Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics.

OBJECTIVES: Autism spectrum disorder is a neurodevelopmental condition that typically displays socio-communicative impairment as well as restricted stereotyped interests and activities, in which gastrointestinal disturbances are commonly reported. We report the case of a boy with Autism Spectrum Disorder (ASD) diagnosis, severe cognitive disability and celiac disease in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment. METHOD: The case study refers to a 12 years old boy with ASD and severe cognitive disability attending the Villa Santa Maria Institute in resident care since 2009. Diagnosis of ASDs according to DSM-V criteria was confirmed by ADOS-2 assessment (Autism Diagnostic Observation Schedule). The medication used was VSL#3, a multi-strain mixture of ten probiotics. The treatment lasted 4 weeks followed by a four month follow-up. The rehabilitation program and the diet was maintained stable in the treatment period and in the follow up. ADOS-2 was assessed six times: two times before starting treatment; two times during the treatment and two times after interruption of the treatment. RESULTS: The probiotic treatment reduced the severity of abdominal symptoms as expected but an improvement in Autistic core symptoms was unexpectedly clinically evident already after few weeks from probiotic treatment start. The score of Social Affect domain of ADOS improved changing from 20 to 18 after two months treatment with a further reduction of 1 point in the following two months. The level 17 of severity remained stable in the follow up period. It is well known that ADOS score does not fluctuate spontaneously along time in ASD and is absolutely stable. CONCLUSIONS: The appropriate use of probiotics deserves further research, which hopefully will open new avenues in the fight against ASD.

Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test.

BACKGROUND & AIMS: Computed tomographic colonography (CTC) is a reliable option for screening subjects who are unable or unwilling to undergo optical colonoscopy (OC). A colon capsule (PillCam Colon2 [CC2]; GivenImaging Ltd., Yokneam, Israel) has shown promising results in detecting polyps larger than 6 mm. We compared the accuracy of CC2 and CTC in identifying individuals with at least 1 polyp greater than 6 mm and subjects' attitude toward the procedures. METHODS: Fifty individuals (mean age, 59.2 ± 5.8 y; 58% male) with positive results from the immunochemical fecal occult blood test (iFOBT-positive) underwent CC2, CTC, and OC. The unblinded colonoscopy, integrating OC, CTC, and CC2 results, was used as the reference standard. In a per-patient analysis, the accuracy of CC2 and CTC were assessed for individuals with at least 1 polyp 6 mm or larger. Individuals were asked to choose which procedure they would be willing to repeat between CTC and CC2. RESULTS: The combination of OC, CTC, and CC2 identified 16 cases with at least 1 polyp 6 mm or larger (reference standard). CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. CC2 identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ratio, and a 0.06 negative likelihood ratio. Thirty-nine subjects (78%) said they preferred CC2 to CTC. CONCLUSIONS: CC2 and CTC detect polyps 6 mm and larger with high levels of accuracy; these techniques are effective in selecting iFOBT-positive individuals who do not need to be referred for colonoscopy. CC2 seems to be better tolerated than CTC, and could be a reliable alternative to CTC for iFOBT-positive individuals who are unable or unwilling to undergo OC. ClinicalTrials.gov number: NCT01744509.

Carbon dioxide insufflation or warm-water infusion versus standard air insufflation for unsedated colonoscopy: a randomized controlled trial.

