Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to promote the growth of CRCs. Although neutrophils were originally considered to have defensive functions against tumor cells, it has been revealed that some populations of neutrophils, called as tumor-associated neutrophils (TANs), have tumor-supportive functions. The plasticity between tumor-suppressive and -supportive neutrophils are regulated by transforming growth factor (TGF)-β and Interferon-β signaling. Some studies have demonstrated that TANs promote the spread of cancer cells to distant organs. TANs contribute to the tumor invasion and angiogenesis through the production of matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the primary and metastatic sites. Neutrophils also promotes tumor cell dissemination by capturing circulating tumor cells using neutrophil extracellular traps and promote their migration to distant sites. The neutrophil-to-lymphocyte ratio is a well-defined predictive marker for CRC patients. In this review, we highlight the molecular signaling between TANs and CRC cells and the possibility of TANs as a potential target for cancer therapy.

The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a promising therapeutic approach, the mechanisms by which inflammatory cells promote CRC tumorigenesis are not well understood. When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4, and plays an important role in the development of CRC. The current therapies targeting PGE2 using non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors have failed due to the global prostanoid suppression resulting in the severe adverse effects despite the fact they could prevent tumorigenesis. Therefore, therapies targeting the specific downstream molecules of PGE2 signaling could be a promising approach. This review highlights the role of each EP receptor in the TME of CRC tumorigenesis and their therapeutic potential.

Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.

The global pandemic of COVID-19 has changed cancer treatment environments. In Japan, cancer screenings were halted and the numbers of endoscopies and surgeries were restricted in some hospitals based on the state of emergency declared. Herein, we investigated the impact of the COVID-19 pandemic on the characteristics of colorectal cancer (CRC) patients in facilities that are on the frontline of both COVID-19 and cancer treatments. We retrospectively analyzed the cases of all of the CRC patients (n = 123) who underwent surgery at our regional cancer treatment center and tertiary emergency hospital in Japan during a 120-day period ranging from before to after the state of emergency declaration. CRC patients during the corresponding period in the previous year were also examined. Although the number of CRC patients did not show a significant change related to the pandemic, the incidence of obstructive CRCs significantly increased after the pandemic's start. The numbers of outpatients and colonoscopies both decreased, which could have resulted in the decrease of CRC patients detected by cancer screening during the pandemic. The numbers of symptomatic CRC patients and emergency admissions both increased significantly during the pandemic. Our findings indicate the possibility that the discovery of CRCs in patients could be delayed due to the halt in screenings caused by the COVID-19 pandemic, resulting in the increase of obstructive CRCs. These results highlight the importance of cancer screening and suggest that the screening system for cancers should be reorganized before future pandemics.

Most colorectal cancers (CRCs) are moderately differentiated or well differentiated, a status that is preserved even in metastatic tumors. However, the molecular mechanisms underlying CRC differentiation remain to be elucidated. Herein, we unravel a potentially novel posttranscriptional regulatory mechanism via a LIN28B/CDX2 signaling axis that plays a critical role in mediating CRC differentiation. Owing to a large number of mRNA targets, the mRNA-binding protein LIN28B has diverse functions in development, metabolism, tissue regeneration, and tumorigenesis. Our RNA-binding protein IP (RIP) assay revealed that LIN28B directly binds CDX2 mRNA, which is a pivotal homeobox transcription factor in normal intestinal epithelial cell identity and differentiation. Furthermore, LIN28B overexpression resulted in enhanced CDX2 expression to promote differentiation in subcutaneous xenograft tumors generated from CRC cells and metastatic tumor colonization through mesenchymal-epithelial transition in CRC liver metastasis mouse models. A ChIP sequence for CDX2 identified α-methylacyl-CoA racemase (AMACR) as a potentially novel transcriptional target of CDX2 in the context of LIN28B overexpression. We also found that AMACR enhanced intestinal alkaline phosphatase activity, which is known as a key component of intestinal differentiation, through the upregulation of butyric acid. Overall, we demonstrated that LIN28B promotes CRC differentiation through the CDX2/AMACR axis.

Omental bleeding is potentially life-threatening. There are many causes of omental bleeding including trauma, neoplasia, arterial aneurysm rupture, omental torsion, vasculitis, or segmental arterial mediolysis (SAM). Without remarkable pathological features, the diagnosis of idiopathic omental bleeding is made. Omental bleeding is relatively a rare disease, and there is no established treatment strategy. A 53-year-old woman was brought to the ED for sudden onset abdominal pain. CT revealed hematoma in the omentum and was diagnosed as idiopathic omental bleeding accordingly. The patient underwent laparoscopic partial omentectomy and was discharged nine days after surgery. The pathological findings of the resected omentum were not remarkable, and the final diagnosis was made as idiopathic omental bleeding. In some case reports of omental bleeding, interventional radiology (IVR) was chosen for hemostasis, but IVR cannot resect tissue of omentum so it is difficult to make a pathological diagnosis. The surgical approach of idiopathic omental bleeding is uncommon. However, the use of the laparoscopic approach hasn't been reported in the literature. Laparoscopic partial omentectomy can provide effective hemostasis. We report laparoscopic partial omentectomy surgical procedure and review of the literature.