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  1. Emad El-Omar,
  2. Severine Vermeire,
  3. Alexander Gerbes, Editor and Deputy Editors

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Ménétrier's disease: what you need to know

Ménétrier's disease (MD) is a rare form of acquired gastropathy characterised by giant rugal folds in the gastric body, foveolar hyperplasia and markedly decreased or absent oxyntic glands. The later explains why most of these patients have hypochlorhydria. The pathogenesis of MD is related to increased epidermal growth factor receptor (EGFR) signalling in the stomach. It is fair to say that most gastroenterologists know little about the condition! Rich et al evaluated 48 individuals over a 10-year period for possible enrolment into a clinical trial utilising Cetuximab, a monoclonal antibody to the EGFR. In this interesting paper, the authors share their extensive experience with this rare condition. They describe the clinical and histological features of MD, characterise the conditions that mimic MD and propose a diagnostic algorithm for clinicians and pathologists when MD is suspected. It is certainly worth a read by all doctors. See page 1617.

Figure1

Endoscopic views of Ménétrier's disease showing the characteristic giant rugal folds with surface erosions and overlying mucus.

High fat diet, obesity and liver damage

High-fat diet leads to obesity, insulin resistance and chronic sub-acute inflammation. Despite the obesity epidemic, very few studies have addressed the obesity-independent role of diet. Dissecting the effects of diet from those of obesity per se will enhance our understanding of the underlying pathogenesis and advance our treatment approaches for obesity and its co-morbidities. Wang et al studied this complex interplay between obesity and diet by using melanin-concentrating hormone (MCH)-deficient mice, which are resistant to diet-induced obesity primarily due to increased locomotor activity. They examined the metabolic and inflammatory consequences of a 15-week consumption of a diet high in saturated fat in MCH-deficient mice and their wild type littermates. MCH-deficient mice resist liver fat accumulation in response to chronic high-fat feeding. Despite their leanness, MCH-deficient mice are prone to high-fat diet induced inflammatory responses, which are liver-confined and involve TLR4- and SOCS3-dependent signalling pathways. In response to high-fat feeding, MCH-deficient mice develop liver-specific insulin resistance, while they have improved total body insulin sensitivity, consistent with their lean phenotype. This work suggests that diets high in saturated fat might have deleterious effects on the liver, even when consumed by lean individuals. Exercise alone is not sufficient to prevent diet-induced insulin resistance, unless it is coupled with appropriate dietary modifications. See page 1625.

E-health empowers patients with ulcerative colitis

The natural history of ulcerative colitis (UC) is characterised by episodes of remission and relapse. Therefore, most patients require frequent outpatient visits to follow-up on their disease status and to adjust therapy where needed. The focus of the European health authorities on e-health is increasing. In this randomised control trial from Denmark and Ireland, 333 patients with mild to moderate UC and 5-Aminosalicylate acid (5ASA) treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control-group continuing the usual care for 12 months. The results show not only that 88% of the web patients preferred the new approach, but also that adherence to 4 weeks of acute treatment was increased by 30–40% compared to the control groups. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in 189 saved Euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The authors conclude that a web-guided approach for patients with UC is feasible, safe and cost effective. See page 1652.

Figure2

Time (days) from the first relapse to remission in web and control patients.

Autologous bone marrow-derived mesenchymal stromal cell treatment in Crohn's disease

Mesenchymal stromal cells (MSCs) are pluripotent cells with immunosuppressive effects in vitro and in experimental colitis. MSC therapy has shown promising results in patients with severe graft versus host disease of the gut. In this early phase study, the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn's disease (CD) was assessed. Ten CD patients underwent bone marrow aspiration to isolate MSCs which were then expanded ex vivo. Nine patients subsequently received two doses of 1–2×106 cells/kg bodyweight, intravenously, with 1-week interval. The authors show similar morphology, phenotype and growth potential of MSCs from CD patients compared to MSCs from healthy donors. The immunomodulatory capacity was intact. MSC infusion was without side effects in all but one patient. The efficacy results showed clinical response (including healing) in three patients, although three other patients needed surgery. Therefore, one can conclude from this study that administration of autologous bone marrow derived MSCs appears safe in refractory CD patients, but efficacy needs to be determined in larger studies. See page 1662.

Figure3

Endoscopy at baseline and 6 weeks after MSC treatment (two administrations of 2×106 autologous bmMSCs) shows clear mucosal healing. Pictures A and B before and after MSC from patient 2, pictures C and D same time points for patient 3.

Hepatology Focus on hepatocellular carcinoma

Worldwide more than half of the new cases of hepatocellular carcinoma (HCC) occur in China. This issue of GUT presents two very interesting studies from China, focusing on early diagnosis of HCC and on prognosis of recurrence, respectively.

GP 73 as a biomarker for HCC

Alpha fetoprotein (AFP) is the only standard marker for HCC as yet. However, in view of the rather poor sensitivity of AFP novel markers have been looked for. Recently GP 73, a Golgi glycoprotein was found to be increased in serum of patients with viral hepatitis, cirrhosis or HCC. In this issue of Gut, Mao et al investigated over 4000 patients and present strong evidence for GP 73 as a novel HCC biomarker. GP 73 was markedly elevated in HCC as compared to cirrhosis patients and healthy subjects, respectively. Moreover, the diagnostic efficiency was clearly superior to AFP (see figure 1). Interestingly, marked increases of GP 73 seem to be rather specific for HCC, since they were not observed in patients with other hepatobiliary tumours nor with cancer of other organs. Whether these findings hold true for Western patients, representing only a small subgroup of the present study, needs further investigation. See page 1687.

Figure4

The GP73 values of HCC-related diseases.

Peritumoural IL-2 and prognosis of HCC

Interleukin-2, a Th1 cytokine has well known antitumoural effects. A decrease of Th1 cytokines and an increase of Th2 cytokines has been observed in livers of patients with HCC and poor outcome. This study from Shanghai investigates whether the reported Th1 to Th2 shift can be used to predict outcome in patients following resection of HCC. Several Th1 and Th2 cytokines were quantified in resected HCC and in liver samples 0.5 cm to 3 cm distant from the resected tumours. The results were verified in another cohort of patients and finally validated in a third cohort. With this careful approach a decrease of IL-2 in peritumoural tissue, but not in HCC or in serum, was observed and identified as an independent predictor of HCC recurrence and of overall survival. Peritumoural IL-2 may add to existing prognostic parameters and scores since it proved to be prognostic even in patients with early HCC and without microvascular invasion (figure 4A). In this Chinese study, HCC was related to Hepatitis B in more than 90% of patients. Thus, further studies are needed to test these very interesting findings in other HCC populations. See page 1699.

Figure5

HRs of peritumoral IL-2 and IL-15 levels for time to recurrence (TTR) and overall survival (OS) in different subgroups of HCC patients.

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