Proton pump inhibitors are not associated with fundic gland polyps - a systematic review that takes into consideration all known confounders.

Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.

Idiopathic multitudinous fundic gland polyposis: A new disease and a management dilemma.

Two patients with idiopathic multitudinous fundic gland polyposis, a hitherto undescribed condition, were reported. They presented incidentally with a multitude of fundic gland polyps, 52 and 147, without a family history of polyposis, and these polyps were not attributable to the chronic use of proton pump inhibitors. All polyps were removed by hot-biopsy polypectomy, and each was individually subjected to pathological examination, which showed no evidence of dysplasia. When confronted with gastric polyps of clinically undetermined origin, endoscopists would, to exclude dysplasia, usually resect all if they are few and sample some and survey the others periodically if they are numerous. The condition reported presents a management dilemma: Because the number of the polyps is such that they are manageable by total polypectomy, should this be carried out, despite the labor intensiveness involved, to exclude dysplasia, and are the polyps a variant of syndromic polyposis and therefore carry a malignant potential and inform the need for periodic surveillance and to investigate the patient's kindred? The frequency of this condition and whether it is truly not associated with dysplasia require further studies.

Novel treatment for gastric intestinal metaplasia, a precursor to cancer.

BACKGROUND AND AIM: Gastric intestinal metaplasia (GIM) is precancerous with a worldwide prevalence of 25%. Eradicating Helicobacter pylori prevented about half of gastric cancers; failure to prevent the rest was attributed to GIM. GIM is irreversible and often extensive. There is no treatment. Existing endoscopic mucosal resection (EMR) is designed to treat early gastric cancer of usually <2 cm. We designed a two-endoscope technique of EMR for extensive lesions such as GIM. METHODS: Forty patients with histologically confirmed moderate to severe GIM (operative link on GIM [OLGIM] classification) received the treatment in a daycare center. Chromoendoscopy with methylene blue was first performed to indicate the GIM. Submucosal saline injections were used to lift the stained mucosa to form multiple safety cushions, which were transformed into artificial polyps by suction and ligation, using a cap familiar to gastroenterologists for ligation of esophageal varices. EMRs were then achieved by snare polypectomy. By rotating two gastroscopes, one was designated to perform lift and snare and the other to perform suction and ligation; cycles of lift-ligate-snare were performed until all stained mucosa was removed. Assessment chromoendoscopy with ≥seven biopsies was performed at 6 months. RESULTS: A total of 227 EMRs were performed, with a median of 3.5 per patient. Bleeding was uncommon and minimal. Gastric perforation ascribable to loss of a safety cushion occurred in one patient. Chromoendoscopy at 6 months in 36 willing patients showed no recurrence of GIM. CONCLUSION: The two-endoscope technique of EMR for GIM was essentially safe and effective, with no recurrence at 6 months. It could be performed by endoscopists with standard skills.

Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection.

The Asia-Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.

Celecoxib-related gastroduodenal ulcer and cardiovascular events in a randomized trial for gastric cancer prevention.

AIM: To evaluate the long-term risk of gastroduodenal ulcer and cardiovascular events induced by celecoxib in a population-based, randomized, double-blind, placebo-controlled study. METHODS: From 2004 to 2006, a total of 1024 Chinese patients (aged 35 to 64 years) with severe chronic atrophic gastritis, intestinal metaplasia or dysplasia were randomly assigned to receive 200 mg of celecoxib twice daily or placebo in Linqu County (Shandong Province, China), a high-risk area of gastric cancer. All gastroduodenal ulcer and cardiovascular events occurred were recorded and the patients were followed up for 1.5 years after treatment. At the end of the trial, a systematic interview survey about other adverse events was conducted. RESULTS: Gastroduodenal ulcer was detected in 19 of 463 (3.72%) patients who received celecoxib and 17 of 473 (3.31%) patients who received placebo, respectively (odds ratio = 1.13, 95% CI = 0.58-2.19). Cardiovascular (CV) events occurred in 4 patients who received celecoxib and in 5 patients who received placebo, respectively. Compared with those who received placebo, patients who received celecoxib had no significant increase in occurrence of CV events (hazard ratio = 0.84, 95% CI = 0.23-3.15). Among the adverse events acquired by interview survey, only the frequency of bloating was significantly higher in patients treated with celecoxib than in those treated with placebo. CONCLUSION: Treatment of gastric cancer with celecoxib is not associated with increased risk of gastroduodenal ulcer and cardiovascular events.

Asia-Pacific consensus guidelines on gastric cancer prevention.

BACKGROUND AND AIM: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. METHODS: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. RESULTS: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. CONCLUSION: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease.

CONTEXT: Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. OBJECTIVES: To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. DESIGN, SETTING, AND PARTICIPANTS: Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. MAIN OUTCOME MEASURES: The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. RESULTS: The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD. CONCLUSIONS: In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.