BACKGROUND: The increasing demand for colonoscopy has renewed the interest for unsedated procedures. Alternative techniques, such as carbon dioxide insufflation and warm-water infusion, have been advocated to improve patient tolerance for colonoscopy in comparison with air insufflation. OBJECTIVE: The aim of this study was to evaluate the benefits of carbon dioxide insufflation and warm-water irrigation over air insufflation in unsedated patients. DESIGN: This study was a randomized, controlled trial. SETTING: This study was conducted at a nonacademic single center. PATIENTS: Consecutive outpatients agreeing to start colonoscopy without premedication were included. INTERVENTIONS: Patients were assigned to either carbon dioxide insufflation, warm-water irrigation, or air insufflation colonoscopy insertion phase. Sedation/analgesia were administered on patient request if significant pain or discomfort occurred. MAIN OUTCOME MEASURES: The primary outcome measured was the percentage of patients requiring sedation/analgesia. Pain and tolerance scores were assessed at discharge by using a 100-mm visual analog scale. RESULTS: Three hundred forty-one subjects (115 in the carbon dioxide, 113 in the warm-water, and 113 in the air group) were enrolled. Intention-to-treat analysis showed that the proportion of patients requesting sedation/analgesia during colonoscopy was 15.5% in the carbon dioxide group, 13.2% in the warm-water group, and 25.6% in the air group (p = 0.04 carbon dioxide vs air; p = 0.03 warm water vs air). Median (interquartile range) scores for pain were 30 (10-50), 28 (15-50), and 46 (22-62) in the carbon dioxide, warm-water, and air groups (carbon dioxide vs air, p < 0.01; warm water vs air, p < 0.01); corresponding figures for tolerance were 20 (5-30), 19 (5-36), and 28 (10-50) (carbon dioxide vs air, p < 0.01; warm water vs air, p < 0.01). LIMITATIONS: This investigation was limited because it was a single-center study and the endoscopists were not blinded to randomization. CONCLUSIONS: Carbon dioxide insufflation was associated with a decrease in the proportion of patients requesting on-demand sedation, improved patient tolerance, and decreased colonoscopy-related pain in comparison with air insufflation. The findings regarding warm-water irrigation confirmed the previously reported advantages, so that warm-water irrigation and carbon dioxide insufflation could represent competitive strategies for colonoscopy in unsedated patients.

Hyoscine N-butylbromide for adenoma detection during colonoscopy: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hyoscine N-butylbromide (HBB), commonly used during colonoscopy to facilitate cecal intubation, has been proposed to increase the adenoma detection rate (ADR). AIMS: To evaluate whether HBB administration increases the adenoma detection rate and influences patients' tolerance. METHODS: Consecutive colonoscopy outpatients were randomized after cecal intubation to receive either 20mg HBB or placebo i.v. The number, size, histology and location of polyps were recorded. The air retained in the abdomen was either indirectly estimated by ΔAC (difference in the abdominal circumference measured before and after colonoscopy) or directly evaluated by patients' perception (visual analogic scale, range 0-100). RESULTS: 402 patients (44% male; mean age 57.7±12.5years) received either HBB or placebo. No differences in ADR (31.7% vs. 28%, p=0.48), advanced-ADR (7.4% vs. 10.5%, p=0.35) were observed between HBB and placebo group, respectively. A significantly lower detection rate of flat/depressed lesions was observed in the HBB group (0.5% vs. 5.5%, p=0.003). The ΔAC and the bloating perception were comparable between the two groups (p=0.22 and p=0.48, respectively). CONCLUSIONS: HBB administered before colonoscope withdrawal does not increase adenoma detection rate and seems to hamper the visualization of flat/depressed lesions. This finding raises concerns on the indiscriminate use of HBB during colonoscopy.

Water-aided colonoscopy: a systematic review.

BACKGROUND: Water-aided methods for colonoscopy are distinguished by the timing of removal of infused water, predominantly during withdrawal (water immersion) or during insertion (water exchange). OBJECTIVE: To discuss the impact of these approaches on colonoscopy pain and adenoma detection rate (ADR). DESIGN: Systematic review. SETTING: Randomized, controlled trial (RCT) that compared water-aided methods and air insufflation during colonoscope insertion. PATIENTS: Patients undergoing colonoscopy. INTERVENTION: Medline, PubMed, and Google searches (January 2008-December 2011) and personal communications of manuscripts in press were considered to identify appropriate RCTs. MAIN OUTCOME MEASUREMENTS: Pain during colonoscopy and ADR. RCTs were grouped according to whether water immersion or water exchange was used. Reported pain scores and ADR were tabulated based on group assignment. RESULTS: Pain during colonoscopy is significantly reduced by both water immersion and water exchange compared with traditional air insufflation. The reduction in pain scores was qualitatively greater with water exchange as compared with water immersion. A mixed pattern of increases and decreases in ADR was observed with water immersion. A higher ADR, especially proximal to the splenic flexure, was obtained when water exchange was implemented. LIMITATIONS: Differences in the reports limit application of meta-analysis. The inability to blind the colonoscopists exposed the observations to uncertain bias. CONCLUSION: Compared with air insufflation, both water immersion and water exchange significantly reduce colonoscopy pain. Water exchange may be superior to water immersion in minimizing colonoscopy discomfort and in increasing ADR. A head-to-head comparison of these 3 approaches is required.

Errors and near misses in digestive endoscopy units.

