Fat-containing hepatocellular carcinoma in patients with cirrhosis: proposal of a diagnostic modification regarding enhancement characteristics.

OBJECTIVES: The aim of this study was to develop and validate an algorithm for the non-invasive diagnosis of these fat-containing HCCs. METHODS: Eighty-four cirrhotic patients with 77 fat-containing HCCs and 11 non-HCC fat-containing nodules were retrospectively included. All MRIs were reviewed; nodule characteristics, European Association for the Study of the Liver (EASL) and LI-RADS classifications, and survival were collected. One of the major features of LI-RADS v2018 (non-rim-like arterial phase hyperenhancement [APHE]) was changed to include different enhancing patterns at arterial phase and a new fat-LI-RADS algorithm was created for fat-containing nodules in cirrhosis. Its diagnostic performance was evaluated in both a derivation and external validation cohort (external cohort including 58 fat-containing HCCs and 10 non-HCC fat nodules). Reproducibility of this new algorithm was assessed. RESULTS: In the derivation cohort, 54/77 (70.1%) fat-containing HCCs had APHE, 62/77 (80.5%) had enhancement compared to the nodule itself at arterial phase (APE), 43/77 (55.8%) had washout, and 20/77 (26.0%) had an enhancing capsule. EASL and LI-RADS had a sensitivity of 37.7% (29/77) and 36.4% (28/77), respectively, for the diagnosis of fat-containing HCC and both had a specificity of 100% (11/11). The new fat-LI-RADS algorithm increased sensitivity to 50.6% (39/77) without decreasing the specificity of 100% (11/11). The validation cohort confirmed the increased sensitivity, with a slight decrease in specificity. The concordance for the diagnosis of HCC for fat-LR5 was 85.3% (58/68). CONCLUSION: The new fat-LI-RADS algorithm proposed here significantly improves the performance of the non-invasive diagnosis of fat-containing HCC and thus could reduce the number of biopsies conducted for fat-containing HCCs. CLINICAL RELEVANCE STATEMENT: The European Association for the Study of the Liver and LI-RADS guidelines are poorly sensitive for the diagnosis of fat-containing HCC, mainly because of the low rate of arterial phase hyperenhancement (APHE) displayed by fat-containing HCC. Using all types of enhancement instead of APHE improves sensitivity of LI-RADS. KEY POINTS: • Fat-containing HCCs on MRI account for 7.5% of HCCs and have different imaging characteristics from non-fatty HCCs. • The European Association for the Study of the Liver and LI-RADS algorithms for the non-invasive diagnosis of HCC have low sensitivity for the diagnosis of fat-containing HCC with MRI (37.7% and 36.4%, respectively). • The new fat-LI-RADS, which includes a slight modification of the "arterial enhancement" criterion, improves the sensitivity for the diagnosis of fat-containing HCC using MRI, without degrading the specificity.

Deep learning HASTE sequence compared with T2-weighted BLADE sequence for liver MRI at 3 Tesla: a qualitative and quantitative prospective study.

OBJECTIVES: To qualitatively and quantitatively compare a single breath-hold fast half-Fourier single-shot turbo spin echo sequence with deep learning reconstruction (DL HASTE) with T2-weighted BLADE sequence for liver MRI at 3 T. METHODS: From December 2020 to January 2021, patients with liver MRI were prospectively included. For qualitative analysis, sequence quality, presence of artifacts, conspicuity, and presumed nature of the smallest lesion were assessed using the chi-squared and McNemar tests. For quantitative analysis, number of liver lesions, size of the smallest lesion, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in both sequences were assessed using the paired Wilcoxon signed-rank test. Intraclass correlation coefficients (ICCs) and kappa coefficients were used to assess agreement between the two readers. RESULTS: One hundred and twelve patients were evaluated. Overall image quality (p = .006), artifacts (p < .001), and conspicuity of the smallest lesion (p = .001) were significantly better for the DL HASTE sequence than for the T2-weighted BLADE sequence. Significantly more liver lesions were detected with the DL HASTE sequence (356 lesions) than with the T2-weighted BLADE sequence (320 lesions; p < .001). CNR was significantly higher for the DL HASTE sequence (p < .001). SNR was higher for the T2-weighted BLADE sequence (p < .001). Interreader agreement was moderate to excellent depending on the sequence. Of the 41 supernumerary lesions visible only on the DL HASTE sequence, 38 (93%) were true-positives. CONCLUSION: The DL HASTE sequence can be used to improve image quality and contrast and reduces artifacts, allowing the detection of more liver lesions than with the T2-weighted BLADE sequence. CLINICAL RELEVANCE STATEMENT: The DL HASTE sequence is superior to the T2-weighted BLADE sequence for the detection of focal liver lesions and can be used in daily practice as a standard sequence. KEY POINTS: • The half-Fourier acquisition single-shot turbo spin echo sequence with deep learning reconstruction (DL HASTE sequence) has better overall image quality, reduced artifacts (particularly motion artifacts), and improved contrast, allowing the detection of more liver lesions than with the T2-weighted BLADE sequence. • The acquisition time of the DL HASTE sequence is at least eight times faster (21 s) than that of the T2-weighted BLADE sequence (3-5 min). • The DL HASTE sequence could replace the conventional T2-weighted BLADE sequence to meet the growing indication for hepatic MRI in clinical practice, given its diagnostic and time-saving performance.

