ABSTRACT Background In recent years, the incidence of early upper gastric cancer has increased, leading to a wider adoption of proximal gastrectomy (PG) as a possible treatment option. PG is preferred over total gastrectomy (TG) due to its superior postoperative nutritional status and improved surgical safety. However, PG is associated with a considerable risk of anastomosis‐related complications, such as gastroesophageal reflux and anastomotic stenosis, which limit its widespread application. Methods We conducted a narrative review of comparative studies, prospective studies and retrospective study, that described reconstructive techniques after PG. End‐points of interest were incidence of reflux esophagitis, anastomotic stenosis, time of follow‐up, nutritional parameters. Results Esophago‐gastrostomy, the simplest reconstruction method, was associated with highest reflux rates of 18%–55% and stenosis rates of 1.1%–27.8%. Anti‐reflux modifications such as side‐overlap, double‐flap technique (DFT) and gastric tube lowered reflux rate distinctly, especially DFT, lowered reflux rates to 2%–16.7%. But DFT carried a 4%–26.3% stenosis risk and longer operative time. Jejunal interposition (JI) gave 2.1%–100% reflux rates and 0%–31.8% stenosis, yet required three anastomoses and limited endoscopic surveillance. Double‐tract reconstruction (DTR) achieved the promising anti‐reflux outcome, with preserved duodenal passage. However, it may increase surgery costs and prolong surgical time. Conclusion Our findings provide a solid foundation for reconstruction methods selection that enhance postoperative quality of life and highlight future directions for improving PG outcomes. DTR and DFT, currently offer the best balance between reflux control and anastomotic stenosis after PG. Prospective clinical research and innovation are expected to further improve these techniques and may discover an optimal universal approach to address long‐term challenges.

Pancreatic β cells play a central role in type 2 diabetes mellitus (T2DM), yet the interactions between β cells and stromal components within the islet microenvironment remain poorly defined. Here, we investigated the contribution of pancreatic fibroblasts to β cell dysfunction and T2DM progression. Here, we employed single-cell sequencing technology and in vitro experiments to investigate the mechanisms by which bariatric surgery ameliorates T2DM. We introduce the novel concept of a “metabolic synapse” to describe the interaction between pancreatic fibroblasts and β cells. Our findings reveal that pancreatic fibroblasts secrete excessive glutamate in the early stages of T2DM. Elevated glutamate concentrations within the islet microenvironment subsequently activate N-methyl-D-aspartic acid receptors (NMDAR), triggering PANoptosis in pancreatic β cells and accelerating T2DM progression. Consistent with this, significant changes in NMDAR expression were observed in human pancreatic samples from patients with T2DM. These findings uncover a previously unrecognized fibroblast-β cell communication pathway in the islet niche, provide mechanistic insights into T2DM pathogenesis, and highlight the glutamate-NMDAR axis as a potential therapeutic target for non-surgical intervention.

The emerging concept of PANoptosis-a lytic cell death pathway integrating apoptosis, pyroptosis, and necroptosis-presents avenues for cancer immunotherapy, yet its therapeutic exploitation remains limited by undefined molecular sensors and induction strategies. Here, we report a tumor-targeting nanozyme, Hemin-His-Mn, that concurrently activates retinoic acid-inducible gene I-mediated PANoptosome assembly and catalyzes reactive oxygen species amplification to achieve precision PANoptosis induction. Mechanistically, Hemin-His-Mn binds to retinoic acid-inducible gene I and alleviates its autoinhibition, initiating PANoptosome formation through the orchestrated recruitment of cell death executioners, thereby identifying retinoic acid-inducible gene I as a master PANoptosis sensor. In parallel, Hemin-His-Mn exerts peroxidase-like activity to generate cytotoxic reactive oxygen species surges, facilitating complete execution of PANoptosis. This dual mechanism promotes potent immunogenicity by releasing damage-associated molecular patterns and enhancing antigen presentation, ultimately eliciting robust T cell-mediated antitumor immunity. In multiple male mouse preclinical models, Hemin-His-Mn reprograms the tumor immune microenvironment and synergizes with immune checkpoint inhibitors. Our study introduces a retinoic acid-inducible gene I-targeting nanotechnology platform that redefines strategies for PANoptosis induction, provides mechanistic insights into PANoptosome assembly, and offers a clinically translatable modality for enhancing cancer immunotherapy.

