The Expression Patterns of Immune Checkpoint Molecules in Colorectal Cancer: An Analysis Based on Microsatellite Status.

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibited concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on microsatellite instability status. The immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: a total of 40 microsatellite-stable (MSS) and 43 microsatellite-instability-high (MSI-H) cancer patients. PD-L1 was more frequently expressed in the tumor center in the MSI-H patients with than that in the MSS patients (18 [41.9%] vs. 3 [7.5%], respectively; p < 0.001), and the same trend was observed for TIM-3 expression (30 [69.8%] vs. 19 [47.5%], respectively; p = 0.047). The concomitant expression of two or more ICMs was more frequently observed than no expression or the expression of a single molecule in both the MSS and MSI-H groups; a total of 34 (79.7%) patients with MSI-H cancer and 23 (57.5%) with MSS cancer showed ICM expression at the tumor center, whereas 34 (79.7%) patients with MSI-H cancer and 22 (55%) with MSS cancer showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H cancer showed higher expression levels of ICMs than those in patients with MSS cancer, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients' colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cut-off values for these three markers. The high-APRIL/TNFSH13-expression group showed a significantly higher rate of metastatic lesions than the low-expression group, whereas the high-MMP-3-expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low-expression group. The five-year disease-free survival of the high-MMP-3-expression group was significantly shorter than that of the low-expression group (65.1% vs. 90.2%, p = 0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed in CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

The Analgesic Efficacy of the Single Erector Spinae Plane Block with Intercostal Nerve Block Is Not Inferior to That of the Thoracic Paravertebral Block with Intercostal Nerve Block in Video-Assisted Thoracic Surgery.

This monocentric, single-blinded, randomized controlled noninferiority trial investigated the analgesic efficacy of erector spinae plane block (ESPB) combined with intercostal nerve block (ICNB) compared to that of thoracic paravertebral block (PVB) with ICNB in 52 patients undergoing video-assisted thoracic surgery (VATS). The endpoints included the difference in visual analog scale (VAS) scores for pain (0-10, where 10 = worst imaginable pain) in the postanesthetic care unit (PACU) and 24 and 48 h postoperatively between the ESPB and PVB groups. The secondary endpoints included patient satisfaction (1-5, where 5 = extremely satisfied) and total analgesic requirement in morphine milligram equivalents (MME). Median VAS scores were not significantly different between the groups (PACU: 2.0 (1.8, 5.3) vs. 2.0 (2.0, 4.0), p = 0.970; 24 h: 2.0 (0.8, 3.0) vs. 2.0 (1.0, 3.5), p = 0.993; 48 h: 1.0 (0.0, 3.5) vs. 1.0 (0.0, 5.0), p = 0.985). The upper limit of the 95% CI for the differences (PACU: 1.428, 24 h: 1.052, 48 h: 1.176) was within the predefined noninferiority margin of 2. Total doses of rescue analgesics (110.24 ± 103.64 vs. 118.40 ± 93.52 MME, p = 0.767) and satisfaction scores (3.5 (3.0, 4.0) vs. 4.0 (3.0, 5.0), p = 0.227) were similar. Thus, the ESPB combined with ICNB may be an efficacious option after VATS.

Pretreatment inflammatory markers predicting treatment outcomes in colorectal cancer.

We aimed to review whether pretreatment inflammatory markers reflect the short- and long-term outcomes of patients with colon cancer, rectal cancer, colon and rectal cancers, and metastatic colorectal cancer (CRC). We found that pretreatment complete blood count and blood chemistry tests reflect short-term and long-term oncological outcomes in patients with CRC. Specifically, in patients with colon cancer, hypoalbuminemia was associated with worse postoperative morbidity, mortality, and inferior survival. In patients with rectal cancer, elevated neutrophil-lymphocyte ratio (NLR) and thrombocytosis were associated with postoperative complications, poor overall survival (OS), and disease-free survival (DFS). A high C-reactive protein/albumin ratio (CAR) was associated with poor OS and DFS. In patients with metastatic CRC, increased NLR and platelet-lymphocyte ratio (PLR) were associated with poor OS, DFS, and progression-free survival (PFS). In addition, high CAR and a low albumin/globulin ratio on blood chemistry tests were associated with poor OS and PFS. Although universal cut-off values were not available, various types of pretreatment laboratory markers could be utilized as adjuncts to predict prognosis in patients with CRC.

Laccase-Mediator System Using a Natural Mediator as a Whitening Agent for the Decolorization of Melanin.

In this study, a laccase-mediator system (LMS) using a natural mediator was developed as a whitening agent for melanin decolorization. Seven natural mediators were used to replace synthetic mediators and successfully overcome the low redox potential of laccase and limited access of melanin to the active site of laccase. The melanin decolorization activity of laccases from Trametes versicolor (lacT) and Myceliophthora thermophila (lacM) was significantly enhanced using natural mediators including acetosyringone, syringaldehyde, and acetovanillone, which showed low cytotoxicity. The methoxy and ketone groups of natural mediators play an important role in melanin decolorization. The specificity constants of lacT and lacM for melanin decolorization were enhanced by 247 and 334, respectively, when acetosyringone was used as a mediator. LMS using lacM and acetosyringone could also decolorize the melanin present in the cellulose hydrogel film, which mimics the skin condition. Furthermore, LMS could decolorize not only synthetic eumelanin analogs prepared by the oxidation of tyrosine but also natural melanin produced by melanoma cells.

Left External Iliac and Common Femoral Artery Occlusion Following Blunt Abdominal Trauma without Associated Bone Injury.

Blunt abdominal trauma may cause peripheral vascular injuries. However, blunt abdominal trauma rarely results in injuries to the external iliac and common femoral arteries, which often stem from regional bone fractures. Here, we present the case of a patient who had experienced trauma in the lower abdominal and groin area three months before presenting to the hospital, but these injuries did not involve bone fractures and had been managed conservatively. The patient came to the hospital because of left lower leg claudication that gradually became severe. Computed tomography angiography confirmed total occlusion of the external iliac and common femoral arteries. The patient underwent femorofemoral bypass grafting and was discharged uneventfully.