BACKGROUND:Natural orifice specimen extraction surgery has been increasingly adopted in rectal cancer surgery, but comparative evidence across natural orifice specimen extraction surgery, laparoscopic surgery, and open surgery remains limited, especially regarding functional and long-term oncological outcomes. OBJECTIVE:To compare short-term recovery, 6-month functional outcomes, and long-term survival among natural orifice specimen extraction surgery, laparoscopic surgery, and open surgery for rectal cancer within a uniform treatment period. DESIGN:Multicenter retrospective analysis of prospectively collected real-world data using inverse probability of treatment weighting. SETTINGS:Four tertiary colorectal cancer centers in China. PATIENTS:A total of 3,385 patients underwent curative-intent resection for rectal adenocarcinoma between 2017 and 2019, including 1379 treated with open surgery, 1520 with laparoscopic surgery, and 486 with natural orifice specimen extraction surgery. MAIN OUTCOME MEASURES:Short-term postoperative recovery, complications, 6-month bowel and urinary function assessed using the low anterior resection syndrome score and the International Prostate Symptom Score, and long-term disease-free survival and overall survival. RESULTS:After weighting, baseline characteristics were well balanced (standardized mean differences < 0.1). Natural orifice specimen extraction surgery showed the fastest short-term recovery among the 3 groups, with significantly shorter time to gastrointestinal recovery, lower pain scores, and fewer wound-related complications compared with both laparoscopic surgery and open surgery. Functional outcomes favored minimally invasive approaches: both natural orifice specimen extraction surgery and laparoscopy surgery showed significantly lower low anterior resection syndrome score and International Prostate Symptom Score than open surgery, with no differences between the 2 minimally invasive approaches. Long-term oncological outcomes were comparable across groups; 5-year disease-free survival was 62.2% for laparoscopic surgery, 63.4% for natural orifice specimen extraction surgery, and 60.5% for open surgery, and 5-year overall survival was 72.2, 74.5, and 73.5%, respectively (all p > 0.05). LIMITATIONS:Retrospective design and potential residual confounding despite weighting. CONCLUSIONS:The short-term recovery advantage of natural orifice specimen extraction surgery was most evident compared with open surgery and more modest relative to laparoscopy surgery, while functional and long-term oncological outcomes remained comparable. When performed under standardized oncological principles, natural orifice specimen extraction surgery is a safe and effective minimally invasive option for selected rectal cancer patients. See Video Abstract.

The optimal number of examined lymph nodes (ELNs) for colon cancer (CC) remains controversial. This study aims to identify patient-specific factors associated with the number of ELNs retrieved in CC patients undergoing hemicolectomy and to explore the potential for establishing a minimum ELNs threshold based on patient characteristics. We retrospectively analyzed data on patients with stage I-III CC from two sources: the Chinese Multi-Institutional Registry (CMIR, N = 10,367; 2010–2018) and the Surveillance, Epidemiology, and End. Results (SEER) database (N = 121,216; 2010–2018). Logistic regression modeling was used to identify patient-specific factors associated with ELN counts. Eight distinct patient cohorts were constructed, and the relationship between ELNs and overall survival (OS) was assessed using restricted cubic spline (RCS) curves and Kaplan-Meier curves. This study was registered with the ChiCT Registry (ChiCTR2400084767). The median ELN count was 16 (IQR 12–22) in the SEER cohort and 15 (IQR 12–20) in the Chinese cohort. Age, tumor size, and location emerged as key factors influencing ELN numbers. Notably, the optimal ELN thresholds for optimal survival across all eight cohorts ranged from 14 to 17, exceeding the current recommendation of 12. Exceeding these cohort-specific thresholds was associated with significantly improved OS in both databases (all P < 0.001). The detailed comparison of ELN-related statistics between the two databases is shown in Supplementary Table X. The present study reveals heterogeneity in the minimum ELN requirements across different patient cohorts with CC. Further prospective studies and randomized controlled trials are warranted to validate these tailored thresholds and inform guideline updates.

