Sonic hedgehog hepatocellular adenoma: magnetic resonance imaging features and correlation with histology.

OBJECTIVES: Sonic hedgehog hepatocellular adenoma (shHCA) is a new hepatocellular adenoma (HCA) subgroup characterized by high risk of hemorrhage. ShHCA account for below 10% of all HCA cases and are often associated with female gender, obesity, and non-alcoholic steatohepatitis. No specific MRI characteristics have been described to date. The objective of this study was to assess the value of using MRI to identify shHCA, and correlate MRI findings with histology. METHODS: We retrospectively collected MRI scans of 29 patients with shHCA from our center and from different liver referral centers to include 35 lesions. Diagnosis of shHCA was assessed by immunohistochemical overexpression of argininosuccinate synthase 1 or prostaglandin D2 synthase, then confirmed by molecular analysis of sonic hedgehog pathway activation and/or by proteomic analysis. RESULTS: In 46% (n = 16/35) of shHCA cases, we detected intralesional fluid-filled cavities defined on MR images as fluid-like foci markedly hyperintense on T2-weighted sequences, and hypointense on T1-weighted sequences, with or without delayed enhancement. Pathologically, these cavities were observed in 54% of cases as vacuoles filled with blood at different stages of degradation. Hemorrhage and/or necrosis were detected among 71% of cases by MRI analysis (n = 25/35) versus 82% pathologically. Seventeen percent of shHCA cases (n = 6/35) were completely homogeneous via MRI and pathological analysis. No MRI criteria was found in favor of focal nodular hyperplasia, HNF1A-mutated HCA, or typical inflammatory HCA. CONCLUSION: We reveal the presence of intralesional fluid-filled cavities among 46% of our shHCA cases that represent a new MRI finding possibly helpful for shHCA diagnosis. CLINICAL RELEVANCE STATEMENT: This multicenter study is the first clinical study about the radiological aspect of this new hepatocellular adenoma subgroup. This highlights a strong correlation between MRI and histological analysis, with a specific pattern emerging for diagnosis. KEY POINTS: • Sonic hedgehog hepatocellular adenoma is a new hepatocellular adenoma subgroup associated with high risk of hemorrhage, but imaging features of this subgroup remain unknown. • Analysis of MR images and correlation with pathology revealed intralesional fluid-filled cavities and necrotic-hemorrhagic changes. • Intralesional fluid-filled cavities have not yet been described in other adenoma subtypes and represent a new MRI finding for sonic hedgehog hepatocellular adenoma.

Waiting for bile duct dilation before repair of bile duct injury: a worthwhile strategy?

BACKGROUND: Hepaticojejunostomy (HJ) is the gold standard procedure for repairing major bile duct injury (BDI). Dilation status of the BD before repair has not been assessed as a risk factor for anastomotic stricture. METHOD: This retrospective single-centre study was performed on a population of 87 patients with BDI repaired by HJ between 2007 and 2021. Dilation status was assessed preoperatively, and dilation was defined as the presence of visible peripheral intrahepatic BDs with remaining BD diameter > 8 mm. The short- and long-term outcomes of HJ were assessed according to preoperative dilation status. RESULTS: Before final repair, the BDs were dilated (dBD) in 56.3% of patients and not dilated (ND) in 43.7%. Patients with ND at the time of repair had more severe BDI injury than those with dBD (94.7% vs. 77.6%, p = 0.026). The rate of preoperative cholangitis was lower in patients with ND than in those with dBD (10.5% vs. 44.9%, p = 0.001). The rate of short-term morbidity after HJ was 33.3% (ND vs. dBD: 38.8% vs. 26.3%, p = 0.32). Long-term anastomotic stricture rate was 5.7% with a mean follow-up period of 61.3 months. There were no differences in long-term biliary complications according to dilation status (ND vs. dBD: 12.2% vs. 10.5%, p = 1). CONCLUSION: Dilation status of the BD before HJ for BDI seemed to have no impact on short- or long-term outcomes. Both surgical and radiological external biliary drainages after BDI appear to be acceptable options to reduce cholangitis before repair without increasing risk for long-term anastomotic stricture.

Hepatocellular Adenoma Risk Factors of Hemorrhage: Size Is Not the Only Concern!: Single-center Retrospective Experience of 261 Patients.

