In-vivo multispectral video endoscopy towards in-vivo hyperspectral video endoscopy.

For in-vivo diagnostics of cancer and pre-cancer in the stomach, there is no endoscopic procedure offering both high sensitivity and high specificity. Our data suggest that multispectral or hyperspectral imaging may be helpful to solve this problem. It is successfully applied to the detection and analysis of easily reachable carcinomas, ex-vivo samples of hollow organ mucosal carcinomas and also histological samples. An endoscopy system which allows flexible multispectral videoendoscopy for in-vivo diagnostics has so far been unavailable. To overcome this problem, we modified a standard Olympus endoscopy system to conduct in-vivo multispectral imaging of the upper GI tract. The pilot study is performed on 14 patients with adeno carcinomas in the stomach. For analysis, Support Vector Machine with linear and Gaussian Kernel, AdaBoost, RobustBoost and Random-Forest-walk are used and compared for the data classification with a leave-one-out strategy. The margin of the carcinoma for the training of the classifier is drawn by expert-labeling. The cancer findings are cross-checked by biopsies. We expect that the present study will help to improve the further development of hyperspectral endoscopy and to overcome some of the problems to be faced in this process.

[Biosimilars in inflammatory bowel disease]. / Biosimilars in der Behandlung chronisch entzündlicher Darmerkrankungen.

After the expiry date of the patent protection for Infliximab in 2013, the biosimilar CT­P13 was approved for indications in Crohn's disease and ulcerative colitis in adults as well as in children. The approval has been based on two randomized clinical studies indicating equivalence for the biosimilar with regard to pharmacokinetics, efficacy, as well as side-effects. The clinical experience since, in addition to multiple non-randomized studies, indicate a comparable efficacy and immunogenicity of the Infliximab biosimilar CT-P13 in inflammatory bowel disease. Thus, the introduction of the biosimilar as primary therapy seems to be justified. Tight monitoring of the safety of biosimilars with regard to efficacy and side effects has to be ensured.

High-definition endoscopy with iScan and Lugol's solution for the detection of inflammation in patients with nonerosive reflux disease: histologic evaluation in comparison with a control group.

Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.

Mesenteric transit time using contrast-enhanced ultrasound (CEUS) does not correlate with disease activity in Crohn's disease.

PURPOSE: Evaluation of mesenteric transit time (MTT) - measured by contrast-enhanced ultrasound - as a marker for inflammatory activity in Crohn's disease. MATERIALS AND METHODS: The time of maximum enhancement of the contrast agent in the superior mesenteric artery and vein was determined visually and by software analysis. The MTT was calculated as the difference between these two time points. Findings were correlated with the Harvey-Bradshaw Index (HBI) using the Pearson correlation coefficient (r). In addition, a healthy control group was evaluated both in the fasting state and 1, 2, 3 and 4 hours postprandially. RESULTS: In 20 healthy controls the mean visual MTT during fasting was 9.76 ± 2.83 sec and decreased to a minimum 1 hour after the meal (6.6 ± 2.27 sec). 45 patients with Crohn's disease (9 males, 36 females, mean age 35 years) had a mean HBI of 5.9 ± 4.7 points. The mean software-based MTT of 9.76 ± 3.7 sec was significantly higher (p = 0.034) than the mean visual MTT of 8.22 ± 3.05 sec. The two figures correlated well (r = 0.72, p < 0.001). The HBI correlated neither with the visual (r = 0.14, p = 0.371) nor with the software-based (r = 0.16, p = 0.293) MTT. CONCLUSION: The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.

[Ultrasound education by simulator training--analysis of the largest simulator-based training in Germany]. / Ausbildung am Ultraschallsimulator--Analyse der größten simulatorbasierten Fortbildung in Deutschland.