Background: Conventional laparoscopic-assisted surgery (CLS) for sigmoid and upper rectal cancer requires an abdominal extraction incision, linked to pain, surgical site infection and poor cosmesis. Natural orifice specimen extraction surgery (NOSES) removes tumours via the anus without abdominal wounds, yet high-quality randomised controlled trial evidence on long-term oncological safety remains scarce. This multicentre trial aimed to verify whether NOSES is non-inferior to CLS regarding 3-year disease-free survival (DFS), alongside evaluating short-term recovery and complications. Methods: This open-label, parallel-group, non-inferiority randomised trial enrolled patients with cT1-3N0-2M0 sigmoid/upper rectal adenocarcinoma across 13 Chinese tertiary centres between Aug 30, 2020, and Nov 5, 2023. Participants were 1:1 allocated via centre-stratified web randomisation; outcome assessors at discharge were masked to group assignment. The prespecified non-inferiority margin for 3-year DFS was 10%. Primary analysis used the modified intention-to-treat (mITT) population; per-protocol (PP) data served for sensitivity analysis. Trial registration: ChiCTR2000036314. Findings: 516 patients were randomised (258 per group). The mITT survival cohort included 205 CLS and 208 NOSES participants, with median follow-up of 36.9 months. 3-year DFS was 89.7% (95% CI 85.1-94.6) for CLS and 94.7% (91.1-98.4) for NOSES (absolute difference 5.0%, 95% CI -3.4 to 13.3, meeting non-inferiority; log-rank p=0.088). 3-year overall survival and local recurrence rates were similar between groups. NOSES patients had earlier first flatus (p<0.001), lower postoperative NRS pain scores, and less rescue analgesic use (17.5% vs 37.4%, p<0.001). Overall 30-day complication rate was numerically lower in NOSES (12.0% vs 18.3%, p=0.056); all incisional surgical site infections occurred only in the CLS group (6.0%). Hospital costs were higher with NOSES (mean difference 6525 CNY, p<0.001). No 30-day deaths occurred in either arm. Interpretation: For selected patients with cT1-3N0-2M0 sigmoid or upper rectal cancer, NOSES performed by experienced surgeons delivers non-inferior long-term oncological outcomes versus CLS, with meaningful improvements in postoperative pain, bowel recovery and surgical site infection risk. NOSES represents a patient-friendly minimally invasive option for suitable candidates.

The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.

AimTo evaluate the safety, feasibility, and long-term efficacy of natural orifice specimen extraction surgery (NOSES) compared with totally laparoscopic right hemicolectomy (TLRH) for right-sided colon cancer.MethodsThis single-center retrospective study included 349 patients who underwent laparoscopic curative resection for stage I-III right-sided colon cancer between January 2018 and January 2023. After 1:1 propensity score matching (PSM) for age, tumor size, BMI, neoadjuvant therapy, and T stage, 115 NOSES patients were compared with 115 TLRH patients. Outcomes included postoperative recovery, perioperative fatigue, complications, pelvic floor function, disease-free survival (DFS), and overall survival (OS).ResultsAfter PSM, baseline characteristics were balanced. Operative time and blood loss did not differ between groups. NOSES was associated with significantly less postoperative pain (P < 0.001) and lower analgesic use (25.2% vs. 47.0%, P < 0.001). Learning curves indicated proficiency after 57 transvaginal and 32 transrectal procedures. Recovery indicators, including time to first flatus, defecation, and hospital stay, were comparable. Incision-related complications occurred more frequently in TLRH (P = 0.024). NOSES patients reported lower fatigue levels on postoperative days 1 and 3 (P < 0.001), with fewer cases of postoperative fatigue syndrome. Pelvic floor and continence outcomes were similar. No local recurrences were observed, and DFS and OS did not differ significantly.ConclusionsNOSES is a safe and effective alternative for selected patients with right-sided colon cancer. It reduces postoperative pain, fatigue, and incision-related complications without compromising oncological outcomes or pelvic floor function, and demonstrates a clear learning curve supporting its broader application.

Abstract The liver is the primary target organ for hematogenous metastasis of colorectal cancer, and colorectal cancer liver metastasis is one of the key and challenging aspects in its treatment. In order to improve the diagnosis and comprehensive treatment of colorectal cancer liver metastasis, the guideline development group has summarized advanced experiences and the latest achievements from both domestic and international sources, and has once again revised and updated the Guideline for the diagnosis and comprehensive treatment of colorectal cancer liver metastases (2025 edition) to continuously provide guidance and reference for clinical practice in this field.

