18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging-Defined Extramural Venous Invasion Predicts Distant Metastasis and Reflects Strong Tumor Invasiveness in Rectal Cancer.

INTRODUCTION: Extramural vascular invasion in patients with rectal cancer is a poor prognostic factor associated with distant metastasis; thus, accurate preoperative diagnosis is important. However, the accurate detection of extramural vascular invasion using magnetic resonance imaging (MRI) is difficult, and an improved diagnostic modality is required. In addition, the factors involved in the formation of extramural venous invasion (EMVI) remain unclear. In this study, we aimed to examine the ability of 18F-fluorodeoxyglucose positron emission tomography/MRI ([18F] FDG PET/MRI) to detect EMVI and elucidate the factors involved in EMVI. METHODS: Thirty-one patients with rectal cancer were enrolled in this study between 2017 and 2021. We preoperatively evaluated the pelvic [18F] FDG PET/MRI to detect extramural vascular invasion ([18F] FDG PET/MRI-defined EMVI: pmrEMVI). To investigate the factors related to pmrEMVI, we confirmed the desmoplastic reaction (DR) and TWIST expression in the primary lesions of rectal cancer and examined its relationship with pmrEMVI. RESULTS: Six of the 31 patients were pmrEMVI positive. Four pmrEMVI-positive patients had distant metastases. The levels of immature DR and TWIST1 expression were significantly higher in cases with pmrEMVI positivity. CONCLUSION: pmrEMVI is a useful biomarker for predicting distant metastasis. In addition, pmrEMVI was significantly correlated with factors related to tumor invasiveness.

[Short-Term Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

In recent years, an increasing number of reports have demonstrated the usefulness of neoadjuvant chemoradiotherapy (NACRT). In our department, we consider cT3-4 and/or cN-positive locally advanced rectal cancer as an indication for NACRT. We have retrospectively evaluated the efficacy and safety of NACRT in 11 patients who underwent NACRT from November 2018 to July 2022. All patients were male, with a median age of 69 years, and cStage was Ⅱa: 1, Ⅱc: 1, Ⅲb: 5, Ⅲc: 3, and Ⅳa: 1. All patients completed NACRT, and there were no cases of CTCAE Grade 3 or higher adverse events or treatment interruptions. The response rate was 72.7%, and histological response grade were Grade 3: 1(9.1%), 2: 4 (36.4%), 1b: 6(54.5%), and surgical margin was negative in all cases. Pathological down stage was obtained in 45.5% of cases, and pCR was obtained in 1 case(9.1%). The median observation period was 17 months, and during the period, 2 cases(18.2%)developed recurrence, both of which were pulmonary metastases, and no local recurrence including pelvic lymph node recurrence was observed. NACRT for locally advanced rectal cancer is considered a relatively safe and highly locally controllable preoperative treatment.

Anti-Prokineticin1 Suppresses Liver Metastatic Tumors in a Mouse Model of Colorectal Cancer with Liver Metastasis.

Multidisciplinary treatment for colorectal cancer (CRC) has undergone significant advances, and molecularly targeted drugs have substantially improved patient prognosis. However, one problem with current molecularly targeted therapeutics is that they must be used in combination with anticancer agents. New molecular targeted therapies that can be used alone are needed. We have previously identified prokineticin1 (PROK1) factor as a therapeutic potential target for CRC. PROK1 factor is involved in the angiogenesis of tissues surrounding CRC tumors. Additionally, PROK1 receptors 1 and 2 are expressed in CRC cell lines, playing roles in cell proliferation via an autocrine mechanism and in the signaling system. In this study, a liver metastasis mouse model was developed using human colorectal cancer cell lines, and mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every three days. The number, size, and cell proliferation ability of metastatic lesions were analyzed. Our results suggested that the number, size, and cancer cell proliferation ability of metastatic lesions decreased, and the survival time significantly increased in the antibody-treated group compared to those in the control group. Thus, the anti-PROK1 antibody therapy suppressed the cell proliferation ability of liver metastatic lesions in a CRC mouse model, suggesting its potential as a novel treatment strategy.

Oxidative Stress as a Biomarker for Predicting the Prognosis of Patients with Colorectal Cancer.

INTRODUCTION: Excess oxidative stress is generated by inflammation and cancer, and it is involved in the development and metastasis of colorectal cancer. However, there are few reports on the relationship between blood oxidative stress and prognosis. This study examined the usefulness of derivatives of reactive oxygen metabolites (d-ROMs), a measure of oxidative stress, and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as prognostic markers in colorectal cancer. METHODS: The study enrolled 163 patients who underwent colorectal cancer resection at our institution between 2013 and 2018. Blood samples were taken preoperatively to measure d-ROMs and NLR. Spearman's correlation analysis was used to examine the relationships between d-ROMs and NLR, and Cox regression analysis was performed to identify factors associated with d-ROMs and NLR. The Kaplan-Meier method was used to calculate disease-specific survival (DSS). RESULTS: There was no correlation between d-ROMs and NLR. Tumor size was significantly associated with d-ROMs and NLR. DSS was significantly worse among patients with high d-ROMs or high NLR, although patients with high d-ROMs and high NLR had the worst DSS. In the multivariate analysis, distant metastasis and the high d-ROM/NLR combination were significant factors associated with DSS (p < 0.001, hazard ratio [HR] = 22.880 and p = 0.049, HR = 2.391, respectively). CONCLUSION: Preoperative d-ROMs and NLR reflect the tumor size among patients with colorectal cancer. The combination of d-ROMs and NLR may effectively predict prognosis in patients with colorectal cancer.