Benign biliary strictures treated with biodegradable stents in patients with surgically altered anatomy using double balloon enteroscopy.

OBJECTIVES: Surgically altered anatomy complicates endoscopical procedures of pancreatobiliary tree. Biliary or hepaticojejunal anastomosis strictures have been managed using percutaneous transhepatic or double balloon enteroscopy (DBE) techniques with multiple plastic stents, or fully covered self-expandable metal stents. We report the first seven cases with surgically altered anatomy treated with biodegradable stents with DBE. MATERIALS AND METHODS: Seven cases with altered anatomy, all with Roux-en-Y hepaticojejunostomy (HJ), were treated for HJ anastomosis strictures (3 cases) and intrahepatic biliary stricture (4 cases). Fujifilm DB enteroscope with a 200 cm long and 3.2 mm wide working channel was used. Balloon dilatations were first performed and then 1-3 biodegradable stents were deployed with a pusher over a guidewire. RESULTS: Two patients had HJ due to liver resections, one due to biliary injury in cholecystectomy and four due to liver transplantation because of primary sclerosing cholangitis (PSC). Median duration of the procedures was 56 min. Deployment of the stents took less than 20 min per patient. There were no stent or cholangiography related adverse events, but one patient required endotracheal intubation for nose bleeding caused by the placement of nasopharyngeal tube. Two PSC patients had recurrent cholangitis in the follow up. There was one stent migration in 90 day follow up. With all the HJ anastomotic strictures resolution of strictures seemed to be achieved. CONCLUSIONS: Treatment of biliary or anastomosis strictures in altered anatomy is complex and time consuming. The biodegradable stent, which can be passed through working channel of a long enteroscope, seems promising in the treatment of these strictures. The benefit is that no stent removal is needed.

Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience.

OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. MATERIAL AND METHODS: The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12-16 weeks in accordance with national guidelines. RESULTS: In the NORDynamIC trial, age < 40 years or achieving HCV RNA < 1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. CONCLUSIONS: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.

[Liver disease and hemostasis--evaluation of bleeding risk]. / Maksan vajaatoiminta ja hemostaasi--verenvuotovaaran arviointi.

In severe liver disease, simultaneous abnormalities in procoagulant and anticoagulant pathways seem to maintain the hemostatic balance, provided that the platelet level is sufficient. Common coagulation screening tests such as INR fail to measure the concomitant anticoagulant deficiencies and fibrinolytic abnormalities, and do not predict bleeding in patients with compensated liver disease undergoing invasive procedures. Thus, specific INR cut-off levels and prophylactic use of fresh-frozen plasma are discouraged. Volume expansion, hemodynamic disruption, endothelial dysfunction, and infections increase the bleeding risk. Individualized bleeding risk assessment mandates evaluation of the patient's clinical condition and a comprehensive assessment of the hemostatic system.

Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn's disease detected by wireless capsule endoscopy.

OBJECTIVE: Data on fecal calprotectin and S100A12 in predicting wireless capsule endoscopy (WCE) findings in suspicion of Crohn's disease (CD) are scarce. Our aim was to study the role of calprotectin and S100A12 in predicting inflammatory lesions of small bowel in patients undergoing WCE. MATERIAL AND METHODS: 84 patients undergoing WCE (77 for suspicion of CD and 7 CD patients for evaluation of disease extent) were prospectively recruited. WCE findings were scored. Patients provided a stool sample for measurements of biomarkers. Patients underwent an esophagogastroduodenoscopy and ileocolonoscopy before WCE. RESULTS: WCE was abnormal in 35 (42%) of 84 patients: 14 patients with CD, 8 with NSAID enteropathies, 8 with angioectasias, 4 with polyps or tumors, and 1 with ischemic stricture. Median calprotectin concentration in the study population was 22 µg/g (range 2-342) and S100A12 concentration 0.048 µg/g (range 0.003-1.215). Fecal calprotectin was significantly higher in CD patients (median 91, range 2-312) compared with those with normal WCE or other abnormalities (p = 0.008), whereas fecal S100A12 (0.087 µg/g, range 0.008-0.896) did not differ between the groups (p = 0.166). In detecting inflammatory small bowel lesions, sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin (cutoff 50 µg/g) were 59%, 71%, 42%, and 83%, and for S100A12 (cutoff 0.06 µg/g) these were 59%, 66%, 38%, and 82%. CONCLUSIONS: In predicting small bowel inflammatory changes, fecal biomarkers calprotectin and S100A12 have moderate specificity, but low sensitivity. Neither fecal calprotectin nor S100A12 can be used for screening or excluding small bowel CD.