This updated analysis of the STELLAR trial reports 5-year outcomes comparing short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy [TNT]) with standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients with distal or middle-third LARC were randomly assigned to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) was 62.0% in the TNT group and 58.7% in the CRT group, with a hazard ratio (HR) for DFS of 0.849 (95% CI, 0.662 to 1.089). Five-year overall survival (OS) was significantly higher with TNT (78.1% v 69.7%; HR, 0.739 [95% CI, 0.550 to 0.993]). Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the two groups. In high-risk patients (per European Society for Medical Oncology criteria), TNT was associated with improved OS (HR, 0.663 [95% CI, 0.469 to 0.937]) and showed a nonsignificant trend toward improved DFS (HR, 0.765 [95% CI, 0.568 to 1.032]). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR, 0.691 [95% CI, 0.497 to 0.961]) and postrecurrence survival (HR, 0.698 [95% CI, 0.490 to 0.994]). These results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to CRT, especially in patients with high-risk disease.

ABSTRACT Background Colorectal cancer (CRC) is one of the most commonly occurring cancers all over the world. Because of the high metastasis rate, the 5‐year survival rate of metastatic CRC is only around 10%. CRC cells trigger the remodeling of the tumor microenvironment (TME), so decoding the TME between metastatic and primary sites becomes crucial. Methods Single‐cell sequencing and analysis were performed on 36 samples from four anatomical locations in nine untreated CRC liver metastasis patients. Cells from primary and metastatic sites were compared, and TMEs were validated. Genes from primary and metastatic sites were compared using a nonparametric test. Results Eleven major cell types were identified, and high heterogeneity of cell distribution among different locations was observed. We revealed several new features in liver metastatic tumors, including CXCL13 + CD4 T cells and regulatory CD4 T cells enriched, exhausted CD8 + T cells (Tex) increased, SPP1+ tumor macrophage increased, IGFBP7+ cancer‐associated fibroblasts in the metastatic TME, and the relative activation of the linoleic acid metabolism pathway. Besides, tumor cells contributed to four distinct biological modules, encompassing apoptosis, epithelial‐mesenchymal transition, the cell cycle, and immune processes. Conclusion Our study contributes new features for the microenvironment of colon cancer and liver metastasis, which may provide unique insights for novel biomarkers and potential treatment strategies.

Robot surgery is an important trend in contemporary colorectal cancer surgical treatment. The Robotic Surgery Group, Colorectal Cancer Committee of Chinese Medical Doctor Association organized experts in relevant fields across the country to update and revise the application standards of robotic colorectal cancer surgery based on the Expert consensus on robotic surgery for colorectal cancer (2015 edition) and the revised version in 2020, in accordance with the development of robotic surgery concepts, technologies, and equipment in recent years, in order to promote the application and promotion of robotic surgery.

Claudin-7, a crucial tight junction protein, governs cell adhesion and permeability, yet its aberrant regulation is a common feature across numerous cancers. Despite this widespread implication, the intricate and context-dependent roles of claudin-7 in different malignancies have remained shrouded in mystery, with existing studies often confining their scope to singular tumor types. This study presents an integrated pan-cancer analysis, meticulously dissecting claudin-7 expression landscapes, prognostic signatures, immune-modulatory prowess, and interactions with therapeutic modalities. In this investigation, we uncover distinct expression profiles of claudin-7 across cancers. Claudin-7 expression is implicated in shaping the tumor immune microenvironment, with its levels correlating with the presence and abundance of various tumor-infiltrating immune cells. Downregulation of claudin-7 in colorectal cancer promotes proliferation and migration. Its downregulation promoted cell EMT and metastasis via upregulating ZEB1. Knockout of claudin-7 also modulates EGFR and several immune signaling pathways. Drug sensitivity analysis suggests that claudin-7 modulates tumor growth through drug sensitivity in colorectal cancer. Our findings underscore the multifaceted significance of claudin-7 in cancer, emphasizing its compelling potential as both a therapeutic target and a biomarker across various cancer types. Together, these revelations illuminate claudin-7's as a sentinel against tumor progression, brandishing its potential as both a linchpin therapeutic target and a potential biomarker.

