Parastomal hernia (PSH) is one of the most frequent long-term complications following abdominoperineal resection (APR) for rectal cancer. The optimal colostomy route to minimize PSH remains controversial. This study aimed to compare PSH risk between extraperitoneal colostomy (EPC) and transperitoneal colostomy (TPC) after laparoscopic APR. A retrospective cohort study was conducted including patients who underwent laparoscopic APR for rectal cancer between 2014 and 2017. Patients were categorized according to colostomy route (EPC vs. TPC). The primary endpoint was PSH, and secondary endpoints included other short- and long-term stoma-related complications and perioperative outcomes. Propensity score matching (1:3) was applied to balance baseline characteristics. Risk factors for PSH were further analyzed using logistic regression. A total of 464 patients were included. After matching, 102 patients in the EPC group and 243 in the TPC group were analyzed. Perioperative outcomes and overall stoma-related complication rates were comparable between groups. However, PSH occurred less frequently in the EPC group than in the TPC group (10/102 [9.8

PURPOSE:To compare the safety and efficacy of preoperative simultaneous integrated boost chemoradiation therapy (SIB-CRT) versus standard chemoradiation therapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS:This prospective, randomized phase II trial (NCT02195141) enrolled patients with stage II/III rectal adenocarcinoma. Patients were randomly assigned (1:1) to CRT (50 Gy/25 fx to the pelvis) or SIB-CRT (50 Gy/25 fx to the pelvis with a simultaneous integrated boost of 56 Gy to PGTV and 60 Gy to lateral metastatic nodes if present). Radical surgery was planned 6-8 weeks after CRT. The primary endpoint was pathologic complete response (pCR) rate; secondary endpoints were disease-free survival (DFS), overall survival, metastasis-free survival, local control, cancer-specific survival, and toxicity. RESULTS:From August 2013 to February 2015, 106 patients were enrolled: 55 in the SIB-CRT group and 51 in the CRT group. Acute grade 3 toxicity occurred in 14.5% (SIB-CRT) and 19.6% (CRT) of patients, primarily manifested as radiation dermatitis. Curative treatment (radical surgery or watch-and-wait) was achieved in 89.1% (49/55) of SIB-CRT patients and 78.4% (40/51) of CRT patients (P = .135). After a median follow-up of 116.6 months, the SIB-CRT group showed superior 9-year outcomes in the intention-to-treat population: DFS (70.8% vs 47.4%; hazard ratio [HR], 0.46; P = .013), overall survival (74.3% vs 48.9%; HR, 0.43; P = .008), metastasis-free survival (70.8% vs 47.2%; HR, 0.48; P = .017), local control (87.1% vs 70.1%; HR, 0.40; P = .038) and cancer-specific survival (77.4% vs 57.2%, P = .027). Similar benefits were observed in the curative treatment cohort. The pCR rates were comparable (15.2% vs 18.4%, P = .695). Exploratory subgroup analysis showed that the survival benefit of SIB-CRT was statistically significant in patients who did not receive perioperative chemotherapy (9-year DFS, 70.8%; HR, 0.343; P = .014), whereas no additional benefit was observed in those receiving chemotherapy. CONCLUSIONS:Dose escalation through simultaneous integrated boost during neoadjuvant CRT translates into superior long-term survival outcomes. Despite comparable pCR rates, the intensified control of both local disease and micrometastases by SIB-CRT, coupled with its significant superiority within the chemotherapy-naive subgroup, likely contributed to these robust results. These findings establish dose escalation as a potent strategy for optimizing long-term cure in the modern management of locally advanced rectal cancer, particularly in chemotherapy-ineligible patients.

