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1.
Nat Commun ; 15(1): 3653, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688896

ABSTRACT

Although nontumor components play an essential role in colon cancer (CC) progression, the intercellular communication between CC cells and adjacent colonic epithelial cells (CECs) remains poorly understood. Here, we show that intact mitochondrial genome (mitochondrial DNA, mtDNA) is enriched in serum extracellular vesicles (EVs) from CC patients and positively correlated with tumor stage. Intriguingly, circular mtDNA transferred via tumor cell-derived EVs (EV-mtDNA) enhances mitochondrial respiration and reactive oxygen species (ROS) production in CECs. Moreover, the EV-mtDNA increases TGFß1 expression in CECs, which in turn promotes tumor progression. Mechanistically, the intercellular mtDNA transfer activates the mitochondrial respiratory chain to induce the ROS-driven RelA nuclear translocation in CECs, thereby transcriptionally regulating TGFß1 expression and promoting tumor progression via the TGFß/Smad pathway. Hence, this study highlights EV-mtDNA as a major driver of paracrine metabolic crosstalk between CC cells and adjacent CECs, possibly identifying it as a potential biomarker and therapeutic target for CC.


Subject(s)
Colonic Neoplasms , DNA, Mitochondrial , Disease Progression , Epithelial Cells , Extracellular Vesicles , Genome, Mitochondrial , Reactive Oxygen Species , Transforming Growth Factor beta1 , Humans , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Reactive Oxygen Species/metabolism , Extracellular Vesicles/metabolism , Animals , Male , Mice , Female , Cell Line, Tumor , Mitochondria/metabolism , Colon/metabolism , Colon/pathology , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Gene Expression Regulation, Neoplastic , Signal Transduction , Middle Aged , Metabolic Reprogramming
2.
BMJ Open ; 13(2): e066981, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36810166

ABSTRACT

INTRODUCTION: In the case of right-sided transverse colon cancer (RTCC) and hepatic flexure colon cancer (HFCC), there is a potential connection of lymph drainage between mesentery and greater omentum. However, most previous reports have been limited case series with No. 206 and No. 204 lymph node (LN) dissection for RTCC and HFCC. METHODS AND ANALYSIS: The InCLART Study is a prospective observational study aiming to enrol 427 patients with RTCC and HFCC treated at 21 high-volume institutions in China. The prevalence of infrapyloric (No. 206) and greater curvature (No. 204) LN metastasis and short-term outcomes will be investigated in a consecutive series of patients with T2 or deeper invasion RTCC or HFCC, following the principle of complete mesocolic excision with central vascular ligation. Primary endpoints were performed to identify the prevalence of No. 206 and No. 204 LN metastasis. Secondary analyses will be used to estimate prognostic outcomes, intraoperative and postoperative complications, the consistency of preoperative evaluation and postoperative pathological results of LN metastasis. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the Ruijin Hospital Ethics Committee (approval number: 2019-081) and has been or will be approved successively by each participating centre's Research Ethics Board. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03936530; https://clinicaltrials.gov/ct2/show/NCT03936530).


Subject(s)
Adenocarcinoma , Colon, Transverse , Colonic Neoplasms , Laparoscopy , Humans , Colon, Transverse/pathology , Colon, Transverse/surgery , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Lymph Node Excision/methods , Colonic Neoplasms/surgery , Adenocarcinoma/pathology , Colectomy/adverse effects , Laparoscopy/methods , Observational Studies as Topic , Multicenter Studies as Topic
3.
Ann Surg Oncol ; 29(4): 2359-2367, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34994886

ABSTRACT

BACKGROUND: This retrospective study aimed to compare the feasibility and effectiveness of a modified Billroth-II with Braun (B-II Braun) reconstruction and those of a Roux-en-Y (R-Y) reconstruction after laparoscopic distal gastrectomy. METHODS: From January 2016 to December 2019, 247 patients underwent total laparoscopic distal gastrectomy (TLDG), with B-II Braun reconstruction for 145 patients and R-Y reconstruction for 102 patients. The patients' data were collected prospectively and reviewed retrospectively. RESULTS: In this study, the median times of the operation were statistically shorter for B-II Braun than for R-Y (167 min [range, 110-331 min] vs 191 min [range, 123-384 min]; p = 0.001), including anastomotic times (33 min [range, 30-42 min] vs 42 min [range, 40-48 min]; p = 0.001). After a short-term follow-up period, endoscopy showed 31 cases of bile reflux (21.4%), 15 cases of grade 2 gastritis (10.3%), and 6 cases of grade 2 food residue (4.1%) in the B-II Braun group after 6 months. After 1 year, 10 patients (6.9%) had grade 2 gastritis and 2 patients (1.4%) had grade 3 gastritis. However, the remnant stomach of the two groups did not differ significantly in the rate of gastric residue (p = 0.112 after 6 months; p = 0.579 after 1 year, respectively), gastritis (p = 0.726 after 6 months; p = 0.261 after 1 year, respectively), or bile reflux (p = 0.262 after 6 months; p = 0.349 after 1 year, respectively). CONCLUSIONS: For gastric cancer patients, TLDG with modified B-II Braun reconstruction could be technically feasible. It has an acceptable range of postoperative complications and is effective in preventing bile reflux into the gastric remnant.


