Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

The Efficacy of an Over-the-Counter Multivitamin and Mineral Supplement to Prevent Infections in Patients With Inflammatory Bowel Disease in Remission With Immunomodulators and/or Biological Agents: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biologic therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections. To evaluate the efficacy of a multivitamin and mineral supplement on the incidence of infections in patients with IBD treated with immunomodulators, biologic therapy, or combination therapy. METHODS: This was a single-center, randomized, double-blind, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (supplemented group) vs identical-in-appearance placebo (placebo group) in a total of 320 non-vitamin-deficient patients with IBD (Crohn's disease or ulcerative colitis) in remission with immunomodulators, biologic therapy, or combination therapy. Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24-week period of follow-up. RESULTS: Treatment arms consisted of 162 and 158 patients for the supplement and placebo, respectively. In both treatment groups, 107 patients reported an infection during the 24-week follow-up period (unadjusted odds ratio, 0.93; 95% confidence interval, 0.56-1.48). In the supplemented group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (unadjusted odds ratio, 1.61; 95% confidence interval, 0.88-2.93). CONCLUSIONS: An over-the-counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators, biologic therapy, or combination therapy.

Patients with inflammatory bowel disease are at increased risk of infections due to vitamin or mineral deficiencies. An over-the-counter supplement did not reduce the risk of infection for patients with inflammatory bowel disease in remission with immunomodulators and/or biologic therapy.

Microbiota diversity and bacterial load after successful treatment of Clostridioides difficile infection with honey lavage in 4 patients.

In this letter, an experimental therapy in four patients with therapy-resistant Clostridioides difficile infection is described. These four patients were treated with Manuka honey via colon lavage. First, the patients received a three-day fidaxomicin treatment. The colon lavage was performed on the third day. During a subsequent ileocolonoscopy, 300 mL 15% Manuka honey was applied via a spray catheter. Patients remained in bed for two hours after the procedure and did not defecate. The patient's microbiomes were tested before treatment, after the fidaxomicin treatment, and after honey lavage. A decrease in C. difficile load was found in their microbiomes. Additionally, restoration of microbiota diversity after the honey lavage was also noted. The four patients experienced complete cessation of watery stools and remain symptom free. These results indicate the need for more clinical research into this matter.

Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC): a multicentre randomised controlled trial.

BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133. FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis. FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

The diagnostic work-up and outcomes of 'presumed' idiopathic acute pancreatitis: A post-hoc analysis of a multicentre observational cohort.

INTRODUCTION: After standard diagnostic work-up, the aetiology of acute pancreatitis remains unknown in 16-27% of cases, a condition referred to as idiopathic acute pancreatitis (IAP). Determining the aetiology of pancreatitis is essential, as it may direct treatment in the acute phase and guides interventions to prevent recurrent pancreatitis. METHODS: Between 2008 and 2015, patients with acute pancreatitis were registered prospectively in 19 Dutch hospitals. Patients who had a negative initial diagnostic work-up with regard to the underlying aetiology of their pancreatitis were labelled 'presumed' IAP. The aim of this study was to assess the use of diagnostic modalities and their yield to establish an aetiology in 'presumed' IAP, and to assess recurrence rates both with and without treatment. RESULTS: Out of the 1632 registered patients, 191 patients had a first episode of 'presumed' IAP, of whom 176 (92%) underwent additional diagnostic testing: CT (n = 124, diagnostic yield 8%), EUS (n = 62, yield 35%), MRI/MRCP (n = 56, yield 33%), repeat ultrasound (n = 97, yield 21%), IgG4 (n = 54, yield 9%) and ERCP (n = 15, yield 47%). In 64 of 176 patients (36%) an aetiological diagnosis was established, mostly biliary (n = 39). In 13 out of 176 of patients (7%) a neoplasm was diagnosed. If additional diagnostic workup revealed an aetiology, the recurrence rate was lower in the treated patients than in the patients without a definite aetiology (15% versus 43%, p = 0.014). CONCLUSION: Additional diagnostic testing revealed an aetiology in one-third of 'presumed' IAP patients. The aetiology found was mostly biliary, but occasionally neoplasms were found. Identification of an aetiology with subsequent treatment reduced the rate of recurrence.

Development of esophageal squamous cell cancer in patients with FAMMM syndrome: Two clinical reports.