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 survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. Group 4 achieved the highest 5-year OS (82.1

Background Gastric cancer (GC) remains a major global health burden, and minimally invasive approaches have become a primary focus in surgical oncology. Natural orifice specimen extraction surgery (NOSES) for GC integrates laparoscopic radical gastrectomy with specimen retrieval via natural orifices, aiming to minimize abdominal wall trauma while ensuring oncologic safety. Methods This guideline was developed through a comprehensive literature review, multidisciplinary expert panel discussions, and synthesis of accumulated clinical experience in GC-NOSES. The recommendations address operative platforms, aseptic and tumor-free techniques, digestive tract reconstruction, and procedure-specific steps. Emphasis was placed on perioperative safety, oncologic principles, and standardization of surgical procedures. Results Although most existing studies are small-scale, single-center, and retrospective, accumulating data suggest that GC-NOSES offers comparable oncological outcomes to conventional laparoscopic gastrectomy while reducing postoperative pain, accelerating gastrointestinal recovery, shortening hospital stay, and improving cosmetic satisfaction. Conclusion GC-NOSES is a promising minimally invasive option with potential benefits in postoperative recovery and quality of life. Standardized procedures, structured training, and high-quality multicenter studies are essential to further confirm its safety, refine indications, and promote global implementation.

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 Background Rectal cancer (RC) is traditionally grouped within colorectal cancer (CRC), despite growing evidence of distinct epidemiologic features. However, global comparative assessments of lifetime risks of RC relative to CRC remain limited. We aimed to estimate lifetime risks of developing and dying from RC and CRC worldwide and to examine geographic, socioeconomic, and temporal variations in the proportional contribution of RC within CRC. Methods Age-specific incidence and mortality estimates for RC and CRC across 185 countries were obtained from GLOBOCAN 2022, together with population and all-cause mortality data from the United Nations. Lifetime risks of incidence (LRI) and mortality (LRM) were calculated using the adjusted-for-multiple-primaries (AMP) method by sex, country, region, and Human Development Index (HDI). The RC-to-CRC lifetime risk ratio quantified the proportional contribution of RC. Temporal trends were assessed in 42 countries using Cancer Incidence in Five Continents Plus (CI5plus) data and average annual percent change (AAPC). Results In 2022, the global lifetime risk of developing RC was 1.61% and dying from RC was 0.95%, accounting for approximately 35% of the corresponding CRC lifetime burden (4.61% and 2.68%). Absolute lifetime risks of both RC and CRC increased with HDI. In contrast, the proportional contribution of RC varied markedly, peaking at 41%–43% in Central and South-Eastern Asia but falling below 20% in the Caribbean and Central America, and showed a negative association with HDI. The LRI/LRM ratio increased with socioeconomic development. Temporal analyses showed increasing LRI trends in 17 of 42 countries for CRC versus 9 for RC, while declines occurred in 14 countries for RC and 11 for CRC. Conclusions RC constitutes a substantial yet epidemiologically distinct component of the global CRC burden. Its proportional contribution varies across regions and does not parallel absolute risk patterns, supporting the need for subsite-specific surveillance and prevention strategies.

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.

2542 Background: KRAS G12V is a prevalent oncogenic driver in solid tumors, particularly pancreatic cancer (PC), occurring in approximately 20-30% of patients (pts). Advanced solid tumors harboring this mutation carry a poor prognosis and limited treatment options following standard chemotherapy. This phase 1 study evaluates a novel TCR-engineered T cell (TCR-T) therapy derived from a naturally occurring, KRAS G12V/HLA-A*11:01–restricted T cell receptor (TCR) isolated from patient tumor-infiltrating lymphocytes. Methods: This open-label, single-arm, dose-escalation phase 1 trial assessed the safety, tolerability, and preliminary efficacy of autologous TCR-T cells in pts with advanced solid tumors. Eligible pts had confirmed KRAS G12V mutation and HLA-A*11:01 positivity. Using a standard 3+3 design, autologous T cells were transduced with a lentiviral vector encoding the TCR and a CD8 co-receptor. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed by a single infusion of TCR-T cells at either 5×10⁹ (DL1) or 1×10¹⁰ (DL2) cells, with adjunctive interleukin-2. Results: As of January 2026, 8 pts were enrolled; of whom 6 (median age 69.5 years, ECOG PS 1) received the planned infusion, including pts with colorectal cancer (n = 2), pancreatic cancer (n = 3), and endometrial cancer (n = 1). All pts had liver or lung metastases and > 2 metastatic sites. No dose-limiting toxicities (DLTs) or grade ≥3 treatment-related adverse events (TRAEs) were observed. The treatment was generally well-tolerated; the most common (≥50%) treatment-emergent adverse events (TEAEs) were pyrexia, cytokine release syndrome (CRS), neutropenia, anemia, and thrombocytopenia. Grade 1-2 CRS occurred in 4/6 pts and resolved without sequelae. No immune effector cell–associated neurotoxicity syndrome (ICANS) was observed. TCR-T cells peaked in peripheral blood at a median of day 4 (range, 1–10), with a median peak expansion of 61,863 copies/µg DNA (range, 40,394–80,824). The objective response rate (ORR) was 50.0% (3/6), with a disease control rate (DCR) of 83.3% (5/6). In the pancreatic cancer subset, the ORR was 66.7% (2/3) and the DCR was 100%. Conclusions: This KRAS G12V/HLA-A*11:01–restricted TCR-T therapy demonstrated a favorable safety profile and encouraging preliminary antitumor activity in advanced solid tumors. Notably, a high response rate was observed in heavily pretreated pancreatic cancer patients, supporting further clinical development of this novel cellular therapy. Clinical trial information: NCT06767046 .

