the upper crypt. Transcriptional assessment of the alpha-, beta- and gamma-subunits that constitute the epithelial Na+ channel revealed that DMH treatment reduces the expression of beta-subunit mRNA. We then examined 36Cl- efflux from isolated colonocytes of normal and carcinogen-treated rats in response to forskolin (0.01 mM). Forskolin induced a marked rise in cAMP in lower crypt cells concomitant with a significant stimulation of 36Cl- efflux. Intracellular cAMP increased in upper crypt cells in response to forskolin without an increase in 36Cl- efflux. By contrast, upper crypt colonocytes from DMH-treated rats showed forskolin-stimulated efflux beginning 4 weeks after initiation of treatment. We conclude that induction of Na+ conductances by glucocorticoids is inhibited during the early stages of chemical carcinogenesis due to lack of induction of the beta-subunit of the channel. By contrast, Cl- transport is stimulated both in surface and lower crypt cell compartments during different stages of chemical carcinogenesis.

Abstract: OBJECTIVES: Bacterial attachment is a prerequisite for colonization of the gastric epithelial surface. Recently, it was demonstrated that the receptor for Helicobacter pylori is the blood group antigen Lewis b, which is exposed only in blood group O. We prospectively examined the prevalence of blood groups in H. pylori-positive and -negative patients. To avoid a genetic bias, we compared blood group prevalence of our patients with the general population of Israel. METHODS: In the 187 consecutive patients we studied, in addition to regular upper endoscopy, H. pylori status and blood group. Exposure to H. pylori was diagnosed when the results of two or more of three methods were found to be positive. RESULTS: Exposure was found in 123 patients and 64 negative. The groups were similar in average age and origin, and no significant difference was demonstrated for blood group. Blood group distribution between any given origin was not significantly different in our patients and in a sample of 182,701 blood donors. CONCLUSIONS: Positivity for H. pylori was not associated with blood group O. Our observation does not support the conclusion that the receptor for H. pylori in the gastric mucosa is the blood group antigen Lewis b.

Abstract: Transient bacteremia during and after endoscopic procedures is a well- documented phenomenon, but complicated bacteremia such as endocarditis in patients at risk is considered to be extremely rare. The recommendations for prophylaxis before endoscopy in patients with valvular heart disease were recently released. We discuss 16 cases of complicated bacteremia that developed after endoscopy (eight cases previously published in the literature and eight cases we encountered). The endoscopic procedures were gastroscopy (five cases), sclerotherapy (six cases), sigmoidoscopy (three cases), and esophageal dilation (two cases). Fourteen patients had underlying disease: valvular heart disease (six patients), cirrhosis of the liver (five patients, one of whom also had a prosthetic knee), valvular heart disease and cirrhosis of the liver (two patients), and gastric carcinoma (one patient). The organisms involved were Streptococcus viridans (six cases), streptococcus group D (three cases), Streptococcus pneumoniae (two cases), Streptococcus microaerophilicus (two cases), Staphylococcus aureus (two cases), and Cardiobacterium hominis (one case). The patients presented with the following infections: endocarditis (12 patients), spontaneous bacterial peritonitis (two patients), septic arthritis (one patient), and brain abscess (one patient). The outcome was good in 15 patients; one patient died. Patients with valvular heart disease, cirrhosis of the liver, ascites, malignancies, or prosthetic joints who undergo endoscopic procedures should be considered for antibiotic prophylaxis.

Abstract: To establish patterns of mucin staining in the colon, a differential staining method was developed separating acid mucins into sialomucins and sulfomucins, and their distribution was studied along the colon of 9 normal subjects, 6 patients with ulcerative colitis in remission and 9 with colon cancer. Serial mucosal biopsies from the cecum to the rectum, were taken at colonoscopy and stained with aldehyde-fuchsin and alcian blue. The mean score of staining intensity in normals for sialomucins was higher than for sulfomucins, 1.85 +/- 0.05 versus 0.60 +/- 0.08 (p < 0.05). A significantly lower staining score for sulfomucins was found in the descending colon and in the cecum when compared with the rectum. Ninety-seven percent of the slides were positive for sialomucins, but only 50% for sulfomucins (p < 0.05). The mean (+/- SE) staining intensity for sialomucins in the ulcerative colitis and cancer group was 1.60 +/- 0.08 and 1.60 +/- 0.05 (p = 0.002 and p < 0.05 when compared with the controls, respectively). A difference in the percentage of biopsies positive for sulfomucins, in controls and proctosigmoiditis groups, was also observed: 50.0 and 33.3%, respectively (p = 0.013). No significant change was demonstrated in the mean sulfomucin staining score comparing normal and colon cancer patients. Our results may be used as a baseline for further research on mucin staining patterns in colorectal inflammatory and neoplastic diseases.

