Adenoma detection with Endocuff colonoscopy versus conventional colonoscopy: a multicentre randomised controlled trial.

BACKGROUND AND AIMS: Colonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC). METHODS: We performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as well as symptomatic patients (>45 years). Consenting patients were randomised 1:1 to EAC or CC. All colonoscopies were performed by experienced colonoscopists (≥500 colonoscopies) who were trained in EAC. All colonoscopy quality indicators were prospectively recorded. FINDINGS: Of the 1063 included patients (52% male, median age 65 years), 530 were allocated to EAC and 533 to CC. More adenomas were detected with EAC, 722 vs 621, but the gain in MAP was not significant: on average 1.36 per patient in the EAC group versus 1.17 in the CC group (p=0.08). In a per-protocol analysis, the gain was 1.44 vs 1.19 (p=0.02), respectively. In the EAC group, 275 patients (52%) had one or more adenomas detected versus 278 in the CC group (52%; p=0.92). For advanced adenomas these numbers were 109 (21%) vs 117 (22%). The adjusted caecal intubation rate was lower with EAC (94% vs 99%; p<0.001), however when allowing crossover from EAC to CC, they were similar in both groups (98% vs 99%; p value=0.25). INTERPRETATION: Though more adenomas are detected with EAC, the routine use of Endocuff does not translate in a higher number of patients with one or more adenomas detected. Whether increased detection ultimately results in a lower rate of interval carcinomas is not yet known. TRIAL REGISTRATION NUMBER: http://www.trialregister.nl Dutch Trial Register: NTR3962.

Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life.

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines.

High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

Practice and yield of early CT scan in acute pancreatitis: a Dutch Observational Multicenter Study.

BACKGROUND: Early computed tomography (CT) (within 4 full days after symptom onset) may be performed to distinguish acute pancreatitis (AP) from other intra-abdominal conditions or to identify early pancreatic necrosis. We analyzed practice and yield of early CT in patients with an established clinical diagnosis of AP in a Dutch cohort (EARL study). METHODS: Multicenter observational study. Etiology, disease course, CT timing, Balthazar CT score, and clinical management were evaluated. RESULTS: First documented hospital admissions of 166 patients were analyzed. Etiology was biliary (42.8%), unknown (20.5%), alcoholic (18.1%), post-endoscopic retrograde cholangiopancreatography (11.4%), and miscellaneous (7.2%). In 89.2% (148/166), the disease course was mild. Out of 18 patients with severe AP, 11 eventually developed (peri)pancreatic necrosis. At least one CT (range 1-12) was performed in 47% (78/166) of all patients and in 62.8% (49/78) it was acquired within 4 full days after symptom onset. Practice, timing, and Balthazar CT score of early CTs were not significantly different between mild and severe AP. None of the early CTs showed necrosis and no alternative diagnoses were established. In 89.8% (44/49), clinical management was not altered after early CT. In 10.2% (5/49), prophylactic antibiotics were started, but in absence of necrosis. CONCLUSIONS: A CT scan was frequently acquired early in the course of AP, but its yield was low and had no implications with regard to clinical management. It seems prudent that clinicians should be more restrictive in the use of early CT, in particular in mild AP, to prevent unnecessary radiation exposure and to save costs.

Colonic work-up after incomplete colonoscopy: significant new findings during follow-up.

BACKGROUND AND STUDY AIMS: Cecal intubation is not achieved in 2 - 23 % of colonoscopies. The efforts made by physicians to visualize the remaining colon and the number of missed significant lesions are unknown. This study evaluates 1) the reasons for incomplete colonoscopy, 2) the rates of complete colonic evaluation after incomplete colonoscopy, and 3) the number of (pre-) malignant lesions missed by incomplete colonoscopy. PATIENTS AND METHODS: In this population-based cohort study index colonoscopies were performed between September and December 2005. Prospectively collected data from consecutive patients with an incomplete colonoscopy were analyzed. For up to 18 months after the index colonoscopy, any further examinations performed in these patients were identified retrospectively. These secondary examinations included: repeat colonoscopy, computed tomography (CT) colonography, barium enema, abdominal CT scan, and surgery involving the colorectum. RESULTS: Of 5278 colonoscopies, 511 were incomplete (9.7 %). The most frequent causes of incomplete colonoscopy were looping of the scope (20.4 %), patient discomfort (15.3 %), and obstructing tumor (13.9 %). Secondary examination was performed in 278 patients (54.4 %) after incomplete colonoscopy. Patients undergoing surveillance after colorectal cancer (CRC) (78.9 %) and those with anemia (73.1 %) most frequently received a secondary examination. Incomplete colonoscopies due to stenosis (78.9 %), severe inflammation (77.8 %) or an obstructing tumor (74.6 %) were most frequently followed by a secondary examination. In all of the follow-up examinations, CRC was diagnosed in 18 patients (3.5 %) and advanced adenoma in four patients (0.8 %). CONCLUSIONS: In 4.3 % of the patients, advanced neoplasia was missed by incomplete colonoscopy. Our data therefore suggest that additional imaging is obligatory to visualize the remaining colon adequately.