BACKGROUND: Not much is known about errors and near misses in digestive endoscopy. AIMS: To verify whether an incident report, with certain facilitating features, gives useful information about unintended events, only excluding errors in medical diagnosis. METHOD: Nine endoscopy units took part in this cross sectional, prospective, multicentre study which lasted for two weeks. Members of the staff were required to report any unintended, potentially dangerous event observed during the daily work. A form was provided with a list of "reminders" and facilitators were appointed to help. The main outcome measurements were type of event, causes, corrective interventions, stage of occurrence in the workflow and qualification of the reporters. RESULTS: A total of 232 errors were reported (two were not related to endoscopy). The remaining 230 amount to 10.3% of 2239 procedures; 66 (29%) were considered errors with consequences, 164 (71%) "near misses". There were 150 pre-operative errors (65%), 22 operative (10%) and 58 post-operative (25%). Corrective interventions were provided for 60 cases of errors and 119 near misses. Most of the events were reported by the nurses (106 out of 232, 46%). CONCLUSIONS: Short-term incident reporting focusing on near misses, using forms with lists of "reminders", and the help of a facilitator, can give useful information on errors and near misses in digestive endoscopy.

Unsedated colonoscopy: A neverending story.

Although sedation and analgesia for patients undergoing colonoscopy is the standard practice in Western countries, unsedated colonoscopy is still routinely provided in Europe and the Far East. This variation in sedation practice relies on the different cultural attitudes of both patients and endoscopists across these countries. Data from the literature consistently report that, in unsedated patients, the use of alternative techniques, such as warm water irrigation or carbon dioxide insufflation, can allow a high quality and well tolerated examination.

Unsedated colonoscopy: an option for some but not for all.

BACKGROUND: The increasing request for colonoscopy in clinical practice, coupled with the lack of time, has led to a renewed interest in unsedated procedures. OBJECTIVE: To evaluate the acceptability of unsedated colonoscopy and to characterize the subset of patients more likely to undergo and complete the procedure without sedation and/or analgesia. DESIGN: Prospective, population study. SETTING: Nonacademic community hospital, 6-month observation period. PATIENTS: Adult outpatients referred for colonoscopy were offered unsedated procedure, with the possibility of on-demand sedation. INTERVENTIONS: Demographics, clinical features, and endoscopy outcomes were recorded. Data were analyzed by stepwise logistic regression analysis, and odds ratio (OR) and 95% confidence interval (CI) are given for significant variables. MAIN OUTCOME MEASUREMENTS: Unsedated colonoscopy acceptance rate. Factors significantly associated with acceptance and completion of unsedated procedures. RESULTS: The acceptance rate for unsedated colonoscopy was 56.2% of 964 consecutive evaluated patients. The cecal intubation rate in unsedated patients was 81.6% and increased to 97.3% with the option of on-demand sedation. At multivariate analysis, factors significantly associated with the acceptance were no previous colonoscopy (OR 1.52; 95% CI, 1.10-2.11), absent/low level of anxiety (OR 3.82; 95% CI, 2.71-5.38), and no concern about the examination (OR 1.80; 95% CI, 1.17-2.77). Fear of procedure-related pain was inversely associated with acceptance (OR 0.28; 95% CI, 0.17-0.35). Factors associated to drug-free colonoscopy completion were absence of preprocedure anxiety (OR 1.87; 95% CI, 1.08-3.21) and male sex (OR 3.59; 95% CI, 2.13-6.05). LIMITATIONS: Single-center study. CONCLUSION: The acceptance rate of unsedated colonoscopy is clinically relevant, and the procedure can be completed without sedation in the majority of patients. Subject-related factors may help to identify patients willing to undergo and potentially complete unsedated procedures.

Anticoagulant or aspirin treatment does not affect the positive predictive value of an immunological fecal occult blood test in patients undergoing colorectal cancer screening: results from a nested in a cohort case-control study.