BACKGROUND:Lymph node (LN) fibrosis occurs in a variety of pathological conditions, including HIV infection, obesity, cancer, and tissue injury. Fibroblastic reticular cells (FRCs) play a critical role in maintaining LN architecture and immune homeostasis, whereas their dysregulation promotes extracellular matrix (ECM) deposition and immune dysfunction. Transforming growth factor-β1 (TGF-β1) is a key profibrotic cytokine. However, reliable and convenient animal models for investigating LN fibrosis remain limited. METHODS:This study comprehensively compared four induction methods: footpad injection of TGF-β1, lymphatic vessel ligation, inguinal subcutaneous injection of TGF-β1, and direct intra-LN injection of TGF-β1. Histological analysis, transcriptomic profiling, flow cytometric analysis, and safety evaluation were performed to assess fibrosis and immune alterations. RESULTS:Among the four approaches, inguinal subcutaneous and intra-LN injection of TGF-β1 successfully induced LN fibrosis without causing significant injury to major organs. Notably, the intra-LN injection model induced fibrosis in both cortical and medullary regions of LNs. Comparing the transcriptomic data of fibrotic and non-fibrotic LNs demonstrated marked changes in fibrosis-related genes, including pro-fibrogenic mediators, collagens and basement membrane-related genes, and TGF-β1-associated signaling pathways. In two fibrotic models, we also noticed increased macrophage infiltration and a drop in CD8+ T cells, suggesting an immune suppressive microenvironment. Furthermore, inhibition of collagen cross-linking partially alleviated fibrotic remodeling in fibrotic LNs. CONCLUSION:We established and characterized two mouse models of LN fibrosis induced by TGF-β1 administration. These models provide valuable tools for investigating the mechanisms of LN fibrosis and its impact on local immune regulation, and may facilitate the development of therapeutic strategies targeting fibrotic LNs.

BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment. However, reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited. AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy. METHODS This retrospective study, conducted at a tertiary center in China, evaluated 74 patients with colorectal cancer, including 17 with deficient mismatch repair (dMMR) and 15 with proficient mismatch repair (pMMR) tumors. Patients underwent neoadjuvant immunotherapy followed by surgery. Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens. RESULTS In the pMMR group (n = 57 evaluable patients), endoscopy identified 11/17 patients who achieved a complete response (CR), while misidentifying 1/40 patients with residual disease as CR (64.7% vs 2.5%, P < 0.01). Conversely, 22/40 patients with residual disease were accurately identified as achieving a partial response (PR), with 1/17 patients who achieved CR misclassified as PR (55.0% vs 5.9%, P < 0.01). The sensitivity, specificity, and accuracy of endoscopic diagnosis for pathological CR were 64.7%, 97.5%, and 87.7%, respectively. In the dMMR cohort, endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR (64.3% vs 66.7%, P = 0.73). The method demonstrated 100% sensitivity and 82.4% accuracy in diagnosing pathological CR. CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort. Despite endoscopic indications of tumor residue, a complete pathological response post-surgery was possible in the dMMR cohort.

BACKGROUND:The current AJCC staging for colorectal cancer liver metastasis (CRLM) classifies stages IVA, IVB, and IVC based on organ metastasis, disregarding lymph node metastasis (LNM). We evaluated the prognostic impact of LNM in CRLM and proposed incorporating LNM into staging criteria. METHODS:Data were extracted from the SEER database (2010-2017) and a Chinese cohort (2009-2018), including 11,266 CRLM patients (9648 SEER; 1618 Chinese cohort). Kaplan-Meier and Cox regression analyses assessed cancer-specific survival (CSS) between LNM and non-LNM groups. Inverse probability treatment weighting (IPTW) was used for primary analysis, with subgroup analyses exploring LNM's prognostic impact. RESULTS:In both the SEER and Chinese cohorts, patients with LNM were significantly associated with worse CSS than patients without LNM before and after IPTW/sIPTW (all p < 0.001). Furthermore, LNM in the M1a subgroup still led to poorer prognosis (all log-rank p < 0.001). In contrast, in the M1b subgroup, the prognostic difference between those with and without LNM was not significant (log-rank p = 0.031 and 0.037, respectively, in the SEER and Chinese cohorts) because the PFDR was set at 0.025. Additionally, in both cohorts, the 5-year CSS rates of M1a stage CRLM patients decreased with advancing N staging, regardless of the resectability of liver metastasis (all log-rank P < 0.001). CONCLUSION:LNM has significant association with worse survival outcomes in CRLM patients, although this prognostic impact exhibits progressive attenuation with increasing liver metastatic burden. For patients with M1a stage CRLM, we suggest that incorporating N staging into their prognostic evaluation can further refine the AJCC TNM staging system.