Repeated high oral doses of omeprazole do not affect intrinsic factor secretion: proof of a selective mode of action.

The effect of 60 mg oral omeprazole daily for 9 days on intrinsic factor and gastric acid secretion was studied in eight healthy volunteers. Gastric secretion studies were performed during saline and 0.1 M HCl perfusion before and after omeprazole administration. During dosing with omeprazole, basal gastric acid output diminished by 94%, and pentagastrin-stimulated acid output by 97%. Basal, peak and steady-state stimulated intrinsic factor output were unaffected by omeprazole. It is concluded that high oral doses of omeprazole suppress gastric acid secretion to very low levels but they do not affect intrinsic factor secretion. Intrinsic factor secretion was also unaffected by profound hypochlorhydria.

Distribution of mesalazine enemas in active and quiescent ulcerative colitis.

BACKGROUND: The efficacy of mesalazine enemas depends on intraluminal concentration of the drug and is therefore limited by the enema distribution in the colon. Active ulcerative colitis changes colon motility and this leads to uncertainty about enema spread. AIM: To assess the influence of disease activity on enema distribution, we conducted a physician-blinded, longitudinal study of the retrograde spread of three mesalazine enemas. METHODS: Thirty-one patients with mild to moderate ulcerative colitis were subdivided into three groups, and treated with 2 g mesalazine in 30 mL (group I, n = 10), 4 g mesalazine in 60 mL (group II, n = 12) or 1 g mesalazine in 100 mL (group III, n = 9). All patients received oral mesalazine 500 mg t.d.s. Enemas were labelled by adding 10 MBq (99mTc)technetium-sulphur colloid. Anterior scintigraphic images were taken at the start of the study and after 12 weeks of therapy; retrograde spread was assessed by calculating the percentage of the enema in each colonic segment. RESULTS: The activity score of ulcerative colitis diminished significantly after 12 weeks of treatment, but five patients dropped out of the study. At the start of treatment enema activity in group I was mainly concentrated in the sigmoid (99%); in group II activity was found in the rectum (9%), the sigmoid (61%) and the descending colon (15%); in group III activity was distributed between the sigmoid (66%) and descending colon (25%). The colonic distribution of mesalazine enemas was not influenced by disease activity. CONCLUSION: Volume, but not disease activity, is the important determinant of retrograde colonic spread of mesalazine enemas in ulcerative colitis.

The clinical relevance of lactose malabsorption in irritable bowel syndrome.

OBJECTIVE: The prevalence of lactose malabsorption (LM) in the Caucasian population of northern Europe is estimated to be low. Irritable bowel syndrome (IBS) is a very common diagnosis, and its symptoms are nearly identical to those of LM. Therefore we investigated the prevalence of LM among IBS patients in comparison with healthy volunteers. DESIGN: A double-blind clinical trial compared with healthy controls. SETTING: One out-patient gastroenterology clinic in the Netherlands. PATIENTS: 70 Caucasian IBS patients and 35 healthy volunteers (staff members). METHODS: All 105 underwent hydrogen (H2) breath and blood glucose tests, after an oral intake of 50 grams of lactose. The IBS patients were treated with a lactose-restricted diet for 6 weeks. They completed a lactose intake score before, and a symptom score scored by six separate criteria, before, during and after treatment. RESULTS: In 17 out of 70 (24.3%) IBS patients LM was detected, in comparison with 2 out of 35 (5.7%) controls (P < 0.009). There was no difference in the pre-entry mean lactose intake and symptom score between the LM positive and negative IBS patients. The mean symptom score of the LM positive group showed a marked decrease after 6 weeks of dietary therapy (P < 0.001). CONCLUSION: A substantial number of IBS patients showed a clinically unrecognized lactose malabsorption, which could not be discriminated by symptoms and dietary history, and which can be treated with a lactose-restricted diet. Therefore LM has to be excluded before the diagnosis IBS is made.

