Dipeptidyl peptidase-3 is associated with severity of liver disease and circulatory complications in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis suffer from a complex multiorgan disturbance and their prognosis is influenced by the development of portal hypertension and systemic circulatory dysfunction. Although non-invasive techniques such as transient elastography aid in early detection, there is an unmet need for reliable markers of these clinically significant complications. METHODS: We conducted an exploratory single-center study investigating dipeptidyl peptidase-3 (DPP3) concentrations in various vascular beds in a cohort of 48 patients with cirrhosis and 16 healthy controls. Liver vein catheterisation with sampling from femoral artery and femoral, renal and hepatic veins as well as measurement of hepatic pressure and liver function via indocyanine green and galactose elimination tests were performed. RESULTS: DPP3 concentrations were higher in cirrhotic patients compared to controls (12.6 vs. 7.4 ng/mL, p = 0.006) and increased according to the severity of cirrhosis. DPP3 associated with MELD-Na score, Child class, indocyanine green clearance, increased DPP3 with the increased hepatic venous pressure gradient (p = 0.015) as well as increased heart rate and reduced systemic vascular resistance. DPP3 concentrations predicted the presence of clinically significant portal hypertension in cirrhotic patients (AUROC 0.78, 95% CI 0.65-0.9). CONCLUSION: DPP3 is a promising marker for portal hypertension and systemic hemodynamic changes in cirrhosis.

Pancreas divisum and recurrent pancreatitis: long-term results of minor papilla sphincterotomy.

Background and aims: Pancreas divisum (PD) is the most common congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic therapy is a therapeutic option for symptomatic PD, but there is limited data on long-term results. We aimed to assess the effect of minor papilla endoscopic sphincterotomy (MiES) in the setting of ARP in patients with PD. Methods: Consecutive patients treated by MiES were included. Clinical data, including gender, age, smoking and drinking habits, number of episodes of acute pancreatitis (AP) as well as technical data pertaining to the endoscopic therapy were reviewed. Patients available for follow-up were contacted to assess the long-term impact of MiES using the Patient's Global Impression of Change (PGIC) questionnaire. Results: A total of 138 patients with PD including 77 patients with ARP underwent MiES; 48 patients were available for long-term follow-up using the PGIC score, with a mean follow-up period of 9.7 years. Procedure-related adverse events developed in 10 cases (12.9%): 5 post-MiES delayed bleeding and 5 mild pancreatitis. MiES was clinically successful in 35 patients (72.9%) who did not experience any more episodes of AP. Improvement in quality of life (PGIC ≥6) occurred in 41/48 patients (85.4%). On multivariate analysis, stenosis of the MiES was the only predictive factor for increased risk of recurrent pancreatitis after initial therapy. Conclusion: MiES resulted an efficient treatment for ARP in patients with PD with clinical benefit, patient satisfaction and improved quality of life even at long-term follow-up.

Endoscopic management of recurrent tracheoesophageal fistula induced by chronic use of nonsteroidal anti-inflammatory drugs: A case report and review of the literature.

Tracheoesophageal fistula (TEF) is frequently congenital and requires surgical correction. TEF can also occur secondary to malignant esophageal tumors or benign diseases and these cases are managed by endoscopic means, such as closing the defect with metallic stents. Although esophageal injury can occur secondary to nonsteroidal anti-inflammatory drugs (NSAIDs), TEF secondary to chronic NSAIDs use has not been described in the literature. We report the case of a male patient with refractory migraine and chronic use of NSAIDs, with a history of esophageal stenosis presenting with acute-onset total dysphagia. Upper gastrointestinal endoscopy and CT-scan revealed TEF located at 25 cm from the incisors. An esophageal stent was placed endoscopically, and 6 weeks a second stent was placed in a stent-in-stent manner to allow removal of both stents. Endoscopic control after the removal of the stents showed the persistence of the fistula, so a third stent was placed as a rescue therapy. Against medical advice, the patient continued to use OTC painkillers and NSAIDs in large doses. Three months later, he was readmitted with total dysphagia and recent-onset dysphonia. CT scan revealed a new fistula above the already placed stent. A second metallic stent was endoscopically placed through the old stent to close the newly developed fistula. The patient was discharged on the third day with no complications and he remains well at 6 months follow-up. Due to small cases studies, recurrent TEF remains a therapeutic challenge. Endoscopic therapy is usually an effective solution, but complex cases might require multiple treatment sessions.

The diagnostic and prognostic value of serum endocan in patients with cirrhotic cardiomyopathy.

BACKGROUND: We aimed to determine the relationship between endocan and cirrhotic cardiomyopathy. MATERIALS AND METHODS: Patients with liver cirrhosis and no heart disease were included in a prospective observational study with liver disease decompensation and death as primary outcomes. RESULTS: 83 cirrhotic patients were included and 32 had cirrhotic cardiomyopathy. Endocan levels were significantly lower in patients with cirrhotic cardiomyopathy (5.6 vs. 7 ng/mL, p = 0.034). Endocan correlated with severity of cirrhosis, time to decompensation or death from liver disease (OR 4.5 95% CI 1.06-31.1). CONCLUSION: Endocan is a promising biomarker of severity of cirrhosis and may help in the diagnosis of cardiac dysfunction in this population.

Vascular endothelial growth factor - key mediator of angiogenesis and promising therapeutical target in ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, triggered by an inappropriate immune response of colonic mucosa. Angiogenesis is an important part of inflammatory process, enhancing inflammation in a vicious circle that aggravates mucosal damage and remodeling. The most important pathway for angiogenesis in ulcerative colitis involves vascular endothelial growth factor (VEGF) and endoglin (CD105) and can be used as target for adjuvant therapy in order to improve patients' outcome. We present a retrospective cohort study evaluating mucosal expression of VEGF and CD105 and their correlation with patients' evolution and risk of relapse. In our study, patients with UC have correlated increases of VEGF expression and microvessel density (evaluated with CD105 staining), sustaining the hypothesis that angiogenesis is not just a passive process driven by inflammation, but an active player of mucosal lesions in ulcerative colitis.

The Impact of Hypoxaemia on the Outcome in Liver Cirrhosis.

BACKGROUND AND AIMS: Prognostic factors for poor evolution are critical in the setting of limited access to liver transplantation for patients with cirrhosis. We aimed to investigate the impact of hypoxaemia on the outcome in cirrhosis and the evolution of arterial oxygen tension during long-term follow-up in these patients. METHODS: Consecutive cirrhotic patients were prospectively enroled and followed-up in our tertiary referral center. Clinical features, biological tests, arterial blood gases, NT-proBNP levels, pulse oximetry measurements, 12-lead ECG, and transthoracic contrast echocardiography were documented on enrolment. The main outcomes were death and decompensation due to liver disease. RESULTS: 87 cirrhotic patients were included in the analysis and followed-up for a mean of 16 months. At enrolment, 27 (31%) patients were hypoxaemic, 19 had hepatopulmonary syndrome (HPS), but only 6 of those who were sampled at follow-up had persistent hypoxaemia. During the study period, 22 patients died of liver-related complications. Nine of them (41%) were hypoxaemic on enrolment but none had severe hypoxaemia. Hypoxaemia present at enrollment was not a risk factor for death (p=0.29) or decompensation of liver disease (p=0.7). A higher MELD score at baseline or increase during follow-up was a risk factor for death (p=0.02) and correlated with the presence of hypoxaemia. Normalization of the arterial oxygen levels was accompanied by a significant decrease in NT-proBNP (83 pg/ml vs 0 pg/mL, p=0.023). CONCLUSION: Mild and moderate hypoxaemia was frequent in our patients but was not associated with adverse outcome in cirrhosis. Repeated arterial blood gas sampling is advisable, especially in patients diagnosed with hepatopulmonary syndrome.

Usefulness of virtual chromoendoscopy in the evaluation of subtle small bowel ulcerative lesions by endoscopists with no experience in videocapsule.

BACKGROUND AND STUDY AIMS: In videocapsule endoscopy examination (VCE), subtle variations in mucosal hue or pattern such as those seen in ulcerations can be difficult to detect, depending on the experience of the reader. Our aim was to test whether virtual chromoendoscopy (VC) techniques, designed to enhance the contrast between the lesion and the normal mucosa, could improve the characterization of ulcerative mucosal lesions. PATIENTS AND METHODS: Fifteen trainees or young gastroenterologists with no experience in VCE were randomly assigned to evaluate 250 true ulcerative and 100 false ulcerative, difficult-to-interpret small bowel lesions, initially as white light images (WLI) and then, in a second round, with the addition of one VC setting or again as WLI, labeling them as real lesions or artifacts. RESULTS: On the overall image evaluation, an improvement in lesion characterization was observed by adding any chromoendoscopy setting, especially Blue mode and FICE 1, with increases in accuracy of 13 % [95 %CI 0.8, 25.3] and 7.1 % [95 %CI - 17.0, 31.3], respectively. However, when only false ulcerative images were considered, with the same presets (Blue mode and FICE 1), there was a loss in accuracy of 10.7 % [95 %CI - 10.9, 32.3] and 7.3 % [95 %CI - 1.3, 16.0], respectively. The interobserver agreement was poor for both readings. CONCLUSIONS: VC helps beginner VCE readers correctly categorize difficult-to-interpret small bowel mucosal ulcerative lesions. However, false lesions tend to be misinterpreted as true ulcerative with the same presets. Therefore care is advised in using VC especially under poor bowel preparation.

Functional dyspepsia today.

Functional dyspepsia (FD) is a disorder presenting with symptoms such as postprandial fullness, early satiety or epigastric pain. Although there is a 10 to 30% reported prevalence worldwide, there is currently no clear explanation of the pathophysiology behind this condition. Motility disorders, visceral hypersensitivity, acid disorders, Helicobacter pylori infection or psychosocial factors have all been reported to play a part in the pathophysiology of FD. The diagnosis of FD is one of exclusion, based on the Rome III criteria. The main therapeutic modalities include lifestyle changes, eradicating Helicobacter pylori infection and treatment with either proton pump inhibitors, prokinetics or antidepressants.