Subject(s)
Gastric Stump , Laparoscopy , Stomach Neoplasms , Anastomosis, Roux-en-Y , Anastomosis, Surgical/adverse effects , Gastrectomy/adverse effects , Gastric Stump/surgery , Gastroenterostomy/adverse effects , Humans , Laparoscopy/adverse effects , Postoperative Complications/etiology , Retrospective Studies , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Treatment Outcome
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-781758

ABSTRACT

Colon cancer is one of the most common malignancies of the alimentary tract, and one main metastatic route is lymph node metastasis. Thorough dissections of regional lymph nodes is one of the core surgical treatment of right colon cancer. D3 lymphadenectomy and complete mesocolic excision (CME) are generally accepted surgical methods for right colon cancer, which can improve the standardization of surgery, improve the quality of tumor resection, and provide more lymph nodes dissectal. Colon cancer of hepatic flexure is likely to have metastasis of the infrapyloric lymph nodes (No.206), which are not regional lymph nodes. Lymph node dissection of No.206 group belongs to extended right hemicolectomy, which involves many vascular variations and complicated peripheral anatomical structure. The theory of fascial surgery provides surgeons with anatomic basis and a clear understanding of the anatomical structure of the infrapyloric region, which is an important theoretical basis for the thorough dissection of lymph nodes in No.206 group, and can completely remove the mass, regional lymph nodes and adipose connective tissue, so as to achieve the goal of non-bleeding surgery. Lymph nodes in No.206 group were dissected, not just the visible lymph nodes, but the entire lymph nodes and lymphatic vessels in the region, including adipose tissue. Extended right hemicolectomy requires higher surgical techniques. The survival benefits of extended right hemicolectomy are not supported by high-level evidence. It is still controversial whether the infrapyloric lymph node dissection should become routine for colon cancer of hepatic flexure. In this article, the metastasis and dissection of infrapyloric lymph node in colon cancer of hepatic flexure is elucidated.


Subject(s)
Humans , Colectomy , Colon, Ascending , Pathology , General Surgery , Colonic Neoplasms , Pathology , General Surgery , Lymph Node Excision , Methods , Lymph Nodes , Pathology , General Surgery , Lymphatic Metastasis , Mesocolon , Pathology , General Surgery
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-800458

ABSTRACT

Colon cancer is one of the most common malignancies of the alimentary tract, and one main metastatic route is lymph node metastasis. Thorough dissections of regional lymph nodes is one of the core surgical treatment of right colon cancer. D3 lymphadenectomy and complete mesocolic excision (CME) are generally accepted surgical methods for right colon cancer, which can improve the standardization of surgery, improve the quality of tumor resection, and provide more lymph nodes dissectal. Colon cancer of hepatic flexure is likely to have metastasis of the infrapyloric lymph nodes (No.206), which are not regional lymph nodes. Lymph node dissection of No.206 group belongs to extended right hemicolectomy, which involves many vascular variations and complicated peripheral anatomical structure. The theory of fascial surgery provides surgeons with anatomic basis and a clear understanding of the anatomical structure of the infrapyloric region, which is an important theoretical basis for the thorough dissection of lymph nodes in No.206 group, and can completely remove the mass, regional lymph nodes and adipose connective tissue, so as to achieve the goal of non-bleeding surgery. Lymph nodes in No.206 group were dissected, not just the visible lymph nodes, but the entire lymph nodes and lymphatic vessels in the region, including adipose tissue. Extended right hemicolectomy requires higher surgical techniques. The survival benefits of extended right hemicolectomy are not supported by high-level evidence. It is still controversial whether the infrapyloric lymph node dissection should become routine for colon cancer of hepatic flexure. In this article, the metastasis and dissection of infrapyloric lymph node in colon cancer of hepatic flexure is elucidated.

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