BACKGROUND & AIMS:The recent approval of pharmacological therapies for fibrotic metabolic dysfunction-associated steatohepatitis (MASH) has increased the need for accurate identification of treatment-eligible patients. Current recommendations increasingly rely on non-invasive tests (NITs), including vibration-controlled transient elastography (VCTE), while multiparametric ultrasound (MPUS) may provide additional opportunities for non-invasive assessment. However, agreement between histology and imaging-based approaches remains uncertain. We compared treatment eligibility based on histology, VCTE, and MPUS in two international biopsy-proven cohorts of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS:We analysed two biopsy-proven MASLD cohorts: CAP-IPDMA (n=1029), including VCTE and controlled attenuation parameter (CAP), and iLEAD (n=124), including MPUS. Treatment eligibility was assessed using histologically confirmed F2/F3 MASH and NIT-based recommendations from international expert panels. RESULTS:In CAP-IPDMA, 277/1029 patients (26.9%) met the histological definition of "at-risk MASH". Depending on the VCTE cut-off, 13.2-32.0% qualified for treatment. Overlap between histological "at-risk MASH" and VCTE thresholds was limited, reaching 27.8% when using VCTE 8-15 kPa, and decreasing when narrower or higher thresholds were applied. Among patients identified only by VCTE 8-15 kPa, males had lower median AST and ALT than those fulfilling only the histological indication (35 vs 48 IU/L p=0.034 and 45 vs 62 IU/L p=0.0072, respectively). In iLEAD, 21/124 patients (16.9%) met the histological definition, while 13.7-16.1% were eligible based on SWE thresholds, again with a similarly limited overlap. CONCLUSIONS:Histology and non-invasive tests capture partly distinct patient populations, meaning that both the number and type of patients selected for therapy depend on the chosen modality and cutoffs. As vibration-controlled transient elastography and multiparametric ultrasound become increasingly accessible in clinical practice, prospective validation is essential for establishing reliable non-invasive treatment pathways. IMPACT AND IMPLICATIONS:The current literature reflects a paradigm shift away from biopsy-based approaches toward NIT-based assessment of treatment eligibility in metabolic dysfunction-associated steatotic liver disease (MASLD), which may substantially affect which patients receive newly approved therapies. Our results are important for clinicians, researchers, and guideline developers because histology and current NIT cut-offs identify only partially overlapping patient populations, implying that different diagnostic strategies select different risk profiles. In practice, these findings support thoughtful implementation of NIT-based treatment pathways, the use of repeated measurements, and prospective validation of NIT thresholds to guide clinical care, trial design, and health policy decisions.
BACKGROUND:Achieving endoscopic remission is a key therapeutic goal in inflammatory bowel disease (IBD) that is associated with improved disease outcome. Transmural and intestinal barrier healing represent emerging targets, as they have similarly been associated with favourable disease behaviour. To date, no study has compared these novel end-points and their impact on avoiding deleterious disease outcome. METHODS:Clinically remittent IBD patients underwent ileocolonoscopy with assessment of intestinal barrier function by endomicroscopy. Transmural healing was assessed by magnetic resonance imaging or intestinal ultrasonography. Endoscopic and histologic disease activity were prospectively assessed along established scores. During subsequent follow-up (FU), patients were closely monitored for disease activity and major adverse outcomes (MAO): Disease flares, IBD-related hospitalization/surgery, initiation or escalation of systemic steroid, immunosuppressive or targeted advanced therapy. RESULTS:Eighty patients (47 Crohn's disease [CD], 33 ulcerative colitis [UC]) were included. During a mean FU of 34 (CD) and 18 (UC) months, 72% of CD and 85% of UC patients experienced MAO. Intestinal barrier healing exhibited the highest accuracy for predicting MAO-free survival in UC and CD patients and outcompeted transmural healing for predicting the further disease course. Both barrier healing and transmural healing showed higher diagnostic accuracy in forecasting the future course of disease when compared to endoscopic and histologic remission. CONCLUSION:Intestinal barrier healing is superior to transmural healing to prevent disease progression in clinical remittent IBD patients while both barrier and transmural healing showed superiority over endoscopic and histologic remission. Hence, barrier and transmural healing are emerging end-points potentially refining disease monitoring and outcome prediction.
