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.

Point-of-care ultrasound in internal medicine: A position paper by the ultrasound working group of the European federation of internal medicine.

Point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. It has many uses in daily clinical practice, including improved diagnostic timeliness and accuracy, and providing information about a patient's prognosis and follow-up. It has been integrated into numerous specialities, but remains relatively undefined in internal medicine training programs. Ultrasonography is a useful tool in the standard clinical practice of internists in numerous clinical scenarios (Emergency Department, hospital ward, general and specific consultations, and home care). Although POCUS has been recently included in the European curriculum of internal medicine, there are differences between European internists in its use, ranging from not at all to well structured educational programs. The use of POCUS needs to be widespread in internal medicine departments, and to accomplish this we must encourage structured training. This document details the consensus-based recommendations by the European Federation of Internal Medicine (EFIM) Ultrasound working group. We establish POCUS core competencies and clinical settings for internists in a symptom-based approach. We also propose training requirements, providing a framework for training programs at a national level.

Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. AIM: To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis. METHODS: Serum samples were available from 138 large-duct primary sclerosing cholangitis patients (of which 102 [74%] with IBD) recruited 2008-2012 and 52 ulcerative colitis patients (controls). The median follow-up time was 2.2 (range 0-4.3) years. Specific biomarkers of type III and V collagen formation (PRO-C3 and PRO-C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinase-1 and hyaluronic acid was assessed for comparison. RESULTS: All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P < 0.001). PRO-C3 showed the largest difference between the two groups with a threefold increase in primary sclerosing cholangitis compared to ulcerative colitis patients. Patients with high baseline serum levels of all markers, except C3M, had shorter survival compared to patients with low baseline serum levels (P < 0.001). Combining PRO-C3 and PRO-C5 the odds ratio for predicting transplant-free survival was 47 compared to the Enhanced Liver Fibrosis test's odds ratio of 11. CONCLUSIONS: Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO-C3 was identified as a potent prognostic marker and an independent predictor of transplant-free survival in primary sclerosing cholangitis.

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.

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.

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.

EFSUMB Statement on Medical Student Education in Ultrasound [long version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we report EFSUMB policy statements on medical student education in ultrasound that in a short version is already published in Ultraschall in der Medizin 1.

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).

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 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).

EFSUMB statement on medical student education in ultrasound [short version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we summarise EFSUMB policy statements on medical student education in ultrasound.

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 II. Diagnostic Ultrasound-Guided Interventional Procedures (Short Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Long Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (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).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part I. General Aspects (long 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 (long version).