Abstract: During 1992-1994 we performed 77 needle liver biopsies on ambulatory patients. 59 patients were observed for 6 hours and then released. 15 who lived more than 40 km away and 3 in whom complications were feared were hospitalized. All were released within 24 hours and there were no complications. We conclude that ambulatory needle biopsy of the liver is safe and cost-effective is selected patients.

Abstract: It has been shown that screening of average risk individuals reduces the incidence of colorectal cancer. The most effective method for screening has yet to be determined in terms of cost-effectiveness, but approximately two-thirds of colorectal neoplastic lesions are within the reach of the flexible sigmoidoscope. It has been estimated that a single such examination at the end of the sixth decade may reduce the colorectal cancer incidence by 60%. As part of a screening program for colon cancer, short colonoscopy was performed on 399 employees of a nuclear research center and 228 members of a collective settlement (kibbutz). The examinations were carried out on individuals aged > or = 40 years by two experienced endoscopists. The splenic flexure or transverse colon was reached in 95% of the procedures. Neoplastic lesions were found in 24 (6.0%) and 8 (3.5%) screenees (not significant) in the Nuclear Research Center and kibbutz populations respectively. Polyps <1 cm in diameter were significantly more common in the Nuclear Research Center population but larger polyps and cancers were not. In 47 Nuclear Research Center screenees with a family history positive in a first-degree relative, findings increased to 14.9% (P = 0.016). A family history of malignancy was found in 33.8% of kibbutz members but in only 11.8% of Nuclear Research Center employees. There was no evidence to suggest that working at the Nuclear Research Center increased the risk of colonic neoplasms. We conclude that flexible sigmoidoscopy is a valuable screening tool, especially for individuals with a first-degree relative with cancer. The yield of neoplastic lesions in the Israeli Nuclear Research Center and kibbutz populations is similar to that of the general population in the western world. Compliance rates are high in well-defined populations.

Abstract: Glucose intolerance is associated with chronic liver disease, particularly cirrhosis, and overt diabetes mellitus is two to four times more common than in the general population. Little attention has been paid to the relationship between the cause of cirrhosis and the development of glucose intolerance or whether cirrhosis is a prerequisite. We found glucose intolerance to be particularly common in patients with chronic hepatitis C, and in this retrospective study we attempt to confirm this possible association. To investigate this question we reviewed the files of 128 patients with chronic hepatitis C and 40 with chronic hepatitis B and active liver disease. Demographic, laboratory, imaging and pathology data were abstracted. The mean fasting blood glucose (+/-SD) in the hepatitis C and B groups was 160 +/- 83 and 103 +/- 18 mg/dl (P < 0.0001) with 2.5% and 39.1% respectively being overtly diabetic (P < 0.00001). However, the mean age of the hepatitis C group was much higher (45.6 +/- 12.5 vs. 60.1 +/- 12.3 years, P < 0.00001). The prevalence of diabetes was much higher among the hepatitis C patients than in the general population. Cirrhosis was not more frequent in biopsies from hepatitis C diabetic patients compared with non-diabetic or hepatitis B patients. Multivariate analysis showed that type of hepatitis and age were significant and independent predictors for developing diabetes. We conclude that there appears to be an association between diabetes mellitus and chronic hepatitis C that is not present in patients with chronic hepatitis B.

