Serum levels of tumor markers, such as carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, are often measured to detect potential malignancy. When these levels are high, the presence or absence of malignancy is confirmed via a more detailed examination using gastrointestinal （GI） endoscopy and computed tomography. The rate of confirmation of malignancy upon such a follow-up is unknown. This study aimed to investigate the malignancy detection rate via GI endoscopy for patients with high levels of serum CEA and CA19-9. All patients who underwent such GI endoscopy between January 2018 and February 2019 at Showa University Hospital were included in this study. The patients were divided into a follow-up group and a screening group, depending on the purpose of measuring their serum CEA/CA19-9 levels. There were 156 patients who underwent GI endoscopy because of high CEA/CA19-9 levels within the study period. Advanced malignant lesions were detected in 10 patients （6.4％）, including seven cases of colorectal cancer and three cases of upper GI malignancies. In the screening group, six cases （5.7％） of GI malignancies were detected, none of which were found in asymptomatic patients without anemia. In the follow-up group, four cases （7.8％） of GI malignancies were detected; three patients were asymptomatic, and one patient had anemia. Our findings suggest that high serum CEA/CA19-9 levels in asymptomatic patients without anemia and without a history of malignancy do not indicate the presence of malignancy. However, high serum CEA/CA19-9 levels may indicate the potential presence of GI malignancies for patients with a history of malignant tumors, even if they are asymptomatic and do not have anemia.

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Reports on surveillance systems useful for determining the risk of developing hepatocellular carcinoma （HCC） after direct-acting antiviral （DAA） treatment for hepatitis C have been published. Liver cirrhosis （LC） is a high-risk factor for HCC, but the evaluation frequency necessary for patients with chronic hepatitis （CH） remains unknown. Here, we aimed to identify how frequent CH patients should be evaluated for HCC, with particular emphasis on patients achieving a sustained virological response （SVR） with DAA treatment. Data were collected pre-treatment （Pre） and at the time of SVR for 141 patients with hepatitis C receiving DAA treatment. We defined LC by a platelet （PLT） count ≤10×104/µl, and CH was defined by a PLT count of ＞10×104/µl. The incidence of HCC in patients with CH after achieving SVR was retrospectively evaluated. In total, 128 patients （CH, n＝102; LC, n＝26） achieved SVR, and 13 developed HCC after SVR during the follow-up period （mean, 748 days）. Although fibrosis-4 （FIB-4） index, the presence of α-fetoprotein, and prothrombin time were significant risk factors for HCC in patients with CH in the univariate analysis, only the Pre-FIB-4 index was an independent predictive factor for HCC development in the multivariate analysis （p＝0.04）. An FIB-4 index ≥3 was a significant risk factor for HCC （p＝0.005）. The cumulative risk for HCC at 1000 days was 2.6％ and 24.2％ in the FIB-4 index ＜3 and FIB-4 index ≥3 groups, respectively （p＝0.004）. Frequent HCC examination is recommended for FIB-4 index ≥3 CH patients who obtain SVR after DAA treatment.

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Although antigen-specific T helper （Th） cells are developed from naive T cells, human Th17 cells are not derived from naive CD4⁺ T cells unlike murine cells. Therefore, the source of human Th17 cells has remained unresolved. In this study, we assessed the early differentiation pathway of human Th17 cells from CD31⁺ thymic naive T cells into stem cell memory CCR6⁺ Th17 precursors and the regulation of this process by cytokines. Peripheral blood mononuclear cells were isolated from healthy volunteers. We found that only CD31^- CCR6⁺ naive type CD4⁺ T cells had the ability to produce IL-17A in response to Th17-inducing stimuli. A cell tracking assay using CD31⁺ CCR6^- cells labeled with carboxyfluorescein diacetate succinimidyl ester revealed that CD31^- CCR6⁺ Th17 precursors were derived from CD31⁺ CCR6^- thymic naive T cells. CD31 is known to suppress IL-17 production by interfering with downstream T cell receptor （TCR） signaling molecules including Lck, which is essential for IL-17 production. The inactive form of Lck was much higher in CD31⁺ T cells than CD31^- T cells after TCR stimulation. In experiments of cytokine-mediated modulation of Th17 cell differentiation, IL-4 suppressed the conversion of CD31⁺ CCR6^- naive T cells into CD31^- CCR6⁺ Th17 precursors by upregulating CD31 expression and suppressing CCR6 expression. In conclusion, CD31^- CCR6⁺ Th17 precursors could be sourced from CD31⁺ CCR6^- naive T cells, and IL-4 regulated the early Th17 differentiation. Our findings provide novel insights into the regulation of differentiation of naive CD4⁺ T cells into Th17 cells in humans. Furthermore, our results may provide hints for further elucidation of the differentiation process of Th17 cells and of the pathology of Th17 cell-related diseases.

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The fast-track surgery protocol, including perioperative immunonutritional management, is increasingly gaining attention for the prevention of surgical site infections （SSIs）. To analyze the association between the fast-track surgery protocol employed at a single center and outcomes, including SSIs and the length of hospital stays. This retrospective analysis included 217 patients who underwent hepatectomy at the study department between January 2009 and February 2014. Patients were divided into two groups: those managed by a conventional protocol （group C, n＝75） and those managed by the fast-track surgery protocol （group F, n＝142）. There were no significant differences in patient characteristics or factors between the two groups. However, serum albumin and total cholesterol levels before surgery were significantly higher in group F than in group C, and pre-hepatectomy C-reactive protein （CRP） levels were lower in group F than in group C. Moreover, serum albumin and CRP levels at postoperative day 7 were better in group F than in group C. The operations were longer in group F than in group C （312 vs. 286 min） and blood loss volume was less （385 g in group F vs. 428 g in group C）. SSI rates were significantly lower in group F （4.2％, n＝6） than in group C （13.3％, n＝10）, and the length of hospital stay was significantly shorter in group F （16.7 days） than in group C （25.8 days）. The fast-track surgery protocol as a perioperative management strategy may improve preoperative nutritional status and postoperative inflammation, with subsequent reductions in SSI rates and the length of hospital stay in patients undergoing hepatectomy.

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Oxidative stress is one cause of atherosclerosis that makes it a lifestyle-related disease. Oxidized low-density lipoprotein （OxLDL） was previously found to be related to oxidative stress, measured using the diacron-reactive oxygen metabolites （d-ROMs） test and showed a negative correlation between biological antioxidant potential （BAP） test results and triglycerides （TG）. In addition, large gender differences exist among vascular disorders caused by arteriosclerosis. However, such gender differences and their correlation with oxidative stress and blood lipids have not been clarified. In this study, gender differences in correlations between oxidative stress and blood lipids as factors in the development of atherosclerosis was addressed. Subjects were 149 individuals who underwent medical examinations conducted in Ashikaga Teishin Clinic in Tochigi, Japan （98 males and 51 females）. A strong positive correlation was observed between d-ROMs test results and OxLDL in men （R＝0.480, P<0.0001）, but no correlation was seen in women. A strong negative correlation between BAP test results and TG was also noted in men （R＝−0.571, P<0.0001）, and a moderate negative correlation was detected in women （R＝−0.344, P＝0.0133）. A positive correlation between d-ROMs tests and OxLDL was seen in women under 50 years of age （R＝0.399, P＝0.0393）, but this correlation was not present in women who were 50 years of age or older （R＝−0.00656, P＝0.976）. Correlations between oxidative stress and OxLDL and between antioxidant potential and TG in men were more prominent than in women. This finding suggests that decreasing oxidative stress in the blood to prevent atherosclerosis is more important for men.

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