Intestinal Ultrasound Early on in Treatment Follow-up Predicts Endoscopic Response to Anti-TNFα Treatment in Crohn's Disease.

BACKGROUND: To assess treatment response, objective measures are superior to clinical improvement in Crohn's disease [CD]. Intestinal ultrasound [IUS] is an attractive, non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment initiation. Therefore, we investigated IUS and contrast-enhanced ultrasound [CEUS] to predict [early] endoscopic treatment response. METHODS: Consecutive patients with endoscopically active CD, starting anti-TNFα therapy, were included. Clinical, biochemical, IUS, and CEUS parameters at baseline [T0], after 4-8 weeks [T1] and 12-34 weeks [T2] were collected. The most severely inflamed segment at endoscopy (highest segmental Simplified Endoscopic Score for Crohn's Disease [SES-CD]) and IUS (highest segmental bowel wall thickness [BWT]) was identified. At T2, endoscopic response [decrease in SES-CD ≥ 50%] and remission [SES-CD = 0] were scored. RESULTS: A total of 40 patients were included: 14 reached endoscopic remission and 17 endoscopic response. At T1 (3.1 mm [1.9-4.2] vs 5.3 mm [3.8-6.9], p = 0.005) and T2 (2.0 mm [1.8-3.1] vs 5.1 [3.0-6.3] mm, p = 0.002) BWT was lower in patients with endoscopic remission. At T1 and T2, 18% (area under the receiver operating curve [AUROC]: 0.77; odds ratio [OR]: 10.80, p = 0.012) and 29% [AUROC: 0.833; OR: 37.50, p = 0.006] BWT decrease predicted endoscopic response, respectively. To determine endoscopic remission, BWT 3.2 mm was most accurate [AUROC: 0.94; OR: 39.42, p < 0.0001] at T2. In addition, absence of colour Doppler signal [OR: 13.76, p = 0.03] and the CEUS parameter wash-out rate [OR: 0.76, p = 0.019] improved the prediction model. CONCLUSIONS: Reduction in BWT, already after 4-8 weeks of follow-up, predicted endoscopic response and remission. CEUS parameters were of limited value. Furthermore, we have provided accurate cut-offs for BWT reflecting endoscopic response and remission at different time points.

Ultrasound for Assessing Disease Activity in IBD Patients: A Systematic Review of Activity Scores.

BACKGROUND AND AIMS: Ultrasound [US] indices for assessing disease activity in IBD patients have never been critically reviewed. We aimed to systematically review the quality and reliability of available ultrasound [US] indices compared with reference standards for grading disease activity in IBD patients. METHODS: Pubmed, Embase and Medline were searched for relevant literature published within the period 1990 to June 2017. Relevant publications were identified through full text review after initial screening by two investigators. Data on methodology and index characteristics were collected. Study quality was assessed using a modified version of the Quadas-2 tool for risk of bias assessment. RESULTS: Of 20 studies with an US index, 11 studies met the inclusion criteria. Out of these 11 studies, 7 and 4 studied Crohn's disease [CD] and ulcerative colitis [UC0 activity indices, respectively. Parameters that were used in these indices included bowel wall thickness [BWT], Doppler signal [DS], wall layer stratification [WLS], compressibility, peristalsis, haustrations, fatty wrapping, contrast enhancement [CE], and strain pattern. Study quality was graded high in 5 studies, moderate in 3 studies and low in 3 studies. Ileocolonoscopy was used as the reference standard in 9 studies. In 1 study a combined index of ileocolonoscopy and barium contrast radiography and in 1 study histology was used as the reference standard. Only 5 studies used an established endoscopic index for comparison with US. CONCLUSIONS: Several US indices for assessing disease activity in IBD are available; however, the methodology for development was suboptimal in most studies. For the development of future indices, stringent methodological design is required.

Gastric accommodation in healthy subjects studied by ultrasound, manometry, and impedancemetry.

BACKGROUND: Gastric accommodation to a meal may be important in the pathogenesis of upper gastrointestinal disorders, but has been difficult to investigate in a minimally invasive fashion. METHODS: We studied gastric and lower esophageal physiology during food intake, combining transabdominal ultrasound, multichannel high-resolution impedance-manometry (HRIM) and a symptom questionnaire. A HRIM catheter was distally positioned at incisura angularis and 300 mL saline with 75 g glucose was ingested. Target variables were recorded for 30 min after fluid intake. KEY RESULTS: Fifteen healthy subjects' participated (11W/4M, median age 23.8 y) and all accepted the meal with few symptoms. At incisura angularis maximum change in pressure from pre-intake values was -7.4 mmHg after 60 s (P < .0001), rising to pre-intake values within 20 min. The corresponding area increased significantly from pre-intake values of 8.0 cm2 to 14.1 cm2 shortly after intake (P = .0012), peaked at 5 min and slowly decreased towards 30 min. The corresponding maximum change in stress from pre-intake pressure values was -59.2 mmHg shortly after (P < .0001), reaching pre-intake values within 20 min. Strain rose from 0 shortly before to 0.36 shortly after (P < .0001), peaking at 5 min. At incisura angularis, fullness was positively correlated with area and to strain, while fullness, area, and stress were negatively correlated with pressure. CONCLUSIONS & INFERENCES: The multimodal method enabled assessment of the gastric accommodation reflex, stress and strain in the stomach. It triggered few symptoms in healthy volunteers. We propose it to be a more physiological replacement of the barostat technique.