Teaching ultrasound (US) has not been sufficiently standardised yet. Most educational devices in US consist of 2-dimensional B-mode images. However, the identification of anatomic structures in the 3-dimensional space can only be learned by practical hands-on education. In US simulators, US images of real pathologies are created by the examination of a dummy with a mock transducer. The resulting US images were previously recorded in a 3-dimensional format and were processed in a way which facilitates the reconstruction and projection of the images on a screen corresponding to the sectional plane of the mock transducer, simulating the conventional B-mode images. This enables standardised, real-time, hands-on training of US pathology detection. In June 2007, a hands-on workshop on US simulators was performed in the 1st Department of Internal Medicine of the Johannes Gutenberg-University in Mainz/Germany. During 15 days, 209 participants from all parts of Germany were trained. The workshop included an evaluation to elucidate the value and acceptance of this kind of US training. 149 evaluation forms could be analysed (72 %). The participants were fairly heterogeneous and belonged to the following subspecialties: internal medicine (50 %), surgery (11 %), others (18 %). 72 % were residents, 22 % consultants. 40 % of the participants worked in university hospitals, 12 % in hospitals of highest clinical level, and 42 % in hospital of basic care. Baseline knowledge in US was quite different, too, reflected in the number of independently performed US examinations prior to this course: 0 - 400 examinations (44 %), 401 - 1000 examinations (14 %), 1001 - 4000 examinations (7 %), and > 4000 examinations (2 %). Of note, 56 % of the participants had not received any kind of formal training in US. In daily practice 77 % were trained by tutors, whose formal qualification in US was unknown. Only a small proportion of the tutors had received training in US according to the standards of the German Association of US in Medicine (DEGUM). This evaluation shows the high level of acceptance of simulator-based training in US despite the heterogeneity of the participants. 95 % rated the teaching value as "high" and 95 % wished an integration of US simulators in training curricula. In summary, this analysis proves the need for standardised training programmes in US teaching in Germany and a high level of acceptance of simulator-based US training.

High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial.

INTRODUCTION: Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma. METHODS: A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions. RESULTS: HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6 %) within the HD+ group. CONCLUSIONS: HD+ colonoscopy with I-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial.

Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy.

BACKGROUND: The EPKi system (Pentax, Japan) enables resolution above HDTV. Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy (Methylene blue 0.1%) in screening for colorectal cancer. We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system. METHODS: The last 30 cm of the colon in a screening population were inspected with HD+ alone, in combination with i-Scan (2:1 randomisation) and subsequently with chromoendoscopy. All lesions were characterized and targeted biopsies were performed. RESULTS: i-Scan augmented in 69 patients the identification of lesions from 176 to 335 (p<0.001) and chromoendoscopy to 646 (p<0.001). The additional lesions were mainly flat (type IIb, 74%), which were only recognized using i-Scan or chromoendoscopy. The amount of neoplasias was not significantly different (HD+: 5, i-Scan: 11, Chromoendoscopy: 11), but all could correctly be predicted using i-Scan or chromoendoscopy. CONCLUSIONS: HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number. However, i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool.

High-definition endoscopy with i-Scan and Lugol's solution for more precise detection of mucosal breaks in patients with reflux symptoms.

BACKGROUND AND STUDY AIMS: Patients with gastroesophageal reflux disease are subdivided into non-erosive (NERD) and erosive reflux disease (ERD). The newly available EPKi processor enables high-definition resolution above HDTV standard (HD+). The aim of the study was to test the efficacy of HD+ esophagogastroduodenoscopy alone and in conjunction with i-Scan (newly developed postprocessing digital filter) and chromoendoscopy (Lugol's solution) for differentiation of reflux patients. METHODS: The distal esophagus of patients with heartburn was inspected with three imaging modalities. HD+ was followed by i-Scan and 15-mL Lugol's solution (1.5 %). The esophagus was evaluated for mucosal breaks (Los Angeles Classification [LA]). Small visible changes were also characterized, and targeted biopsies were performed. End points of the study were the presence and grade of esophagitis and the number of circumscribed changes. RESULTS: A total of 50 patients were included (female 29; mean age 54.7 years). HD+ identified nine patients with mucosal breaks (LA 7A; 2C), i-Scan was able to detect 12 patients (LA 8A; 2B; 2C; 0D) ( P = n. s.) and chromoendoscopy identified 25 patients (LA 16A; 7B; 1C, 1D) ( P < 0.01). Furthermore, a higher grade of esophagitis was recognized by using i-Scan and Lugol's solution in 19 patients. The number of circumscribed lesions could be increased from 21 (HD+) to 58 (i-Scan) ( P < 0.01), and up to 85 after Lugol spraying ( P < 0.01). CONCLUSIONS: Lugol's solution in conjunction with HD+ endoscopy significantly improves the identification of patients with esophagitis and reduces misclassification. The i-Scan filter and chromoendoscopy help to identify reflux-associated lesions.

The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease.

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet-deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.

Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo.

The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppression of colitis activity and induction of apoptosis, indicating that sIL-6R prevents mucosal T-cell apoptosis. In patients with CD, mucosal T cells showed strong evidence for IL-6 trans signaling, with activation of signal transducer and activator of transcription 3, bcl-2 and bcl-xl. Blockade of IL-6 trans signaling caused T-cell apoptosis, indicating that the IL-6-sIL-6R system mediates the resistance of T cells to apoptosis in CD. These data indicate that a pathway of T-cell activation driven by IL-6-sIL-6R contributes to the perpetuation of chronic intestinal inflammation. Specific targeting of this pathway may be a promising new approach for the treatment of CD.