Preoperative Magnetic Resonance Enterography to Predict Pathological Specimen Length in Crohn's Disease.

BACKGROUND: The European Crohn's and Colitis Organization guidelines have highlighted the importance of the preoperative evaluation of the affected segment length in patients with ileocolic Crohn's disease to determine the best surgical approach. OBJECTIVE: This study aimed to evaluate the accuracy of preoperative magnetic resonance enterography in assessing the length of the affected segment in patients with ileocolic Crohn's disease. DESIGN: This observational study was conducted with a prospectively maintained database and retrospective analysis. SETTINGS: This study was conducted in a tertiary center. PATIENTS: This study included consecutive patients undergoing ileocolic resection for Crohn's disease between August 2014 and June 2020. All patients underwent a preoperative magnetic resonance enterography. MAIN OUTCOME MEASURES: The correlation between the length measured on magnetic resonance enterography and pathological examination was evaluated. RESULTS: A total of 96 patients were included. The median time between magnetic resonance enterography and surgery was 65.5 (3-331) days. The length of the affected segment on magnetic resonance enterography was correlated with the length assessed on pathological evaluation ( R = 0.48, p < 0.001). No correlation was found between the 2 measurements when imaging was performed >6 months before surgery ( R = 0.14, p = 0.62). The presence of an abscess underestimated the length affected by Crohn's disease on imaging compared to pathology, whereas the presence of a fistula was associated with magnetic resonance enterography overestimation of the length of the affected segment. LIMITATIONS: Limitations included single-center study and retrospective analysis. CONCLUSION: In Crohn's disease, preoperative magnetic resonance enterography is a highly reliable tool for predicting the length of the affected segment compared to pathology examination in the absence of an abscess or fistula. See Video Abstract at http://links.lww.com/DCR/C26 . ENTEROGRAFA POR RESONANCIA MAGNTICA PREOPERATORIA PARA PREDECIR LA LONGITUD DE MUESTRAS PATOLGICAS EN LA ENFERMEDAD DE CROHN: ANTECEDENTES:Las guías de la Organización Europea de Crohn y Colitis han resaltado la importancia de la evaluación preoperatoria de la longitud del segmento afectado para determinar el mejor abordaje quirúrgico.OBJETIVO:Evaluamos la precisión de la enterografía por resonancia magnética preoperatoria para evaluar la longitud del segmento afectado en pacientes con enfermedad de Crohn ileocólica.DISEÑO:Realizamos un estudio observacional con una base de datos mantenida prospectivamente y un análisis retrospectivo.CONFIGURACIÓN:Este estudio se realizó en un centro terciario.PACIENTES:Se incluyeron pacientes consecutivos sometidos a resección ileocólica por enfermedad de Crohn entre Agosto de 2014 y Junio de 2020. A todos los pacientes se les realizó una enterografía por resonancia magnética preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluó la correlación entre la longitud medida en la enterografía por resonancia magnética y el examen patológico.RESULTADOS:Se incluyeron un total de 96 pacientes. El tiempo mediano entre la enterografía por resonancia magnética y la cirugía fue de 65,5 (3-331) días. La longitud del segmento afectado en la enterografía por resonancia magnética se correlacionó con la longitud evaluada en la evaluación patológica ( R = 0,48, p < 0,001). No hubo correlación entre las 2 mediciones cuando las imágenes se realizaron más de 6 meses antes de la cirugía ( R = 0,14, p = 0,62). La presencia de un absceso subestimó la longitud afectada por la enfermedad de Crohn en las imágenes en comparación con la patología, mientras que la presencia de una fístula se asoció con una sobrestimación de la longitud del segmento afectado por enterografía por resonancia magnética.LIMITACIONES:Las limitaciones incluyeron un estudio de un solo centro y un análisis retrospectivo.CONCLUSIÓNES:En la enfermedad de Crohn, la enterografía por resonancia magnética preoperatoria es una herramienta altamente confiable para predecir la longitud del segmento afectado en comparación con el examen de patología, en ausencia de absceso o fístula. Consulte el Video Resumen en http://links.lww.com/DCR/C26 . (Traducción-Dr. Yesenia Rojas-Khalil ).