Increasing prevalence of advanced colonic polyps in young patients undergoing colonoscopy in a referral academic hospital in Hong Kong.

AIM: To investigate the distribution and frequency of advanced polyps over eight years. METHODS: 6424 colonoscopies were reviewed during the study period 1998 to 2005. The study period was subdivided into period I: 1998 to 2001 and period II: 2002-2005. RESULTS: 1856 polyps (33% advanced polyps) and 328 CRCs were detected. The mean ages of the patients with advanced polyps and cancer were 69.2 +/- 12.0 and 71.6 +/- 13.8 years, respectively. Advanced polyps were mainly left sided (59.5%). Advanced polyps were found in patients 0.05). CONCLUSION: Advanced polyps increased significantly in the younger male group in the most recent period and there seems to be a shift towards a proximal location.

Influence of positive family history on clinical characteristics of functional constipation.

BACKGROUND & AIMS: We observed that there is familial aggregation in patients with functional constipation. Their clinical characteristics have not been studied. The aim of this study was to investigate the clinical characteristics of patients with functional constipation with and without a positive family history. METHODS: Patients with functional constipation satisfying Rome II criteria were recruited. A Rome II questionnaire on constipation was given to the patients' families to identify whether there were any family members with idiopathic constipation. The clinical characteristics between those with and without positive family history were evaluated. RESULTS: There were 118 patients with at least one first-degree relative with idiopathic constipation and 114 patients without a positive family history. The patients in the 2 groups were comparable in mean age (P = .3) and sex distribution (P = .09). Patients with positive family history had a younger age of onset (median, 11-20 years vs 21-30 years, P < .0001); longer duration of constipation (20 +/- 14 vs 15 +/- 13, P = .016); more complications, eg, symptomatic hemorrhoids, anal fissure, and rectal prolapse (54.2% vs 40.4%, P = .034); less precipitating factors leading to the onset of constipation (35.6% vs 49.1%, P = .037); more frequent use of digital evacuation (27.1% vs 13.2%, P = .008), but no difference in the association with psychological disorders (P = .3); transit time (P = .5); or manometric dyssynergia (P = .5). CONCLUSIONS: Patients with idiopathic constipation and with a positive family history exhibited different clinical characteristics. This might be related to the early age of onset of the symptoms, which might, in turn, give clues to the underlying etiology.

An inverse correlation between Interleukin-6 and select gene promoter methylation in patients with gastric cancer.

BACKGROUND: Both serum IL-6 levels and CpG island methylation have been shown to have prognostic significance in gastric cancer, it was suggested that an important link existed between IL-6 and methylation of cancers. AIM: To investigate the prognostic value of IL-6 serum level and the association between serum IL-6 levels and CpG island methylation at p16, DAPK, MGMT and E-cadherin in patients with gastric cancer. PATIENTS AND METHODS: Methylation status was assessed by MSP in 75 surgical specimens of gastric adenocarcinoma. IL-6 serum levels were measured by chemiluminescent enzyme immunoassay (CLEIA). RESULTS: Methylation of p16, DAPK, MGMT, and E-cadherin were present in 53, 48, 32, and 59% of patients. Patients with tumors methylated at p16 and DAPK had lower serum levels of IL-6 compared to unmethylated tumors (1.8 vs. 4.8 pg/ml, p = 0.01 for p16; 1.5 vs. 6.2 pg/ml, p = 0.0001 for DAPK). But there was no difference with MGMT and E-cadherin methylation status. Serum IL-6 levels were also associated with TNM stage (p = 0.001), depth of tumor invasion (p = 0.002), lymphatic invasion (p = 0.01), vascular invasion (p = 0.008), metastasis (p = 0.002) and signet cell histology (p = 0.001). CONCLUSION: IL-6 is of prognostic value for patients of gastric cancer. Low serum IL-6 levels were associated with p16 or DAPK gene methylation in patients with gastric cancer.

Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications.

BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain, although it has been recommended for patients who have gastrointestinal intolerance to aspirin. We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications. METHODS: This was a prospective, double-blind, randomized, controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005. After healing of ulcers and eradication of Helicobacter pylori, if present, patients were assigned randomly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The primary end point was recurrent ulcer complications. RESULTS: During a median follow-up period of 52 weeks, no patient in the esomeprazole group, as compared with 9 patients in the clopidogrel group, developed recurrent ulcer complications. The cumulative incidences of recurrent ulcer complications were 0% in patients receiving esomeprazole and aspirin and 13.6% in patients receiving clopidogrel (absolute difference, 13.6%; 95% confidence interval for the difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding.

Colonoscopy demand and practice in a regional hospital over 9 years in Hong Kong: resource implication for cancer screening.

BACKGROUND: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain. AIM: To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years. METHODS: Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared. RESULTS: There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001). CONCLUSION: The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.

Effects of cyclooxygenase-1 and -2 gene disruption on Helicobacter pylori-induced gastric inflammation.