The LI-RADS diagnostic algorithm uses imaging features in contrast-enhanced ultrasound (CEUS) to standardize the diagnosis of hepatocellular carcinoma (HCC) in at-risk patients. However, the diagnostic performance of specific major feature combinations has not been comprehensively evaluated. To evaluate the diagnostic performance of CEUS LI-RADs version 2017 major feature combinations for (HCC) in at-risk individuals across LI-RADS categories 3–5. A living systematic review and individual participant data (IPD) meta-analysis was conducted, including studies using CEUS LI-RADS v2016 or v2017 in at-risk patients, identified through database searches updated to February 2024. Eligible observations were categorized per LI-RADS guidelines, and PPVs for HCC were calculated for all major feature combinations in LI-RADS categories 3–5 using a random-effects one-step model. Risk of bias was assessed independently using a customized QUADAS-2 tool. Thirteen studies were included, comprising 1575 patients (mean age, 62.8 ± 11.2 years; 79.3
In addition to avoidance of radiation exposure, the main advantages of ultrasound diagnostics in inflammatory bowel disease (IBD) patients are its' immediate availability, also as a component of the physical examination (extended point of care), its' repeatability and its' high patient comfort. The fact that the examination is carried out directly by the treating physician and is not delegated to the radiologist increases compliance and therapy adherence of the patients.In the current series of papers a synopsis of recommendations for ultrasound in IBD guidelines, ultrasound parameters in inflammatory bowel disease including activities scores, the value of contrast enhanced ultrasound (CEUS), small intestinal contrast ultrasound (SICUS) and elastography, perineal ultrasound (PNUS), endoscopic ultrasound (EUS) including endorectal ultrasound (ERUS), interventional ultrasound (INVUS), detection of disease complications (stenoses, fistula, abscess), extraintestinal manifestations, differential diagnosis, evaluation of treatment response and outlook are discussed and illustrated.
BACKGROUND:The international bowel ultrasound group-segmental activity score (IBUS-SAS) is a validated tool with high interobserver agreement for accurately detecting disease activity in Crohn's disease (CD). Here, we addressed whether the IBUS-SAS is also suitable to assess disease activity in ulcerative colitis (UC). METHODS:The IBUS-SAS and Limberg scores were determined in the sigmoid colon of patients with UC. The results were correlated to established scores of clinical, endoscopic and histologic disease activity (partial [pMS] and endoscopic [eMS] Mayo-Score, ulcerative colitis endoscopic index of severity [UCEIS], histologic Nancy index) and/or biomarkers of inflammation (C-reactive protein [CRP], fecal calprotectin). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) for IBUS-SAS and the Limberg score to predict endoscopic and histologic disease activity were computed by receiver operating characteristics (ROC)-analysis. RESULTS:Fifty-eight patients with UC were enrolled. The median IBUS-SAS was 34.8. It was significantly correlated with pMS, eMS, UCEIS, Nancy index, CRP and fecal calprotectin. On ROC-analysis, a cut-off of 15.9 was reached with 100% sensitivity and 80.0% specificity for the prediction of endoscopic activity, resulting in a PPV of 94.7% and an NPV of 100%. The Limberg score performed only slightly worse (100.0%, 60.0%, 89.9%, 100%, respectively). Comparable results were found regarding the Nancy index for sensitivity (93.9% vs. 93.9%), specificity (57.1% vs. 42.9%), PPV (91.4% vs. 88.9%) and NPV (65.7% vs. 59.0%). CONCLUSIONS:This study highlights the potential of IUS for the non-invasive quantification of disease activity in UC and suggests that the IBUS-SAS should be considered as a diagnostic tool in trials and real-world management of UC.
Intestinal ultrasound had been performed in several countries for more than 30 years, but for a longer period had been inthe hands of few experts. With new evidence showing that the method is accurate and has excellent performance especially intreatment monitoring and detection of complications of IBD, there is a growing interest in performing this method by thosephysicians who care for IBD patients in in- and outpatient settings. The authors are convinced that intestinal ultrasound is helping to reduce radiation exposure and enables fast and less expensive decision-making by taking patients' needs into account. This paper series contains three parts. This first part summarizes guideline recommendations on the use of ultrasound in IBD, describes the typical findings that can be obtained at the point of care without advanced ultrasound technologies and helps tostandardize documentation. The second part will provide an overview on actual ultrasound-activity-scores in IBD and report about advanced multimodal ultrasound modalities and endoscopic and interventional ultrasound. These modalities should be provided by specialized IBD centers. The third part will enhance a wider overview of treatment control, mural and extramural disease complications as well as extraintestinal manifestations. Advantages and limitations of the method are discussed, with an outlook how to optimize implementation in the future.
Background: Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose: To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods: This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 124 participants (mean age, 53 years +/- 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion: Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license.