OBJECTIVE: Our aim was to determine independent risk factors of clinical bleeding of hepatocellular adenoma (HCA) to define a better management strategy. SUMMARY BACKGROUND DATA: HCA is a rare benign liver tumor with severe complications: malignant transformation that is rare (5%-8%) and more often, hemorrhage (20%-27%). To date, only size > 5 cm and histological subtype (possibly sonic hedgehog) are associated with bleeding, but these criteria are not clearly established. METHODS: We retrospectively collected data from a cohort of 268 patients with HCA managed in our tertiary center, from 1984 to 2020 and focused on clinical bleeding. Hemorrhage was considered severe when it required intensive care and moderate when bleeding symptoms required a hospitalization. We included 261 patients, of whom 130 (49.8%) had multiple HCAs or liver adenomatosis. All surgical specimen and liver biopsy were reviewed by an experienced liver pathologist and reclassified in the light of the current immunohistochemistry. Mean duration of follow-up was 93.3 months (range 1-363). We analyzed type, frequency, consequences of bleeding, and risk factors among clinical data and HCA characteristics. RESULTS: Eighty-three HCA (31.8%) were hemorrhagic. There were 4 pregnant women with 1 newborn death. One patient died before treatment. Surgery was performed in 78 (94.0%) patients. Mortality was nil and severe complications occurred in 11.5%. Multivariate analysis identified size (OR 1.02 [1.01-1.02], P < 0.001), shHCA (OR 21.02 [5.05-87.52], P < 0.001), b-catenin mutation on exon 7/8 (OR 6.47 [1.78-23.55], P = 0.0046), chronic alcohol consumption (OR 9.16 [2.47-34.01], P < 0.001) as independent risk factors of clinical bleeding. CONCLUSIONS: This series, focused on the hemorrhagic risk of HCA, shows that size, but rather more molecular subtype is determinant in the natural history of HCA.

Proteomic Profiling of Hepatocellular Adenomas Paves the Way to Diagnostic and Prognostic Approaches.

BACKGROUND AND AIMS: Through an exploratory proteomic approach based on typical hepatocellular adenomas (HCAs), we previously identified a diagnostic biomarker for a distinctive subtype of HCA with high risk of bleeding, already validated on a multicenter cohort. We hypothesized that the whole protein expression deregulation profile could deliver much more informative data for tumor characterization. Therefore, we pursued our analysis with the characterization of HCA proteomic profiles, evaluating their correspondence with the established genotype/phenotype classification and assessing whether they could provide added diagnosis and prognosis values. APPROACH AND RESULTS: From a collection of 260 cases, we selected 52 typical cases of all different subgroups on which we built a reference HCA proteomics database. Combining laser microdissection and mass-spectrometry-based proteomic analysis, we compared the relative protein abundances between tumoral (T) and nontumoral (NT) liver tissues from each patient and we defined a specific proteomic profile of each of the HCA subgroups. Next, we built a matching algorithm comparing the proteomic profile extracted from a patient with our reference HCA database. Proteomic profiles allowed HCA classification and made diagnosis possible, even for complex cases with immunohistological or genomic analysis that did not lead to a formal conclusion. Despite a well-established pathomolecular classification, clinical practices have not substantially changed and the HCA management link to the assessment of the malignant transformation risk remains delicate for many surgeons. That is why we also identified and validated a proteomic profile that would directly evaluate malignant transformation risk regardless of HCA subtype. CONCLUSIONS: This work proposes a proteomic-based machine learning tool, operational on fixed biopsies, that can improve diagnosis and prognosis and therefore patient management for HCAs.

Changes in inulin and soluble sugar concentration in artichokes (Cynara scolymus L.) during storage.

BACKGROUND: The artichoke (Cynara scolymus L.) accumulates about 50-70 g kg(-1) of its fresh weight as inulin-type fructan. Inulin fermentation increases gas production and thereby provokes intestinal discomfort in some people. The present research focuses on the changes in carbohydrate composition occurring in artichoke heads during storage under different conditions (18 degrees C, 4 degrees C and 4 degrees C under polypropylene film packing). RESULTS: Carbohydrate content and composition were determined by anion-exchange high-performance liquid chromatography with pulsed amperometric detection. Storage time caused a decrease in inulin content and an average degree of polymerization, accompanied by an increase of free fructose and sucrose due to depolymerization of inulin. CONCLUSION: Higher-temperature storage and storage without packing induce strong carbohydrate changes. Thereby, eating stored artichoke leads to consumption of an inulin quantity that does not provoke unwanted symptoms related to gas production but sufficient to have a prebiotic effect.