The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a cell population potentially involved in endothelial damage. CD4+CD28null T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin–like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities. To test the hypothesis that the KIR2DS2 gene is involved in the development of vasculitis, association studies were performed. The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001). Also, the distribution of human histocompatibility leukocyte antigen (HLA)-C, the putative ligand for KIRs, was significantly different in patients with rheumatoid vasculitis in comparison with the control populations. These data suggest that HLA class I–recognizing receptors and HLA class I genes are genetic risk determinants that modulate the pattern of RA expression. Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4+CD28null T cells.

Background-CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood. Methods and Results-Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4 ϩ CD28 null T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161 ϩ and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4 ϩ CD28 null T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4 ϩ T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I-recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4 ϩ CD28 null T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion. Conclusions-In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability.Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell-mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes. (Circulation. 2002;105:570-575.)

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In this pilot study, we were unable to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers. However, this does not necessarily mean that periodontitis does not contribute to the total burden of inflammation as there was a tendency for hs-CRP to decrease following successful periodontal treatment. Large-scale studies are clearly needed to determine the impact of periodontal disease on systemic inflammation.