Sleeve gastrectomy (SG) effectively improves metabolic disorders in individuals with obesity and type 2 diabetes (T2DM), but its molecular mechanism remains unclear. Interleukin 27 (IL-27) improves obesity, insulin resistance and white adipose tissue browning; however, its role in SG-mediated metabolic improvement is unconfirmed. This study aimed to explore the role of IL-27 in metabolic disorders improved by SG in obese T2DM rats. Obese T2DM rats were established and randomly divided into an SG group and a sham operation (control) group. Body weight, food intake, fasting blood glucose levels and insulin resistance indicators were dynamically monitored. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT‒PCR) and immunohistochemistry were used to measure the levels of IL-27 and adiponectin in rat plasma, as well as the expression levels of related molecules in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT); 3T3-L1 adipocyte experiments were performed to clarify the regulatory relationship between IL-27 and adiponectin. Compared with the control group, SG significantly reduced body weight, food intake, fasting blood glucose, and insulin resistance in obese T2DM rats (all P < 0.05); it also significantly increased the IL-27 levels in plasma, eWAT, and iWAT, and upregulated the expression of the IL-27 receptor (IL-27Rα) in eWAT, and the expression of p38 mitogen-activated protein kinase (p38 MAPK), peroxisome proliferator-activated receptor α (PPAR-α), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and uncoupling protein 1 (UCP-1) in eWAT, as well as UCP-1 in iWAT (all P < 0.05). In vivo experiments revealed a significant positive correlation between IL-27 and adiponectin levels (P < 0.05); in vitro experiments confirmed that IL-27 directly promoted adiponectin expression, whereas adiponectin did not significantly affect IL-27 expression (P > 0.05). SG is associated with elevated IL-27 levels and activation of the eWAT p38 MAPK-PGC-1α pathway in obese T2DM rats, accompanied by improved metabolic parameters, suggesting that IL-27 may play a role in SG-induced metabolic improvement.

Gastric cancer (GC) remains a major global health burden, with limited effective therapies and poor prognosis. Quercetin (Que), a natural flavonoid, exhibits anticancer activity but suffers from poor water solubility, limited oral bioavailability, and rapid metabolic clearance, which severely restrict its clinical translation. These pharmacokinetic limitations necessitate an efficient delivery system capable of stabilizing Que in circulation and enabling tumor-specific release. To address these limitations, a zeolitic imidazolate framework-8 (ZIF-8) was developed based on nanoparticles that encapsulate Que (ZIF-8@Que), enabling high loading efficiency and pH-responsive release. ZIF-8@Que was efficiently internalized by GC cells and localized within lysosomes, where the acidic environment accelerated drug release. This process coincided with marked reactive oxygen species (ROS) generation, leading to mitochondrial membrane depolarization, ATP depletion, and ultrastructural damage. Cellular analyses further revealed features consistent with pyroptotic cell death, including lactate dehydrogenase (LDH) release, increased staining for cleaved caspase-1 and cleaved gasdermin-D (GSDMD), and enhanced TUNEL-positive signals. Compared with free Que or empty ZIF-8, ZIF-8@Que demonstrated stronger inhibition of proliferation, migration, and invasion in vitro, while in vivo studies confirmed preferential tumor accumulation, robust tumor suppression, and minimal systemic toxicity. Collectively, these findings highlight ZIF-8@Que as a safe and effective nanoparticle that integrates drug delivery with ROS-mediated pyroptosis, offering a promising strategy to overcome the limitations of Que monotherapy and advance GC therapy.

Background:Repetitive elements account for a large proportion of the human genome and undergo alterations during early tumorigenesis. However, the exclusive fragmentation pattern of DNA-derived cell-free repetitive elements (cfREs) remains unclear. Methods:This study enrolled 32 healthy volunteers and 112 patients with five types of cancer. A novel repetitive fragmentomics approach was proposed to profile cfREs using low-pass whole genome sequencing (WGS). Five innovative repetitive fragmentomic features were designed: fragment ratio, fragment length, fragment distribution, fragment complexity, and fragment expansion. A machine learning-based multimodal model was developed using these features. Results:The multimodal model achieved high prediction performance for early tumor detection, even at ultra-low sequencing depths (0.1×, AUC = 0.9824). Alu and short tandem repeat (STR) were identified as the primary cfREs after filtering out low-efficiency subfamilies. Characterization of cfREs within tumor-specific regulatory regions enabled accurate tissue-of-origin (TOO) prediction (0.1×, accuracy = 0.8286) and identified aberrantly transcribed tumor driver genes. Conclusion:This study highlights the abundance of repetitive DNA in plasma. The innovative fragmentomics approach provides a sensitive, robust, and cost-effective method for early tumor detection and localization.