BACKGROUND AND AIM: The immunochemical fecal occult blood test (i-FOBT) is widely used as a recommended screening strategy for colorectal cancer (CRC). A growing number of patients potentially targeted by CRC screening programs are on oral anticoagulant or chronic low-dose aspirin therapy, mainly for primary or secondary cardiovascular prophylaxis. This study aims at evaluating whether the use of these medications may impact on the diagnostic performances of i-FOBT for CRC screening. METHODS: All i-FOBT-positive patients on anticoagulant or chronic low-dose aspirin therapy recorded in a regional mass screening program database were enrolled as cases. Control groups were derived from the same database and included drug-naive i-FOBT-positive patients, matched in a ratio of 1 : 2 for age (± 3 years of age), sex, date of colonoscopy, and practice site. Information about the use of medications was collected by cross-checking patients' interview before colonoscopy and data recorded in the provincial electronic registry of medical prescriptions. The positive predictive value of i-FOBT for significant neoplasia (high-risk adenoma and CRC) was calculated in the case and control groups. RESULTS: In a 2-year study period, 2376 patients were recorded in the regional database. Of these patients, 53 (2%) were on anticoagulation (control group of 106 patients) and 172 (6.6%) were on chronic low-dose aspirin treatment (control group of 344 patients). Significant neoplasia was detected in 15 (28.3%) patients on anticoagulants and in 37 (34.9%) corresponding controls (P=0.45). Significant neoplasia was detected in 50 (29.1%) patients on chronic low-dose aspirin and in 107 (31.1%) corresponding controls (P=0.64). CONCLUSION: The positive predictive value of i-FOBT for significant neoplasia is not affected by ongoing anticoagulant or chronic low-dose aspirin therapy. This finding suggests that there is no need to interrupt these treatments before i-FOBT for CRC screening.

Management of warfarin-associated coagulopathy in patients with acute gastrointestinal bleeding: a cross-sectional physician survey of current practice.

BACKGROUND: The management of vitamin K antagonists (VKAs) associated coagulopathy is a cornerstone of pre-endoscopic assessment of anticoagulated patients presenting with acute gastrointestinal bleeding. AIMS: To evaluate physician attitudes in the management of VKAs-associated coagulopathy in patients presenting with gastrointestinal bleeding and to assess their compliance to current practice guidelines. DESIGN: Cross sectional physician web-based survey amongst regional members of three Italian Gastroenterological Societies (AIGO, SIED, SIGE) practicing in academic medical centres or community hospitals. Physicians were asked to provide management preferences in four hypothetical case-scenarios describing patients with warfarin-associated coagulopathy presenting with gastrointestinal bleeding of varying severity. RESULTS: A total of 105 out of 238 (48%) members responded; mean age±SD: 46.3±9.8 years, 68% male. The adherence to practice guidelines for the reversal of warfarin-induced anticoagulation ranged from 24% to 86% and it was not dependent on age, years and type of specialisation, hospital setting and active performance of "on call" emergency endoscopy or not. CONCLUSIONS: There is a considerable variability amongst physicians in the management of gastrointestinal bleeding patients with VKAs-associated coagulopathy and a poor compliance to practice guidelines. These data indicate that better education is needed in this area.

Warm water infusion versus air insufflation for unsedated colonoscopy: a randomized, controlled trial.

BACKGROUND: Uncontrolled data suggest that warm water infusion (WWI) instead of air insufflation (AI) during the insertion phase of unsedated colonoscopy improves patient tolerance and satisfaction. OBJECTIVE: We tested the hypothesis that water could increase the proportion of patients able to complete unsedated colonoscopy and improve patient tolerance compared with the conventional procedure. DESIGN: Randomized, controlled trial. SETTING: Single center, community hospital. PATIENTS: Consecutive outpatients agreeing to start colonoscopy without premedication. METHODS: Patients were randomly assigned to either WWI or AI insertion phase of colonoscopy. Sedation and/or analgesia were administered on patient request if significant pain or discomfort occurred. MAIN OUTCOME MEASUREMENTS: Percentage of patients requiring sedation/analgesia. Pain and tolerance scores were assessed at discharge by using a 100-mm visual analog scale. RESULTS: A total of 230 subjects (116 in the WWI group and 114 in the AI group) were enrolled. Intention-to-treat analysis showed that the proportion of patients requesting sedation/analgesia during the procedure (main outcome measurement) was 12.9% in the WWI group and 21.9% in AI group (P = .07). Cecal intubation rates were 94% in the WWI group and 95.6% in the AI group (P = .57). Median (interquartile range) scores for pain were 28 (12-44) and 39 (14-54) in WWI and AI groups, respectively (P = .05); corresponding figures for tolerance were 10 (3-18) and 14 (5-42), respectively (P = .01). The adenoma detection rates were 25% and 40.1% for the WWI and AI groups, respectively (P = .013). LIMITATIONS: Single-center study, endoscopists not blinded to randomization. CONCLUSIONS: WWI instead of AI is not associated with a statistically significant decrease in the number of patients requiring on-demand sedation, although it significantly improves the overall patient tolerance of colonoscopy. The finding of a lower adenoma detection rate in the WWI group calls for further evaluations. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00905554).