A Magnetic Resonance Imaging Index to Predict Crohn's Disease Postoperative Recurrence: The MONITOR Index.

BACKGROUND & AIMS: We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). METHODS: Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. RESULTS: Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. CONCLUSIONS: The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.

Grain carbon isotope composition is a marker for allocation and harvest index in wheat.

The natural 13 C abundance (δ13 C) in plant leaves has been used for decades with great success in agronomy to monitor water-use efficiency and select modern cultivars adapted to dry conditions. However, in wheat, it is also important to find genotypes with high carbon allocation to spikes and grains, and thus with a high harvest index (HI) and/or low carbon losses via respiration. Finding isotope-based markers of carbon partitioning to grains would be extremely useful since isotope analyses are inexpensive and can be performed routinely at high throughput. Here, we took the advantage of a set of field trials made of more than 600 plots with several wheat cultivars and measured agronomic parameters as well as δ13 C values in leaves and grains. We find a linear relationship between the apparent isotope discrimination between leaves and grain (denoted as Δδcorr ), and the respiration use efficiency-to-HI ratio. It means that overall, efficient carbon allocation to grains is associated with a small isotopic difference between leaves and grains. This effect is explained by postphotosynthetic isotope fractionations, and we show that this can be modelled by equations describing the carbon isotope composition in grains along the wheat growth cycle. Our results show that 13 C natural abundance in grains could be useful to find genotypes with better carbon allocation properties and assist current wheat breeding technologies.

New magnetic resonance imaging sequences for fibrosis assessment in Crohn's disease: a pilot study.

BACKGROUND AND OBJECTIVE: Patients with Crohn's disease can develop intestinal strictures, containing various degrees of inflammation and fibrosis. Differentiation of the main component of a structuring lesion is the key for defining the therapeutic management. We evaluated new magnetic resonance imaging sequences (IVIM (Intravoxel Incoherent Motion imaging) and T1 mapping) for assessing fibrosis in Crohn's disease. METHODS: This was a prospective, single-center study of adult patients with Crohn's disease and magnetic resonance imaging examination, including IVIM and T1 mapping sequences, between March 2021 and April 2021. The association between the perfusion fraction (IVIM), reduction of relaxation time between pre- and postcontrast enhancement (T1 mapping), and the degree of fibrosis assessed by a visual analog scale from 0 to 10 was evaluated. RESULTS: A total of 33 patients were included. The perfusion fraction was significantly correlated with fibrosis, with lower perfusion fraction in severe fibrosis (p = .002). T1 mapping sequence was also correlated with the degree of fibrosis, reduction of relaxation time was higher in patients with severe fibrosis than in patients with mild fibrosis (p = .05). CONCLUSION: In Crohn's disease, these new tools could improve the performance of magnetic resonance imaging for transmural fibrosis quantification, and may be useful for improving care.

Role of Cross-Sectional Imaging in Pediatric Inflammatory Bowel Disease.

