[Clinical pathological characteristics of 4 cases of gastric gland-derived tumors].

Objective: To investigate the pathological features of gastric tumor originated from the fundic gland, including oxyntic gland adenoma (OGA) and gastric adenocarcinoma of the fundic gland (GA-FG). Methods: A retrospective analysis of 2 cases of OGA and 2 cases of GA-FG admitted to our hospital from February 2019 to September 2019 was performed. The histological features were analyzed by immunohistochemical staining combined with endoscopic observation. Results: The four cases arose from the deep layer of the lamina propria mucosae and well differentiated. Two cases of OGA confined to the mucosa, including 1 case of irregular tubules showing low-degree dysplasia and another case of irregular branching and anastomosing tubules showing high-degree dysplasia. Two cases of GA-FG combined with submucosal invasion, showed irregular branching and anastomosing tubules and formed a so-called "endless glands" pattern. Atypia, helicobacter pylori (HP) infection, chronic gastritis, intestinal metaplasia, or gastric atrophy were not observed in the superficial epithelium covering the tumor extent. Two cases of OGA and 2 cases of GA-FG showed the same result of immunohistochemical staining: pepsinogen-1 was diffusely positive in the tumor tissues and indicated chief cell differentiation, while positive ATPase and PDGFRA-α indicated parietal cells differentiation. The expression of Syn were positive in all cases, while CD10, MUC2 and CD-X2 were negative. The upregulation of p53 protein or nuclear positivity of ß-catenin was not observed. The Ki-67 labeling index in the hot area was approximately 1-5%. Conclusions: GA-FG is a well-differentiated, low-grade malignant novel subtype of gastric cancer. The immunohistochemical markers and narrowband imaging combined with magnifying endoscopy (NBI-ME) enhance the diagnostic sensitivity. Whether Syn positive expression can be one of the diagnostic item needs to be further investigate. The process of tumorigenesis of GA-FG might be the transition from low-grade dysplasia to high-grade dysplasia of OGA and further to submucosal infiltration. However, the mechanism of GAFG was still unclear. Disregulation of the Shh and Wnt/ß-catenin signaling pathway might be associated with tumorigenesis of GA-FG. Endoscopic submucosal dissection (ESD) is often the preferred and curative treatment.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Augmentation by converting enzyme inhibition of accelerated endothelin release from rat mesenteric arteries following nephrectomy.

We investigated the release of endothelin-1 (ET) from rat mesenteric arteries to clarify its pathophysiological role in the sustained hypertension of spontaneously hypertensive rats (SHR) following nephrectomy and the regulatory mechanism of the ET release which might be modified by vascular angiotensins and bradykinins. Nephrectomy increased the plasma level of ET and enhanced the ET release in both SHR and Wistar-Kyoto rats (WKY). CV-11974, an angiotensin II receptor antagonist, did not affect the ET release from arteries of nephrectomized rats. On the contrary, infusion of captopril, a converting enzyme inhibitor, further enhanced the ET release in both intact and nephrectomized rats. These findings suggest that the release of ET from mesenteric arteries may be regulated by bradykinins, but not by angiotensins. This pressor substance does not contribute to the sustained hypertension because the enhanced production of ET observed in both SHR and WKY. However, there is a possibility that the exaggerated responsiveness of vascular ET may in part account for local vascular tone and vascular remodeling in renal dysfunction.