The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study.

DESIGN AND METHODS: Prospectively, the effect of a lactose-restricted diet was evaluated among irritable bowel syndrome patients with lactose malabsorption. Lactose malabsorption was defined by a positive hydrogen breath test and a positive blood-glucose test. An analysis of symptoms was completed before, during, 6 weeks after and 5 years after starting the diet. In addition, the number of visits made by the patients to the outpatient clinic was scored during 6 years. RESULTS: In 17 out of 70 irritable bowel syndrome patients (24.3%), lactose malabsorption was detected. There was no difference in the symptom score between patients with a positive lactose tolerance test and patients with a negative lactose tolerance test. After 6 weeks of the lactose-restricted diet, symptoms were markedly improved in lactose malabsorption-positive patients (P < 0.001). After 5 years, one patient was lost for follow-up, and 14 out of the remaining 16 lactose malabsorption patients (87.5%) still had no complaints during the lactose-restricted diet. Two patients chose not to follow the diet continuously and accepted the discomfort caused by lactose intake. Only two out of 16 patients (12.5%) no longer experienced any benefit from lactose restriction. In the 5 years before their diagnosis of lactose malabsorption, these 16 patients visited the outpatient clinic a total of 192 times (mean 2.4 visits per year per person; range 1-7 visits). In the 5 years after diagnosis, they visited the outpatient clinic a total of 45 times (mean 0.6 visits per year per person; range 0-6 visits; P < 0.0001). CONCLUSIONS: In a large majority of irritable bowel syndrome patients with lactose malabsorption, which was previously clinically unrecognized, a lactose-restricted diet improved symptoms markedly both in the short term and the long term. Furthermore, visits by all patients to the outpatient clinic were reduced by 75%. We conclude that diet therapy is extremely cost- and time-saving. Therefore, it is strongly recommended that lactose malabsorption, which is easily treatable, is excluded before diagnosing irritable bowel syndrome.

Percutaneous endoscopic gastrostomy: complications and suggestions to avoid them.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) tubes have become an excellent alternative for the long-term management of patients with proximal obstructions of the gastrointestinal tract. However, their use has limitations and can be associated with serious complications. We therefore studied the frequency and severity of complications related to the use of PEG tubes in our clinic. DESIGN: All adults (aged 18 years and above) in whom a PEG tube was placed between January 1 1994 and January 1 1999 at the Free University Hospital in Amsterdam were included in this study. In initial cases, the indication and procedure were individually judged according to a liberal protocol. However, after several major complications, a strict procedure protocol was implemented in September 1996. RESULTS: During the study period, 263 PEG tubes were placed in 254 patients with head and neck cancer (n = 183; 70%), neurological disorders (n = 52; 20%) or severe upper gastrointestinal motility disorders (n = 28; 11%). In period I, 167 PEG tubes were placed and in period II, 96 PEG tubes were inserted. Patients were followed for a median 111 days. Minor complications occurred in 13% of the patients. Major complications occurred in 8% of the patients. In period I, the percentage of major complications was higher than in period II (9.5% versus 6%). CONCLUSION: PEG tube placement is a safe procedure when performed according to strict guidelines. By doing so, PEG tubes allow optimal feeding for prolonged periods with the occasional need for replacement of the tube. PEG tubes should not be introduced in acutely ill patients, patients with a short life expectancy and preferably not to patients with severe coughing.

Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Dutch Pentasa Study Group.

OBJECTIVE: To investigate a possible dose-effect relationship with two dosages of oral slow-release mesalazine in patients with quiescent ulcerative colitis. METHOD: One hundred and sixty-nine patients with ulcerative colitis in remission were treated with either 1.5 or 3.0 g/day mesalazine for 1 year or until relapse into active colitis. RESULTS: Fewer of the 3.0 g dose group relapsed than of the 1.5 g dose group (33 compared with 46%). This difference failed to reach statistical significance (P = 0.057). A significant relationship between age and relapse rate was established. No dose-related adverse events were found. Three serious drug-related adverse events were, however, reported. All of the serious adverse reactions resolved after the medication was discontinued. CONCLUSION: There is a trend for high doses of oral mesalazine to be more effective in prevention of relapse of ulcerative colitis. These higher doses are not associated with a higher incidence of adverse reactions.