Abstract: BACKGROUND: A knowledge of the clinical and epidemiological features of duodenal and gastric ulcer is of importance to clinicians and other health care providers. These aspects of ulcer disease have not been studied previously in the Negev region of southern Israel, which is home to 300,000 Jews and 60,000 Bedouin Arabs. METHODS: Clinical, demographic and risk factors were analyzed in a case series of benign duodenal and gastric ulcers (first or recurrent attack) diagnosed at endoscopy at the Soroka Medical Center in the years 1989-1990. RESULTS: There were 336 cases of duodenal ulcer (321 cases in Jews, 15 in Bedouins) and 79 cases of gastric ulcer (all in Jews). The annual rate of endoscopically-detected duodenal ulcer was 54/10(5) in Jews and 13/10(5) in Bedouins. The annual ratio of endoscopically-detected gastric ulcer in Jews was 13/10(5). The ratio of male to female patients was 2.7 for duodenal ulcer in Jews and Bedouins, and 1.9 for gastric ulcer in Jews. The mean age +/- standard deviation at diagnosis was 48 +/- 17 years for duodenal ulcer and 63 +/- 15 years for gastric ulcer (p < 0.001). Duodenal ulcer was significantly commoner than gastric ulcer at all ages, but the ratio DU:GU decreased with increasing age, so that by age 48 years, 20% of all endoscopically-diagnosed ulcers were GU. Of several risk factors examined, smoking was associated with duodenal ulcer (p < 0.05) but not gastric ulcer. Occupation was not a risk factor. Duodenal ulcer was 1.3 times more frequent in winter than summer. CONCLUSIONS: Endoscopically-diagnosed duodenal and gastric ulcer is commoner in Jews than Bedouins and in men than women. Duodenal ulcer is commoner than gastric ulcer and presents at a younger age. Smoking is a risk factor for duodenal ulcer, and European and American ethnic origin is a risk factor for duodenal and gastric ulcers. Bleeding is associated with one-third of endoscopically-diagnosed ulcers in this institution.

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Abstract: In the present study we have determined membrane, cytosolic, and cytoskeleton-associated tyrosine protein kinase (TPK) activity in human colon cancer cell lines exposed to (i) the differentiation-promoting agents sodium butyrate and 8-chloro-cyclic-adenosine 3',5'-monophosphate (8-Cl-cAMP), (ii) tyrphostins, specific TPK inhibitors, or (iii) differentiation-inducing culture manipulations. Treatment of human colon cancer cell lines, LS 174T, COLO 205, and SW620, with sodium butyrate and 8-Cl-cAMP or tyrphostins AG-30 and AG-34, significantly attenuated TPK activity concomitantly with an increase in the activity of alkaline phosphatase, an enzymatic marker of intestinal cell differentiation. The differentiated phenotype induced in Caco-2 and HT-29 colon cancer cells by culture manipulation was associated with a significant decrease in cytoskeleton-associated TPK activity and marked activity of alkaline phosphatase (AP). Electron microscopy and freeze-fracturing analysis of HT-29 cells showed that the gradual transition from the undifferentiated to the differentiated phenotype resulted in the acquisition of a distinct polarized morphology. Immunocytochemical phosphotyrosine analysis of cultured SW620 cells showed positive staining mostly localized in zones of focal contacts. A marked reduction in phosphotyrosine staining with notable changes in cell morphology was observed in SW620 cells exposed to tyrphostins. Cumulatively, the present results indicate that the induction of the differentiated phenotype in colon cancer cells is associated with a marked decrease in TPK activity and tyrosine phosphorylation.

Abstract: Amalgam, the most prevalent dental restoration material used in dentistry, is potentially toxic because it contains mercury. Recent international publications confirm that mercury is potentially hazardous to dental personnel, who are exposed to mercury vapors both during their work at the office and from amalgam restorations in their own oral cavities. The purpose of our study was to compare urinary mercury levels of dental personnel with a control group, and to explore possible correlations between environmental factors in the dental office and the urinary level of the personnel. Our results indicate that the urinary mercury levels of the tested dental professionals were significantly higher than those of the control group (2.39 +/- 0.319 vs. 0.899 +/- 0.34 micrograms mercury/g creatinine). Of the dental personnel examined, 72% had detectable levels of urinary mercury, compared to 27% of the control group. Although mercury levels in all participants did not exceed the toxic limit, the above findings clearly point to the need for a continuation of this survey.