Background: Medically intractable ascites causes substantial distress in patients with palliative disease. Tunneled peritoneal catheters have been established as a feasible treatment option allowing patient-controlled paracentesis in a homecare setting. However, while a range of complications is associated with these drainages, risk factors for complications have not been identified so far. Objectives: To explore potential risk factors associated with complications of tunneled peritoneal catheters. Design: Retrospective observational cohort study. Methods: Single-center cohort comprising 49 patients with palliative disease receiving 57 tunneled peritoneal catheters at a tertiary care hospital. Results: Catheter placement was successful in all patients and associated with low numbers of severe complications. Our data suggest a higher risk for severe late complications in patients with benign disease, with drainage replacement, and when performed by less experienced physicians. Conclusion: Tunneled peritoneal catheters are an effective and safe option to treat symptomatic ascites in patients with end-stage palliative disease. The indication should be carefully considered in patients with benign disease and after removal or dislocation of a previous catheter.
Ultrasound (US) can be performed at the point of care by the treating physician, is safe, well tolerated and, therefore, can be repeated as often as clinically required and shortens the time to decision. An invaluable advantage of US is that the imaging is real-time and pathophysiological phenomena can be visualized dynamically. In addition, the multiparametric capabilities of US facilitate the evaluation of intestinal, peri-intestinal and some of the extra-intestinal manifestations of inflammatory boweldiseases (IBD).In the current series of papers a synopsis of recommendations for ultrasound in IBD guidelines, ultrasound parameters in inflammatory bowel disease including activities scores, the value of contrast enhanced ultrasound (CEUS), small intestinal contrast ultrasound (SICUS) and elastography, perineal ultrasound (PNUS), endoscopic ultrasound (EUS) including endorectal ultrasound (ERUS) and interventional ultrasound (INVUS) have been discussed and illustrated. This review discusses advantages, accuracy and limitations of ultrasound techniques for the diagnosis of intestinal, periintestinal and extra-intestinal complications of MC and CU and for monitoring treatment response.
BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.MethodsExosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.ResultsPDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).ConclusionWith exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
Technological progress and the development of complex mathematical models that allow the analysis of large and partially unstructured data have led to the rapid development of artificial intelligence (AI) since the 2010 s [1]. New AI applications, such as the recent "chatbot" ChatGPT, regularly attract a great deal of media attention with headlines ranging from euphoric to critical. As a result, the population developed specific expectations of the benefits, but also concerns about the potential risks of AI. In a survey published in 2023 by the digital association Bitkom, 73 % of the 1007 people surveyed saw AI as an opportunity [2]. Two thirds wanted AI to be used when it would bring specific benefits, for example in medicine or transportation. 14 % and 10 % of respondents saw AI rather or exclusively as a risk, respectively. The majority of respondents assumed that AI would noticeably change our society in the coming years. These survey results impressively show how much is already expected of AI. And indeed, AI accompanies us consciously or unconsciously in many everyday situations. There are also several examples in clinical medicine, e. g., in the automated evaluation of ECGs, differential blood counts, etc. [1]. Intensive research has been carried out into the possible use of AI in medical imaging since its beginnings over 80 years ago. In addition to approaches for image optimization, this primarily includes automated diagnosis for disease detection and classification as well as therapeutic monitoring. Enormous progress has been made in the field of imaging in recent years through the use of deep learning (DL) technologies. In contrast to classic forms of machine learning (ML), DL is based on neural networks in which several network levels are linked together [3]. Convolutional neural networks (CNNs) are frequently used in the field of image recognition. These are characterized by a hierarchical recognition of image patterns by the different network levels [3]. If initial structures such as corners, edges, or simple shapes are recognized, the linking of these simple structures in the deeper network levels enables the classification of complex structures such as malignancies in clinical imaging. In addition to better predictability, CNNs are more flexible than traditional ML. Furthermore, the time-consuming extraction of diagnostically relevant image information ("feature extraction"), which is necessary with classic ML, is no longer required, as image features are recognized independently by CNNs.
Objectives Point shear-wave elastography (pSWE) alias acoustic radiation force impulse (ARFI) imaging is a well-established ultrasound-based technique for the non-invasive assessment of liver tissue stiffness. As cut-off values for liver cirrhosis cannot be transferred from one ultrasound system to another, this study aimed at determining cut-off values for the newly developed Siemens ACUSON Sequoia ultrasound system. Methods In a pilot study phase, two independent examiners conducted 10 pSWE measurements in an elasticity phantom and 32 healthy individuals for the determination of inter-examiner agreement. Afterwards, 22 cirrhotic patients and 57 patients with chronic liver disease undergoing liver biopsy underwent pSWE. Patient characteristics and stiffness values were compared for individuals with and without liver cirrhosis. Diagnostic accuracies of cut-off values for the diagnosis of liver cirrhosis were calculated using areas under the receiver operating characteristics analysis and Youden’s index. In a subsequent validation study phase, these cut-off values were validated prospectively in 107 cirrhotic and 68 non-cirrhotic patients. Results Inter-examiner agreement was excellent for measurements in the elasticity phantom (intra-class correlation coefficient [ICC] = 0.998; P < 0.001), and good for measurements in patients (ICC = 0.844; P < 0.001). The best cut-off value for the diagnosis of liver cirrhosis was 1.405 m/s with an AUC of 0.872, a sensitivity of 88.2% and a specificity of 88.2% ( P < 0.001). Conclusion ARFI elastography using the Siemens ACUSON Sequoia showed a good inter-examiner agreement. The optimal cut-off value was lower than the cut-off values described for former generations of ultrasound devices. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.