High-fat diet (HFD) promotes adipose tissue senescence, which in turn disrupts insulin-mediated glycemic homeostasis. The underlying mechanisms remain unclear. Through clinical survey data, animal models, and primary adipose-derived mesenchymal stem cells (ADSC), we investigated how dietary patterns influence adipocyte senescence. We found that elevated fatty acid levels enhance the interaction between the E3 ubiquitin ligase TRIP12 and Cyclin-dependent kinase 4 (CDK4) in ADSCs, triggering CDK4 ubiquitination and degradation. As a process associated with this disruption in cell cycle progression, cellular senescence may represent a key outcome. Consequently, senescent ADSC-derived mature adipocytes (ADSC-MA) exhibit impaired insulin-stimulated GLUT4 membrane translocation and reduced glucose uptake. In contrast, within an HFD setting, dietary fiber supplementation is associated with the reversal of cellular senescence. The gut microbiota–short-chain fatty acids (SCFAs) axis may be involved in the restoration of cell cycle progression and the amelioration of ADSC senescence, correlating with a partial recovery of glucose uptake capacity in ADSC-MAs. Our study highlights potential strategies to reverse cellular senescence and identifies promising therapeutic targets for impaired glucose tolerance.

Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research. Genetics and transcriptomics reveal shared mechanisms of psychiatric and gastrointestinal disorders, highlighting neurological pathways and pleiotropic loci. Genes BSN, CELF4, NRXN1 regulate gut-brain axis, revealing potential therapeutic targets.

Anastomotic leak (AL) remains a critical complication following laparoscopic rectal cancer surgery, significantly impacting patient outcomes and recovery. Although transanal drainage tubes (TDT) theoretically protect anastomoses by decreasing intraluminal pressure, clinical studies have reported inconsistent benefits. Recent evidence indicates that the duration of postoperative TDT placement may influence its protective efficacy. C-reactive protein (CRP), a reliable acute-phase reactant indicating systemic inflammation and local infection severity, may serve as a useful biomarker for guiding individualized decisions regarding the optimal duration of TDT use. This prospective, single-center cohort study included 516 patients undergoing laparoscopic anterior resection for rectal cancer without protective stomas. Patients were assigned into two groups: a historical control group (n = 258, April 2021–April 2023) managed without TDT, and a prospective cohort (n = 258, April 2023–April 2025) managed using individualized TDT placement guided by postoperative CRP trajectory. Daily CRP monitoring determined TDT removal timing: patients with declining CRP levels underwent early removal (postoperative day 5), while those with persistent or rising CRP levels continued TDT decompression until clinical improvement. The primary outcome was the 30-day incidence of AL. Inverse probability of treatment weighting (IPTW) based on propensity scores adjusted for baseline covariate differences between groups. The CRP-guided TDT group demonstrated a significantly lower incidence of AL at 30 days (3.5%, 9/258) compared to the historical control group (8.5%, 22/258; weighted odds ratio, 0.37; 95% CI, 0.16–0.83; P = 0.017). Distinct CRP trajectory patterns were observed among patients without AL, those with AL, and those exhibiting risk trajectories without overt AL. No severe complications directly attributable to TDT placement occurred. Individualized, CRP trajectory–guided TDT management significantly reduces AL incidence following laparoscopic rectal cancer surgery without protective stoma. This biomarker-driven approach represents a feasible and effective clinical strategy to enhance anastomotic safety and optimize postoperative patient care.

Introduction & Objective: T2DM can be effectively treated by sleeve gastrectomy (SG), albeit the mechanisms underlying is elusive. Postoperative changes in serum bile acid have been found contributing to metabolism improvement. This study aims to determine the overall changes of bile acid enterohepatic circulation following SG. Methods: SG model was established in T2DM rats. Alterations of bile acids in the bile, intestine, portal vein and inferior vena cava were evaluated by liquid chromatography-mass spectrometry. Bile acid transporters were also evaluated. Results: Metabolism was significantly improved after SG. Intraluminal bile acids were altered from the duodenum to the colon, with glycine/taurine conjugated bile acid ratio being increased. Peripheral blood total bile acids exhibited an elevation, accompanied by intricate alterations in the composition of bile acids within both the bile and the portal vein. Postoperative liver bile acid absorption transporter NTCP, OATP and efflux transporter BSEP, MDR3 were significantly decreased, whereas intestinal uptake transporter ASBT was increased and bile acid binding protein IBABP was decreased (P<0.05 all). Conclusion: The entire pathway of bile acid enterohepatic circulation exhibited complicated changes following SG. The impact of the changes on postoperative metabolism improvement warrants further research. Disclosure X. Zhao: None. Z. Liu: None. G. Yang: None. Z. Ge: None. S. Dong: None. X. Zhang: None. Z. Cheng: None. K. Wang: None. Funding National Natural Science Foundation of China (82070852, 82270901)