BACKGROUND: The association between radiological remission and natural history of disease in children with inflammatory bowel diseases (IBD) is poorly known. AIMS: (i) To assess the correlation between cross-sectional imaging (CSI) (ultrasound and magnetic resonance imaging) and clinical, biomarker and endoscopic disease activity; (ii) to evaluate the impact of radiological activity on the occurrence of complications in pediatric patients with IBD. METHODS: A retrospective study including pediatric patients with IBD and radiological follow-up of at least one year was conducted between 2003 and 2019 at the Nancy University Hospital. RESULTS: In total, 118 patients (66 Crohn's disease (CD) and 52 ulcerative colitis (UC)) were included. Median follow-up duration was 5.2 years (range: 1.1-15.4). Seventeen (25.8%) patients with CD and 7 (13.5%) patients with UC achieved and maintained radiological remission until last follow-up. No IBD patient achieving radiological remission experienced complications or relapse. In patients not achieving radiologic remission, complications and surgery occurred in 13/49 (26.5%) and 8/49 (16.3%) patients with CD and in 5/45 (11.1%) and 5 (11.1%) subjects with UC. Among patients with CD, the association for remission status between radiological and endoscopic assessment was excellent (Cramer's V test (V) = 0.50), and moderate between radiological and either clinical (V = 0.30) or biochemical (V = 0.33) assessments. In UC, the association for remission status between radiological and either endoscopic or clinical assessments were weak (V = 0.19 and V = 0.20 respectively), and moderate (V = 0.23) between radiological and biochemical assessments. CONCLUSION: CSI may replace endoscopic monitoring in pediatric CD. Radiological remission status predicts long-term disease outcomes.

Magnetic Resonance Elastography for Assessing Fibrosis in Patients with Crohn's Disease: A Pilot Study.

BACKGROUND: Patients with Crohn's disease can develop intestinal strictures, containing various degrees of inflammation and fibrosis. Differentiation of the main component of a stricturing lesion is the key for defining the therapeutic management. AIMS: We assessed for the first time the accuracy of magnetic resonance elastography in detecting intestinal fibrosis and predicting clinical course in patients with Crohn's disease. METHODS: This was a prospective study of adult patients with Crohn's disease and magnetic resonance imaging examination, including magnetic resonance elastography, between April 2019 and February 2020. The association between the bowel stiffness value and the degree of fibrosis was evaluated. The relationship between the stiffness value and the occurrence of clinical events was also investigated. RESULTS: A total of 69 patients were included. The stiffness value measured by magnetic resonance elastography was correlated with the degree of fibrosis (p < 0.001). A bowel stiffness ≥ 3.57 kPa predicted the occurrence of clinical events with an area under the curve of 0.82 (95% CI 0.71-0.93). Bowel stiffness ≥ 3.57 kPa was associated with an increased risk of clinical events (p < 0.0001). CONCLUSION: In Crohn's disease, magnetic resonance elastography is a reliable tool for detecting intestinal fibrosis and predicting a worse disease outcome.

Infliximab Exposure Associates With Radiologic Evidence of Healing in Patients With Crohn's Disease.

BACKGROUND & AIMS: Higher infliximab trough levels are associated with clinical and endoscopic remission in patients with Crohn's disease (CD). We investigated pharmacodynamic features of infliximab and radiological healing. METHODS: We performed a substudy of the TAILORIX trial (patients with active luminal CD in Europe, treated with infliximab), analyzing baseline and week 54 magnetic resonance enterography (MRE) data. MREs were scored using the MaRIA score by blinded central readers. Radiologic response and remission were defined, based on MaRIA criteria in all segments, as scores below 11 and 7, respectively. We collected data on infliximab trough levels, biomarkers, and endoscopic findings. Our primary aim was to evaluate pharmacodynamic features associated with radiologic response and remission, based on MRE assessments at baseline and at 54 weeks after initiation of infliximab therapy. RESULTS: We analyzed data from 36 patients (50% female; median age 35.7 years; interquartile age range, 25.6-48.6 years; median disease duration, 1.5 months; interquartile duration range, 0.6-22.4 months). At week 54 of treatment, 36.4% of patients had a radiologic response, 30.3% of patients were in remission, and 71% had endoscopic features of remission. At baseline, there was a correlation between the CD endoscopic index of severity and MaRIA scores (κ = 0.46; P = .008), but we found no correlation at week 54 (κ = 0.06; P = .75). Radiologic remission correlated with infliximab trough level at week 14 (P = .049) when the infliximab trough level cut-off value was set at 7.8 µg/mL (area under the curve, 0.74; 75% sensitivity; 86% specificity; 90% negative predictive value; 57% positive predictive value). Radiologic response correlated with infliximab trough levels at week 14 (P = .048) when the infliximab trough level cut-off value was set at 7.8 µg/mL (area under the curve, 0.73; 70% sensitivity; 90% specificity; 86% negative predictive value; 78% positive predictive value) and with continuous pharmacologic evidence of response (infliximab trough levels above 5.0 µg/mL at all time points) (P = .034). CONCLUSIONS: In a substudy of data from the TAILORIX trial of patients with active luminal CD, we identified a relationship between exposure to infliximab and radiologic evidence of outcomes.

Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs.

BACKGROUND & AIMS: The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). METHODS: Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1-3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. RESULTS: A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7-91.1) for ECA-MRI and 68.1% (95% CI 56.0-78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2-3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1-2 cm in size, specificity dropped to 66.1% (95% CI 52.2-78.2) for HBA-MRI vs. 85.7% (95% CI 73.8-93.6) for ECA-MRI. CONCLUSIONS: HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. LAY SUMMARY: There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. CLINICAL TRIAL NUMBER: NCT00848952.

Use of Cross-Sectional Imaging for Tight Monitoring of Inflammatory Bowel Diseases.

A treat-to-target strategy with close monitoring of intestinal inflammation is recommended in inflammatory bowel disease (IBD). Ileocolonoscopy remains the gold standard for assessing disease activity in IBD but is a relatively invasive procedure and is impossible to repeat in the context of tight monitoring strategies. In addition to biomarkers, cross-sectional imaging increasingly is used in these patients. Computed tomography is limited by the use of radiation, while the use of magnetic resonance enterography (MRE) is limited by its cost and access. There is growing interest in bowel ultrasound that represents a cost-effective, noninvasive, and well-tolerated modality in clinical practice, but it is operator dependent. Compared with ileocolonoscopy and MRE, bowel US has been shown to have the same level of accuracy in assessing and monitoring disease activity for both CD and UC and thus can be considered a point-of-care test. Diffusion-weighted imaging (DWI) is a MR imaging technique that increasingly is used in both IBD and non-IBD conditions and has been shown to be a valuable and accurate tool for assessing and monitoring IBD activity. Compared with conventional MRE, DWI is quicker, less time consuming, may not require intravenous contrast agent, fasting, bowel cleansing, oral preparation, or rectal preparation. This review discusses the role of these cross-sectional imaging techniques for the management of patients with IBD. In the near future, the value of DWI and ultrasound in assessing IBD will require further investigation in the era of transmural healing in CD and complete mucosal healing, including histologic remission, in ulcerative colitis.

Displacement fields using correlation methods as a tool to investigate cell migration in 3D collagen gels.

Living cells embedded in a complex extra-cellular matrix migrate in a sophisticated way thanks to adhesions to matrix fibres and contractility. It is important to know what kind of forces are exerted by the cells. Here, we use reflectance confocal microscopy to locate fibres accurately and determine displacement fields. Correlation techniques are used to this aim, coupled with proper digital image processing. Benchmark tests validate the method in the case of shear and stretching motions. Finally, the method is tested successfully for studying cancer cells migrating in collagen gels of different concentration.

Mechanosensitivity of Cancer Cells in Contact with Soft Substrates Using AFM.

Cancer cells are usually found to be softer than normal cells, but their stiffness changes when they are in contact with different environments because of mechanosensitivity. For example, they adhere to a given substrate by tuning their cytoskeleton, thus affecting their rheological properties. This mechanism could become efficient when cancer cells invade the surrounding tissues, and they have to remodel their cytoskeleton in order to achieve particular deformations. Here we use an atomic force microscope in force modulation mode to study how local rheological properties of cancer cells are affected by a change of the environment. Cancer cells were plated on functionalized polyacrylamide substrates of different stiffnesses as well as on an endothelium substrate. A new correction of the Hertz model was developed because measurements require one to account for the precise properties of the thin, layered viscoelastic substrates. The main results show the influence of local cell rheology (the nucleus, perinuclear region, and edge locations) and the role of invasiveness. A general mechanosensitive trend is found by which the cell elastic modulus and transition frequency increase with substrate elasticity, but this tendency breaks down with a real endothelium substrate. These effects are investigated further during cell transmigration, when the actin cytoskeleton undergoes a rapid reorganization process necessary to push through the endothelial gap, in agreement with the local viscoelastic changes measured by atomic force microscopy. Taken together, these results introduce a paradigm for a new-to our knowledge-possible extravasation mechanism.