AIM:Proficiency acquisition in minimally invasive surgery requires rigorous evaluation of learning curves. While natural orifice specimen extraction surgery (NOSES) offers enhanced minimally invasive potential compared to conventional laparoscopy, comprehensive analyses of procedure-specific learning trajectories remain underexplored. This study quantitatively evaluates the learning curves and associated clinical outcomes for three NOSES procedures in colorectal cancer (CRC): eversion resection, extraction resection and resection extraction. METHOD:We screened multiple patient cohorts from the NOSES national database between May 2010 and February 2022. A total of fifteen patient cohorts were included, with five patient cohorts for each NOSES procedure. The learning curve was determined based on the analysis of operation time and blood loss. Cumulative sum (CUSUM) analysis was applied to identify the learning curve turning points (TP). RESULTS:The pooled mean CUSUM curve (for operation time) of the eversion-resection technique group showed that TP was 21 cases, 28 cases and 22 cases of the extraction-resection and resection-extraction technique groups, respectively. The pooled mean CUSUM curve (for blood loss) of the eversion-resection technique group showed that TP was 18 cases and 24 cases and 17 cases of the extraction-resection and resection-extraction technique groups, respectively. Overall, surgical outcomes post-TP were superior to pre-TP. The surgical outcomes improved with the increase in surgical experience. CONCLUSION:We determined the evolving trend of the three learning curves for CRC-NOSES procedures. The demonstrated association between surgical experience and outcome optimization underscores the importance of structured training programmes to facilitate safe adoption of these advanced techniques.

Peritoneal metastasis (PM) after radical surgery is an important cause of treatment failure in colorectal cancer (CRC). Intraoperative intraperitoneal perfusion chemotherapy may be an effective method for preventing postoperative PM in patients with CRC. This study aimed to explore the safety and feasibility of intraoperatively preventive intraperitoneal perfusion chemotherapy using lobaplatin for CRC. Between 12 December 2017 and 17 October 2019, 720 eligible CRC patients with T4 or N + clinical TNM stage were recruited from 25 hospitals in China. Eligible patients were randomised in a 1:1 ratio to undergo resection of CRC only (control group) or resection of CRC with intraperitoneal perfusion chemotherapy with lobaplatin intraoperatively (lobaplatin group). The primary endpoint of this trial was the rate of PM after surgery, while secondary endpoints included safety, overall survival (OS) time, recurrence-free survival (RFS) time, peritoneal recurrence-free survival (PRFS) time, and the rate of liver metastasis. Of 716 patients included in the full analysis set (FAS), 352 were assigned to the lobaplatin group and 364 to the control group. In the FAS population, adding intraoperatively preventive intraperitoneal perfusion chemotherapy with lobaplatin decreased the primary end point rate of 3-year PM (3.56

ObjectiveThe retrieval of 12 lymph nodes (LNs) remains a crucial criterion for accurate staging and prognosis evaluation in rectal cancer (RC). However, some patients fail to meet this threshold after surgery. This study developed a nomogram model based on clinical variables to predict the probability of retrieving 12 LNs postoperatively.MethodsPatients who underwent radical RC surgery at Shanxi Cancer Hospital between 2015 and 2020 were retrospectively analyzed. Continuous variables were converted into categorical variables. Chi-square tests were used to identify key factors influencing the retrieval of 12 LNs. Significant variables were incorporated into a nomogram model. The model’s discrimination ability was evaluated based on the receiver operating characteristic (ROC) curve, while model calibration was assessed using calibration plots. The clinical utility of the model was determined using decision curve analysis (DCA).ResultsA total of 2,724 RC patients were included; 1,906 cases were assigned to the training dataset, while 818 were assigned to the internal validation dataset. Chi-square analysis identified age, T stage, N stage, tumor size, Carcinoembryonic Antigen, CA19-9, hemoglobin, and platelet count as significant factors associated with 12 LN retrieval. The nomogram indicated that T stage, N stage, and tumor size contributed most significantly. The areas under the ROC curves of the model were 0.669 for the training dataset and 0.689 for the internal validation dataset. The calibration plots showed good agreement between the predicted probabilities and actual outcomes. The DCA curves demonstrated a favorable net benefit across a wide range of threshold probabilities.ConclusionThe nomogram model can effectively predict the likelihood of retrieving 12 LNs following RC surgery. The model also provides a valuable tool for preoperative risk stratification and personalized clinical decision-making.