Pharmacology of pepsinogen secretion: influence of pentagastrin on pepsinogen secretion in man.

To investigate the effect of pentagastrin on serum and urinary pepsinogens and gastric pepsin, eight healthy male volunteers were studied twice during continuous intragastric perfusion with either NaCl 0.9% or 0.1 M HCl in random order. To the perfusate 3 mg/ml phenol red was added as inert recovery marker. Gastric content was aspirated in 15-minute samples, 4 basally and subsequently 6 during continuous i.v. infusion of pentagastrin 1.5 micrograms/kg/h. Furthermore, serum and urine samples were collected immediately before and after each test. Gastric pepsin output increased after pentagastrin. There were no differences in basal or stimulated pepsin output during saline or HCl perfusion despite marked differences in intra-gastric acidity and acid delivery to the duodenum. In addition, no significant changes in serum pepsinogen levels or urinary pepsinogen excretion were observed after pentagastrin infusion. It is concluded that pentagastrin stimulates gastric pepsin secretion directly, but does not stimulate the release of pepsinogens into the systemic circulation.

[Acute transit symptoms caused by spontaneous rupture of the esophagus]. / Acute passageklachten veroorzaakt door een spontane intramurale ruptuur van de oesofagus.

A 44-year-old woman was admitted to our hospital with acute severe chest pain and dysphagia, without an assignable cause. Radiological investigation of the oesophagus with water soluble contrast revealed an intramural rupture. Conservative management led to complete recovery within eight days. Spontaneous intramural rupture of the oesophagus is a very uncommon disease requiring adequate differentiation from other more serious diseases in order to apply correct therapy.

Nutritional management of patients with acute pancreatitis: a Dutch observational multicentre study.

BACKGROUND: Following a nil per os (NPO) regimen, most patients with acute pancreatitis (AP) can resume normal oral intake within 1 week. If not tolerated, it is recommended to initiate artificial feeding, preferably by the enteral route. AIM: To evaluate the nutritional management of patients with AP in a Dutch cohort (EARL study). METHODS: Observational study in 18 hospitals. Total days of NPO, tube feeding (TF) with/without oral feeding, total parenteral nutrition (TPN) and total starvation time were analysed. RESULTS: In mild AP, a majority of cases (80.7%, 117/145) were managed with an NPO regimen only. Twenty-seven patients (18.6%) with mild AP additionally received TF; one received TPN. Of those with severe AP, more than half of the patients (56.2%, nine of 16) were treated with TF besides an NPO regimen; four received TPN. TF was delivered preferably via the jejunal route. The median period of total starvation was 2 days for both mild and severe AP. Only 5.5% (nine of 164) of patients had a prolonged starvation time of more than 5 days. CONCLUSIONS: The total time of starvation was limited in a majority of patients admitted for AP. According to international guidelines, additional nutritional interventions were quickly undertaken with enteral feeding via the jejunum as the preferred route.

Lack of effect of antacids on plasma concentrations of omeprazole given as enteric-coated granules.

Twelve male volunteers were studied after a single oral dose of 20 mg omeprazole given as enteric-coated granules with and without concomitant administration of 10 ml of a potent liquid antacid (buffering capacity 56.6 mmol 10 ml-1) under fasting conditions. No statistically significant differences were detected in median Cmax (0.41 approximately equal to 0.53 mumol l-1), the geometric mean AUC (0.80 approximately equal to 0.81 mumol l-1 h) or median tmax (1.25 h), with and without antacid.

The effect of ethylurethane on hematocrit, blood pressure and plasma-glucose.