Capsule endoscopy in pediatric patients: technique and results in our first 100 consecutive children.

OBJECTIVE: Capsule endoscopy (CE) offers noninvasive methods to assess small bowel pathology but only limited data are available on the feasibility, safety, and findings in children. In this study, we report our results of 100 consecutive CE in children. MATERIAL AND METHODS: Single center retrospective study. All pediatric patients (mean age 119 months, range from 8 to 188 months) undergoing CE were included until 100 investigations were completed. The indications for CE were: suspicion or evaluation of Crohn's disease (n = 35) or ulcerative colitis (n = 24), gastrointestinal bleeding (n = 18), and miscellaneous (n = 23). RESULTS: The youngest patients able to swallow the capsule were 84 months old. When the patient was unable to swallow the capsule (n = 51), it was guided into the duodenum with endoscope. In two patients, the capsule remained in the stomach during the 8 h of recording and in 23 cases the capsule failed to reach the cecum. The capsule was expelled naturally in all except one patient. In 39% of the patients, CE revealed a significant finding (multiple ulcers, bleeding, tumors, strictures). In patients examined for bleeding or for a suspicion of Crohn's disease, the respective proportions were 50% and 60%. CONCLUSIONS: This study shows that CE is a feasible diagnostic method to study the small intestine in pediatric patients and that CE can be done in children as young as 8 months old. The diagnostic yield is highest in cases with bleeding or a high suspicion of Crohn's disease.

Endoscopic evaluation of Crohn's disease activity: comparison of the CDEIS and the SES-CD.

BACKGROUND: Few data exist of prospective parallel scoring of the validated endoscopic scores in Crohn's disease (CD), Crohn's Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn's Disease (SES-CD). METHODS: Both the CDEIS and the SES-D were scored immediately after each endoscopy of 86 CD patients referred for ileocolonoscopy in a cross-sectional study. Furthermore, after CD therapy, 32 CD patients underwent a follow-up endoscopy with scoring of the CDEIS and SES-CD. Endoscopic scorings were graded as inactive, mild, moderate, or severe. Clinical activity was assessed with the Crohn's Disease Activity Index (CDAI) and serum C-reactive protein (CRP) was measured. RESULTS: The SES-CD correlated with the CDEIS significantly (Spearman's r = 0.938, P < 0.0001). Weaker correlations were detected between the SES-CD and the CDAI (r = 0.473) or CRP (r = 0.525, both P < 0.0001). Grading of SES-CD from inactive to severe correlated significantly with grading of the CDEIS (r = 0.859, P < 0.0001). Changes between baseline and follow-up endoscopy scores correlated significantly (r = 0.828 between delta-CDEIS and delta-SES-CD, P < 0.001), but failed to correlate with delta-CDAI or delta-CRP (all P > 0.05). CONCLUSIONS: Both validated endoscopic scores, the CDEIS and SES-CD, and their changes during CD therapy demonstrated a close correlation. For scoring of endoscopic activity in clinical routine, the SES-CD could replace the CDEIS.

Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn's disease treatment.

OBJECTIVE: Serial monitoring data for faecal calprotectin and lactoferrin during Crohn's disease (CD) therapy are scarce. The aim of this research was to study the behaviour of faecal biomarkers during CD therapy. MATERIAL AND METHODS: Adult CD patients (n = 19) needing therapy enhancement were prospectively recruited. The simple endoscopic score for Crohn's disease (SES-CD) was administered before and 4-6 months after therapy. At baseline and at 2-3 and 4-6 months, patients provided faecal samples for measurements of calprotectin and lactoferrin. RESULTS: Of 19 patients, seven were endoscopic responders, three were partial responders and nine were non-responders. During therapy, both faecal-biomarker concentrations decreased significantly in responders: median calprotectin from 1282 microg/g (range 156-2277 microg/g) to 73 microg/g (range 7-2222; P = 0.005) and lactoferrin from 233 microg/g (range 2.8-802 microg/g) to 0.0 microg/g (range 0.0-420 microg/g; P = 0.005), and these changes correlated significantly with changes in the SES-CD. In non-responders, changes in faecal biomarkers were non-significant: calprotectin decreased from 1017 microg/g (range 53-3928 microg/g) to 223 microg/g (range 35-15330 microg/g; P = 0.594) and lactoferrin from 22.5 microg/g (range 2.1-629 microg/g) to 13.0 microg/g (range 3.5-1259 microg/g; P = 0.515). CONCLUSIONS: The faecal neutrophil-derived proteins calprotectin and lactoferrin are reliable surrogate markers of mucosal improvement. Endoscopic responders achieved normalization of faecal biomarkers, whereas in the majority of endoscopic non-responders these markers remained abnormal.

