Hiroyuki Yajima

Early and long-term outcomes of endoscopic submucosal dissection for early gastric cancer in a large patient series.

Endoscopic submucosal dissection (ESD) enables the curative resection of early gastric cancer (EGC); however, little information is available on the long-term outcomes of ESD. This study was conducted to clarify the clinical outcomes of a large number of patients with EGC who underwent ESD. The early outcomes were assessed in 1,209 patients and the long-term outcomes were assessed in 300 patients at a follow-up >5 years after the ESD procedure. The overall survival rates were compared between indication and expanded-indication groups, and between the patients who did or did not undergo additional surgery in an out-of-indication group. Overall survival rates were also compared among different age groups. In total, 617 lesions were classed as the indication group, 507 as the expanded-indication group and 208 as the out-of-indication group. Curative resection rates were 96.6% and 91.5% in the indication and expanded-indication groups, respectively. In terms of the long-term outcomes, 20 of the 146 patients in the indication group, 15 of the 105 patients in the expanded-indication group and one of the 23 patients who underwent additional surgery in the out-of-indication group succumbed due to causes other than gastric cancer. Among the 26 patients who did not undergo additional surgery in the out-of-indication group, 10 mortalities occurred, including one due to gastric cancer. The five-year survival rates were not significantly different between the indication and expanded-indication groups. In the out-of-indication group, the five-year survival rate for the patients who did not undergo additional surgery (65.0%) was significantly lower than that for those who did undergo additional surgery (100%) (P<0.01). The five-year survival rate of patients aged >80 years (67.1%) was significantly lower than that of the younger patients (<60 years, 91.6%; sixties, 93.0%; seventies, 84.5%) (P<0.0001). In conclusion, although expanded-indication of ESD for EGC is appropriate, comorbidities require consideration in elderly patients.

Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management

AIM To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps. METHODS Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations. RESULTS NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8. CONCLUSION We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.

Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease

Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohns disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs.

Hepatitis C virus-related symptoms, but not quality of life, were improved by treatment with direct-acting antivirals

Direct‐acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection have a significantly high sustained virologic response rate after a short treatment course and do not have any severe adverse effects. Patient‐reported outcomes (PROs) have become increasingly important to assess the total impact of a chronic disease. We aimed to evaluate the changes in symptoms of patients with HCV infection treated with DAAs by using PROs.