We present the case of a 70-year-old patient of Caucasian origin under palliative chemotherapy for metastasized colorectal cancer, who presented with signs of complete small bowel obstruction six months after placement of a diverting ileostomy. Following previous tumor perforation, he was not considered a candidate for further surgical intervention. Thus, endoscopic ultrasound-guided enterocolostomy (i.e., ileosigmoidostomy) with a lumen-apposing metal stent was successfully performed in a coloenteric approach to restore the passage. Oral nutrition could be resumed the next day, and the patient could be discharged in substantially improved condition after three days.
Background Paraduodenal pancreatitis (PP) is an inflammation involving the groove zone, delimited by the duodenum lumen, bile duct, and the head of the pancreas. This area may also be involved during acute pancreatitis (AP). The differential diagnosis is clinically relevant, since PP generallypersists, whereas AP resolves. Hence, we compared a cohort of patients with PP and AP involving the groove area. Methods We retrospectively evaluated patients with pathology involving the groove area. The primary aim was to define the diagnostic features of PP compared to non-PP pancreatitis involving the groove area. PP was diagnosed by imaging, while AP was diagnosed according to the revised Atlanta classification and the clinical course, to exclude chronic pancreatitis. Results The study population consisted of 37 patients (32 men, age 56.9 +/- 9.1 years), 25 with a diagnosis of PP (23 men, mean age 54.9 +/- 8.5 years), and 12 (9 men, mean age 61.2 +/- 9.2 years) with AP involving the groove. All 25 patients with PP and 4 (33.3%) with AP reported a history of alcohol abuse, 23 patients (92%) with PP, and 3 (25%) with AP had a history of smoking. On imaging, PP patients presented a signifi & Oslash;tly thicker duodenal wall compared to the AP group (P=0.010). Chronic pancreatitis in the body/tail and exocrine insufficiency was prevalent in PP (P<0.001 and P=0.02). The medial displacement of the gastroduodenal artery was more frequent in the PP group (P=0.011). Conclusion PP has a different clinical and imaging profile compared to AP involving the groove area.
Aim: Numerous studies have evaluated elastography for the staging of liver fibrosis. Fewer studies were performed investigating the prognostic relevance using transient elastography (TE), although with promising results. This study was designed to evaluate the prognostic relevance of ARFI elastography. Material and method: Patients receiving ARFI elastography in our ultrasound department between 2010 and 2012 were initially screened for an ARFI examination with a clinical follow-up of at least 5 years. The following events were recorded: liver related death, liver unrelated death, HCC, liver decompensation/variceal bleeding. Results: A total of 335 patients were included in the final analysis with an ARFI examination of the liver and a follow-up of 60 months. Within the observation interval the number of events with corresponding AUROCs (shown with 95% confidence interval) were: overall death (n=49, 0.76 [0.69-0.83]), liver related death (n=25, 0.85 [0.77-0.93]), liver unrelated death (n=24, 0.66 [0.55-0.77]), HCC (n=15, 0.80 [0.72-0.87]), liver related complications/variceal bleeding (n=34, 0.87 [0.82-0.93]). In the group of patients with ARFI values suggestive of cirrhosis (equal to or above 1.80 m/s; n=110) higher values (<2.5 m/s vs. >= 2.5 m/s) where associated with a significant decline in liver related survival (p=0.007). Conclusion: ARFI elastography seems to have a good diagnostic accuracy for the prediction of liver related death and decompensation. Further it seems to allow a risk stratification in patients with cirrhosis suspicious elastography values.
Einleitung und Fragestellung Für die Punktscherwellenelastographie (pSWE) am Ultraschallsystem Siemens ACUSON Sequoia gibt es bisher keine publizierten Cut-Off Werte für den Nachweis einer Leberzirrhose. Herstellerangaben beziehen sich auf Studiendaten für das Ultraschallsystem Siemens S 2000 mit Cut-off Werten von 1.7 m/s bzw.1,8 m/s für den Nachweis einer Leberzirrhose Ziel der vorliegenden Arbeit war die Validierung von Cut-Off-Werten für Leberzirrhose für das ACUSON Sequoia System.