Navigated retrograde endoscopic myotomy (REM) for the treatment of therapy-resistant achalasia.

BACKGROUND: In achalasia, muscle spasm may involve the proximal esophagus. When the muscle spasm is located in the proximal esophagus, conventional per oral endoscopic myotomy (POEM) may not be sufficient to relieve symptoms. In this paper, we describe retrograde endoscopic myotomy (REM) as a novel approach to perform myotomy of the proximal esophagus, with the application of a navigation tool for anatomical guidance during REM. We aim to evaluate the feasibility and safety of REM and usefulness of the navigation during REM. METHOD: A 42-year-old male with type III achalasia who was treated with laparoscopic myotomy with fundoplication, multiple pneumatic balloon dilations, Botox injections and anterior POEM of the middle and distal esophagus without symptomatic effect. Repeated high-resolution- manometry (HRM) revealed occluding contractions of high amplitude around and above the aortic arch. A probe-based real-time electromagnetic navigation platform was used to facilitate real-time anatomical orientation and to evaluate myotomy position and length during REM. RESULTS: The navigation system aided in identifying the major structures of the mediastinum, and position and length of the myotomy. Twelve weeks after REM, the Eckardt score fell from seven at baseline seven to two. We also observed improvement with reduction of the pressure at the level of previous spasms in the proximal esophagus from 124 mmHg to 8 mmHg on HRM. CONCLUSION: REM makes the proximal esophagus accessible for endoscopic myotomy. Potential indication for REM is motility disorders in the proximal esophagus and therapy failure after POEM.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided Therapeutic Interventions (short version).

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions: General Aspects and EUS-guided Sampling (Short Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

Differentiation of Metastatic and Non-Metastatic Mesenteric Lymph Nodes by Strain Elastography in Surgical Specimens.

PURPOSE: To investigate if strain elastography could differentiate between metastatic and non-metastatic mesenteric lymph nodes ex-vivo. MATERIALS AND METHODS: 90 mesenteric lymph nodes were examined shortly after resection from 25 patients including 17 patients with colorectal cancer and 8 patients with Crohn's disease. Ultrasound-based strain elastography was performed with a linear probe. Tissue hardness in lymph nodes was assessed using visual scales and measuring the strain ratio. B-mode characteristics were also recorded. Pathological diagnosis with grading of fibrosis served as the reference standard. RESULTS: 20 lymph nodes were metastatic and 70 lymph nodes were non-metastatic. The strain ratios of metastatic and non-metastatic lymph nodes were significantly different (1.83 vs. 1.42, p = 0.021). The VAS scale (0 - 100) for tissue hardness gave higher mean values for metastatic than non-metastatic nodes, but the difference was not significant (65.5 vs. 55.0, p = 0.055). There was no difference between lymph nodes in Crohn's and non-metastatic cancer specimens. The metastatic lymph nodes were significantly more fibrotic than the non-metastatic lymph nodes by the ordinal fibrosis score (0 - 3). In an ROC analysis, quantitative strain imaging was not superior to the measurement of the short-axis diameter of lymph nodes in differentiating metastatic from non-metastatic mesenteric lymph nodes ex-vivo. CONCLUSION: Strain elastography is correlated to fibrosis in lymph nodes and a significant difference was observed on a group level using the strain ratio. Due to measurement overlap, individual mesenteric lymph nodes could not be identified accurately as metastatic or not in this ex-vivo model by strain imaging alone.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Short Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Long Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided Interventions: General aspects and EUS-guided sampling (Long Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V.

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part I. General Aspects (Short Version).

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (short version; the long version is published online).

Multimodal approach to assess tumour vasculature and potential treatment effect with DCE-US and DCE-MRI quantification in CWR22 prostate tumour xenografts.

The aim of this study was to compare intratumoural heterogeneity and longitudinal changes assessed by dynamic contrast-enhanced ultrasound (DCE-US) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in prostate tumour xenografts. In vivo DCE-US and DCE-MRI were obtained 24 h pre- (day 0) and post- (day 2) radiation treatment with a single dose of 7.5 Gy. Characterization of the tumour vasculature was determined by Brix pharmacokinetic analysis of the time-intensity curves. Histogram analysis of voxels showed significant changes (p < 0.001) from day 0 to day 2 in both modalities for kep , the exchange rate constant from the extracellular extravascular space to the plasma, and kel , the elimination rate constant of the contrast. In addition, kep and kel values from DCE-US were significantly higher than those derived from DCE-MRI at day 0 (p < 0.0001) for both groups. At day 2, kel followed the same tendency for both groups, whereas kep showed this tendency only for the treated group in intermediate-enhancement regions. Regarding kep median values, longitudinal changes were not found for any modality. However, at day 2, kep linked to DCE-US was correlated to MVD in high-enhancement areas for the treated group (p = 0.05). In contrast, correlation to necrosis was detected for the control group in intermediate-enhancement areas (p < 0.1). Intratumoural heterogeneity and longitudinal changes in tumour vasculature were assessed for both modalities. Microvascular parameters derived from DCE-US seem to provide reliable biomarkers during radiotherapy as validated by histology. Furthermore, DCE-US could be a stand-alone or a complementary technique.

