Chihiro Dohi

Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer

Cell‐free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer.

Droplet digital PCR measurement of HER2 in patients with gastric cancer

Background:Although there are some new criteria for human epidermal growth factor receptor 2 (HER2) expression with immunohistochemistry/fluorescence in situ hybridisation (IHC/FISH) in gastric cancer, the method is still ambiguous and is somewhat dependent on the subjective qualities of the evaluator.Methods:We used droplet digital polymerase chain reaction (ddPCR) to evaluate HER2 amplification in formalin-fixed and paraffin-embedded (FFPE) samples and cell-free serum circulating tumour DNA (ctDNA) in 25 patients with gastric cancer.Results:The concordance rate of HER2 amplification examined in FFPE samples with ddPCR and IHC/FISH was 92% (23 out of 25). The concordance rate of FFPE with ctDNA was not high (62.5%); however, patients who were HER2-positive by ctDNA had significantly shorter survival compared with HER2-negative patients.Conclusions:Our results demonstrated that this ddPCR method was as effective as IHC/FISH and therefore might become a standard method for analysing not only FFPE but also ctDNA.

Use of non-invasive serum glycan markers to distinguish non-alcoholic steatohepatitis from simple steatosis

Serum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non‐alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non‐alcoholic steatohepatitis (NASH) from simple steatosis (SS).

Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma

Most of the modification of N‐glycosylation reported in cancers including hepatocellular carcinoma (HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N‐glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application.

Potential of alpha‐fetoprotein as a prognostic marker after curative radiofrequency ablation of hepatocellular carcinoma

Recurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by α‐fetoprotein (AFP).

Application of Radiofrequency Ablation for the Treatment of Intermediate-Stage Hepatocellular Carcinoma.

Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate‐stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate‐stage HCC.

Alteration of serum N-glycan profile in patients with autoimmune pancreatitis

OBJECTIVES The aims of this study were to determine the change in whole-serum N-glycan profile in autoimmune pancreatitis (AIP) patients and to investigate its clinical utility. METHODS We collected serum from 21 AIP patients before any treatment, and from 60 healthy volunteers (HLTs). Serum glycan profile was measured by comprehensive and quantitative high-throughput glycome analysis. RESULTS Of the 53 glycans detected, 14 were differentially expressed in AIP patients. Pathway analysis demonstrated that agalactosyl and monogalactosyl bi-antennary glycans were elevated in AIP patients. Among the 14 glycans, #3410, #3510, and #4510 showed high area under receiver operating characteristic (AUROC) values (0.955, 0.964, and 0.968 respectively) for the diagnosis of AIP. These three glycans were mainly bound to immunoglobulin G; however, their serum levels were significantly higher, even in AIP patients who showed lower serum IgG4 levels, than in HLTs. CONCLUSIONS We demonstrated, for the first time, whole-serum glycan profiles of AIP patients and showed that the levels of glycans #3410, #3510, and #4510 were increased in AIP patients. These glycans might be valuable biomarkers of AIP.

Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer

ABSTRACT Introduction: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods. Methods: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes. We also compared these mutations with cytology results. Results: 57.1% of DNA samples from tumor tissue were positive for a mutation. In these patients, 87.5% of the bile circulating tumor DNA (ctDNA) samples had the same mutation. The concordance rate between bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies detected in ctDNA were approximately half of what was detected in tumor tissue DNA. On the other hand, the sensitivity of the cytological and bile ctDNA analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology and bile ctDNA analyses was 87.5%. Conclusions: Mutated tumor DNA could be detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa because of higher sensitivity and positive predict value compared to cytology with ERCP.