Abstract: OBJECTIVE: Alkaline tide is the observed alkalinization of blood and urine after stimulation of gastric acid secretion. In previous studies, we found good correlation between gastric acid output and alkaline tide in arterialized venous blood. METHODS: In the present study, the alkaline tide phenomenon was further investigated in 26 duodenal ulcer patients (seven post-vagotomy) after a test meal, before and after cimetidine pretreatment. RESULTS: Alkaline tide was demonstrated in everyone of the 19 duodenal ulcer nonvagotomized patients but in only two of the seven vagotomized patients; base excess mean rise of 1.05 +/- 0.14 mEq/L/45 min versus -.07 +/- 0.23 mEq/L/45 min (mean +/- SE, p < 0.001). Decrease in alkaline tide after cimetidine was demonstrated in the nonvagotomized group: 1.05 +/- 0.14 mEq/45 min versus -0.03 +/- 0.16 mEq/45 min, before and after cimetidine, respectively (mean +/- SE, p < 0.001). Urinary alkaline tide was demonstrated in only 4/19 and 2/19 of the first group (with and without cimetidine, respectively) and in only 1/7 of the post-vagotomy group. CONCLUSIONS: Our results suggest an association between gastric acid secretion and blood alkaline tide, because both are inhibited by cimetidine or vagotomy.

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Abstract: We previously showed that repeated stimulation of the gastrin receptor may lead to down-regulation. We hypothesized that entry of extracellular Ca2+ may replenish cytosolic Ca2+ and enable continuation of the acid-secretion process. Pentagastrin-stimulated alkaline-tide study was performed in seven duodenal ulcer patients on 2 separate days--with and without pretreatment with verapamil (Ca2+ channel blocker). The alkaline-tide test may substitute the conventional gastric acid collection as previously described. A significant rise in base excess after pentagastrin injection was found on the first day of the study, from 0.400 +/- 1.233 to 2.230 +/- 1.330 (mean +/- SD, P = 0.02). On the second day the rise was not statistically significant, from -0.200 +/- 0.838 to 0.440 +/- 1.200 (mean +/- SD, P = 0.27). In 6 of the 7 patients the alkaline-tide decreased from 45.29 +/- 21.75 mEq/45 min on the first day to 21.56 +/- 17.48 mEq/45 min on the second day of the study (mean +/- SD, P = 0.029), a decrease of 63.6 +/- 36.2%. Our findings may support a dual source for Ca2+, the second messenger in gastrin-dependent gastric acid secretion. The first increase of intracellular Ca2+ comes from cellular stores, and the second from extracellular source by Ca2+ channels, which can be blocked by verapamil.

Abstract: Cholecystectomy is recommended for symptomatic gallstone disease, however atypical abdominal symptoms may be incorrectly attributed to gallstones found by chance at ultrasound. High rates of post-cholecystectomy symptoms confirm that surgery is often performed inappropriately in patients whose complaints do not derive from the biliary tract. We therefore performed esophagogastroduodenoscopy (EGD) in 56 symptomatic patients with gallstones to determine if there was an alternative explanation for patient symptoms. A surgeon then assessed the patient in the light of these findings and decided whether to operate. Of 41 patients who were questioned 12.4 +/- 7.3 months after entry, 1 of 22 patients who underwent surgery, and 5 of 19 patients treated conservatively, were symptomatic (P < 0.05). In the surgical group, one of seven patients with an endoscopic finding remained symptomatic, and in the nonsurgical group one of nine patients remained symptomatic (NS). However, in patients without endoscopic findings, none of the 15 surgical patients but 4 of 10 nonsurgical patients (40.0%) remained symptomatic (P < 0.01). We conclude that patients with gallstone disease and negative EGD who undergo cholecystectomy are less likely to remain symptomatic than those treated conservatively. Thus, endoscopy of the upper gastrointestinal tract in patients with gallstones may provide important information for the surgeon, prior to the making of therapeutic decisions.

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Abstract: A positive correlation has been described between mucin synthesis, tumorigenicity, and a poor prognosis in human colorectal cancer. Serum growth factors and hormones have been implicated in the regulation of biological behavior of the neoplasm, including growth and differentiation. Growth and differentiation of cancer cells have been observed to be involved in altered expression of mucin mRNA and synthesis. In the present study, the relationship between serum growth factors and mucin synthesis was studied in LS174T colon cancer cells grown in medium with different serum concentrations, and with 20% serum that was heated to 80 degrees C for 60 min or dialysed against saline. Mucin synthesis was estimated by measuring the amount of [3H]glucosamine-labeled glycoprotein excluded on a Sepharose CL-4B column. When the cells were compared on the basis of the same cell number, the higher the serum concentration of the medium, the more mucin produced. There was no decrease in mucin production after heating or after dialysis, indicating that there is a heat-stable non-dializable serum factor which induces mucin synthesis.