BACKGROUND: Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. METHODS: Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1+/- and COX-2+/-), and homozygous COX-deficient (COX-1-/- and COX-2-/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. RESULTS: COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B4 and LTC4 levels were increased to a similar extent in infected WT and COX-deficient mice. CONCLUSIONS: COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.

Inhibition of human telomerase reverse transcriptase by nonsteroidal antiinflammatory drugs in colon carcinoma.

BACKGROUND: Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT. METHODS: Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT. RESULTS: Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment -145 to -330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent. CONCLUSION: NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment -145 to -330 bp may be the cis-response element to NSAIDs.

Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications.

PURPOSE: Selective cyclooxygenase-2 (COX-2) inhibitors cause significantly fewer peptic ulcers than conventional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at low risk or high risk for peptic ulcers. On the other hand, proton pump inhibitor co-therapy has also been shown to be effective in preventing relapse of peptic ulcers in high-risk patients using nonselective NSAIDs. We compared the efficacy of a selective COX-2 inhibitor with that of proton pump inhibitor co-therapy in the reduction in the incidence of ulcer relapse in patients with a history of NSAID-related peptic ulcers. MATERIALS AND METHODS: For this study, we recruited 224 patients who developed ulcer complications after NSAID use. We excluded patients who required concomitant aspirin treatment and who had renal impairment. After healing of ulcers and eradication of Helicobacter pylori, patients were randomly assigned to treatment with celecoxib 200 mg daily (n = 120) or naproxen 750 mg daily and lansoprazole 30 mg daily (n = 122) for 24 weeks. The primary endpoint was recurrent ulcer complications. RESULTS: During a median follow-up of 24 weeks, 4 (3.7%, 95% confidence interval [CI] 0.0%-7.3%) patients in the celecoxib group, compared with 7 patients (6.3%, 95% CI 1.6%-11.1%) in the lansoprazole group, developed recurrent ulcer complications (absolute difference -2.6%; 95% CI for the difference -9.1%-3.7%). Celecoxib was statistically non-inferior to lansoprazole co-therapy in the prevention of recurrent ulcer complications. Concomitant illness (hazard ratio 4.72, 95% CI 1.24-18.18) and age 65 years or more (hazard ratio 18.52, 95% CI 2.26-142.86) were independent risk factors for ulcer recurrences. Significantly more patients receiving celecoxib (15.0%, 95% CI 9.7-22.5) developed dyspepsia than patients receiving lansoprazole (5.7%, 95% CI 2.8-11.4. P = .02). CONCLUSIONS: Celecoxib was as effective as lansoprazole co-therapy in the prevention of recurrences of ulcer complications in subjects with a history of NSAID-related complicated peptic ulcers. However, celecoxib, similar to lansoprazole co-therapy, was still associated with a significant proportion of ulcer complication recurrences. In addition, more patients receiving celecoxib developed dyspepsia than patients receiving lansoprazole and naproxen.

Differing coping mechanisms, stress level and anorectal physiology in patients with functional constipation.

AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls. METHODS: Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed. RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P<0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs 95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of 'monitoring' coping strategy (14+/-6 vs 9+/-3, P = 0.001), which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03). CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.

Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E-cadherin.

BACKGROUND: Currently, to the authors' knowledge, there is no serum marker to predict disease recurrence after patients undergo curative resection for gastric carcinoma. Previous reports have indicated that serum levels of soluble E-cadherin had prognostic value in these patients. The objective of the current study was to determine whether soluble E-cadherin levels could predict disease recurrence in patients with gastric carcinoma who underwent curative surgery. METHODS: Sixty-nine patients who underwent curative surgery for gastric carcinoma after December 1997 were followed prospectively. Venous blood samples were collected preoperatively, 1 month after surgery, and every 3 months thereafter. The blood samples were assayed for soluble E-cadherin and for carcinoembryonic antigen (CEA) using commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curves were used to define a cut-off level of E-cadherin for the optimal sensitivity and specificity for predicting disease recurrence. RESULTS: The median follow-up was 21 months for patients with recurrent disease (n = 17 patients) and 36 months for patients without recurrent disease (n = 52 patients; P = 0.007). The optimal cut-off level of E-cadherin was 10,000 ng/mL. The sensitivity for predicting prediction disease recurrence using this cut-off level at 3 months and at 6 months postsurgery was 47% and 59% respectively, which was significantly better compared with the sensitivity of CEA using the conventional cut-off level (6% at 3 months postsurgery and 6% at 6 months postsurgery; P = 0.004 and P < 0.0001, respectively). The median time between the elevated E-cadherin level and documented disease recurrence was 13 months (range, 3-20 months), compared with 4 months (range, 1-20 months) for CEA. CONCLUSIONS: Serum soluble E-cadherin was a good marker for predicting disease recurrence in the first 3-6 months after surgery, with a median of 13 months before clinical recurrence. The use of this marker may allow time for vigilant surveillance and consideration of adjuvant therapy.