Circulating miR-203 derived from metastatic tissues promotes myopenia in colorectal cancer patients

Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell-to-cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre-operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR-203 expression levels in CRC tissues and pre-operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR-203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35-89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well-established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour-node-metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log-rank test) and disease-free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log-rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19-10, P = 0.0001) and disease-free survival (hazard ratio: 2.33, 95% CI: 1.14-4.77, P = 0.021) in CRC patients. Serum miR-203 expression negatively correlated with pre-operative PMI level (P = 0.0001, ρ = -0.25), and multivariate logistic regression analysis revealed that elevated serum miR-203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8-14.8, P = 0.002). Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via down-regulation of BIRC5 (survivin) expression in human SkMC line. Assessment of serum miR-203 expression could be used for risk assessment of myopenia, and miR-203 might be a novel therapeutic target for inhibition of myopenia in CRC

Vasohibin-1 Increases the Malignant Potential of Colorectal Cancer and Is a Biomarker of Poor Prognosis

application/pdf内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 病態修復医学講座 消化管・小児外科学教育研究分

Vasohibin-1 Increases the Malignant Potential of Colorectal Cancer and Is a Biomarker of Poor Prognosis

application/pdfBackground: Vasohibin-1 (VASHI) is related to angiogenesis and poor prognosis in several types of cancers. However, the biological function and clinical significance of VASHI in colorectal cancer (CRC) are not fully known. Materials and Methods: The associations between VASHI expression and clinicopathological features were investigated by immunohistochemistry in 429 CRC tissues. To evaluate the function of VASHI in vitro, small-interfering VASHT targeting RNA was transfected into human CRC cell lines. Results: We found that VASHI was highly expressed in the cytoplasm of CRC tissues. High VASHI expression in the cytoplasm was significantly associated with tumor progression, such as larger tumor size, advanced T-stage, lymph node metastasis, distant metastasis and poor prognosis. Moreover, a significant positive correlation was detected between VASH1 expression and microvessel density. VASHI siRNA inhibited CRC cell proliferation, migration, and invasion, and promoted anoikis. Conclusion: Overexpression of VASHI in CRC cells increased malignant potential and promoted metastasis.本文 / Department of Gastrointestinal and Pediatric Surgery，Mie University Graduate School of Medicine10

Double inferior vena cava, an uncommon but relevant anatomical anomaly in surgery for lower rectal cancer: a report of two cases

Abstract Background Double inferior vena cava (DIVC) is rare and usually detected incidentally. DIVC may be associated with several anatomical variants of the retroperitoneal and pelvic veins. These variants can pose a clinical problem during colorectal surgery. We present two patients with lower rectal cancer who also had a DIVC. Case presentation Case 1 was a 72-year-old man with advanced lower rectal cancer (T3N0M0) who underwent robot-assisted low anterior resection after neoadjuvant therapy. A DIVC was detected on preoperative computed tomography (CT). During the operation, a presacral vein was injured while mobilizing the rectum and hemostasis could not be achieved. We converted to open surgery and packed the pelvic cavity for hemostasis. Retrospective analysis suggested the injured vein arose from an interiliac vein of the presacral pelvic venous plexus. Case 2 was a 50-year-old woman with lower rectal cancer (T3N0M0), immune thrombocytopenic purpura, and a DIVC. Although preoperative three-dimensional CT angiography showed no obvious pelvic vein abnormalities, a short course of preoperative radiotherapy was delivered to avoid lateral pelvic lymph node dissection. Chemotherapy was deferred owing to her thrombocytopenic disease. Laparoscopic abdominoperineal resection was performed meticulously to minimize bleeding and achieve rapid hemostasis. No intraoperative complications occurred. Conclusion DIVC is often accompanied by venous malformations that may pose a problem when mobilizing the mesorectum from the retroperitoneum. Preoperative assessment of pelvic vessel anatomy using three-dimensional CT is essential in patients with a DIVC who undergo rectal surgery

Clinical Relevance of Myopenia and Myosteatosis in Colorectal Cancer

Sarcopenia was initially described as a decrease in muscle mass associated with aging and subsequently also as a consequence of underlying disease, including advanced malignancy. Accumulating evidence shows that sarcopenia has clinically significant effects in patients with malignancy, including an increased risk of adverse events associated with medical treatment, postoperative complications, and a poor survival outcome. Colorectal cancer (CRC) is one of the most common cancers worldwide, and several lines of evidence suggest that preoperative sarcopenia negatively impacts various outcomes in patients with CRC. In this review, we summarize the current evidence in this field and the clinical relevance of sarcopenia in patients with CRC from three standpoints, namely, the adverse effects of medical treatment, postoperative infectious complications, and oncological outcomes

Extraction of a metallic susceptor after accidental ingestion of the heated tobaccostick TEREA™: a case report

Abstract Background Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. Case presentation A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. Conclusions Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting