Image-guided point-shear-wave elastography: a valid and reliable technique for liver fibrotic staging.

PURPOSE: Despite progressive implementation of image-guided point-shear wave elastography (pSWE) in guidelines as an alternative to transient elastography for the staging of fibrotic liver disease, pSWE is not widely adopted in clinical workflow. More information on reliability and validity of pSWE systems is needed. Therefore, we performed a phantom study to evaluate the validity and reliability of pSWE with ultrasound systems. METHODS: Validity and reliability of pSWE measurements from three ultrasound systems were evaluated. Measurements were performed on an elasticity phantom with reference elasticities of 7 ± 1 (low) (median ± interquartile range (IQR)), 14 ± 2 (medium) and 26 ± 3 (high) kPa. Measurements were repeated in tenfold for each reference at 2, 3 and 4 cm depth. Results were considered valid when median elasticity ± IQR was between the uncertainty limits (IQR) for each reference elasticity value and reliable when IQR/median < 0.30. RESULTS: pSWE with the systems provided valid results for all reference elasticities and focal depths, except for overestimation of high reference elasticity at 2 and 4 cm depth for one system (41.5 ± 4.3 and 39.0 ± 1.2 kPa, respectively). Measurements were reliable with a maximum IQR/median of 0.13, well below the guideline of IQR/median < 0.30. DISCUSSION: The results support the use of pSWE as an alternative to invasive or non-image guided noninvasive techniques for liver fibrotic staging. CONCLUSIONS: pSWE with ultrasound systems from different vendors is valid and reliable and can therefore be implemented to optimize clinical workflow by performing imaging and elastography simultaneously.

Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients.

Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

Equivalent Helicobacter pylori infection rates in Lynch syndrome mutation carriers with and without a first-degree relative with gastric cancer.

BACKGROUND: Patients with Lynch syndrome (LS) are at an increased risk of developing gastric cancer. In 2010, a guideline that recommended to screen all patients for Helicobacter pylori was implemented in the Netherlands. H. pylori is an important risk factor in the development of gastric cancer in the general population, and eradication of the bacterium reduces this risk. We aimed to assess the proportion of LS patients being tested and the yield and also addressed the question whether H. pylori infection is more prevalent in LS families with known cases of gastric cancer. METHODS: Proven mutation carriers from five different Dutch hospitals were included. The implementation of H. pylori screening and its outcome was examined. The observation period was 2008-2013. The presence of first-degree family members with gastric cancer was noted, and it was observed if H. pylori infection was more prevalent in Lynch families with known cases of gastric cancer. Obtainable endoscopy reports were reviewed. RESULTS: Four hundred forty-three (male, 184) proven mutation carriers were included. The proportion of patients screened increased after 2010, from 37 to 68%. Twenty percent of the patients were infected. The 25 patients who had a first-degree family member with gastric cancer did not have a higher infection rate. In 30% of cases, an endoscopy was performed; in four patients, intestinal metaplasia and in eight patients, gastric cancer was found. CONCLUSION: The recommendation to screen for H. pylori is increasingly followed. The prevalence of infection in this patient group does not differ from the general population. Patients who had a first-degree family member with gastric cancer did not have a higher infection rate.

Performance of the Montreal classification for inflammatory bowel diseases.

AIM: To validate the Montreal classification system for Crohn's disease (CD) and ulcerative colitis (UC) within the Netherlands. METHODS: A selection of 20 de-identified medical records with an appropriate representation of the inflammatory bowel disease (IBD) sub phenotypes were scored by 30 observers with different professions (gastroenterologist specialist in IBD, gastroenterologist in training and IBD-nurses) and experience level with IBD patient care. Patients were classified according to the Montreal classification. In addition, participants were asked to score extra-intestinal manifestations (EIM) and disease severity in CD based on their clinical judgment. The inter-observer agreement was calculated by percentages of correct answers (answers identical to the "expert evaluation") and Fleiss-kappa (κ). Kappa cut-offs: < 0.4-poor; 0.41-0.6-moderate; 0.61-0.8-good; > 0.8 excellent. RESULTS: The inter-observer agreement was excellent for diagnosis (κ = 0.96), perianal disease (κ = 0.92) and disease location in CD (κ = 0.82) and good for age of onset (κ = 0.67), upper gastrointestinal disease (κ = 0.62), disease behaviour in CD (κ = 0.79) and disease extent in UC (κ = 0.65). Disease severity in UC was scored poor (κ = 0.23). The additional items resulted in a good inter-observer agreement for EIM (κ = 0.68) and a moderate agreement for disease severity in CD (κ = 0.44). Percentages of correct answers over all Montreal items give a good reflection of the inter-observer agreement (> 80%), except for disease severity (48%-74%). IBD-nurses were significantly worse in scoring upper gastrointestinal disease in CD compared to gastroenterologists (P = 0.008) and gastroenterologists in training (P = 0.040). Observers with less than 10 years of experience were significantly better at scoring UC severity than observers with 10-20 years (P = 0.003) and more than 20 years (P = 0.003) of experience with IBD patient care. Observers with 10-20 years of experience with IBD patient care were significantly better at scoring upper gastrointestinal disease in CD than observers with less than 10 years (P = 0.007) and more than 20 years (P = 0.007) of experience with IBD patient care. CONCLUSION: We found a good to excellent inter-observer agreement for all Montreal items except for disease severity in UC (poor).