Half doses of PEG-ES and senna vs. high-dose senna for bowel cleansing before colonoscopy: a randomized, investigator-blinded trial.

OBJECTIVES: Patients' compliance with and tolerance of large-volume polyethylene glycol electrolyte solution (PEG-ES) have prompted continuous investigation with alternative forms of cleansing. High-dose senna is superior to PEG-ES for the quality of bowel cleansing, patient compliance, and tolerance, but its acceptance may be influenced by the incidence of abdominal pain. We hypothesized that a combination of half doses of PEG-ES and senna could minimize the incidence of abdominal pain without affecting the quality of bowel preparation. METHODS: This randomized, investigator-blinded trial has been conducted on consecutive outpatients scheduled for elective colonoscopy at a single community-based hospital. Patients were randomly assigned to receive either 12 tablets of 12 mg senna and 2 l of PEG-ES (half-dose group, HDG) or 24 tablets of senna divided in two doses (senna group, SG) the day before colonoscopy. The main outcome measures were the quality of colon cleansing (Aronchick scoring scale) and the incidence of preparation-related abdominal pain. Secondary outcome measures were patients' compliance with the cleansing regimen, overall tolerability, prevalence of predefined side effects, and quality of right colon cleansing. RESULTS: A total of 296 patients were enrolled (HDG=151 and SG=145). Overall cleansing was excellent to good in 90.1 and 88.3% patients in HDG and SG, respectively (P=0.62). Preparation-related moderate-to-severe abdominal pain was reported by 6% patients in HDG and 15.2% in SG (P=0.009). No significant differences were observed for secondary outcomes. CONCLUSIONS: The regimen combining half doses of PEG-ES and senna provides high-quality bowel preparation and acceptable patient tolerance, with less abdominal pain compared with high-dose senna.

Constipation in the elderly: management strategies.

Constipation is a highly prevalent and bothersome disorder that negatively affects patients' social and professional lives and places a great economic burden on both patients and national health services. An accurate determination of the prevalence of constipation is difficult because of the various definitions used, but many epidemiological studies have shown that it affects up to 20% of the population at any one time. Although constipation is not a physiological consequence of normal aging, decreased mobility and other co-morbid medical conditions may contribute to its prevalence in older adults. Functional constipation is diagnosed when no secondary causes can be identified. Patients have some unusual beliefs about their bowel habits. Systematic attention to history, examination and investigation, especially in older people, can be highly effective in resolving problems and in enhancing quality of life. There is a considerable range of treatment modalities available for patients with constipation, but the clinical evidence supporting their use varies widely. However, if constipation is not managed proactively, patients can experience negative consequences, such as anorexia, nausea, bowel impaction or bowel perforation. The clinical benefits of various traditional pharmacological and non-pharmacological agents remain unclear. The first steps in the treatment of simple constipation include increasing intake of dietary fibre and the use of a fibre supplement. Patients with severe constipation or those unable to comply with the recommended intake of fibre may benefit from the addition of laxatives. More recently, newer agents (e.g. tegaserod and lubiprostone), have been approved for the treatment of patients with chronic constipation. Additional work is needed to determine what role, if any, these agents may play in the treatment of patients with chronic constipation. The purpose of this review is to identify evidence-based interventions for the prevention and management of constipation in the elderly.

The impact of narrow band imaging in screening colonoscopy: a randomized controlled trial.

BACKGROUND & AIMS: Narrow band imaging (NBI) is an imaging technique that allows a better definition of capillary pattern and improves the contrast between adenomas and the surrounding mucosa. Conflicting data exist on the ability of NBI to improve detection of colonic neoplasm; the impact of NBI is being tested in several screening scenarios. We evaluated whether the routine use of NBI, compared with white light (WL), during the withdrawal phase of screening colonoscopy improved adenoma detection. METHODS: This randomized controlled study included consecutive 50- to 69-year-old patients with positive immunologic fecal occult blood tests. They were randomly assigned to groups that were examined with WL (n = 108) or NBI (n = 103) during the withdrawal phase of their colonoscopies. The primary end point was the adenoma detection rate. The prevalence of non-polypoid and the total number of adenomas were also evaluated. RESULTS: The number of total and mean per-patient adenomas were 201 (1.95 +/- 2.3) and 198 (1.83 +/- 2.1) in the NBI and WL groups, respectively (P = .69). The adenoma detection rates were 57.3% for patients examined by NBI and 58.3% for those examined by WL (P = .88). A total of 41 non-polypoid adenomas were identified (26 in the NBI and 15 in the WL groups, P = .16). The flat adenoma detection rates were 21.4% and 9.3% in the NBI and WL groups, respectively (P = .019). CONCLUSIONS: The routine use of NBI in screening colonoscopy did not increase the adenoma detection rate. NBI seems to improve the detection of flat adenomas, although additional studies are necessary.

