Hervé Trillaud

Hepatocellular adenoma management and phenotypic classification: The Bordeaux experience

We took advantage of the reported genotype/phenotype classification to analyze our surgical series of hepatocellular adenoma (HCA). The series without specific known etiologies included 128 cases (116 women). The number of nodules varies from single, <5, and ≥5 in 78, 38, and 12 cases, respectively. The resection was complete in 95 cases. We identified 46 HNF1α‐inactivated HCAs (44 women), 63 inflammatory HCAs (IHCA, 53 women) of which nine were also β‐catenin–activated, and seven β‐catenin–activated HCAs (all women); six additional cases had no known phenotypic marker and six others could not be phenotypically analyzed. Twenty‐three of 128 HCAs showed bleeding. No differences were observed in solitary or multiple tumors in terms of hemorrhagic manifestations between groups. In contrast, differences were observed between the two main groups. Steatosis (tumor), microadenomas (resected specimen), and additional benign nodules were more frequently observed in HNF1α‐inactivated HCAs (P < 0.01) than in IHCAs. Body mass index > 25, peliosis (tumor), and steatosis in background liver were more frequent in IHCA (P < 0.01). After complete resection, new HCAs in the centimetric range were more frequently found during follow‐up (>1 year) in HNF1α‐inactivated HCA. After incomplete resection (HCA left in nonresected liver), the majority of HCA remained stable in the two main groups and even sometimes regressed. Six patients of 128 developed hepatocellular carcinoma (HCC) (all were β‐catenin–activated, whether inflammatory or not). Conclusion: There were noticeable clinical differences between HNF1α–inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related to the number of HCAs; β‐catenin–activated HCAs are at higher risk of HCC. As a consequence, we believe that management of HCA needs to be adapted to the phenotype of these tumors. (HEPATOLOGY 2009.)

Hepatocellular adenomas: Magnetic resonance imaging features as a function of molecular pathological classification

Hepatocellular adenomas (HCAs) are a group of benign tumors forming three molecular pathological subgroups: (1) hepatocyte nuclear factor 1α (HNF‐1α)–inactivated, (2) β‐catenin–activated, and (3) inflammatory. Some HCAs present both β‐catenin activation and inflammation. We analyzed magnetic resonance imaging (MRI) data for correlations between features on imaging and pathological classification of HCAs. We included 50 cases for which pathology specimens were classified into three groups based on immunohistochemical staining. Two characteristic MRI profiles were identified corresponding to HNF‐1α–inactivated and inflammatory HCAs. Fifteen HCAs were HNF‐1α–inactivated. The corresponding lesions showed (1) diffuse signal dropout on T1‐weighted chemical shift sequence due to steatosis, (2) isosignal or slight hypersignal on T2‐weighted (T2W) images, and (3) moderate enhancement in the arterial phase, with no persistent enhancement in the portal venous and delayed phases. For the diagnosis of HNF‐1α–inactivated HCA, the positive predictive value of homogeneous signal dropout on chemical shift images was 100%, the negative predictive value was 94.7%, the sensitivity was 86.7%, and the specificity was 100%. Twenty‐three HCAs were inflammatory and showed (1) an absence or only focal signal dropout on chemical shift sequence; (2) marked hypersignal on T2W sequences, with a stronger signal in the outer part of the lesions, correlating with sinusoidal dilatation areas; and (3) strong arterial enhancement, with persistent enhancement in the portal venous and delayed phases. Marked hypersignal on T2W sequences associated with delayed persistent enhancement had a positive predictive value of 88.5%, a negative predictive value of 84%, a sensitivity of 85.2%, and a specificity of 87.5% for the diagnosis of inflammatory HCA. Conclusion: HNF‐1α–mutated HCAs and inflammatory HCAs were associated with specific MRI patterns related to diffuse fat repartition and sinusoidal dilatation, respectively. (HEPATOLOGY 2008.)

