A preliminary study suggests that intestinal-wall assessment by means of noninvasive multispectral optoacoustic tomography may distinguish remission from active disease in patients with Crohn’s ...disease.
To the Editor:
In chronic inflammatory diseases, uncontrolled inflammation is associated with increased rates of hospitalization, complications, and death. Because of the potential severity of these conditions, there is an increased demand for new diagnostic approaches.
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Multispectral optoacoustic tomography (MSOT) is a new imaging technique that permits the noninvasive quantification of hemoglobin-dependent tissue perfusion and oxygenation as surrogates of inflammation.
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This approach uses the excitation of short-pulsed laser light with near-infrared wavelengths to induce the photoacoustic effect in targeted tissues, which results in detectable sound waves induced by thermoelastic expansion.
In this single-center, cross-sectional diagnostic study (ClinicalTrials.gov number, NCT02622139), . . .
Highlights • ARFI elastography of the pancreas is feasible . • Shear wave velocities in patients with acute or chronic pancreatitis or carcinoma are higher than those occurring in normal tissue . • ...ARFI values considerable overlap between different pathologies.
Objectives
We compared the interobserver agreement for the recently introduced contrast-enhanced ultrasound (CEUS)-based algorithm CEUS-LI-RADS (Liver Imaging Reporting and Data System) versus the ...well-established magnetic resonance imaging (MRI)-LI-RADS for non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.
Methods
Focal liver lesions in 50 high-risk patients (mean age 66.2 ± 11.8 years; 39 male) were assessed retrospectively with CEUS and MRI. Two independent observers reviewed CEUS and MRI examinations, separately, classifying observations according to CEUS-LI-RADSv.2016 and MRI-LI-RADSv.2014. Interobserver agreement was assessed with Cohen’s kappa.
Results
Forty-three lesions were HCCs; two were intrahepatic cholangiocarcinomas; five were benign lesions. Arterial phase hyperenhancement was perceived less frequently with CEUS than with MRI (37/50 / 38/50 lesions = 74%/78% CEUS; observer 1/observer 2 versus 46/50 / 44/50 lesions = 92%/88% MRI; observer 1/observer 2). Washout appearance was observed in 34/50 / 20/50 lesions = 68%/40% with CEUS and 31/50 / 31/50 lesions = 62%/62%) with MRI. Interobserver agreement was moderate for arterial hyperenhancement (ĸ = 0.511/0.565 CEUS/MRI) and “washout” (ĸ = 0.490/0.582 CEUS/MRI), fair for CEUS-LI-RADS category (ĸ = 0.309) and substantial for MRI-LI-RADS category (ĸ = 0.609). Intermodality agreement was fair for arterial hyperenhancement (ĸ = 0.329), slight to fair for “washout” (ĸ = 0.202) and LI-RADS category (ĸ = 0.218)
Conclusion
Interobserver agreement is substantial for MRI-LI-RADS and only fair for CEUS-LI-RADS. This is mostly because interobserver agreement in the perception of washout appearance is better in MRI than in CEUS. Further refinement of the LI-RADS algorithms and increasing education and practice may be necessary to improve the concordance between CEUS and MRI for the final LI-RADS categorization.
Key Points
• CEUS-LI-RADS and MRI-LIRADS enable standardized non-invasive diagnosis of HCC in high-risk patients.
• With CEUS, interobserver agreement is better for arterial hyperenhancement than for “washout”.
• Interobserver agreement for major features is moderate for both CEUS and MRI.
• Interobserver agreement for LI-RADS category is substantial for MRI, and fair for CEUS.
• Interobserver-agreement for CEUS-LI-RADS will presumably improve with ongoing use of the algorithm.
Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B ...oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma.
Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days. Animals were assessed for survival, tumour size and spread, and tumour and immune related histological markers after 120 days. Peripheral blood mononuclear cells were tested for tumour-specific T cell activation and cytotoxicity. Immune modulatory cytokines tumour necrosis factor α, interleukin (IL)-2/IL-8/IL-10/IL-12 and interferon γ, and vascular endothelial growth factor were measured in serum.
Mean survival of untreated animals was 36 days, as compared with 97, 78 and 114 days for RFA, CpG and combination therapy, respectively. Compared with untreated controls, antitumour T cell stimulation/cytotoxicity increased 26/16-fold, 32/17-fold and 50/38-fold 2 weeks after RFA, CpG and combination treatments, respectively. The combination inhibited tumour spread to lungs and peritoneum significantly and prohibited new tumour growth in animals receiving a secondary systemic tumour cell injection. RFA alone induced a Th1 cytokine pattern, while IL-8 and IL-10 were only upregulated in CpG treated animals and controls.