High-dose senna compared with conventional PEG-ES lavage as bowel preparation for elective colonoscopy: a prospective, randomized, investigator-blinded trial.

OBJECTIVE: To compare the efficacy and patient acceptance of an oral high dose of senna to conventional polyethylene glycol-electrolyte lavage solution (PEG-ES) in adults undergoing elective colonoscopy. METHODS: Consecutive outpatients referred for elective colonoscopy were prospectively randomly assigned to receive, the day before the procedure, either 24 tablets of 12 mg senna, divided into two doses at 1 p.m. and 9 p.m. (senna group, n=191), or standard 4-L PEG-ES (PEG-ES group, n=92). The overall quality of colon cleansing (primary outcome measure) and cleansing in the right colon were evaluated using the Aronchick scoring scale (1=excellent to 4=inadequate) by the investigator/endoscopist who was blinded to the treatment assignment. Patient acceptance and the safety of the preparation were assessed by a nurse, using a structured questionnaire covering compliance with the dosing, overall tolerance of the preparation (1=none or mild discomfort to 4=severely distressing), and adverse events. RESULTS: The quality of colon cleansing, overall tolerance of the preparation, and compliance were significantly better with senna; overall cleansing was excellent or good in 90.6% of patients in the senna group and in 79.7% in the PEG-ES group (p= 0.003). The percentage of procedures rescheduled because of insufficient colon cleansing was 7.3% in the PEG-ES group and 2.6% in the senna group (p=0.035). Multivariate logistic regression modeling showed the PEG-ES preparation as negative independent predictor of unsuccessful bowel cleansing. The incidence of adverse reactions was similar in the two groups; patients who received senna experienced significantly less nausea and vomiting, but more abdominal pain. CONCLUSIONS: An oral high dose of senna is a valid alternative to standard PEG-ES for outpatient colonoscopy preparation.

Prophylaxis of ERCP-related pancreatitis: a randomized, controlled trial of somatostatin and gabexate mesylate.

BACKGROUND & AIMS: It still is debated whether post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented by administering either somatostatin or gabexate mesylate. The aim of the study is to assess the efficacy of a 6.5-hour infusion of somatostatin or gabexate mesylate in preventing ERCP-related complications. METHODS: In a double-blind multicenter trial, 1127 patients undergoing ERCP were randomly assigned to intravenous administration of somatostatin (750 microg; n = 351), gabexate mesylate (500 mg; n = 381), or placebo (saline; n = 395). The drug infusion started 30 minutes before and continued for 6 hours after endoscopy. Patients were evaluated clinically, and serum amylase levels were determined at 4, 24, and 48 hours after endoscopy. RESULTS: No significant differences in incidences of pancreatitis, hyperamylasemia, or abdominal pain were observed among the placebo (4.8%, 32.6%, and 5.3%, respectively), somatostatin (6.3%, 26.8%, and 5.1%, respectively), and gabexate mesylate groups (5.8%, 31.5%, and 6.3%, respectively). Univariate analysis of patient characteristics and endoscopic maneuvers showed that a Freeman score >1 (P < 0.0001), >/=3 pancreatic injections (P < 0.00001), and precut sphincterotomy (P = 0.01) were significantly associated with post-ERCP pancreatitis. At multiple logistic regression analysis, >/=3 pancreatic injections (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.45-2.63) and a Freeman score >1 (OR, 1.47; 95% CI, 1.11-1.94) retained their predictive power. CONCLUSIONS: Long-term (6.5-hr) administration of either somatostatin or gabexate mesylate is ineffective for the prevention of post-ERCP pancreatitis. Pancreatic injury seems to be related to difficulty in common bile duct access.