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary syndrome characterized by multiple dysplastic nevi and melanoma. Patients with FAMMM may have a heterozygous, inactivating, pathogenic germline variant in the CDKN2A gene, especially the NM_000077.4: c.225_243del19 (p.p75fs) variant, also known as p16-Leiden variant. Patients with this variant are at high risk for developing melanomas and pancreatic cancer due to somatic inactivation of the wild-type CDKN2A allele. The combination of an inactivating germline CDKN2A mutation and somatic inactivation of the wild-type CDKN2A allele in the same cell results in tumor formation. It has been suggested that carriers of a germline CDKN2A mutation are also at increased risk for several other cancer types, including esophageal cancer. Here, we describe two unrelated patients with the p16-Leiden variant who developed esophageal squamous cell cancer. Evidence of loss of the wild-type CDKN2A allele was obtained in the tumor tissue of both patients indicating biallelic inactivation of p16 in the tumor cells. These results suggest that these patients developed esophageal squamous cell cancer in the context of FAMMM syndrome.

Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial.

BACKGROUND: Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium. METHODS: This was a randomised, controlled, single-centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819. FINDINGS: Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1·24, 95% CI 0·92-1·68, p=0·16). No adverse events were noted in patients or staff. INTERPRETATION: DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy. FUNDING: None.

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

BACKGROUND: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. METHODS/DESIGN: The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. DISCUSSION: The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

Low fecal calprotectin predicts sustained clinical remission in inflammatory bowel disease patients: a plea for deep remission.

BACKGROUND AND AIMS: Mucosal healing has become the treatment goal in patients with ulcerative colitis (UC) and Crohn's disease (CD). Whether low fecal calprotectin levels and histological healing combined with mucosal healing is associated with a further reduced risk of relapses is unknown. METHODS: Patients with CD, UC or inflammatory bowel disease-unclassified (IBD-U) scheduled for surveillance colonoscopy collected a stool sample prior to bowel cleansing. Only patients with mucosal healing (MAYO endoscopic score of 0) were included. Fecal calprotectin was measured using a quantitative enzyme-linked immunosorbent assay (R-Biopharm, Germany). Biopsies were obtained from four colonic segments, and histological disease severity was assessed using the Geboes scoring system. Patients were followed until the last outpatient clinic visit or the development of a relapse, which was defined as IBD-related hospitalization, surgery or step-up in IBD medication. RESULTS: Of the 164 patients undergoing surveillance colonoscopy, 92 patients were excluded due to active inflammation or missing biopsies. Of the remaining 72 patients (20 CD, 52 UC or IBD-U), six patients (8%) relapsed after a median follow-up of 11 months (range 5-15 months). Median fecal calprotectin levels at baseline were significantly higher for patients who relapsed compared with patients who maintained remission (284 mg/kg vs. 37 mg/kg. p < 0.01). Fecal calprotectin below 56 mg/kg was found to optimally predict absence of relapse during follow-up with 64% sensitivity, 100% specificity, 100% negative predictive value and 20% positive predictive value. The presence or absence of active inflammation determined by Geboes cut-off score of 3.1 was less strongly associated with the risk of relapse (64% sensitivity, 33% specificity, 9% negative predictive value and 92% positive predictive value. CONCLUSION: Low calprotectin levels identify IBD patients who remain in stable remission during follow-up.

Fecal calprotectin testing can identify ineffective colorectal cancer surveillance procedures in patients with longstanding colitis.

BACKGROUND: Active colitis impairs neoplasia detection during colonoscopic surveillance for colorectal cancer in patients with inflammatory bowel disease. We investigated whether fecal calprotectin testing before surveillance colonoscopy might identify ineffective surveillance procedures. METHODS: All consecutive patients with Crohn's disease or ulcerative colitis scheduled for surveillance colonoscopy were asked to collect a stool sample before the start of bowel cleansing. Ineffective surveillance was defined as at least 1 colonic segment with moderate or severe inflammation. Calprotectin was analyzed using an enzyme-linked immunosorbent assay (Ridascreen; R-Biopharm). Receiver operator characteristics statistics were used to determine the optimal cutoff for calprotectin. RESULTS: A total of 176 surveillance colonoscopies were performed in 164 patients, of which 83 had Crohn's disease and 81 had ulcerative colitis or inflammatory bowel disease-unclassified. Complete endoscopic remission or mild inflammation categorized as effective surveillance was observed in 151 colonoscopies (86%), whereas moderate or severe inflammation categorized as ineffective surveillance was observed in 25 colonoscopies (14%). Median calprotectin levels for the effective and ineffective surveillance group were 84 mg/kg (range, 20-4609) and 1605 mg/kg (range, 66-26,336), respectively (P < 0.01). A cutoff of 539 mg/kg identified patients with ineffective surveillance with 84% sensitivity, 89% specificity, 55% positive predictive value, 97% negative predictive value, and an area under the curve of 0.89. CONCLUSIONS: Low fecal calprotectin accurately identifies inflammatory bowel disease patients without colonic inflammation in whom colorectal cancer surveillance is most effective.

Fecal hemoglobin and calprotectin are equally effective in identifying patients with inflammatory bowel disease with active endoscopic inflammation.