Strain assessment in surgically resected inflammatory and neoplastic bowel lesions.

PURPOSE: To investigate whether ultrasound-based strain imaging can discriminate between colorectal adenocarcinomas and stenotic Crohn's lesions in newly resected surgical specimens. MATERIALS AND METHODS: Resected surgical specimens from 27 patients electively operated for colorectal tumors or stenotic lesions from Crohn's disease were prospectively examined with ultrasonography using a Hitachi HV 900 US scanner with real-time elastography (RTE). Three different methods were applied to assess tissue strain: A four-level categorical visual classification, a continuous visual analog scale (VAS, 0 - 100) and a strain ratio (SR) measurement between the lesion and surrounding reference tissue. The imaged sections were marked and subsequently examined by a pathologist. Results from RTE were evaluated according to diagnosis, degree of fibrosis, inflammatory parameters, tumor stage and grade. RESULTS: 16 sections from Crohn's lesions, 18 sections from adenocarcinomas and 4 sections from adenomas were examined. Both adenocarcinomas and Crohn's lesions were found to be harder than the surrounding tissue, but they could not be discriminated from each other by any of the strain imaging evaluation methods. All adenocarcinomas had significantly higher strain ratios than adenomas. The categorical classification differentiated poorly between Crohn's lesions, adenocarcinomas and adenomas. Categorical evaluation and VAS score showed fair interobserver agreement. SR measurements provided semi-quantitative strain data and added improved information about elasticity properties, despite substantial intra-observer variation. CONCLUSION: Sonoelastography with SR measurements and visual evaluation of strain differences could not differentiate stenotic Crohn's lesions from adenocarcinomas in resected bowel specimens. A small number of adenomas were found to be significantly softer than adenocarcinomas using the same evaluation methods. The tumor stage or grade did not have a significant impact on the elastography results.

Elastography and strain rate imaging of the gastrointestinal tract.

Ultrasound based elastography of the gastrointestinal tract may be a useful approach to improved tissue characterisation. Distinguishing malignant lesions from benign may be one useful application. Monitoring of inflammatory bowel lesions for degree of inflammation or fibrosis would be another clinically useful tool. The anatomy of the bowel, however, raises many challenges for strain or shear wave imaging due to thin structures, non-constant boundary conditions and intrinsic contractility. Pathological lesions tend to increase bowel wall thickness and may ease elastography imaging. Very few studies have addressed issues of bowel wall elastography so far, and both inflammatory and neoplastic lesions seem to increase tissue hardness in the bowel wall.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications.

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology.

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts.

Controversies in dyspepsia.

Even in the absence of visible lesions like an ulcer, cancer or oesophagitis, patients with functional dyspepsia may complain of severe dyspeptic symptoms and have a poor quality of life. Characteristically, these patients also often have a low estimate of their own health and have complaints from several organ systems. The cause of the disease is not known. Both central nervous system and gastric disturbances appear to be involved, and their relative importance is controversial. There is no clear beneficial effect of acid suppression or H. pylori eradication although effects of such therapy may be seen in minor subgroups. New findings emphasise the importance of distinguishing between functional dyspepsia and gastro-oesophageal reflux disease, which exhibit completely different gastric accommodation patterns to a meal and have very different therapeutic potential. The effect of drugs like glyceryl trinitrate, glucagon, sumatriptan and buspirone which all concomitantly improve symptoms and gastric accommodation support the important role of abnormal gastric accommodation to meals in patients with functional dyspepsia. A hypothetical model for the pathogenesis of functional dyspepsia is presented. It incorporates four established abnormalities: various psychological abnormalities, low vagal tone, impaired gastric relaxation, and visceral hypersensitivity, in a logical interplay along the brain-gut axis.

[Intraluminal sonography in the diagnosis of gastrointestinal diseases]. / Intraluminale Sonographie in der Diagnostik von gastrointestinalen Krankheiten.

Endosonography is an imaging method whereby a high frequency ultrasound probe is inserted into a body cavity with or without under endoscopic control. Examination of the gastrointestinal tract is performed using special echo-endoscopes or trans-endoscopic mini-probes. The gastrointestinal wall, mediastinum, pancreas, bile ducts, retroperitoneum, and other structures surrounding the gastrointestinal tract are target organs for endosonography. A detailed image of pathological processes can thus be obtained. The method can be used both for primary diagnosis of lesions and in follow-up of gastrointestinal diseases. It is accurate in local staging of cancer and in detecting small lesions. There are some limitations for optimal examination like stenoses or other factors prohibiting a precise positioning of the ultrasound transducer. The clinical importance of endo-sonographic examinations must be continuously evaluated on the basis of new technical modalities and changes in therapeutic procedures.