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

BACKGROUND: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma. METHODS: SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. FINDINGS: Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. INTERPRETATION: In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. FUNDING: Sirtex Medical Inc.

Unraveling the Receptor-Ligand Interactions between Bladder Cancer Cells and the Endothelium Using AFM.

Adhesion of cancer cells to endothelial cells is a key step in cancer metastasis; therefore, identifying the key molecules involved during this process promises to aid in efforts to block the metastatic cascade. We have previously shown that intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is involved in the interactions of bladder cancer cells (BCs) with the endothelium. However, the ICAM-1 ligands have never been investigated. In this study, we combined adhesion assays and atomic force microscopy (AFM) to identify the ligands involved and to quantify the forces relevant in such interactions. We report the expression of MUC1 and CD43 on BCs, and demonstrate that these ligands interact with ICAM-1 to mediate cancer cell-endothelial cell adhesion in the case of the more invasive BCs. This was achieved with the use of adhesion assays, which showed a strong decrease in the attachment of BCs to endothelial cells when MUC1 and CD43 were blocked by antibodies. In addition, AFM measurements showed a similar decrease, by up to 70%, in the number of rupture events that occurred when MUC1 and CD43 were blocked. When we applied a Gaussian mixture model to the AFM data, we observed a distinct force range for receptor-ligand bonds, which allowed us to precisely identify the interactions of ICAM-1 with MUC1 or CD43. Furthermore, a detailed analysis of the rupture events suggested that CD43 is strongly connected to the cytoskeleton and that its interaction with ICAM-1 mainly corresponds to force ramps followed by sudden jumps. In contrast, MUC1 seems to be weakly connected to the cytoskeleton, as its interactions with ICAM-1 are mainly associated with the formation of tethers. This analysis is quite promising and may also be applied to other types of cancer cells.

Efficacy and safety of extracorporeal shock wave lithotripsy for chronic pancreatitis.

INTRODUCTION: There is still uncertainty regarding the efficacy and optimal modalities of extracorporeal shock wave lithotripsy (ESWL) in the treatment of chronic pancreatitis. The aims of the present study were to assess the safety and the efficacy of ESWL, either alone or followed by therapeutic endoscopic retrograde cholangiopancreatography (adjuvant ERCP) and to determine predictive factors of efficacy, in a real-life setting. PATIENTS AND METHODS: This study included all consecutive patients who underwent an ESWL in a single University Hospital between 2001 and 2012. The indication for ESWL was obstructive stone(s) of the main pancreatic duct resulting in either painful chronic pancreatitis or recurrent acute pancreatitis. Success was defined by resolution of pain, no analgesic treatment, no acute pancreatitis and no surgical treatment for chronic pancreatitis 6 months after the ESWL. RESULTS: One hundred and forty-six patients were studied; 6/146 (4%) had a complication of ESWL. Among the 132 patients in whom follow-up was completed, 91 (69%) had an adjuvant ERCP. After 6 months of follow-up, 100/132 (76%) patients achieved success. In multivariate analysis, the single significant predictive factor of the success of the ESWL treatment was chronic pain (p = 0.03). Patients who had chronic pain and needed opioid treatment had less chance of success than patients without chronic pain (OR 95%CI 0.31 [0.07-1.14]). We found no difference in the success rates between patients who underwent adjuvant ERCP and those who had ESWL only (p = 0.93). CONCLUSION: This study shows that the ESWL is a safe and effective treatment for patients with chronic pancreatitis and obstructive stones within the main pancreatic duct. Systematic association with therapeutic ERCP appears to provide no additional benefit and is therefore not recommended.

Hepatic involvement in HELLP syndrome: an update with emphasis on imaging features.

HELLP syndrome, which consists of hemolysis, elevated liver enzymes, and low platelet count is an unusual complication of pregnancy that is observed in only 10% to 15% of women with preeclampsia. Hepatic involvement in HELLP syndrome may present with various imaging features depending on the specific condition that includes nonspecific abnormalities such as perihepatic free fluid, hepatic steatosis, liver enlargement, and periportal halo that may precede more severe conditions such as hepatic hematoma and hepatic rupture with hemoperitoneum. Maternal clinical symptoms may be nonspecific and easily mistaken for a variety of other conditions that should be recognized. Because hepatic hematoma occurring in association with preeclampsia and HELLP syndrome is a potentially life-threatening complication, prompt depiction is critical and may help reduce morbidity and mortality. This review provides an update on demographics, risk factors, pathophysiology, and clinical features of hepatic complications due to HELLP syndrome along with a special emphasis on the imaging features of these uncommon conditions.