Three-generation familial visceral myopathy with alpha-actin-positive inclusion bodies in intestinal smooth muscle.

We report the clinical and histopathologic findings of a family with 7 affected members in 3 generations suffering from autosomal dominant visceral myopathy. All patients presented with chronic intestinal pseudo-obstruction affecting especially the entire small bowel. Histologic abnormalities involved intestinal smooth muscle, with degeneration and fibrosis of the muscularis propria. In addition, the inner circular layer of the muscularis propria contained alpha-smooth muscle actin-positive and, in more advanced disease, also periodic acid-Schiff-positive inclusion bodies. The inclusions were invisible in routine hematoxylin-eosin-stained sections, but were visible in immunohistochemical stainings for alpha-smooth muscle actin. No abnormality was evident in muscularis mucosae or in blood vessels, and the findings remained unidentified in mucosal biopsy specimens. To our knowledge, this is the first reported alpha-actin-positive inclusion body finding in familial visceral myopathy.

Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn's disease.

BACKGROUND: Fecal calprotectin and lactoferrin are promising noninvasive biomarkers for intestinal inflammation. In Crohn's disease (CD), during anti-TNF-alpha (TNF-alpha) treatment, the clinical significance of these markers has, however, been insufficiently explored. METHODS: Among CD patients receiving anti-TNF-alpha therapy we assessed the role of fecal calprotectin and lactoferrin as surrogate markers for mucosal healing. Before and 3 months after the beginning of anti-TNF-alpha induction, 15 patients underwent ileocolonoscopy with scoring of the Crohn's Disease Index of Severity (CDEIS). Fecal samples for calprotectin and for lactoferrin measurements were collected and the Crohn's Disease Activity Index (CDAI) was calculated at the time of the endoscopies and 2 and 8 weeks after the first treatment. RESULTS: The median CDEIS fell from 13.0 to 4.8 (P = 0.002) and CDAI from 158 to 68 (P = 0.005). Accordingly, the median fecal calprotectin concentration fell from 1173 microg/g to 130 microg/g (P = 0.001) and fecal lactoferrin from 105.0 microg/g to 2.7 microg/g (P = 0.001). Of the 15 patients, 11 (73%) showed an endoscopic response to treatment and 5 of these achieved endoscopic remission (CDEIS < 3). In those 5 patients the fecal calprotectin concentration declined from 1891 mug/g (range 813-2434) to 27 microg/g (13-130) and lactoferrin from 92.4 microg/g (35.5-235.6) to 1.9 microg/g (0.0-2.1). CONCLUSIONS: Compared to pretreatment values, concentrations of fecal calprotectin and lactoferrin after the anti-TNF-alpha treatment were significantly lower. During anti-TNF-alpha therapy these fecal neutrophil-derived proteins may thus be useful surrogate markers for mucosal healing.

Crohn's disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn's disease activity index and endoscopic findings.

BACKGROUND: Correlation of endoscopic Crohn's disease activity with fecal calprotectin and lactoferrin is insufficiently studied. We evaluated the clinical significance of these neutrofil-derived proteins in assessment of Crohn's disease activity by comparing them with endoscopic disease activity and with Crohn's disease activity index (CDAI) and serum CRP. METHODS: A total of 77 CD patients underwent one or more ileocolonoscopies (n = 106) with scoring of Crohn's disease index of severity (CDEIS). Patients provided stool samples for calprotectin and lactoferrin measurements and blood samples for CRP. Clinical activity was based on the CDAI. RESULTS: Both fecal calprotectin and lactoferrin correlated significantly with CDEIS (Spearman's r 0.729 and 0.773, P < 0.001). With a cutoff level of 200 microg/g for a raised fecal calprotectin concentration, sensitivity was 70%, specificity 92%, positive predictive value (PPV) 94%, and negative predictive value (NPV) 61% in predicting endoscopically active disease (CDEIS >/= 3). A fecal lactoferrin concentration of 10 microg/g as the cutoff value gave a sensitivity, specificity, PPV, and NPV of 66%, 92%, 94%, and 59%. Sensitivity of CDAI >/= 150 to detect endoscopically active disease was only 27%, specificity 94%, PPV 91%, and NPV 40%. A raised serum CRP (> 5 mg/l) gave a sensitivity, specificity, PPV, and NPV of 48%, 91%, 91%, and 48%. CONCLUSIONS: For evaluation of Crohn's disease activity, based on endoscopic findings, more sensitive surrogate markers than is CDAI or CRP are fecal calprotectin and lactoferrin. These prove to be useful tools for estimation of disease activity in Crohn's disease.