Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

Target Door-to-Needle Time for Tissue Plasminogen Activator Treatment with Magnetic Resonance Imaging Screening Can Be Reduced to 45 min.

OBJECTIVE: The purpose of this study was to demonstrate that the median door-to-needle (DTN) time for intravenous tissue plasminogen activator (tPA) treatment can be reduced to 45 min in a primary stroke centre with MRI-based screening for acute ischaemic stroke (AIS). METHODS: From February 2015 to February 2017, the stroke unit of Perpignan general hospital, France, implemented a quality-improvement (QI) process. During this period, patients who received tPA within 4.5 h after AIS onset were included in the QI cohort. Their clinical characteristics and timing metrics were compared each semester and also with those of 135 consecutive patients with AIS treated by tPA during the 1-year pre-QI period (pre-QI cohort). RESULTS: In the QI cohort, 274 patients (92.5%) underwent MRI screening. While the demographic and baseline characteristics were not significantly different between cohorts, the median DTN time was significantly lower in the QI than in the pre-QI cohort (52 vs. 84 min; p < 0.00001). Within the QI cohort, the median DTN time for each semester decreased from 65 to 44 min (p < 0.00001) and the proportion of treated patients with a DTN time ≤45 min increased from 25 to 58.9% (p < 0.0001). Overall, DTN time improvement was associated with a better outcome at 3 months (patients with a modified Rankin Scale score between 0 and 2: 61.8% in the QI vs. 39.3% in the pre-QI cohort; p < 0.0001). CONCLUSIONS: A QI process can reduce the DTN within 45 min with MRI as a screening tool.

Contrast-enhanced ultrasound (CEUS) follow-up after radiofrequency ablation or cryoablation of focal liver lesions: treated-area patterns and their changes over time.

OBJECTIVES: To describe the early patterns of liver lesions successfully treated with radiofrequency ablation (RFA) or cryoablation (CA) and their changes over time. METHODS: Twenty-two RFA-treated and 17 CA-treated patients underwent CEUS from week 1 to year 3 post-ablation. Patterns, margins and volumes of RF-induced and cryolesions were evaluated and compared over time. RESULTS: After contrast enhancement, shortly after ablation, undefined margins with persistent enhancing small vessels penetrating >2 mm into the treated zone were significantly more frequent after CA (67 %) than RFA (22 %) (P < 0.02). During the arterial phase, a thin, enhancing marginal rim was seen during week 1 (T1) in around 28 % of RF lesions, while 75 % of cryolesions had thick enhancing rims (P < 0.02). The mean RF-induced lesion volume, maximum at T1 (44.1 ± 37.5 ml), shrank slowly over time, remaining clearly visible at 1 year (8.3 ± 7.4 ml). Cryolesions shrank faster (P = 0.009), from an average of 16.6 ± 7.1 ml at T1 to 1.7 ± 1.3 ml 1-year post-ablation. CONCLUSION: RF-induced and cryolesions differ, particularly their margins and shrinkage rates. Knowing these differences allows avoidance of incomplete treatment or falsely diagnosed recurrence, especially after CA. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) provides new follow-up information following hepatic radiological inyervention. • CEUS provides good visualisation of vascular modifications after thermoablation. • RFA-induced lesions and cryoablated lesions differ. • Knowledge about RF and cryolesion patterns is essential for correct CEUS follow-up. • Cryolesions have thicker peripheral inflammatory reactions and shrink faster than RFA-induced lesions.

Evaluation of shearwave elastography for the characterisation of focal liver lesions on ultrasound.

OBJECTIVES: To determine the elasticity characteristics of focal liver lesions (FLLs) by shearwave elastography (SWE). METHODS: We used SWE in 108 patients with 161 FLLs and in the adjacent liver for quantitative and qualitative FLLs stiffness assessment. The Mann-Whitney test was used to assess the difference between the groups of lesions where a P value less than 0.05 was considered significant. RESULTS: SWE acquisitions failed in 22 nodules (14 %) in 13 patients. For the 139 lesions successfully evaluated, SWE values were (in kPa), for the 3 focal fatty sparings (FFS) 6.6 ± 0.3, for the 10 adenomas 9.4 ± 4.3, for the 22 haemangiomas 13.8 ± -5.5, for the 16 focal nodular hyperplasias (FNHs) 33 ± -14.7, for the 2 scars 53.7 ± 4.7, for the 26 HCCs 14.86 ± 10, for the 53 metastasis 28.8 ± 16, and for the 7 cholangiocarcinomas 56.9 ± 25.6. FNHs had significant differences in stiffness compared with adenomas (P = 0.0002). Fifty percent of the FNHs had a radial pattern of elevated elasticity. A significant difference was also found between HCCs and cholangiocarcinomas elasticity (P = 0.0004). CONCLUSIONS: SWE could be useful in differentiating FNHs and adenomas, or HCCs and cholangiocarcinomas by ultrasound.

Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation.

OBJECTIVE: To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE). METHODS: In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour's major diameter and the viable tumour's major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher's test were used to compare treatment groups. RESULTS: At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up. CONCLUSIONS: One parameter, TVI, could evaluate the morphological and functional response to treatments.

Psoas muscle index is not representative of skeletal muscle index for evaluating cancer sarcopenia.

BACKGROUND: A common method for diagnosing sarcopenia involves estimating the muscle mass by computed tomography (CT) via measurements of the cross-sectional muscle area (CSMA) of all muscles at the third lumbar vertebra (L3) level. Recently, single-muscle measurements of the psoas major muscle at L3 have emerged as a surrogate for sarcopenia detection, but its reliability and accuracy remain to be demonstrated. METHODS: This prospective cross-sectional study involved 29 healthcare establishments and recruited patients with metastatic cancers. The correlation between skeletal muscle index (SMI = CSMA of all muscles at L3/height2 , cm2 /m2 ) and psoas muscle index (PMI = CSMA of psoas at L3/height2 , cm2 /m2 ) was determined (Pearson's r). ROC curves were prepared based on SMI data from a development population (n = 488) to estimate suitable PMI thresholds. International low SMI cut-offs according to gender were studied for males (<55cm2 /m2 ) and for females (<39 cm2 /m2 ). Youden's index (J) and Cohen's kappa (κ) were calculated to estimate the test's accuracy and reliability. PMI cut-offs were validated in a validation population (n = 243) by estimating the percentage concordance of sarcopenia diagnoses with the SMI thresholds. RESULTS: Seven hundred and sixty-six patients were analysed (mean age 65.0 ± 11.8 years, 50.1% female). Low SMI prevalence was 69.1%. Correlation between the SMI and PMI for the entire population was 0.69 (n = 731, P < 0.01). PMI cut-offs for sarcopenia were estimated in the development population at <6.6cm2 /m2 in males and at <4.8 cm2 /m2 for females. The J and κ coefficients for PMI diagnostic tests were weak. The PMI cut-offs were tested in the validation population where 33.3% of the PMI measurements were dichotomously discordant. CONCLUSIONS: A diagnostic test employing single-muscle measurements of the psoas major muscle as a surrogate for sarcopenia detection was evaluated but found to be unreliable. The CSMA of all muscles must be considered for evaluating cancer sarcopenia at L3.

Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy.

PURPOSE: To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. MATERIALS AND METHODS: All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, high-acoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves reflects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests. RESULTS: The lowest excised mean tumor weights (+/- standard deviation) corresponded to the longest bevacizumab-treatment duration: 1.4 g +/- 1.1 (continuous-treatment) compared with 2.3 g +/- 2.1 (discontinued) and 3.7 g +/- 1.9 (control) (P = .01). On day 35, the respective control and continuously treated groups had comparable and significantly larger necrotic areas: 37% +/- 14 and 32% +/- 17 larger than the discontinued-treatment group (15% +/- 9; P < .05). Normalized perfusion increased significantly with time (P = .02) in the discontinued-treatment group after therapy ceased (day 22). CONCLUSION: Noninvasively measured contrast-enhanced US parameters demonstrated tumor revascularization after stopping antiangiogenic therapy in this murine tumor model.

Acute complications of Crohn's disease: comparison of multidetector-row computed tomographic enterography with magnetic resonance enterography.

OBJECTIVE: To compare multidetector-row computed tomographic (MDCT) enterography with magnetic resonance (MR) enterography performed upon acute exacerbation of Crohn's disease. SUBJECTS AND METHODS: Fifty-seven patients (mean age 33.5) with proven Crohn's disease and symptoms suggesting acute exacerbation were prospectively included. After oral administration of 1-2 liters of 5% methylcellulose, MDCT and MR enterography were performed on each patient (mean delay <24 h). Three radiologists blindly and independently evaluated each examination for technical quality and in terms of 8 pathological features of Crohn's disease. Observers' agreement, sensitivity and specificity resulted from comparison with the reference standard [surgery (n = 24), endoscopy (n = 17) and long-term follow-up (n = 16)]. RESULTS: MDCT enterography demonstrated fewer artifacts than MR enterography (p < 0.0001). In 48 MDCT/MR enterography examinations, active disease was demonstrated: abscesses (n = 11), fistulas (n = 13), stenoses (n = 23) and/or intestinal inflammation (n = 38). Observers' agreement (range 0.56-0.87) was not significantly different between MDCT and MR enterography, neither in terms of sensitivity (range 58-95%) nor specificity (range 67-100%) for each of the 8 pathological features. CONCLUSION: Statistically, MR enterography is of similar diagnostic value as MDCT enterography for acute complications of Crohn's disease. Since the typical Crohn's disease patient is young and will very likely undergo life-long imaging, and given concerns about radiation exposure with MDCT, MR enterography should be the preferred modality.

Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations?

Since 2004, four antiangiogenic drugs have been approved for clinical use in patients with advanced solid cancers, on the basis of their capacity to improve survival in phase III clinical studies. These achievements validated the concept introduced by Judah Folkman that the inhibition of tumor angiogenesis could control tumor growth. It has been suggested that biomarkers of angiogenesis would greatly facilitate the clinical development of antiangiogenic therapies. For these four drugs, the pharmacodynamic effects observed in early clinical studies were important to corroborate activities, but were not essential for the continuation of clinical development and approval. Furthermore, no validated biomarkers of angiogenesis or antiangiogenesis are available for routine clinical use. Thus, the quest for biomarkers of angiogenesis and their successful use in the development of antiangiogenic therapies are challenges in clinical oncology and translational cancer research. We review critical points resulting from the successful clinical trials, review current biomarkers, and discuss their potential impact on improving the clinical use of available antiangiogenic drugs and the development of new ones.

Multi-detector row CT and postprocessing techniques in the assessment of diffuse lung disease.

Many acute and chronic lung diseases are characterized by diffuse infiltration of the lung parenchyma. High-resolution computed tomography (CT) has been widely accepted as the imaging standard of reference for the assessment of these diseases. However, only approximately 10% of the lung parenchyma is scanned with high-resolution CT, and characteristic foci of disease may be missed. With use of the established characteristic high-resolution CT patterns, multi-detector row chest CT has revolutionized the evaluation of diffuse lung disease. Multi-detector row CT generates isotropic volumetric high-resolution data, allowing contiguous three-dimensional (3D) visualization of the lung parenchyma, with the capacity to create high-quality two-dimensional (2D) and 3D reformatted images. Minimum intensity projection is the postprocessing technique of choice for the detection and characterization of most patterns of diffuse lung disease. Maximum intensity projection (MIP) allows the detection and characterization of micronodules; the recognition of enlarged pulmonary veins, which is extremely useful in the diagnosis of pulmonary edema and the assessment of mosaic perfusion; and differentiation between perilymphatic, miliary, and centrilobular distribution. MIP can also help differentiate between constrictive bronchiolitis and mixed emphysema. Two-dimensional reformatted images are now of equal importance with the 2D axial images in diagnosing specific diffuse lung diseases. In the future, 3D reformatted images may be used to help quantify these disorders.

Focal nodular hyperplasia and hepatocellular adenoma: The value of shear wave elastography for differential diagnosis.

OBJECTIVE: This study assessed the clinical usefulness of shear wave elastography (SWE) during ultrasound for differentiating between focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HAs). MATERIALS AND METHODS: SWE was performed on 56 patients presenting with 76 liver lesions (57 FNHs and 19HAs) that were confirmed by MRI and contrast-enhanced ultrasound (CEUS) (n=55) or by histology (n=21). A mean elasticity value was obtained for each lesion. The ratios of the elasticity of the lesions to the elasticity of the surrounding liver were determined. The optimal elasticity cut-off value for distinguishing between the two lesion types was determined using ROC analysis. All lesions that were classified as "undetermined" after CEUS were reclassified using the elasticity values. RESULTS: The mean elasticity value was 46.99 ± 31.15 kPa for FNHs and 12.08 ± 10.68 kPa for HAs (p<0.0001). The mean relative elasticity ratio values were 7.94 ± 6.43 and 1.91 ± 1.70, respectively (p<0.0001). The ROC analysis showed a maximal accuracy of 95% for identification with a cut-off of 18.8 kPa for lesion elasticity (accuracy of 96% with a cut-off of 1.98 for the relative elasticity ratio). A total of 68 CEUS were performed, and 17 lesions (25%) were classified as "undetermined" after CEUS. With these cut-off values 16 lesions (94.1%) were correctly reclassified as FNHs. CONCLUSION: SWE is a useful adjunctive tool for differentiation between FNH and HA during ultrasound examination.

Prognostic factors in patients with refractory ascites treated by transjugular intrahepatic porto-systemic shunt: From the liver to the kidney.

