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Celiacomesenteric trunk is a rare variant of celiac artery anatomical variations. Stenosis of celiacomesenteric trunk is a severe usually symptomatic condition which might jeopardize the arterial supply of both supramesocolic organs and the midgut. It was diagnosed in a 79-year-old male during the preoperative workup for a pancreatic adenocarcinoma. Highly developed arterial anastomotic arcades, and mainly Riolan arcade, allowed to bypass this stenosis and to avoid digestive ischemia. Arterial anastomotic arcades are of paramount interest to ensure sufficient supply to the corresponding organs and must be thoroughly evaluated before planned surgery to avoid postoperative ischemia.

Background & Aims: Oxidative stress is recognized as a major driver of non-alcoholic steatohepatitis (NASH) progression. The transcription factor NRF2 and its negative regulator KEAP1 are master regulators of redox, metabolic and protein homeostasis, as well as detoxification, and thus appear to be attractive targets for the treatment of NASH. Methods: Molecular modeling and X-ray crystallography were used to design S217879 – a small molecule that could disrupt the KEAP1-NRF2 interaction. S217879 was highly characterized using various molecular and cellular assays. It was then evaluated in two different NASH-relevant preclinical models, namely the methionine and choline-deficient diet (MCDD) and diet-induced obesity NASH (DIO NASH) models. Results: Molecular and cell-based assays confirmed that S217879 is a highly potent and selective NRF2 activator with marked anti-inflammatory properties, as shown in primary human peripheral blood mononuclear cells. In MCDD mice, S217879 treatment for 2 weeks led to a dose-dependent reduction in NAFLD activity score while significantly increasing liver Nqo1 mRNA levels, a specific NRF2 target engagement biomarker. In DIO NASH mice, S217879 treatment resulted in a significant improvement of established liver injury, with a clear reduction in both NAS and liver fibrosis. αSMA and Col1A1 staining, as well as quantification of liver hydroxyproline levels, confirmed the reduction in liver fibrosis in response to S217879. RNA-sequencing analyses revealed major alterations in the liver transcriptome in response to S217879, with activation of NRF2-dependent gene transcription and marked inhibition of key signaling pathways that drive disease progression. Conclusions: These results highlight the potential of selective disruption of the NRF2-KEAP1 interaction for the treatment of NASH and liver fibrosis. Impact and implications: We report the discovery of S217879 – a potent and selective NRF2 activator with good pharmacokinetic properties. By disrupting the KEAP1-NRF2 interaction, S217879 triggers the upregulation of the antioxidant response and the coordinated regulation of a wide spectrum of genes involved in NASH disease progression, leading ultimately to the reduction of both NASH and liver fibrosis progression in mice.

Background and aimsNonalcoholic Steatohepatitis (NASH) is a major cause of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma resulting ultimately in increased liver-related mortality. Fibrosis is the main driver of mortality in NASH. Procollagen C-Proteinase Enhancer-1 (PCPE-1) plays a key role in procollagen maturation and collagen fibril formation. To assess its role in liver fibrosis and NASH progression, knock-out mice were evaluated in a dietary NASH model.MethodsGlobal constitutive Pcolce-/- and WT male mice were fed with a Choline Deficient Amino acid defined High Fat Diet (CDA HFD) for 8 weeks. Liver triglycerides, steatosis, inflammation and fibrosis were assessed at histological, biochemical and gene expression levels. In addition, human liver samples from control and NASH patients were used to evaluate the expression of PCPE-1 at both mRNA and protein levels.ResultsPcolce gene deficiency prevented diet-induced liver enlargement but not liver dysfunction. Furthermore, liver triglycerides, steatosis and inflammation were not modified in Pcolce-/- male mice compared to WT under CDA HFD. However, a significant decrease in liver fibrosis was observed in Pcolce-/- mice compared to WT under NASH diet, associated with a decrease in total and insoluble collagen content without any significant modifications in the expression of genes involved in fibrosis and extracellular matrix remodeling. Finally, PCPE-1 protein expression was increased in cirrhotic liver samples from both NASH and Hepatitis C patients.ConclusionsPcolce deficiency limits fibrosis but not NASH progression in CDA HFD fed mice.