BACKGROUND: Fecal calprotectin can be used as a noninvasive tool to assess inflammation in patients with inflammatory bowel disease (IBD). However, the diagnostic accuracy of calprotectin is modest, and therefore additional markers are needed. We compared the efficacy of fecal hemoglobin and calprotectin as markers for endoscopic inflammation in patients with IBD. METHODS: Consecutive patients with Crohn's disease or ulcerative colitis scheduled for surveillance colonoscopy collected a stool sample before bowel preparation. Experienced endoscopists assessed the presence of inflammation in each colonic segment. Fecal calprotectin and hemoglobin were analyzed with an enzyme-linked immunosorbent assay. Receiver operator characteristic statistics were used to determine cutoff values for calprotectin and hemoglobin. RESULTS: A total of 176 surveillance colonoscopies were performed in 164 patients, of which 83 patients had Crohn's disease, 74 had ulcerative colitis, and 7 IBD-unclassified. Median (interquartile range) calprotectin and hemoglobin concentrations were 137 mg/kg (interquartile range, 33-494) and 0.51 µg/g (interquartile range, 0.18-8.50), respectively. For calprotectin, a cutoff value of 140 mg/kg predicted endoscopic inflammation with 86% sensitivity, 72% specificity, 64% positive predictive value, 90% negative predictive value, and an area under the curve of 0.87. For hemoglobin, a cutoff value of 1.51 µg/g indicated endoscopic inflammation with 74% sensitivity, 84% specificity, 72% positive predictive value, 84% negative predictive value, and an area under the curve of 0.81. Combining both tests did not increase the predictive accuracy substantially compared with calprotectin or hemoglobin alone (area under the curve, 0.88). CONCLUSIONS: Fecal hemoglobin can identify patients with IBD with active inflammation with a predictive accuracy similar to calprotectin.

Antidepressants and gastrointestinal symptoms in the general Dutch adult population.

BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general adult population. METHODS: We assessed gastrointestinal symptoms, medication use, and comorbidity through structured questionnaires in randomly selected individuals. We compared presence of gastrointestinal symptoms in respondents who reported antidepressant use with those who did not. We used multivariable regression analysis to verify the association between antidepressant use and gastrointestinal symptoms. RESULTS: In total, 16,758 questionnaires were returned and eligible for analysis. Antidepressant use was reported by 701 respondents (4.2%). Gastrointestinal symptoms were more frequently reported by antidepressant users compared with nonusers (40% vs 25%, P < 0.01). This apparent association between antidepressant use and gastrointestinal symptoms did not remain after adjusting for demographic factors, comorbidity, and use of other medications (adjusted odds ratio, 0.94; 95% confidence interval, 0.74-1.18). CONCLUSIONS: In our cross-sectional population-based study, we did not find an association between antidepressant use and gastrointestinal symptoms.

Nurse-led follow-up at home vs. conventional medical outpatient clinic follow-up in patients with incurable upper gastrointestinal cancer: a randomized study.

CONTEXT: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic. OBJECTIVES: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer. METHODS: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months. RESULTS: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits. CONCLUSION: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits.

Symptoms associated with finding colorectal cancer during colonoscopy.

BACKGROUND: Patients with an increased risk of having colorectal cancer (CRC) should have priority on the colonoscopy list. OBJECTIVE: To investigate whether presenting symptoms of patients referred for colonoscopy could help in identifying patients with an increased risk of CRC. PATIENTS AND METHODS: Between February 2007 and November 2010, random outpatients referred for colonoscopy were asked to fill out a questionnaire with respect to symptoms for which the colonoscopy was performed. Informed consent was obtained to review the colonoscopy and histology reports. Multivariate logistic regression was performed to identify predictors for CRC. RESULTS: In total, 1458 (21%) patients returned the questionnaire, of whom 925 (63.4%) had undergone previous sigmoidoscopy or colonoscopy. CRC was detected in 41 patients (2.8%). Age over 50 years [adjusted odds ratio (aOR) 3.00; 95% confidence interval (CI) 1.30-6.91] and presenting symptoms of rectal blood loss (aOR 4.62; 95% CI 2.31-9.22) and a change in bowel habits (aOR 3.33; 95% CI 1.50-7.40) were associated independently with an increased risk of finding CRC. Previous sigmoidoscopy or colonoscopy (aOR 0.24; 95% CI 0.12-0.49) and fatigue as presenting symptoms (aOR 0.22; 95% CI 0.09-0.56) were associated with a decreased risk of CRC. Weight loss, self-reported anemia, and abdominal pain were not associated with CRC in this study. CONCLUSION: Patients presenting with rectal blood loss, change in bowel habits, and those older than 50 years of age have an increased risk of a finding of CRC during colonoscopy. We recommend that these risk groups should be prioritized on the colonoscopy list over patients who have undergone a previous endoscopy or who are presenting with fatigue.

Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands.

BACKGROUND: Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms. RESULTS: A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43-1.77), asthma/COPD (aOR 1.47, 95% CI 1.21-1.79), use of paracetamol (aOR 1.33, 95% CI 1.20-1.47), antidepressants (aOR 1.56, 95% CI 1.22-2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65-0.87), and use of statins (aOR 0.75, 95% CI 0.61-0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01). CONCLUSIONS: Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.

Dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of Legionnaires' disease.

STUDY OBJECTIVE: Absolute lymphocytopenia is recognised as an important hallmark of the immune response to severe infection and observed in patients with Legionnaires' disease. To explore the immune response, we studied the dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of LD. METHODS AND RESULTS: EDTA-anticoagulated blood was obtained from eight patients on the day the diagnosis was made through detection of L. pneumophila serogroup 1 antigen in urine. A second blood sample was obtained in the subacute phase. Multiparametric flow cytometry was used to calculate lymphocyte counts and values for B-cells, T-cells, NK cells, CD4+ and CD8+ T-cells. Expression of activation markers was analysed. The values obtained in the subacute phase were compared with an age and gender matched control group. Absolute lymphocyte count (×109/l, median and range) significantly increased from 0.8 (0.4-1.6) in the acute phase to 1.4 (0.8-3.4) in the subacute phase. B-cell count showed no significant change, while T-cell count (×106/l, median and range) significantly increased in the subacute phase (495 (182-1024) versus 979 (507-2708), p = 0.012) as a result of significant increases in both CD4+ and CD8+ T-cell counts (374 (146-629) versus 763 (400-1507), p = 0.012 and 119 (29-328) versus 224 (107-862), p = 0.012). In the subacute phase of LD, significant increases were observed in absolute counts of activated CD4+ T-cells, naïve CD4+ T-cells and memory CD4+ T-cells. In the CD8+ T-cell compartment, activated CD8+ T-cells, naïve CD8+ T-cell and memory CD8+ T-cells were significantly increased (p<0.05). CONCLUSION: The acute phase of LD is characterized by absolute lymphocytopenia, which recovers in the subacute phase with an increase in absolute T-cells and re-emergence of activated CD4+ and CD8+ T cells. These observations are in line with the suggested role for T-cell activation in the immune response to LD.

CT-colonography after incomplete colonoscopy: what is the diagnostic yield?

BACKGROUND: Computed tomography-colonography is a diagnostic modality that can be used when the colon is not completely intubated during colonoscopy. It may have the additional advantage that information on extracolonic lesions can be obtained. OBJECTIVE: The aim of this study was to investigate the yield of CT-colonography of relevant intra- and extracolonic findings in patients after incomplete colonoscopy. DESIGN: This was an observational, retrospective study. DATA SOURCES: Data were be obtained from standardized radiology and endoscopy reports and electronic medical records. STUDY SELECTION: In total, 136 consecutive CT-colonographies performed after incomplete colonoscopy were evaluated. MAIN OUTCOME MEASURES: All intra- and extracolonic findings on CT-colonography were recorded and interpreted for clinical relevance, and it was determined whether further diagnostic and/or therapeutic workup was indicated. RESULTS: Major indications for colonoscopy included iron-deficiency anemia (25.7%), hematochezia (20.6%), change in bowel habits (18.4%), and colorectal cancer screening or surveillance (11.0%). Major reasons for incomplete colonoscopy were a fixed colon (34.6%) and strong angulation of the sigmoid colon (17.6%). Introduction of the colonoscope was limited to the left-sided colon in 53.7% of cases. Incomplete colonoscopy detected colorectal cancer in 12 (8.8%) patients and adenomatous polyps in 27 (19.9%) patients. CT-colonography after incomplete colonoscopy additionally revealed 19 polyps in 15 (11.0%) and a nonsynchronous colorectal cancer in 4 (2.9%) patients. CT-colonography also detected extracolonic findings with clinical consequences in 8 (5.9%) patients, including fistulizing diverticulitis (n = 3), gastric tumor (n = 2), liver abscess (n = 1), osteomyelitis (n = 1), and an infected embolus in both renal arteries (n = 1). LIMITATIONS: This study was limited by the lack of confirmation of intraluminal CT-colonography findings in a subset of patients. CONCLUSIONS: Computed tomography-colonography can be of added value in patients with incomplete colonoscopy, because it revealed 27 relevant additional (both intra- and extracolonic) lesions in 19.1% of patients. In cases where CT-colonography detected colorectal cancer after incomplete colonoscopy, it can also be used for staging purposes.

Similar fecal immunochemical test results in screening and referral colorectal cancer.

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.