Nomenclature and Definition of Atrophic Lesions in Small Bowel Capsule Endoscopy: A Delphi Consensus Statement of the International CApsule endoscopy REsearch (I-CARE) Group.

(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.

Prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome.

OBJECTIVE: A considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome. DESIGN: In this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months. RESULTS: Of 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%). CONCLUSION: In light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure. TRAIL REGISTRATION NUMBER: This study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).

PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Chronic inflammatory IFN-γ signaling suppresses hepatocarcinogenesis in mice by sensitizing hepatocytes for apoptosis.

Chronic liver inflammation is a critical component of hepatocarcinogenesis. Indeed, inflammatory mediators are believed to promote liver cancer by upholding compensatory proliferation of hepatocytes in response to tissue damage. However, inflammation can also mediate the depletion of malignant cells, but the difference between tumor-suppressive and tumor-promoting inflammation is not defined at the molecular level. Here, we analyzed the role of the major inflammatory mediator IFN-γ in chemical hepatocarcinogenesis of transgenic mice that overexpress IFN-γ in the liver; these mice manifest severe chronic inflammatory liver damage and lasting compensatory regeneration. We found that chronic exposure to IFN-γ suppressed chemical hepatocarcinogenesis, despite overt liver injury. Indeed, IFN-γ-transgenic mice had significantly fewer and significantly less advanced malignant lesions than nontransgenic mice. This tumor-suppressive effect of IFN-γ seemed to be mediated in part by its known immune activating function, indicated by infiltration of IFN-γ-transgenic livers with CD8 T cells, natural killer T cells, and natural killer cells. However, IFN-γ seemed to prevent carcinogenesis also by activating the cell-intrinsic p53 tumor suppressor pathway. Indeed, exposure to IFN-γ in vivo or in vitro was associated with accumulation of p53 in hepatocytes and the sensitization of hepatocytes to apoptosis induced by genotoxic stress. The IFN-γ-induced increase in apoptosis of hepatocytes seemed to be p53 dependent. Thus, chronic inflammation dominated by IFN-γ may prevent hepatocarcinogenesis, despite continued inflammatory liver injury and regeneration. Therefore, the carcinogenic potential of inflammation seems to be determined by type and composition of its mediators and manipulating the type of chronic inflammation may serve the prevention of cancer.

[A young man with chronic diarrhea and epigastric pain]. / Junger Mann mit chronischer Diarrhö und Oberbauchschmerzen.

CASE REPORT: A 26-year-old man was admitted to hospital with a 6-month history of diarrhea and abdominal pain. Before admission, upper and lower gastrointestinal endoscopy had shown a mild erosive duodenitis and the patient was started on a proton pump inhibitor. Physical examination and laboratory tests on admission were not constructive. In addition, repeated gastrointestinal endoscopy, cross-sectional imaging and neuroendocrine markers did not point to a specific etiology. Therefore, as a provocation test, the proton pump inhibitor therapy was discontinued. Discontinuation resulted in a progression of the patient's symptoms and an endoscopic detection of duodenal ulcers. Except for the normal serum gastrin levels, this constellation was suggestive of a gastrinoma, so that further investigations were initiated. Subsequently, the diagnosis could be confirmed and the gastrinoma located. After successful pancreaticoduodenectomy, the patient was symptom-free. CONCLUSION: As part of a systematic investigation on chronic diarrhea, the work-up for neuroendocrine causes can play an important role. In this context, it should be kept in mind that some gastrinoma patients present without an elevation of serum gastrin levels. Regardless of a negative gastrin test, a typical symptom constellation should therefore prompt further investigations.