The combination of TLR9 stimulation with RFA resulted in a potentiated antitumour T cell response and cytotoxicity in the VX2 tumour model. Only this combination prevented subsequent tumour spread and resulted in a significantly improved survival, justifying the need for further exploration of the combination of ablative therapies and TLR9 agonists in liver cancer.
Purpose
We evaluated ileal bowel wall thickness and semiquantitative vascularization by ultrasound in correlation with the presence or absence of histopathological inflammation in patients with ...Crohn’s disease (CD).
Methods
We conducted a retrospective analysis of 221 ultrasound examinations of the terminal ileum or neoterminal ileum in CD patients with biopsies of the ileum during colonoscopies within 8 weeks of the ultrasound. Ultrasound data were obtained from an inflammatory bowel disease ultrasound register from 2011 to 2017. Bowel wall ultrasound was performed by a high-frequency, linear transducer (7–12 MHz). Presence of bowel wall thickening (> 3 mm), vascularization by the Limberg score, and presence of ileal histopathological inflammation were analyzed.
Results
In 221 bowel wall ultrasound examinations of CD patients (128 female, 93 male, mean age 37.5 years), a thickened bowel wall was found in 140 (63.3%) and hypervascularization (corresponding to a Limberg score ≥ 2) in 96 (43.4%) cases. In 187 (84.6%) cases, ileal inflammation was confirmed by histopathology and in 34 (15.4%) cases no inflammation was shown. Bowel wall thickening showed a sensitivity of 70.1%, a negative predictive value (NPV) of 30.9%, a specificity of 73.5% and a positive predictive value (PPV) of 93.6% for the detection of histopathological ileal inflammation. Hypervasularization had a low sensitivity (49.7%) and NPV (24.8%), but high specificity (91.2%) and PPV (96.9%).
Conclusion
In this CD subcohort of an ultrasound register, pathologic ultrasound findings were quite common. Bowel wall thickening (> 3 mm) and hypervascularization are good predictors of histopathological inflammation within the terminal ileum or neoterminal ileum. Normal ultrasound findings without bowel wall thickening and without hypervascularization do not rule out histopathological inflammation.
Transjugular intrahepatic portosystemic shunt (TIPS) can treat portal hypertensive complications and modifies hepatic hemodynamics. Modification of liver perfusion can alter contrast enhancement ...dynamics of liver nodules. This study investigated the diagnostic performance of contrast-enhanced ultrasound (CEUS) to diagnose hepatocellular carcinoma (HCC) in cirrhosis with TIPS. In this prospective monocentric observational study, CEUS was used to characterize focal liver lesions in patients at risk for HCC with and without TIPS. Times of arterial phase hyperenhancement (APHE) und washout were quantified. Perfusion-index (PI) and resistance-index (RI) of hepatic artery and portal venous flow parameters were measured via doppler ultrasonography. Diagnostic gold standard was MRI/CT or histology. This study included 49 liver lesions 23 TIPS (11 HCC), 26 no TIPS (15 HCC). 26 were diagnosed as HCC by gold standard. Sensitivity and specificity of CEUS to diagnose HCC with and without TIPS were 93.3% and 100% vs. 90.9% and 93.3%, respectively. APHE appeared significantly earlier in patients with TIPS compared to patients without TIPS. TIPS significantly accentuates APHE of HCC in CEUS. CEUS has good diagnostic performance for diagnosis of HCC in patients with TIPS.
Purpose
Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma.
Methods
In total, 21 patients with ...liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria.
Results
Inter-observer-correlation (
r
) of DCE-US parameters time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF) at baseline, day 15, and day 56 was highly significant (
r
-range 0.73–0.97, all
p
< 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (
p
= 0.034) and at day 56 for both investigators (
p
= 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (
p
= 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis.
Conclusion
An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma.
AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard ...comprising CT, MRI and clinical/histological data. METHODS： It is an international multicenter study, and there were 12 centres and 125 patients （64 males, 61 females, aged 59 ± 11 years） involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a Iow-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS： CEUS with SonoVue increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS （55）, triple-phase spiral CT （61） and HRI with a liverspecific contrast agent （53）. Accuracy of detection of metastatic disease （i.e. at least one metastatic lesion） was significantly higher for CEUS （91.2%） than for unenhanced sonography （81.4%） and was similar to that of triple-phase spiral CT （89.2 %）. In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients （94.4%）. CONCLUSION： CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.
Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin ...induction therapy.
We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC.
Monocentric, prospective study.
We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy.
Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated.
Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies.
Not applicable.
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