Intraperitoneal (i.p.) injection of 25% ethylurethane (i.e. 2.8 M) in a dose of 1 g/kg causes a rise in hematocrit (Hct) accompanied by an identical rise in erythrocyte count but by a fall in plasma protein. This effect is absent after intra-arterial (i.a.) and oral administration and much reduced after subcutaneous (s.c.) injection. The hemoconcentration is not caused by osmotic attraction of fluid but by leakage of blood plasma into the peritoneal cavity. The higly concentrated urethane solution causes superificial damage of intra-abdominal organs. Extensive local damage is also observed after s.c. and intramuscular injection of 25% urethane. The fall in blood pressure which is found after i.p. injection, but is absent after i.a. injection, can be explained by the loss of blood plasma. Plasma-glucose rises after i.p. injection but not after i.a. injection. This hyperglycemia may be initiated by stimuli arising in the damaged tissues.

Predictive value of inflammatory and coagulation parameters in the course of severe ulcerative colitis.

Alterations in markers of coagulation have been found in patients with inflammatory bowel disease. Our aim was to study the predictive value of coagulation and inflammatory parameters in the course of severe ulcerative colitis. Twenty-seven patients were included. The disease course was followed for one year. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratio, as well as the clinical predictive value of laboratory variables were calculated. Inflammatory variables, such as ESR, CRP, and leukocyte and platelet count showed poor diagnostic accuracy. Several coagulation parameters, such as fibrinogen and fibrin(ogen) degradation products, were increased in patients with active ulcerative colitis, whereas coagulation factor XIII was decreased. No significant relationship between clinical course and coagulation parameters was demonstrated, though both inflammatory and coagulation parameters were useful in the assessment of disease activity in patients with active ulcerative colitis.

Effect of high dose omeprazole on gastric pepsin secretion and serum pepsinogen levels in man.

To investigate the effect of omeprazole on serum and urinary pepsinogens and on gastric pepsin, 8 healthy male volunteers were studied before and after 9 days of treatment with omeprazole 60 mg/day p.o. Fasting serum samples and 24 h urine specimens were obtained, and gastric contents were aspirated at 15-min intervals, 4 prior to and 6 during pentagastrin 1.5 micrograms.kg-1.h-1 i.v. during intra-gastric perfusion with NaCl 0.9% and phenol red 3 mg.ml-1 as an inert recovery marker. Basal and pentagastrin-stimulated volume and acid secretion were significantly decreased. The basal and pentagastrin stimulated pepsin output remained unchanged but pepsin concentration in gastric secretion was increased. Administration of omeprazole resulted in a significant increase in the serum PGA and PGC levels. The 24-h urinary excretion of PGA increased, but that of PGC remained unchanged, and so did the renal clearances of creatinine and pepsinogen A. The renal clearance of pepsinogen C decreased. It was concluded that omeprazole did not affect gastric pepsin output, but, due to the decreased volume output, the concentration of pepsin in the gastric secretion was increased. Omeprazole increased the serum levels of pepsinogen A and C because more pepsinogen was released into the systemic circulation. This might be due to greater back-diffusion of pepsinogen from the gastric mucosa into the systemic circulation as a result of the higher pepsinogen concentration in gastric secretion.

Fibrinolytic split products, fibrinolysis, and factor XIII activity in inflammatory bowel disease.

BACKGROUND: Factor XIII (F XIII), the last coagulation factor in the clotting cascade, plays a role in mucosal repair. Beneficial effects of F XIII supplementation in severe ulcerative colitis (UC) have been observed. The aim of this study was to relate plasma F XIII activity to the severity of inflammatory bowel disease (IBD). METHODS: A transversional and, in part, longitudinal study of F XIII activity and related clotting products was performed in 39 patients with UC, 31 patients with Crohn's disease (CD), and 20 controls. Disease activity was assessed with a combined activity score in UC and with the Dutch Activity Index in CD. RESULTS: F XIII activity was decreased in active UC (p < 0.05) and active CD (p < 0.05) and was inversely correlated with severity in both UC (r = -0.30) and CD (r = -0.46). In six patients with UC (15%) and six patients with CD (19%) F XIII activity was below the lower range of normal. In these patients apparent rectal bleeding was only found in severe UC. Hyperfibrinolysis was indicated by elevated levels of D-dimer (p < 0.001) notwithstanding increased concentrations of alpha-2 antiplasmin (p < 0.05). CONCLUSIONS: In active IBD we found decreased plasma F XIII activity and hyperfibrinolysis. Decreased F XIII activity was not associated with apparent rectal bleeding in IBD.