Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Superselective arterial embolisation with a liquid polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage.

OBJECTIVES: To evaluate the results of emergency embolisation in acute arterial bleeding of the gastrointestinal tract with a liquid polyvinyl alcohol copolymer from two centres. METHODS: We retrospectively analysed 16 cases (15 patients) of acute arterial bleeding of the gastrointestinal tract where emergency embolotherapy was performed by using the copolymer when acute haemorrhage was not treatable with endoscopic techniques alone. Cause of haemorrhage and technical and clinical success were documented. RESULTS: Arterial embolotherapy was successful in all 16 cases. The technical success rate was 100%. The cause of bleeding was pancreatitis in four, graft-versus-host disease (GVHD) of the colon in three, malignancy in three, angiodysplasia in two, ulcer in two and panarteritis nodosa and trauma in one each. There were no procedure-related complications. No bowel necrosis occurred because of embolisation. In 13 cases, the patients were discharged in good condition (81%); the three patients with GVHD died because of the underlying disease. CONCLUSIONS: The copolymer seems to have great potential in embolotherapy of acute arterial gastrointestinal bleeding. In our series none of the patients had rebleeding at the site of embolisation and no clinically obvious bowel necrosis occurred.

Persistent diarrhea.

A 63-year-old man presented with massive diarrhea and weight loss. This was preceded by nonspecific symptoms for three years, which resembled sarcoidosis. By duodenal biopsy, the diagnosis of Whipples disease was confirmed. Antibiotic treatment resulted in rapid and complete disappearance of signs and symptoms.

Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis.

OBJECTIVE: The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes. MATERIAL AND METHODS: A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis. RESULTS: CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas. CONCLUSIONS: Patients homozygous for the 1007fs mutation had an early disease onset with long-segment ileal stenoses and entero-enteral fistulas. They frequently needed surgical intervention and had a high risk of re-stenosis. Genotyping therefore appears to be an important diagnostic tool in identifying severely affected patients requiring individualized treatment strategies at an early stage of the disease.

Increased prevalence of colorectal adenomas in women with breast cancer.

BACKGROUND: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. DESIGN: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. RESULTS: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p=0.047, OR 1.7, 95% CI 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p=0.004, OR 3.8, 95% CI 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p=0.053, OR 0.16, 95% CI 0.0-1.1). CONCLUSIONS: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years.

Role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease.

AIM: To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD). METHODS: We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs, the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63), or as indeterminate status (n = 10). RESULTS: No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD examined. CONCLUSION: There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.

Infliximab for acute, not steroid-refractory ulcerative colitis: a randomized pilot study.

OBJECTIVE: Therapeutic alternatives for patients with acute ulcerative colitis in whom steroids would usually be contraindicated are rare. The antibody to tumor necrosis factor alpha, infliximab, has shown to be effective in the treatment of steroid-refractory ulcerative colitis in pilot studies. We therefore evaluated whether infliximab can achieve remission in patients with acute ulcerative pancolitis who were not steroid-refractory. METHODS AND DESIGN: Patients were eligible if they had acute disease with a modified Truelove and Witts activity score of more than 10 for at least 2 weeks and if they were currently not receiving immunomodulators or more than 10 mg/day prednisolone. Patients were randomly assigned to receive either three intravenous infusions of infliximab at 5 mg/kg (group A) or high-dose prednisolone (1.5 mg/kg body weight) daily for 2 weeks, followed by 1 mg/kg for 1 week, followed by a weekly reduction of 5 mg (group B). Therapy success was defined as clinical response in terms of a decrease of more than 5 points from the baseline score and to less than 10 points total after 3 weeks as well as after 13 weeks. RESULTS: Thirteen patients (seven women, six men) were randomized (six for group A and seven for group B). The median baseline activity scores were 13.5 (12-18) in group A and 14.0 (11-18) in group B. Five of six patients in group A and six of seven patients in group B showed therapy success after 3 weeks as well as after 13 weeks. CONCLUSIONS: Infliximab could be effective in the treatment of acute moderate or severe ulcerative colitis. The obtained data call for larger controlled trials.

Sensitivity of a novel stool antigen test for detection of Helicobacter pylori in adult outpatients before and after eradication therapy.

We investigated whether a novel monoclonal stool antigen test for detection of Helicobacter pylori performs with the same accuracy as the (13)C-urea breath test (UBT) for adult outpatients in the setting of a private office. The two tests showed identical levels of sensitivity when used to identify H. pylori-infected patients before and after eradication therapy.

Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A randomized, placebo-controlled study.

BACKGROUND: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. METHODS: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. RESULTS: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 micromol/l, 0.9-1.8) than in group B (0.7 micromol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. CONCLUSIONS: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation.

Low sensitivity of the ki-ras polymerase chain reaction for diagnosing pancreatic cancer from pancreatic juice and bile: a multicenter prospective trial.

