Gastric cancer metastasis to the transverse colon requiring differentiation from early-stage colorectal cancer

Aim. The aim of the study was to evaluate costs associated with colonic endoscopic submucosal dissection (ESD) for treatment of colorectal cancer. Methods. The study is a retrospective analysis of data on 395 patients treated by colonic ESD. Results. The operation, consumable items, and medication accounted for 71% of the total costs for colonic ESD treatment. Medication and consumable items’ costs were higher if lesions occurred in the transverse colon and right hemicolon compared to the left hemicolon. Medication, consumable items, and total costs were higher for larger lesions. Lesion numbers and carcinoma were associated with higher medication, consumable items, operation, and total costs. Positive surgical margins and complications of hemorrhage or perforation were positively correlated with higher costs for medication, consumable items, and total costs. Conclusion. Labor costs for doctors and nurses remain low in China. Costs for medication and consumable items were higher for treatment involving the transverse colon or right hemicolon (vs. the left hemicolon), larger lesions, carcinoma, and a positive surgical margin. A benchmark cost estimate for ESD treatment including 4 days of postoperative hospitalization was determined to be approximately 5400 USD.

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Novel genomic classifier for early stage colorectal cancer patients

Annals of Oncology ◽

10.1093/annonc/mdy269.105 ◽

2018 ◽

Vol 29 ◽

pp. viii33-viii34

Author(s):

E. Letellier ◽

M. Schmitz ◽

A. Ginolhac ◽

E. Koncina ◽

M. Marchese ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Early Stage ◽

Colorectal Cancer Patients

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FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽

10.1007/s13577-021-00500-8 ◽

2021 ◽

Author(s):

Yan Lu ◽

Yushuang Zheng ◽

Yuhong Wang ◽

Dongmei Gu ◽

Jun Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Metastasis ◽

Lung Tumor ◽

Early Stage ◽

High Rate ◽

Early Stage Lung Cancer ◽

Lung Cancer Metastasis ◽

Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

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Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines

Cell Death and Differentiation ◽

10.1038/s41418-021-00779-y ◽

2021 ◽

Author(s):

Liping Yang ◽

Yixuan Hou ◽

Yan-e Du ◽

Qiao Li ◽

Fanlin Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Lipid Metabolism ◽

Gastric Cancer Cell ◽

Cancer Metastasis ◽

Host Gene ◽

Diagnostic Biomarker ◽

Invasion And Metastasis ◽

Gastric Cancer Cells ◽

Tumor Progress ◽

Abnormal Lipid Metabolism

AbstractThe aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene Abhd16a with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate Abhd16a and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene Abhd16a mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.

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MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly

Cell Death and Differentiation ◽

10.1038/s41418-021-00813-z ◽

2021 ◽

Author(s):

Yan Zhong ◽

Ting Long ◽

Chuan-Sha Gu ◽

Jing-Yi Tang ◽

Ling-Fang Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Focal Adhesion ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Integrin Β1 ◽

Independent Manner ◽

Interacting Protein ◽

Tumour Metastasis ◽

Elevated Expression ◽

Dependent Polarization

AbstractTumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368–411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin β1 and Talin-1, which facilitated to integrin β1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.

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A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting

Cancers ◽

10.3390/cancers13112762 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2762

Author(s):

Samantha Di Donato ◽

Alessia Vignoli ◽

Chiara Biagioni ◽

Luca Malorni ◽

Elena Mori ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Stratification ◽

Elderly Patients ◽

Metastatic Colorectal Cancer ◽

Early Stage ◽

Prospective Trial ◽

Proton Nuclear Magnetic Resonance ◽

P Value ◽

Resonance Spectroscopy ◽

Metabolomic Fingerprinting

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

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IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R

Cell Death and Disease ◽

10.1038/s41419-021-03833-2 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Chenyang Qiao ◽

Wenjie Huang ◽

Jie Chen ◽

Weibo Feng ◽

Tongyue Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Cancer Metastasis ◽

Combined Treatment ◽

Insulin Like Growth Factor ◽

Atp Citrate Lyase ◽

Citrate Lyase ◽

Elevated Expression ◽

Igf1r Inhibitor ◽

Colorectal Cancer Metastasis

AbstractMetastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.

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IgG4-related gastric disease with plasma cell-rich obliterative arteritis accompanied by early-stage gastric cancer: a case report

Surgical Case Reports ◽

10.1186/s40792-021-01126-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Masayoshi Obatake ◽

Koichi Sato ◽

Shigehiko Yagi ◽

Hiromi Ohtani ◽

Katsumi Kito

Keyword(s):

Gastric Cancer ◽

Plasma Cell ◽

Early Stage ◽

Vascular Lesions ◽

Gastric Disease ◽

Inflammatory Disorder ◽

Obliterative Phlebitis ◽

Regional Lymph Node Dissection ◽

Serum Igg4 ◽

Storiform Fibrosis

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated inflammatory disorder that can involve multiple organs. It is characterized by IgG4-positive plasma cell-rich storiform fibrosis and obliterative phlebitis associated with a high serum IgG4 level. There are few reports of gastric IgG4-RD, especially those detected prior to systemic or other organ involvement. Case presentation: A 70-year-old man was diagnosed with type 0–IIc gastric cancer at the anterior wall of the gastric corpus by upper gastrointestinal endoscopy. In addition, a submucosal tumor (SMT) 7 mm in diameter was found at the greater curvature of the angulus. Laparoscopic distal gastrectomy with regional lymph node dissection was performed. Pathology revealed a poorly differentiated adenocarcinoma in the type 0–IIc lesion and storiform fibrosis with infiltration of a large number of IgG4-positive plasma cells in the SMT. Postoperative laboratory testing showed elevation of serum IgG4 levels; thus, we diagnosed the SMT as IgG4-RD. Intriguingly, the gastric IgG4-RD lesion demonstrated IgG4-positive plasma cell-rich arteritis as well as typical obstructive phlebitis. The patient has been followed for 2 years after surgery without recurrence of cancer, but skin lesions of IgG4-RD have appeared. Conclusion We report a rare case of IgG4-RD presenting as a gastric SMT, accompanied by early-stage gastric cancer. Our case may support a newly proposed relationship between IgG4-RD and malignancies. The gastric IgG4-RD lesion showed arteritis as well as obliterative phlebitis, potentially providing novel insight into IgG4-related vascular lesions.

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