Abstract: Hyperbaric oxygen has been used in the management of perianal Crohn's disease on the assumption that tissue oxygenation is impaired. The Dead Sea region of Israel is the lowest point on earth (402 m below sea level), and therefore the oxygen pressure is increased. We hypothesized that this elevation in oxygen pressure over an extended time might be as effective as shorter periods of high-pressure oxygen in a hyperbaric chamber. So we investigated whether the Dead Sea environment might affect the activity and perianal complications of Crohn's disease. Six patients with Crohn's disease unresponsive to medical treatment spent periods of 1-3 weeks at the Dead Sea. Four patients had discharging perianal fistulas. All were given advice concerning diet, physical activity, and immersion in the Dead Sea. The Clamp-Softley modification of the Harvey-Bradshaw Crohn's disease activity index was used to assess disease activity initially and at weekly intervals during treatment. Drug therapy was tailored to patient symptoms. Mean disease activity index before treatment was 9.0 +/- 1.4 (mean +/- SEM) and after a week at the Dead Sea 3.5 +/- 1.4 (p = 0.006). After 2 weeks the index decreased to 2.0 +/- 0.4 (p = 0.037) in four patients. In one patient, complete healing of perianal fistulae occurred after 2 weeks, and in two others there was striking improvement. Two patients with active Crohn's disease and on high-dose corticosteroids were able to stop all medication during their stay. Decrease in activity index occurred rapidly, whereas the improvement in perianal disease was more gradual. The Dead Sea environment was highly effective in managing patients with severe Crohn's disease, including perianal complications in this small, uncontrolled series.

Abstract: We describe two elderly men with preexisting coronary heart disease (CHD) and prostatic carcinoma who presented with intractable anemia due to radiation-induced rectal telangiectases and bleeding. Remission of the bleeding was achieved in both patients by treatment with an estrogen-progestin preparation. However, aggravation of the CHD occurred in both patients. We believe that estrogen-progestin preparations have a potential in the treatment of men with radiation-induced rectal telangiectases, but additional studies are needed to evaluate their long-term effects and optimal dose.

Abstract: The main aim of this study was to determine whether changes in mucin production/secretion during the growth phases of a human adenocarcinoma cell line, HT-29, are associated with a different tumorigenic potential. HT-29 cells cultured in DMEM supplemented with 10% FCS were harvested in the exponential and post-confluent phases of growth. Metabolic labeling of the cells was performed using [3H]-glucosamine. Following a 24 hr-incubation period, radioactivity was measured in 1 ml-aliquots of cell cytosol and culture medium. Concurrently, mucin synthesis was assessed by size exclusion chromatography of [3H]-glucosamine-labeled glycoprotein in a Sepharose CL-4B column. Clonigenic assay in soft agar of pre- and post-confluent HT-29 cells was determined by scoring viable colonies according to size and number using phase-contrast microscopy. To assess in vivo tumorigenicity, pre-and post-confluent HT-29 cells (4 x 10(6)) in 0.2 ml DMEM were inoculated into nude mice. Tumor size and volume were recorded for 31 days. H-29 cells grew as multilayers of unpolarized, undifferentiated cells. Colony forming efficiency was similar at all growth stages. A significant increase in mucin synthesis was noted in HT-29 cells harvested in the exponential phase of growth compared to the stationary phase (148.3 +/- 41.9 versus 49.1 +/- 5.0, mean +/- SE, dpm/4 x 10(3) cells, p < 0.05). Mucin secretion was not significantly changed. Tumorigenicity in nude mice was consistently higher when the cells were injected in the exponential phase of growth. On day 31 after cell inoculation the average tumor volume/site was 332.7 mm3 in mice injected with HT-29 cells in log phase compared to 142.7 mm3 (p < 0.01) in animals which received post-confluent cells. Tumor weights were 0.36 g and 0.22 g respectively (p < 0.05). The present results indicate a definitive correlation between growth phases of HT-29 cells and mucin synthesis: mucin production was significantly higher in exponentially growing cells. The cloning efficiency in soft agar, a marker of in vitro tumorigenicity, was similar in HT-29 cells irrespective of the growth stage. A main finding of the present study was the increased in vivo tumorigenicity of colon cancer cells inoculated into athymic mice in the log phase of growth compared to cells harvested at post-confluence. These results are consistent with the view that mucin plays an important contributory role in determining tumorigenicity.

Abstract: OBJECTIVES: To evaluate the specificity, sensitivity, and positive predictive value of fecal occult blood testing (FOBT) in symptomatic patients, with colonoscopy as the gold standard, and to assess the usefulness of FOBT as an ancillary examination in symptomatic patients for whom total colonoscopy is indicated. METHODS: We studied 439 consecutive patients who underwent Hemoccult II testing before total colonoscopy. RESULTS: The sensitivity, specificity, and positive predictive value for colorectal neoplasia (cancer and adenomatous polyps) was 76.5%, 56.7%, and 27.6%, respectively. The sensitivity, specificity, and positive predictive value for colorectal cancer were 69.2%, 73.2%, and 7.3%, respectively. CONCLUSIONS: The sensitivity, specificity, and positive predictive value of FOBT are difficult to estimate from screening programs, because Hemoccult-negative individuals do not undergo examination of the colon, and many of the Hemoccult-positive cases do not undergo total colonoscopy. With total colonoscopy serving as the gold standard, FOBT does not appear to be of much value as an ancillary examination in patients with symptoms potentially attributable to the lower gastrointestinal tract.

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Abstract: Sulindac, a nonsteroidal anti-inflammatory drug, causes regression of polyps in familial polyposis coli and may prevent new lesions. However, it is not clear whether the effect of sulindac in preventing polyps also applies to carcinoma. This case report describes a patient with familial polyposis coli who developed a carcinoma in a rectal segment after subtotal colectomy and ileorectal anastomosis. She had been treated with 450 mg sulindac daily for 28 months and was free of polyps during the latter 12 months of this period. However, despite intensive endoscopic follow-up, she developed an adenocarcinoma of the rectum. This finding may have important implications for our understanding of the development of colon cancer in familial polyposis coli and the use of sulindac to prevent it. Development of de novo carcinoma in microadenomatous tissue of the rectal mucosa, which bypasses the polyp-cancer sequence, must be considered as a possibility in these patients.

Abstract: BACKGROUND/AIMS: Postconfluence differentiation followed by a decrease in mucin synthesis has been described for the colonic adenocarcinoma cell line Caco-2. Because the onset of differentiation usually heralds the end of proliferation, we expected Caco-2 would be more tumorigenic in the exponential phase. Thus, we compared tumorigenicity, clonigenicity, and mucin synthesis in the exponential and stationary growth phases. METHODS: We estimated mucin synthesis in Caco-2 cells by measuring the amount of high-molecular-weight [3H]glucosamine-labeled glycoprotein released into the culture medium and in the cytosolic fraction. Colony forming efficiency in soft agar and tumorigenicity in nude mice were assessed. RESULTS: Cells in the exponential phase synthesized significantly more mucin compared with stationary phase cells. Pretreatment with benzyl-GalNAc reduced production in both phases but did not change clonigenicity. Colonies did not grow from cells seeded in the exponential phase. The average weight of xenografts raised from postconfluence cells was twice that of xenografts raised from cells in the exponential phase. CONCLUSIONS: Neither exponential cell growth nor increased mucin production predicts clonigenicity and tumorigenicity. It is speculated that a stable process takes place in Caco-2 cells after confluence which makes them more clonigenic in vitro and enhances tumor growth in vivo.

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Abstract: The relationship between diminished response to hepatitis B vaccine in renal failure patients and serum creatinine level, age and other factors is unknown. The immune response of patients with renal failure of varying severity to hepatitis B vaccine was determined in this study. Sixty-eight patients with renal failure of varying severity who were negative for hepatitis B markers received four doses of hepatitis B vaccine, and anti-HBs titers were determined at 0, 1, 2, 3, 6, 8 and 12 months. Maximum anti-HBs titers were seen at 8 months. At this time 86% of patients with creatinine < or = 4 mg/dl but only 37% with creatinine > 4.0 mg/dl had a protective titer of > or = 10 mIU/ml (p < 0.002). Age was inversely related to anti-HBs titer (p = 0.045) and was independent of serum creatinine in predicting antibody response. We conclude that all patients with chronic renal failure should be immunized against hepatitis B as early as possible in the development of their disease, to ensure maximum response, and to minimize the effects of elevated serum creatinine and increasing age.

Abstract: An epiphrenic diverticulum is usually accompanied by esophageal motor disorders, diaphragmatic hernia, or esophagitis. Symptoms are rarely attributable to the diverticulum except very rarely when no other explanation for dysphagia or chest pain is demonstrated. We describe acute esophageal obstruction from food accumulating in an epiphrenic diverticulum and compressing the gastroesophageal junction, and we confirm the mechanism with an artificial balloon.