Despite considerable advancements in the treatment of colorectal cancer (CRC), the overall survival rate for patients with advanced CRC remains below 50%, primarily due to challenges posed by drug resistance and metastasis. Here, a novel "Three-in-One" Cu-based metal-organic framework nanozyme with peroxidase-like (POD-like) activity has been successfully developed, aiming to promote CRC cell death by dual targeting of oxidative stress and copper ion homeostasis, which could promote CRC cell death via apoptosis and cuproptosis, and facilitate hypoxia-inducible factor 1α (HIF-1α) degradation, leading to the reversal of chemoresistance in tumor therapy. These nanozymes, composed of copper and 2-propylimidazole (Cu-PrIm), feature a distorted Cu-N4 catalytic active center that mimics natural enzyme structures consisting of copper and histidine residues, endowing them with enzyme-like activities. The antitumor efficacy of Cu-PrIm nanozymes is validated in various in vivo models of CRC. Especially Cu-PrIm nanozymes exhibit excellent biocompatibility, biodegradability, and a tolerable toxicity profile in mouse models, making them a strong candidate for clinical translation. Taken together, the study introduces a novel therapeutic paradigm in CRC treatment by targeting these vulnerabilities and leveraging the potential using "Three-in-One" Cu-PrIm nanozymes to address multiple pathways simultaneously.

BACKGROUND:Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. METHODS:High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. RESULTS:DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. CONCLUSIONS:DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway-and not solely by improving blood glucose-to improve oxidative stress in the heart of diabetic cardiomyopathy rats.

BackgroundPlacement of an indwelling transanal drainage tube (TDT) to prevent anastomotic leakage (AL) after anterior rectal cancer surgery has become a routine choice for surgeons in the recent years. However, the specific indwelling time of the TDT has not been explored. We performed this meta-analysis and considered the indwelling time a critical factor in re-analyzing the effectiveness of TDT placement in prevention of AL after anterior rectal cancer surgery.MethodsRandomized controlled trials (RCTs) and cohort studies which evaluated the effectiveness of TDT in prevention of AL after rectal cancer surgery and considered the indwelling time of TDT were identified using a predesigned search strategy in databases up to November 2022. This meta-analysis was performed to estimate the pooled AL rates (Overall and different AL grades) and reoperation rates at different TDT indwelling times and stoma statuses.ResultsThree RCTs and 15 cohort studies including 2381 cases with TDT and 2494 cases without TDT were considered eligible for inclusion. Our meta-analysis showed that the indwelling time of TDT for ≥5-days was associated with a significant reduction (TDT vs. Non-TDT) in overall AL (OR=0.46,95% CI 0.34-0.60, p<0.01), grade A+B AL (OR=0.64, 95% CI 0.42-0.97, p=0.03), grade C AL (OR=0.35, 95% CI 0.24-0.53, p<0.01), overall reoperation rate (OR=0.36, 95%CI 0.24-0.53, p<0.01) and that in patients without a prophylactic diverting stoma (DS) (OR=0.24, 95%CI 0.14-0.41, p<0.01). There were no statistically significant differences in any of the abovementioned indicators (p>0.05) when the indwelling time of TDT was less than 5 days.ConclusionExtending the postoperative indwelling time of TDT to 5 days may reduce the overall AL and the need for reoperation in patients without a prophylactic DS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407451, identifier CRD42023407451.

Background:The obesity epidemic has been on the rise due to changes in living standards and lifestyles. To combat this issue, sleeve gastrectomy (SG) has emerged as a prominent bariatric surgery technique, offering substantial weight reduction. Nevertheless, the mechanisms that underlie SG-related bodyweight loss are not fully understood. Methods:In this study, we conducted a collection of preoperative and 3-month postoperative serum and fecal samples from patients who underwent laparoscopic SG at the First Affiliated Hospital of Shandong First Medical University (Jinan, China). Here, we took an unbiased approach of multi-omics to investigate the role of SG-altered gut microbiota in anti-obesity of these patients. Non-target metabolome sequencing was performed using the fecal and serum samples. Results:Our data show that SG markedly increased microbiota diversity and Rikenellaceae, Alistipes, Parabacteroides, Bactreoidales, and Enterobacteraies robustly increased. These compositional changes were positively correlated with lipid metabolites, including sphingolipids, glycerophospholipids, and unsaturated fatty acids. Increases of Rikenellaceae, Alistipes, and Parabacteroide were reversely correlated with body mass index (BMI). Conclusion:In conclusion, our findings provide evidence that SG induces significant alterations in the abundances of Rikenellaceae, Alistipes, Parabacteroides, and Bacteroidales, as well as changes in lipid metabolism-related metabolites. Importantly, these changes were found to be closely linked to the alleviation of obesity. On the basis of these findings, we have identified a number of microbiotas that could be potential targets for treatment of obesity.

