Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma

A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.journal articl

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Pharmacological Treatments Available for Immune-Checkpoint-Inhibitor-Induced Colitis

Immune checkpoint inhibitor treatment has shown revolutionary therapeutic effects in various carcinomas. However, immune-related adverse events (irAE) following this treatment can sometimes lead to treatment discontinuation. One such frequently encountered adverse event is immune-related colitis (irAE colitis). Corticosteroids (CS) are the first-line treatment for irAE colitis, but we often encounter CS-refractory or -resistant cases. The application of multiple biologics has been proposed as a therapy to be administered after CS treatment; however, the efficacy and safety of biologics for patients with irAE colitis who do not respond to CS have not been established. This review summarizes the treatment regimens available for irAE colitis, focusing on the mechanism of action of corticosteroids, infliximab, vedolizumab, and other drugs

Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

AIM: To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer