Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia.

Biliary atresia (BA) is a life-threatening cholangiopathy occurring in infancy, the most common indication for pediatric liver transplantation. The etiology of BA remains unknown; however, a viral etiology has been proposed as multiple viruses have been detected in explants of infants afflicted with BA. In the murine model of BA, Rhesus rotavirus (RRV) infection of newborn BALB/c pups results in a cholangiopathy that mirrors human BA. Infected BALB/c pups experience 100% symptomatology and mortality, while C57BL/6 mice are asymptomatic. Interferon-λ (IFN-λ) is an epithelial cytokine that provides protection against viral infection. We demonstrated that IFN-λ is highly expressed in C57BL/6, leading to reduced RRV replication. RRV-infection of C57BL/6 IFN-λ receptor knockout (C57BL/6 IFN-λR KO) pups resulted in 90% developing obstructive symptoms and 45% mortality with a higher viral titer in bile ducts and profound periportal inflammation compared to C57BL/6. Histology revealed complete biliary obstruction in symptomatic C57BL/6 IFN-λR KO pups, while C57BL/6 ducts were patent. These findings suggest that IFN-λ is critical in preventing RRV replication. Deficiency in IFN-λ permits RRV infection, which triggers the inflammatory cascade causing biliary obstruction. Further IFN-λ study is warranted as it may play an important role in infant susceptibility to BA.

Liver Transplantation for Colorectal Liver Metastases: Is It Appropriate?

Colorectal cancer with liver metastases is a condition with significant morbidity and mortality that affects many people around the world. Many treatments exist to target liver metastases, including surgical resection, chemotherapy, nonsurgical liver-directed therapies, and liver transplantation. The field of transplant oncology is emerging as a promising alternative to palliative chemotherapy alone in appropriately selected patients. Though few clinical trials have been completed to evaluate safety of liver transplant for colorectal cancer metastases, there are several ongoing trials to hopefully make transplant a viable option for more patients with limited options.

Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis.

Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma (HCC). GPC3 undergoes extensive posttranslational modification (PTM) including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the PTM of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial-mesenchymal transition, and drug development. Through review of current literature, this article provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of PTM on GPC3 function at the molecular, cellular, and disease level.

Transplant for colorectal cancer liver metastases.

Colorectal cancer with unresectable liver metastases has significant mortality when treated with chemotherapy alone. In appropriately selected patients, liver transplant is emerging as a treatment alternative for this population. Some key clinical trials, including SECA-I and SECA-II, have shown promising survival results: more trials are being conducted to evaluate safety of this practice.

Ovarian volume ratio is a reliable predictor of ovarian torsion in girls without an adnexal mass.

PURPOSE: The aims of this study were to identify ultrasound-based predictors of ovarian torsion in girls without an adnexal mass and establish a set of normal values for ovarian volume ratio (OVR). METHODS: A retrospective review was performed of all premenarchal patients ≥3 years of age with a normal pelvic ultrasound between January 2016 and January 2019. A comparison group of premenarchal girls presenting between 2011 and 2019 with torsion in the absence of an adnexal mass was utilized. RESULTS: Five-hundred and four premenarchal girls underwent pelvic ultrasound evaluation with a normal examination. The mean OVR was 1.6 ±â€¯0.7 (range 1.0-6.5). OVR did not vary with age (r = -0.06) as compared to ovarian width which increased steadily with age (r = 0.53, p < 0.001). OVR was increased in girls with torsion (7.6 vs 1.4, p < 0.0001), and by receiver operating characteristic (ROC) analysis a cutoff value of >2.5 demonstrated the best diagnostic accuracy of any predictive variable (sensitivity 100%, specificity 94%, AUC 0.991, p < 0.001). CONCLUSIONS: OVR is an excellent predictor of ovarian torsion in premenarchal girls without an adnexal mass. Unlike ovarian width, OVR does not increase with age, and a cutoff OVR > 2.5 demonstrates high sensitivity and specificity for identifying ovarian torsion in this population. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: Level III.

Molecular classification of patients with grade II/III glioma using quantitative MRI characteristics.

BACKGROUND: Molecular markers of WHO grade II/III glioma are known to have important prognostic and predictive implications and may be associated with unique imaging phenotypes. The purpose of this study is to determine whether three clinically relevant molecular markers identified in gliomas-IDH, 1p/19q, and MGMT status-show distinct quantitative MRI characteristics on FLAIR imaging. METHODS: Sixty-one patients with grade II/III gliomas who had molecular data and MRI available prior to radiation were included. Quantitative MRI features were extracted that measured tissue heterogeneity (homogeneity and pixel correlation) and FLAIR border distinctiveness (edge contrast; EC). T-tests were conducted to determine whether patients with different genotypes differ across the features. Logistic regression with LASSO regularization was used to determine the optimal combination of MRI and clinical features for predicting molecular subtypes. RESULTS: Patients with IDH wildtype tumors showed greater signal heterogeneity (p = 0.001) and lower EC (p = 0.008) within the FLAIR region compared to IDH mutant tumors. Among patients with IDH mutant tumors, 1p/19q co-deleted tumors had greater signal heterogeneity (p = 0.002) and lower EC (p = 0.005) compared to 1p/19q intact tumors. MGMT methylated tumors showed lower EC (p = 0.03) compared to the unmethylated group. The combination of FLAIR border distinctness, heterogeneity, and pixel correlation optimally classified tumors by IDH status. CONCLUSION: Quantitative imaging characteristics of FLAIR heterogeneity and border pattern in grade II/III gliomas may provide unique information for determining molecular status at time of initial diagnostic imaging, which may then guide subsequent surgical and medical management.