Abstract: Despite the decline in the number of operations for intractable duodenal ulcer disease, there are still many patients who suffer from the side effects of vagotomy. Incomplete vagotomy may be a significant cause of surgical treatment failure. Diagnosis of incomplete vagotomy is not easy since there is no reliable, safe, single test available for this purpose. We hypothesized that incomplete vagotomy can be made temporarily complete in response to a muscarinic blocking agent. A gastric cannula was inserted and vagotomy performed in 12 female dogs, which was incomplete in 6 and complete in 6 dogs. Gastric acid secretion was stimulated for 2 h with i.v. pentagastrin at a rate of 6 micrograms/kg per h. After the first hour 6 mg/kg pirenzepine (M1 muscarinic receptor antagonist which may block the effect of intact vagal fibers on postganglionic submucosal neurons) was added i.v. In the complete vagotomy dogs there was no significant decrease in gastric output rate: 12.28 +/- 4.06 mEq/h in the first hour, and 12.00 +/- 3.80 mEq/h in the second hour (mean +/- SE, P = 0.963, t = 0.048). In the incomplete vagotomy dogs a significant decrease in gastric acid output rate was observed: 10.19 +/- 1.10 mEq/h in the first hour, and 4.33 +/- 0.95 mEq/h in the second hour (mean +/- SE, P = 0.002, t = 4.029). We conclude that a pentagastrin/pirenzepine test may differentiate between complete and incomplete vagotomy in the dog.

Abstract: To prove that ingestion of unpeeled persimmon is necessary for the development of a persimmon phytobezoar, we interviewed 15 patients, in most of whom this condition developed after peptic ulcer surgery. We compared the study group with a control group of 15 patients who had undergone peptic ulcer surgery but did not have a bezoar. In contrast with the control group, most patients with bezoars had ingested unpeeled fruits (p < 0.01). While ingestion of persimmon carried a 9.8-fold risk of bezoar development, ingestion of the unpeeled fruit increased the risk of this complication 56 times over that of age- and sex-matched controls. We recommend that patients who have undergone ulcer surgery be warned particularly against eating unpeeled persimmons.

Abstract: Hyperplastic polyps are regarded as non-neoplastic lesions with no malignant potential. However, several case reports and a clustering phenomenon suggest that they may arise in abnormal colonic that is predisposed to develop neoplastic lesions. The hyperplastic polyp also displays markers associated with colorectal cancer. In addition, several recent articles have addressed the question of hyperplastic polyp in the distal colon as a marker of more proximal adenomatous polyp. Many endoscopists discovering a distal hyperplastic polyp will wish to ensure the absence of a proximal neoplastic lesion.

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Abstract: It has been shown that the transient increase in total body bicarbonate that accompanies any acceleration of gastric acid secretion (the 'alkaline tide') is derivable from the associated changes in base excess in arterial blood and is precisely equivalent to the amount of acid secreted when the latter is simultaneously recovered. For the alkaline tide to qualify as a 'tubeless' measure of acid secretion, its equivalence to the latter has to be demonstrated without simultaneous aspiration of gastric juice. We therefore studied the course of the alkaline tide following pentagastrin injection and its relationship to pentagastrin-stimulated acid secretion as measured by aspiration on a separate occasion. In 12 duodenal ulcer patients, the sequential changes in base excess in arterial blood in response to pentagastrin invariably described coherent curves. Peak values occurred most frequently 45 min after injection. In 12 similar patients, alkaline tide 45 min after pentagastrin, as per analysis of arterialized venous blood, correlated well (r = 0.86) with 'peak acid output' (PAO) as measured by aspiration at another time. In 14 patients post vagotomy and pyloroplasty for duodenal ulcer, the 45-min alkaline tide was determined as above and PAO was predicted from the previously established regression-line: The 3 patients with recurrent duodenal ulceration had the highest predicted values for PAO, clearly discriminating them from the others. Measurement of alkaline tide holds promise as a valuable substitute for conventional gastric analysis. For the sake of accuracy, readings should be based on individually constructed time-curves of base excess, in preference to the raw data. Arterialized venous blood appears to be satisfactory substitute for arterial blood for studies of this type.

Abstract: The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.