[Unexpected good news after major surgery: a lesson in communication]. / Onverwacht goed nieuws na ingrijpende operatie: een les in communicatie.

When dealing with choices concerning life-threatening or major surgery shared decision making, continuous tuning in with colleagues and monitoring direction is a necessity. The gastroenterologist detected a pancreatic tumour in a 53-year-old man. The patient was told that this tumour was almost surely malignant and that he would die within a year. A pylorus-preserving pancreatoduodenectomy was advised and performed. However, the final outcome was an IgG4-mediated autoimmune pancreatitis. The patient felt betrayed by the doctors. Crucial episodes of communication were analysed and we concluded the following. First, in decision-making on life and death, most doctors unconsciously assume a paternalistic attitude, which is not always preferred by the patient. Second, excessive emotional distress of the patient impedes counselling. Third, even in a case of perceived medical urgency, most patients should be allowed some time for reflection. Finally, multidisciplinary consultation may lead to an indistinct ownership of responsibilities by the doctors.

Vascular events after liver transplantation: a long-term follow-up study.

Long-term follow-up studies on the impact of vascular events (VE) and risk factors of liver transplant recipients are scarce. In this study, 311 recipients of a first isolated liver transplant who survived at least 1 year were followed up from 1979 to 2002. The median follow-up duration was 6.2 (range1-22.7) years. Overall median survival was 18.7 [95% confidence interval (CI): 15.5-20.1] years and this was significantly lower compared with age- and sex-matched controls. Eleven (21%) of the patients had a vascular cause of death and VE were the third cause of death. VE occurred later compared with other causes of death (mean 10.3 years vs. 4.5 years, P < 0.0001, 95% CI: 2.7-8.9). Systolic hypertension, systolic blood pressure, smoking, renal failure, age, hypertriglyceridemia, serum total cholesterol levels and hypercholesterolemia at the 1-year follow-up visit were associated with the occurrence of VE, but renal failure and age at 1 year after transplantation were the only independent risk factors for vascular death (hazard ratio 0.06, 95% CI: 0.01-0.41 and hazard ratio 1.17, 95% CI: 1.02-1.34, respectively). Finally, it was shown that the adequate treatment of hypertension was associated with a significant reduced risk of vascular death. Therefore, vascular risk factors should be treated aggressively to prevent VE in the long term.

Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori.

Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment outcome may partially be explained by changes in oxygen pressure in the gastric environment, as metronidazole-resistant (MtzR) H. pylori isolates become metronidazole-susceptible (MtzS) under low oxygen conditions in vitro. In H. pylori the rdxA and frxA genes encode reductases which are required for the activation of metronidazole, and inactivation of these genes results in metronidazole resistance. Here the role of inactivating mutations in these genes on the reversibility of metronidazole resistance under low oxygen conditions is established. Clinical H. pylori isolates containing mutations resulting in a truncated RdxA and/or FrxA protein were selected and incubated under anaerobic conditions, and the effect of these conditions on the MICs of metronidazole, amoxycillin, clarithromycin and tetracycline, and cell viability were determined. While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline resistance, all isolates lost their metronidazole resistance when cultured under anaerobic conditions. This loss of metronidazole resistance also occurred in the presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that activate metronidazole under low oxygen tension are not specifically induced by low oxygen conditions, but are already present under microaerophilic conditions. As there were no significant differences in cell viability between the clinical isolates, it is likely that neither the rdxA nor the frxA gene participates in the reversibility of metronidazole resistance.