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Although 5-fluorouracil (5-FU) is the primary chemotherapy treatment for colorectal cancer (CRC), its efficacy is limited by drug resistance. Ferroptosis activation is a promising treatment for 5-FU-resistant cancer cells; however, potential therapeutic targets remain elusive. This study investigated ferroptosis vulnerability and dihydroorotate dehydrogenase (DHODH) activity using stable, 5-FU-resistant CRC cell lines and xenograft models. Ferroptosis was characterized by measuring malondialdehyde levels, assessing lipid metabolism and peroxidation, and using mitochondrial imaging and assays. DHODH function is investigated through gene knockdown experiments, tumor behavior assays, mitochondrial import reactions, intramitochondrial localization, enzymatic activity analyses, and metabolomics assessments. Intracellular lipid accumulation and mitochondrial DHODH deficiency led to lipid peroxidation overload, weakening the defense system of 5-FU-resistant CRC cells against ferroptosis. DHODH, primarily located within the inner mitochondrial membrane, played a crucial role in driving intracellular pyrimidine biosynthesis and was redistributed to the cytosol in 5-FU-resistant CRC cells. Cytosolic DHODH, like its mitochondrial counterpart, exhibited dihydroorotate catalytic activity and participated in pyrimidine biosynthesis. This amplified intracellular pyrimidine pools, thereby impeding the efficacy of 5-FU treatment through molecular competition. These findings contribute to the understanding of 5-FU resistance mechanisms and suggest that ferroptosis and DHODH are promising therapeutic targets for patients with CRC exhibiting resistance to 5-FU.

Introduction: While intracorporeal anastomosis (IA) has been widely used in totally laparoscopic right colectomy, its application in laparoscopic segmental left colectomy for splenic flexure cancer remains underexplored, particularly in large-scale studies with long-term outcomes. This research aims to assess the technical feasibility and oncological efficacy of IA in treating colonic splenic flexure carcinoma, drawing insights from both short-term and long-term outcomes of a retrospective cohort. Materials and methods: A retrospective analysis was conducted on 342 patients diagnosed with colonic splenic flexure carcinoma in three Chinese medical centers. These patients underwent laparoscopic segmental left colectomy between December 2014 and December 2019 across three medical institutions. Comprehensive data encompassing demographics, disease features, pathological characteristics, operative details, and both short-term and long-term outcomes were gathered and scrutinized. Using propensity scores, each patient from the IA cohort was paired with a counterpart from the extracorporeal anastomosis (EA) cohort. Results: IA was performed on 129 patients, while 213 underwent EA. Post-propensity score matching resulted in 129 matched pairs. After matching, many baseline characteristics were balanced. The IA cohort exhibited several advantages, including shorter incision lengths (P < 0.001) and more extensive proximal and distal resection margins (P=0.003, P < 0.001). Additionally, the IA method facilitated a more rapid postoperative recovery as indicated by quicker return of bowel movements (resumption of passing flatus [2.7 (1.0-7.0) days vs. 3.3 (2.0-8.0) days, P < 0.001] and defecation [3.7 (1.0-9.0)] days vs. 4.5 (2.0-9.0) days, P < 0.001]), faster discharges [6.6 (3.0-15.0) days vs. 8.3 (5.0-20.0) days, P < 0.001], and decreased need for rescue analgesics (P < 0.001). The rate of postoperative complications, as rated by the Clavien-Dindo classification, remained consistent across both techniques (P=0.087). Furthermore, the cosmetic outcome rated by Patient Scar Assessment Questionnaire and Scoring System (PSAQ) was markedly superior in the IA group (P < 0.001). Both approaches demonstrated equivalent 5-year overall (82.7% vs. 82.1%, P = 0.419) and disease-free survival (80.9% vs. 78.1%, P = 0.476). Subsequent stratification analysis revealed that IA achieved comparable 5-year overall (80.7% vs. 82.0%, P = 0.647) and disease-free survival (78.1% vs. 76.4%, P = 0.734) in patients with locally advanced colon cancer. Conclusion: Employing IA for laparoscopic segmental left colectomy in cases of splenic flexure carcinoma is not only safe but also offers enhanced cosmetic results and expedited postoperative recovery. Oncologically speaking, IA in left segmental colectomy for splenic flexure carcinoma can yield therapeutic outcomes comparable to those of EA, even in patients with locally advanced colon cancer.