Background: In otherwise normal boys with undescended testes, early orchidopexy is recommended to preserve fertility, to decrease the risk of testicular cancer, and to facilitate its detection. Indeed, compared to the general population, the risk of testicular cancer is increased two- to eight-fold in isolated cryptorchidism and usually occurs before the age of 40 years. By contrast, when cryptorchidism is associated with congenital hypogonadotropic hypogonadism, the risk of testicular cancer is unknown. Objective: The aim of this study was to determine the characteristics of testicular cancer when cryptorchidism is associated with congenital hypogonadotropic hypogonadism. Methods: We conducted a PubMed research without date limits including the following key words: hypogonadism, hypogonadotropic hypogonadism, testicular cancer, testicular germ cell tumors, undescended testis, Kallmann syndrome, FSH, AFP (α foeto protein), βHCG. Results: Only 3 patients with testicular cancer and congenital hypogonadotropic hypogonadism have been published in the past 4 decades and two were diagnosed at 50 and 64 years. Conclusion: Gonadotropin deficiency may protect against testicular cancer, and orchidopexy in this context may be deferred. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is a growing cause of liver cirrhosis and cancer. The performance of the magnetic resonance elastography (MRE) visco‐elastic parameters in diagnosing progressive forms of NAFLD, including nonalcoholic steatohepatitis (NASH) and substantial fibrosis (F ≥ 2), needs to be clarified. Purpose: To assess the value of three‐dimensional MRE visco‐elastic parameters as markers of NASH and substantial fibrosis in mice with NAFLD. Study Type: Prospective. Animal Model: Two mouse models of NAFLD were induced by feeding with high fat diet or high fat, choline‐deficient, amino acid‐defined diet. Field Strength/Sequence: 7T/multi‐slice multi‐echo spin‐echo MRE at 400 Hz with motion encoding in the three spatial directions. Assessment: Hepatic storage and loss moduli were calculated. Histological analysis was based on the NASH Clinical Research Network criteria. Statistical Tests: Mann–Whitney, Kruskal–Wallis tests, Spearman rank correlations and multiple regressions were used. Diagnostic performance was assessed with areas under the receiver operating characteristic curves (AUCs). P value <0.05 was considered significant. Results: Among the 59 mice with NAFLD, 21 had NASH and 20 had substantial fibrosis (including 8 mice without and 12 mice with NASH). The storage and loss moduli had similar moderate accuracy for diagnosing NASH with AUCs of 0.67 and 0.66, respectively. For diagnosing substantial fibrosis, the AUC of the storage modulus was 0.73 and the AUC of the loss modulus was 0.81, indicating good diagnostic performance. Using Spearman correlations, histological fibrosis, inflammation and steatosis, but not ballooning, were significantly correlated with the visco‐elastic parameters. Using multiple regression, fibrosis was the only histological feature independently associated with the visco‐elastic parameters. Conclusion: MRE in mice with NAFLD suggests that the storage and loss moduli have good diagnostic performance for detecting progressive NAFLD defined as substantial fibrosis rather than NASH. Evidence Level: 1 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background & Aims: Patients with non‐alcoholic fatty liver disease (NAFLD) have impaired liver regeneration. Liver endothelial cells play a key role in liver regeneration. In non‐alcoholic steatohepatitis (NASH), liver endothelial cells display a defect in autophagy, contributing to NASH progression. We aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD. Methods: First, we assessed autophagy in primary endothelial cells from wild type mice fed a high fat diet and subjected to partial hepatectomy. Then, we assessed liver regeneration after partial hepatectomy in mice deficient (Atg5lox/lox;VE‐cadherin‐Cre+) or not (Atg5lox/lox) in endothelial autophagy and fed a high fat diet. The role of endothelial autophagy in liver regeneration was also assessed in ApoE−/− hypercholesterolemic mice and in mice with NASH induced by methionine‐ and choline‐deficient diet. Results: First, autophagy (LC3II/protein) was strongly increased in liver endothelial cells following hepatectomy. Then, we observed at 40 and 48 h and at 7 days after partial hepatectomy, that Atg5lox/lox;VE‐cadherin‐Cre+ mice fed a high fat diet had similar liver weight, plasma AST, ALT and albumin concentration, and liver protein expression of proliferation (PCNA), cell‐cycle (Cyclin D1, BrdU incorporation, phospho‐Histone H3) and apoptosis markers (cleaved Caspase‐3) as Atg5lox/lox mice fed a high fat diet. Same results were obtained in ApoE−/− and methionine‐ and choline‐deficient diet fed mice, 40 h after hepatectomy. Conclusion: These results demonstrate that the defect in endothelial autophagy occurring in NASH does not account for the impaired liver regeneration occurring in this setting. [ABSTRACT FROM AUTHOR]