BACKGROUND: The aim of this retrospective study was to evaluate the prognostic value of different scores (including Child-Pugh and Model for End Stage Liver Diseases) in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt for refractory ascites. METHODS: Overall, 111 patients with transjugular intrahepatic porto-systemic shunt insertion between January 1998 and July 2012 were included. RESULTS: Survival rates (without transplantation) were 82.0% at 3 months, and 59.4% at 1 year. In addition to standard parameters, a new simple classification based on platelet count and glomerular filtration rate showed strong prognostic ability and could distinguish 3 groups of patients (Log-rank test, p<0.001): a "good-prognosis" group with platelet counts above 125×10(9)L(-1) and a glomerular filtration rate above 90 mL/min (1-year survival rate 92%), a "poor-prognosis" group with platelet counts below 125×10(9)L(-1) and a glomerular filtration rate below 90 mL/min (1-year survival rate 34.8%), and an "intermediate-prognosis" group (1-year survival rate 58.2%). Multivariate analysis showed a hazard ratio of 6.34 for the intermediate class and of 12.623 for the high class. CONCLUSIONS: A new and simple classification including platelet count and glomerular filtration rate is highly predictive of survival in patients with refractory ascites treated with transjugular intrahepatic porto-systemic shunt and could be used to select patients for this procedure.

Neuroendocrine neoplasms of the jejunum: a heterogeneous group with distinctive proximal and distal subsets.

Neuroendocrine tumors (NETs) of the jejunum are rare and usually grouped with either duodenal or ileal NETs. We aimed at better evaluating their characteristics by studying 116 cases of small-bowel NETs for which a precise anatomical location was available. Thirty-four cases were duodenal. Eighty-two were located after the duodenojejunal ligament, including ten cases in the first 50 cm, four cases between 50 and 100 cm, and six cases between 100 and 250 cm. All tumors located after 50 cm from the duodenojejunal ligament were enterochromaffin neoplasms. In contrast, the ten tumors located before this point formed a heterogeneous group. They included two cases of gastrin-expressing tumors in the first 10 cm and one case of enterochromaffin tumor located at 45 cm. The seven remaining cases were large tumors, located between 10 and 50 cm, of intermediate or high histological grade (four out of seven G2 or G3), locally invasive and usually metastatic (five out of seven with liver metastases); their survival was comparable to that of duodenal NETs. Patients with tumors located in the duodenum or the first 50 cm of the jejunum had longer survivals than those with lower jejunal and ileal tumors (p = 0.024). In conclusion, our study underlines the heterogeneity of jejunal NETs and supports the distinction between "upper" and "lower" jejunal tumors, which, for prognostic purposes, might be grouped with, respectively, duodenal and ileal NETs. Our data suggest that the arbitrary limit between upper and lower jejunal tumors might be fixed at 50 cm from the duodenojejunal ligament.

Correlation and agreement between contrast-enhanced ultrasonography and perfusion computed tomography for assessment of liver metastases from endocrine tumors: normalization enhances correlation.

We studied correlation and agreement between perfusion parameters derived from contrast-enhanced ultrasonography (CEUS) and computed tomography (CT). Both techniques were performed in 16 patients with proven liver metastases from endocrine tumor. Replenishment study after ultrasound-induced destruction of microbubbles was used for CEUS quantification. CEUS-derived relative values of blood flow, blood volume and mean transit time were compared with perfusion CT-derived parameters measured in the same tumors. Significant correlation was observed between CEUS normalized values and CT absolute tumor values for blood flow (r = 0.58; p = 0.018), blood volume (r = 0.61; p = 0.012) and mean transit time (r = 0.52; p = 0.037). Correlation was not significant for non-normalized values. Agreement between CEUS normalized values and perfusion CT relative values was significant (p < 0.04). Estimated bias between CEUS and CT for relative perfusion values was -1.38 (-5.02; 2.27) for blood flow, +0.26 (-0.79; 1.31) for blood volume and +0.21 (-0.46; 0.87) for mean transit time. We conclude that normalization markedly increased correlation between CEUS- and CT-derived perfusion values and allowed agreement assessment.

Long-term survival after pancreaticoduodenectomy for endocrine tumors of the ampulla of Vater and minor papilla.

OBJECTIVE: Endocrine tumors of the ampullary region are rare, and accurate indications for their management are lacking. We aimed to evaluate the outcome of surgical treatment in this indication. METHOD: We reviewed all patients who submitted to a pancreaticoduodenectomy for ampullary endocrine tumors between 1982 and 2003 in our center. RESULTS: Eight patients, 3 men and 5 women, with a mean age of 47.8 years (range, 37-57 years) were included. Two patients presented with Zollinger-Ellison syndrome, and 1 had neurofibromatosis. Operative mortality was nil. The mean size of the tumors was 17.4 mm (range, 5-40 mm). There were 7 well-differentiated and 1 poorly differentiated endocrine carcinomas. Seven patients had satellite lymph node metastases, and 1 had diffuse liver metastases. Median follow-up was 131 months (range, 17-315 months). At the end of the follow-up period, 5 patients were alive and disease-free; 1 patient was alive with stable liver metastases. Two patients died 17 months and 13 years after surgery, respectively, from metastasis and an unrelated cause. CONCLUSION: This study demonstrates the high frequency of lymph node invasion in these uncommon tumors, even at an early clinical stage. Pancreaticoduodenectomy may result in prolonged survival of patients with well-differentiated tumors.