In conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.

KRAS-mutant colorectal cancer (CRC) is a highly malignant cancer with a poor prognosis, however specific therapies targeting KRAS mutations do not yet exist. Anti-epidermal growth factor receptor (EGFR) agents, including cetuximab and panitumumab, are effective for the treatment of certain patients with CRC. However, these anti-EGFR treatments have no effect on KRAS-mutant CRC. Therefore, new therapeutic strategies targeting KRAS-mutant CRC are urgently needed. To clarify the direct effect of KRAS gene mutations, the present study transduced mutant forms of the KRAS gene (G12D, G12V and G13D) into CACO-2 cells. A drug-screening system (Mix Culture assay) was then applied, revealing that the cells were most sensitive to the MEK inhibitor trametinib among tested drugs, Cetuximab, Panitumumab, Regorafenib, Vemurafenib, BEZ-235 and Palbociclib. Trametinib suppressed phosphorylated ERK (p-ERK) expression and inhibited the proliferation of KRAS-mutant CACO-2 cells. However, low-dose treatment with trametinib also increased the expression of the anti-apoptotic protein Bcl-xL in a dose-dependent manner, leading to drug resistance. To overcome the resistance of KRAS-mutant CRC to apoptosis, the combination of trametinib and the Bcl-xL antagonist ABT263 was assessed by in vitro and in vivo experiments. Compared with the effects of low-dose trametinib monotherapy, combination treatment with ABT263 had a synergistic effect on apoptosis in mutant KRAS transductants in vitro. Furthermore, in vivo combination therapy using low-dose trametinib and ABT263 against a KRAS-mutant (G12V) xenograft synergistically suppressed growth, with an increase in apoptosis compared with the effects of trametinib monotherapy. These data suggest that a low dose of trametinib (10 nM), rather than the usual dose of 100 nM, in combination with ABT263 can overcome the resistance to apoptosis induced by Bcl-xL expression, which occurs concurrently with p-ERK suppression in KRAS-mutant cells. This strategy may represent a promising new approach for treating KRAS-mutant CRC.

No abstract

Gastric hamartomatous inverted polyp (GHIP) is rare, with few reports of carcinogenesis from GHIP during long‐term follow‐up. A 51‐year‐old woman was diagnosed as having a submucosal tumor (SMT) during esophagogastroduodenoscopy (EGD) in 2008. In 2016, although the size and height of the lesion had not changed, she was referred to our hospital for further investigation of the lesion. EGD depicted a gastric SMT of 20 mm in diameter in the greater curvature of the upper gastric body, and a biopsy specimen showed a well to poorly differentiated adenocarcinoma. Following successful laparoscopic total gastrectomy, histopathological examination revealed an intramucosal adenocarcinoma arising in GHIP.

<b><i>Introduction:</i></b> Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. <b><i>Methods:</i></b> In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. <b><i>Results:</i></b> Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (<i>p</i> = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; <i>p</i> = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; <i>p</i> = 0.022). <b><i>Conclusions:</i></b> Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.