Blue laser imaging (BLI) and linked color imaging (LCI) are the color enhancement features of the LASEREO endoscopic system, which provide a narrow band light observation function and expansion and reduction of the color information, respectively. We examined 82 patients with early gastric cancer (EGC) diagnosed between April 2014 and August 2015. Five expert and 5 non-expert endoscopists retrospectively compared images obtained on non-magnifying BLI bright mode (BLI-BRT) and LCI with those obtained via conventional white light imaging (WLI). Interobserver agreement was also assessed. In experts’ evaluation of the images, an improvement in visibility was observed in 73% (60/82) and 20% (16/82) of cases under LCI and BLI-BRT, respectively. In non-experts’ evaluation of the images, an improvement in visibility was observed in 76.8% (63/82) and 24.3% (20/82) of cases under LCI and BLI-BRT, respectively. There were no significant differences between experts and non-experts in the evaluation of the images. The improvement in visibility was significantly higher with LCI than with BLI-BRT in experts and non-experts (p < 0.01). With regard to tumor color on WLI, the improvement in the visibility of reddish and whitish tumors was significantly higher than that of isochromatic tumors when LCI was used. The improvement in visibility with LCI was observed in 71% (12/17) and 74% (48/65) of patients with and without Helicobacter pylori (Hp) eradication, respectively; no significant difference in improvement was observed between these groups. The interobserver agreement was good to satisfactory at ≥ 0.62. In conclusion, our study showed that LCI improved the visibility of EGC, regardless of the level of endoscopists’ experience or Hp eradication in patients, particularly for EGCs with a reddish or whitish color. The improvement in visibility was significantly higher with LCI than that with BLI.

A previous genome‐wide association study identified two novel esophageal squamous cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the characteristics of ESCC, and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 risk alleles. One hundred and seventeen superficial ESCC patients who underwent treatment with endoscopic submucosal dissection (ESD) were followed up using endoscopy for ≥12 months. First, we performed a replication analysis to confirm the relationship between ESCC and the ADH1B & ALDH2 risk alleles using 117 superficial ESCC cases and 1125 healthy controls. Next, we investigated the incidence and genetic/environmental factors associated with metachronous SCC development after ESD. We also analyzed the potential risk factors for metachronous SCC development using Cox's proportional hazards model. rs1229984 GG located on ADH1B and rs671 GA located on ALDH2 were significantly associated with ESCC progression (P = 7.93 × 10⁻⁴ and P = 1.04 × 10⁻⁵). Patients with rs1229984 GG, those with rs671 GA, smokers, heavy alcohol drinkers (44 g/day ethanol), and presence of multiple Lugol‐voiding lesions (LVLs) developed metachronous SCC more frequently (P = 3.20 × 10⁻³, 7.00 × 10⁻⁴, 4.00 × 10⁻⁴, 2.15 × 10⁻², and 4.41 × 10⁻³, respectively), with hazard ratios were 2.84 (95% confidence interval [CI] = 1.43–5.63), 4.57 (95% CI = 1.80–15.42), 4.84 (95% CI = 1.89–16.41), and 2.34 (95% CI = 1.12–5.31), respectively. Multiple logistic regression analysis revealed that rs1229984 GG, rs671 GA, and smoking status were independently associated with the risk of developing metachronous SCCs after ESD. Moreover, we found cumulative effects of these two genetic factors (rs1229984 GG and rs671 GA) and one environmental factor (tobacco smoking) which appear to increase metachrous SCCs after ESD of ESCC risk approximately nearly 12‐fold. Our findings elucidated the crucial role of multiple genetic variations in ADH1B and ALDH2 as biomarkers of metachronous ESCC.

Most patients with gastric mucosa‐associated lymphoid tissue (MALT) lymphoma are infected with Helicobacter pylori, and eradication therapy is the first‐line treatment for localized disease with H pylori infection. However, there were several reports showing effectiveness of eradication therapy in even H pylori negative cases. Gastric MALT lymphomas are endoscopically classified into three common types: superficial, ulcerative, and elevated types. For the past 20 years, we have encountered 200 cases of localized gastric MALT lymphoma. Among them, only 4 cases (2%) showed similar macroscopic findings to those of nodular gastritis (gastric MALT lymphoma with nodular gastritis‐like appearance; M‐NGA). Here, we compared clinicopathological characteristics and prevalence of non‐H pylori Helicobacter (NHPH) infection between M‐NGA and other common types of gastric MALT lymphoma. To examine the prevalence of NHPH infection, DNA was extracted from formalin‐fixed paraffin‐embedded biopsy tissues from four cases of M‐NGA, 20 cases of common endoscopic types of gastric MALT lymphoma, and 10 cases of nodular gastritis. We used a highly sensitive polymerase chain reaction assay to detect the presence of five species of NHPH (Helicobacter suis, H felis, H bizzozeronii, H salomonis, and H heilmannii). H suis infection was detected in 4, 2, and 0 of the 4, 20, and 10 cases of M‐NGA, other types of gastric MALT lymphoma, and nodular gastritis, respectively. Other NHPH species were not detected in any cases. Complete response rate by eradication therapy was 4/4 in M‐NGA cases. Therefore, nodular gastritis‐like MALT lymphoma, which shows a very rare phenotype, is closely associated with NHPH infection, and eradication therapy may be the first‐choice treatment.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.