Is intraoperative ultrasound still useful for the detection of colorectal cancer liver metastases?

BACKGROUND: Debate on the optimal mode of preoperative imaging in the management of colorectal liver metastases (CRLM) is ongoing and, despite its longstanding use, the precise role of intraoperative ultrasonography (IOUS) is not well established. This study evaluates the impact of IOUS in the era of high-quality, cross-sectional imaging techniques. METHODS: All patients who underwent liver resection for CRLM in a tertiary care referral centre from January 2006 to December 2013 were included. All patients were submitted to computed tomography (CT) and/or liver magnetic resonance imaging (MRI) before surgery. Intraoperative US was performed mainly to detect previously non-diagnosed tumours that would change the surgical strategy. RESULTS: A total of 225 liver resections were performed. Liver MRI and CT scans were available for 202 patients (89.8%) and 225 patients (100%), respectively. Radiological reports recorded 632 liver tumours in 219 patients (i.e. 2.9 lesions per patient). The median time between preoperative liver MRI and surgical resection was 36 days. Intraoperative inspection, palpation and US found 20 additional lesions in 18 patients (8.0%), in three of whom lesions were diagnosed only on IOUS (1.4%). Overall, only 12 of the 20 lesions were malignant. CONCLUSIONS: Although CT and liver MRI are commonly used, IOUS alone allows the discovery of a few additional lesions that result in a change of surgical strategy in 1.4% of cases.

Rectal cancer in inflammatory bowel diseases: MR imaging findings.

PURPOSE: To retrospectively analyze the MR imaging features of rectal cancer in patients with inflammatory bowel diseases (IBD). MATERIALS AND METHODS: The MR imaging examinations of 13 patients with IBD-related rectal cancer were retrospectively reviewed. MR imaging included T2-weighted, diffusion-weighted (DW), and gadolinium chelate-enhanced MR imaging. MR imaging findings were analyzed and compared with endoscopic and histopathological findings. RESULTS: Eight patients (8/13; 62%) had active IBD and five (5/13; 38%) had quiescent IBD on MR imaging. Two different tumor patterns were individualized including clearly visible soft-tissue mass (4/13; 31%) (Type 1 tumor) and marked circumferential rectal wall thickening (9/13; 69%) (Type 2 tumor). Twelve tumors (12/13; 92%) showed high signal intensity on T2-weighted MR images. All six tumors studied with DW-MR imaging (6/6; 100%) showed high signal on DW-MR imaging with restricted diffusion on apparent diffusion coefficient (ADC) map. On gadolinium chelate-enhanced MR imaging, heterogeneous enhancement was observed in one tumor (1/13; 8%), whereas 12 tumors (12/13; 92%) showed homogeneous enhancement. MR imaging showed pelvic fistula and intrapelvic abscess in association with four (4/13; 31%) and two tumors (2/13; 15%), respectively. CONCLUSION: Our limited retrospective study demonstrates that rectal cancer in IBD patients can present as a circumferential wall thickening resembling inflammation and can occur in the absence of fistula or abscess. The use of T2-weighted and DW-MR imaging is recommended to improve rectal cancer detection in patients with long-standing IBD.

Magnetic resonance imaging of cystic pancreatic lesions in adults: an update in current diagnostic features and management.

Magnetic resonance (MR) imaging has become a widespread diagnostic solving tool for the detection and characterization of a large range of pancreatic cystic lesions. Benign and malignant cystic lesions of the pancreas including serous microcystic adenoma, mucinous cystic tumor, intraductal papillary mucinous tumor, solid pseudopapillary tumor, and also the less common lesions such as cystic endocrine tumors, cystic metastases, and lymphangiomas have suggestive MR imaging presentation that allows them to be differentiated from each other. Knowledge of MR imaging findings of cystic pancreatic lesions is critical to help suggest the diagnosis and chose the best therapeutic approach. The purpose of this review is to discuss and illustrate MR imaging features that are helpful for pancreatic cystic lesion detection and characterization and to provide an update in current MR imaging diagnostic features and management.