PURPOSE: Early detection of pancreatic cancer using molecular markers may improve outcome. Mutations of the ki-ras oncogene are detected in 70% to 90% of pancreatic adenocarcinomas. A prospective, partially blinded, multicenter diagnostic trial was performed to test the sensitivity and specificity of the ki-ras polymerase chain reaction (PCR) analysis of pancreatic juice and bile specimens. PATIENTS AND METHODS: Specimens of pancreatic juice and bile were collected from 532 consecutive patients. Mutations in codon 12 of the ki-ras gene were identified by two independent enrichment PCRs and confirmed by direct sequencing. RESULTS: One hundred seventy-four of 532 patients were excluded from the final analysis (reasons: no amplifiable DNA, no specimen or only duodenal juice sent, lost to follow-up). Sixty-three of 358 patients had ductal pancreatic cancer. In 24 (38.1%) of 63 patients, a mutated ki-ras gene was identified in pancreatic juice and/or bile. Ki-ras mutations were found in four (8%) of 50 cases of chronic pancreatitis, in 10 (18.7%) of 53 cases of other malignancies of the pancreaticobiliary tree, and in 14 (7.3%) of 192 cases of benign diseases or normal findings. Sensitivity and specificity of the ki-ras PCR analysis for the detection of pancreatic cancer was 38.1% and 90.5%, respectively. CONCLUSION: In this prospective trial performed in nonselected patients, mutations of the ki-ras gene were detected in 38.1% of cases with pancreatic cancer. This test in its present form is not appropriate to confirm or screen for pancreatic cancer. More sensitive and/or quantitative PCR tests may improve the molecular diagnosis of pancreatic cancer.

Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease.

OBJECTIVES: Fistulas occur in about one third of patients with Crohn's disease and rarely heal spontaneously. Conventional medical and surgical therapy often fails. The anti-TNF-alpha antibody infliximab offers a novel therapeutic option. By this approach, closure of fistulas was reported in 45% of cases. However, after discontinuation of therapy, most fistulas recurred. Azathioprine and 6-mercaptopurine (6-MP) are effective drugs in Crohn's disease and lead to closure of fistulas in 30-40% of cases. Thus, the aim of this study was to evaluate the combination of infliximab with 6-mercaptopurine/azathioprine as therapy for fistulas in patients with Crohn's disease. METHODS: A total of 16 patients (mean age 37 yr) with Crohn's fistulas resistant to conventional measures were treated with a combination of three or four infusions of infliximab and long term 6-MP/azathioprine. In all, 13 patients had perianal fistulas, two had abdominal fistulas, and one patient had both perianal and recto-vaginal fistulas. Therapy success was defined as complete closure of fistulas for a minimum observation period of 6 months after fistula closure. RESULTS: In 12 (75%) of the 16 patients, we observed complete closure of the fistulas that persisted for >6 months (median follow-up 10 months, range 6-11 months). The median time to complete closure of fistulas was 14 days (range 2-36 days). In four patients, therapy success was not achieved. CONCLUSION: Our pilot study reveals that concomitant and long term 6-MP/azathioprine therapy could prolong the effect of an initial infliximab therapy on fistula closure in patients with Crohn's disease. These data prompt larger controlled trials.

The presence of immunoglobulins in the gastric juice of patients infected with Helicobacter pylori is related to a reduced secretion of acid.

BACKGROUND: It has been reported that treatment with proton pump inhibitors (PPI) leads to partial elimination and suppression of Helicobacter pylori. In theory, since acid is known to denature immunoglobulins, this antibacterial activity of PPI may be due to a reduction in the acid output favouring humoral immunity. MATERIALS AND METHODS: We analysed prospectively fasting gastric juice in 54 consecutive patients attending upper endoscopy for pH and levels of IgG, IgA and IgM. In addition, two antral and two corpus biopsies were obtained and histologically examined for the presence of H. pylori. RESULTS: 41/54 patients were infected with H. pylori. Immunoglobulines in the gastric juice of these patients were found in 25/41 (IgG), 27/41 (IgA), and 29/41 (IgM) patients. There was a highly significant difference in the gastric pH when H. pylori infected patients with measurable IgG, IgA, or IgM were compared with those in whom no immunoglobulines were found (median pH: 6 vs. 2 in each group; p <.001) CONCLUSIONS: There is a close correlation between a high gastric pH and the presence of IgG, IgA, and IgM antibodies. Hence, it may be speculated that the efficacy of humoral immunity following H. pylori infection depends on a high pH such as resulting from PPI treatment.

Patient controlled analgesia for extracorporeal shock wave lithotripsy of gallstones.

Sixty patients undergoing shock wave lithotripsy of gallbladder stones (ESWL) were randomly assigned to receive alfentanil either by infusion controlled by the attending anesthesiologist (standard treatment group, n = 31) or by analgesia controlled by the patient (PCA group, n = 29). Patients using PCA were allowed to self-administer 0.25 mg of alfentanil i.v. every minute as required. Data collected during treatment included the total dose of drug required, transcutaneous pCO2 values, verbal pain and sedation scores, visual analogue scale (VAS) patient satisfaction scores, and the incidence of nausea or vomiting. PCA patients used less alfentanil than the standard treatment group (PCA group: 12.8 micrograms/kg; standard treatment group: 44.3 micrograms/kg; mean values, P = 0.0001), tolerated significantly higher pain intensities and self-administered the narcotic only to moderate levels of pain but not to pronounced analgesia. Standard treatment patients reported lower levels of pain, were more sedated (P less than 0.05) and showed significantly higher transcutaneous pCO2 values. There was a trend towards a lower incidence of nausea or vomiting in PCA patients without reaching statistical significance. No significant difference with regard to patient satisfaction with pain relief could be demonstrated. Self-administered alfentanil during ESWL of gallbladder stones provided adequate analgesia with minimal side effects and high patient satisfaction. ESWL may represent a new and useful indication for PCA.