Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

Detection of Intestinal Pneumatosis Location by Following Hyperechoic Foci in the Portal Vein Along Its Branches With Real‐time Ultrasound

Portal venous gas is occasionally encountered in children with intestinal pneumatosis, identified on real‐time ultrasound imaging as hyperechoic foci with quick movement. The origin of the portal venous gas can be identified by following the hyperechoic foci along the branches of the portal vein, providing an estimate of the location of intestinal pneumatosis. This approach may be useful for predicting the patient's prognosis. Our report describes 2 cases of portal venous gas while estimating the area of intestinal pneumatosis, which were evaluated with real‐time ultrasound.     

Spatial and temporal expansion of intrahepatic metastasis by molecularly‐defined clonality in multiple liver cancers

Multiple hepatocellular carcinoma (HCC) is divided into two categories: intrahepatic metastasis (IM), which is a true relapse of HCC, and multicentric origin (MO), which is a second primary tumor. Clinical diagnosis of multiple HCC is usually made based on tumor location and/or time to recurrence; however, it is often difficult to distinguish the two types of multiple HCC. Using 41 matched pairs of multiple HCC specimens, we confirmed the accuracy of clinical diagnoses using exome sequence data and investigated the importance of discriminating the type of multiple HCC. Genomic analysis revealed that 18 (43.9%) patients diagnosed as having genomic IM had common mutations in a pair of HCC tumors with the main tumor of these patients being more progressive compared to those with genomic MO. The accuracy of clinical diagnosis based on lobe (Definition 1) and segment (Definition 2) were 68.3% and 78.0%, respectively. Intriguingly, recurrence ≥2 years after initial surgery for 3 patients was IM. The survival of patients with clinical IM was significantly shorter than for those with clinical MO based on both Definition 1 (P = 0.045) and Definition 2 (P = 0.043). However, mean survival was not different between the patients with genomic IM and those with MO (P = 0.364). Taken together, genomic analysis elucidated that liver cancer may spread more extensively and more slowly than previously thought. In addition, distinguishing multiple HCC as IM or MC may have provided biological information but was not of clinical importance with respect to patient prognosis.     

Neighborhood effect and obesity in adult survivors of pediatric cancer: A report from the St. Jude lifetime cohort study

Survivors of childhood cancer are at risk for obesity, a condition potentially modifiable if dietary intake and physical activity are optimized. These health behaviors are likely influenced by neighborhood of residence, a determinant of access to healthy, affordable food and safe and easy exercise opportunities. We examined associations between neighborhood level factors and obesity among survivors in the St. Jude Lifetime cohort and community comparison group members. Persons with residential addresses available for geocoding were eligible for analysis (n = 2,265, mean age 32.5 [SD 9.1] years, 46% female, 85% white). Survivors completed questionnaires regarding individual behaviors; percent body fat was assessed via dual X-ray absorptiometry (obesity: ≥25% males; ≥35% females); neighborhood effect was characterized using census tract of residence (e.g., neighborhood socioeconomic status [SES], rurality). Structural equation modeling was used to determine associations between neighborhood effect, physical activity, diet, smoking, treatment exposures and obesity. Obese survivors (n = 1,420, 62.7%) were more likely to live in neighborhoods with lower SES (RR: 1.23, 95% CI: 1.10–1.38) and rural areas (RR: 1.22, 95% CI: 1.07–1.39) compared to survivors with normal percent body fat. Resource-poor neighborhoods (standardized effect: 0.06, p < 0.001) and cranial radiation (0.16, p < 0.001) had direct effects on percent body fat. Associations between neighborhood of residence and percent body fat were increased (0.01, p = 0.04) among individuals with a poor diet. Neighborhoods where survivors reside as an adult is associated with obesity. Interventions targeting survivors should incorporate strategies that address environmental influences on obesity.