Real-time MR temperature mapping of rabbit liver in vivo during thermal ablation

It has been shown that quantitative MRI thermometry using the proton resonance frequency (PRF) method can be used to noninvasively monitor the evolution of tissue temperature, and to guide minimally‐invasive tumor ablation based on local hyperthermia. Although hepatic tumors are among the main targets for thermal ablation, PRF‐based temperature MRI of the liver is difficult to perform because of motion artifacts, fat content, and low T  *2 . In this study the stability of real‐time thermometry was tested on a clinical 1.5 T scanner for rabbit liver in vivo. The fast segmented EPI principle was used together with respiratory gating to limit respiratory motion artifacts. Lipid signal suppression was achieved with a binomial excitation pulse. Saturation slabs were applied to suppress artifacts due to flowing blood. The respiratory‐gated MR thermometry in the rabbit liver in vivo showed a standard deviation (SD) of 1–3°C with a temporal resolution of 3 s per slice and 1.4 mm × 1.9 mm spatial resolution in plane (slice thickness = 5 mm). The method was used to guide thermal ablation experiments with a clinical infrared laser. The estimated size of the necrotic area, based on the thermal dose calculated from MR temperature maps, corresponded well with the actual lesion size determined by histology and conventional MR images obtained 5 days posttreatment. These results show that quantitative MR temperature mapping can be obtained in the liver in vivo, and can be used for real‐time control of thermal ablation and for lesion size prediction. Magn Reson Med 50:322–330, 2003.

Stability of real-time MR temperature mapping in healthy and diseased human liver

To determine the stability and quality of MR temperature mapping using the proton resonance frequency (PRF) method in the liver of hepatic tumor patients.

Real-time monitoring of radiofrequency ablation of rabbit liver by respiratory-gated quantitative temperature MRI

To evaluate the feasibility and precision of magnetic resonance imaging (MRI) thermometry for monitoring radiofrequency (RF) liver ablation in vivo and predicting the size of the ablation zone.

Real time monitoring of radiofrequency ablation based on MR thermometry and thermal dose in the pig liver in vivo

To evaluate the feasibility and accuracy of MR thermometry based on the thermal dose (TD) concept for monitoring radiofrequency (RF) ablations, 13 RF ablations in pig livers were performed under continuous MR thermometry at 1.5 T with a filtered clinical RF device. Respiratory gated fast gradient echo images were acquired simultaneously to RF deposition for providing MR temperature maps with the proton resonant frequency technique. Residual motion, signal to noise ratio (SNR) and standard deviation (SD) of MR temperature images were quantitatively analyzed to detect and reject artifacted images in the time series. SD of temperature measurement remained under 2°C. Macroscopic analysis of liver ablations showed a white zone (Wz) surrounded by a red zone (Rz). A detailed histological analysis confirmed the ongoing nature of the coagulation necrosis in both Wz and Rz. Average differences (±SD) between macroscopic size measurements of Wz and Rz and TD predictions of ablation zones were 4.1 (±1.93) mm and −0.71 (±2.47) mm, respectively. Correlation values between TD and Wz and TD and Rz were 0.97 and 0.99, respectively. MR thermometry monitoring based on TD is an accurate method to delineate the size of the ablation zone during the RF procedure and provides a clinical endpoint.

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety μmol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty‐four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages. Magn Reson Med 41:156‐162, 1999.

Locally Advanced Pancreatic Adenocarcinoma: Reassessment of Response with CT after Neoadjuvant Chemotherapy and Radiation Therapy

PURPOSE To prospectively evaluate the utility of computed tomography (CT) for determination of tumor response and prediction of resectability after neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with nonmetastatic locally advanced pancreatic cancer. MATERIALS AND METHODS This study received institutional review board approval, and all participants provided written informed consent. Consecutive patients with cephalic locally advanced pancreatic cancer who underwent surgical exploration and/or resection following neoadjuvant CRT were prospectively enrolled from June 2009 to May 2013. Two radiologists independently analyzed the baseline and post-CRT CT scans for the size, attenuation, and circumferential vascular contacts of the tumor. Associations between the postoperative histologic grade of the tumor response (pTNM) and the clinical, biologic, and CT criteria were assessed by using Spearman correlation coefficients. CT criteria related to the presence of complete (ie, R0) resection were assessed by using logistic regression. RESULTS Forty-seven patients were included, 33 with an R0 resection and 14 with positive margins (ie, R1) or no resection. Variables demonstrating a significant correlation with the histologic tumor classification of tumor response were post-CRT carbohydrate antigen 19-9 level (r = 0.46), post-CRT largest tumor axis (r = 0.44), post-CRT sum of the largest and smallest tumor axes (r = 0.46), change in the largest axis (r = -0.31), change in the sum of the largest and smallest axes (r = -0.39), change in superior mesenteric vein (SMV) and/or portal vein (hereafter, SMV/portal vein) contact (r = -0.38), and post-CRT superior mesenteric artery contact (r = 0.34). Partial regression of tumor contact with the SMV/portal vein was associated in all cases with R0 resection (10 of 10 patients, positive predictive value = 100%), and partial regression of tumor contact with any peripancreatic vascular axis was associated with R0 resection in 91% of cases (20 of 22 patients, positive predictive value = 91%). Persistence of SMV/portal vein stenosis after CRT was not predictive of R1 resection. CONCLUSION Partial regression of tumor-vessel contact indicates suitability for surgical exploration, irrespective of the degree of decrease in tumor size or the degree of residual vascular involvement.

The identification of small nodules in liver adenomatosis.

BACKGROUND/AIMS Liver adenomatosis is characterized by the presence of multiple adenomas of various sizes in the liver. The aim of this study was to characterize the morphology of small nodules which can be difficult to identify. METHODS Seven patients included in this study underwent surgery for the removal of one or several nodules. All, but one, were females. Three out of seven presented with acute bleeding. Five had six or more nodules at presentation, and two only one, who developed nodules later on during follow-up. RESULTS All of the large nodules that were >2 cm, except one, were typical adenomas with or without hemorrhagic areas. Smaller nodules (1-2 cm), some of which discovered on the resected specimen were either typical adenomas or non-typical nodules. These non-typical nodules were characterized by a polylobulated aspect with steatotic zones, and in between, bands of non-steatotic hepatocytes with portal tracts-like structures containing occasional cytokeratin 7 and less often cytokeratin 19 positive biliary cells. Numerous steatotic foci were also seen in four cases. They were isolated or grouped forming microadenomas or non-typical micronodules (<1 cm) containing biliary elements. Our findings lead to the following hypothesis: adenomatosis is characterized by the simultaneous occurrence of multiple adenomas; if several adenomatous foci expand at the same time in the same area, they will form one polylobulated nodule containing non-adenomatous tissue with portal tracts in between areas of adenomatous tissue (non-typical micronodule). Such a small micronodule may in turn expand and join another micronodule to form a bigger one by the same process (non-typical nodule). As nodules grow, their non-adenomatous components including hepatocytic plates and portal tracts constituents will progressively disappear to end up with the classical aspect of an adenoma. CONCLUSIONS This hypothesis supports the concept that non-typical nodules/micronodules are adenomas precursors. However, they can be difficult to classify since they resemble focal nodular hyperplasia precursor.

Role of Contrast-Enhanced Sonography in Differentiation of Subtypes of Hepatocellular Adenoma: Correlation with MRI Findings

OBJECTIVE Hepatocellular adenomas (HCAs) are divided into three subtypes according to genotype and phenotype. The two main subgroups are hepatocyte nuclear factor 1α (HNF1α)-inactivated HCA and inflammatory HCA. Specific imaging features of these subgroups of adenoma have been delineated with MRI. The aim of this study was to document the contrast-enhanced sonographic (CEUS) features specific for adenoma subtypes and to correlate them with MRI findings. MATERIALS AND METHODS We retrospectively analyzed data on 38 patients with HCA confirmed at pathologic examination in all cases. All cases were classified with MRI. RESULTS HNF1α-inactivated HCA (n = 16) was found to have a homogeneous hyperechoic aspect at baseline gray-scale sonography, isovascularity or moderate hypervascularity with mixed filling in the arterial phase, and isoechogenicity in the portal and late portal venous phases. Homogeneous hyperechogenicity during B-mode sonography was the most specific pattern (sensitivity, 88%; specificity, 91%) and correlated with diffuse fat repartition observed on MR images obtained with chemical-shift sequences. In inflammatory HCA (n = 17) the association of arterial hypervascularity with centripetal filling, linear vascularities, peripheral rim of sustained enhancement, and central washout in the late venous phase was specific (sensitivity, 64%; specificity, 100%). Discrepancy between delayed washout during CEUS and sustained enhancement during MRI could be related to differences between gadolinium and microbubbles in diffusing in the interstitial spaces. In the five other HCA cases (four unclassified, one β-catenin activated) CEUS showed characteristics of benign hepatocellular tumors with no specific features. CONCLUSION HNF1α-inactivated HCA and inflammatory HCA had characteristic CEUS patterns. Delayed washout, an unusual finding in benign hepatic lesions, is of particular interest and was a characteristic of inflammatory HCA subtype.