BACKGROUND:Parastomal hernia (PSH) is a frequent complication of abdominoperineal resection (APR), yet large-scale studies characterizing its long-term incidence and tools for individualized risk stratification remain lacking. To determine the long-term incidence, independent risk factors, and develop a clinical prediction model for PSH after APR in rectal cancer patients. METHODS:We conducted a retrospective cohort study of 836 patients with rectal adenocarcinoma who underwent APR and permanent end colostomy at a high-volume tertiary center (2014-2018). PSH was diagnosed according to the European Hernia Society criteria. Independent risk factors were identified using Cox regression, and a nomogram was developed to predict 1- to 5-year PSH probabilities. Model discrimination was assessed using time-dependent AUC. RESULTS:During a median follow-up period of 85 months, 207 patients (24.8%) developed PSH, with a cumulative incidence of 26.2% at 5 years. Independent risk factors included female sex (HR = 2.28, 95% CI: 1.73-3.01), age ≥ 60 years (HR = 5.17, 95% CI: 3.72-7.18), BMI ≥ 24 kg/m2 (HR = 2.10, 95% CI: 1.57-2.80), and transperitoneal stoma route (HR = 4.11, 95% CI: 2.63-6.41; all P < 0.001). The nomogram demonstrated strong discrimination with 1-, 2-, 3-, 4-, and 5-year AUCs of 0.65, 0.70, 0.76, 0.80, and 0.83, respectively. CONCLUSION:This study provides evidence on PSH incidence and risk factors, introducing a nomogram for personalized risk stratification. The nomogram allows clinicians to identify high-risk patients and tailor preventive strategies, such as extraperitoneal stoma creation or prophylactic mesh placement, to reduce PSH burden.

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.

This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling. We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM. Pathological evaluations were used to assess immune cell infiltration and histological features. The CRLM patients with LNM had significantly shorter CSS than patients without LNM in two large cohorts. Our results showed that nonmetastatic TDLNs exhibited a greater abundance of immune cells, including CD4+ T cells, CD8+ T cells, and CD19+ B cells, whereas metastatic TDLNs were enriched with fibroblasts, endothelial cells, and macrophages. Immunohistochemical analysis confirmed elevated levels of CD3+ T cells, CD8+ T cells, and CD19+ B cells in nonmetastatic TDLNs. The presence of nonmetastatic TDLNs was associated with enhanced antitumor immune responses in primary tumors, characterized by a higher Klintrup–Makinen (KM) grade and the presence of tertiary lymphoid structures. Furthermore, liver metastasis in patients with nonmetastatic TDLNs were predominantly of the desmoplastic growth pattern (dHGP), while those with metastatic TDLNs were predominantly of the replacement growth pattern (rHGP). This research highlights the adverse prognostic impact of LNM on patients with CRLM and reveals potential related mechanisms through multiomics analysis. Our research paves the way for further refinement of the AJCC TNM staging system for CRLM in clinical practice.

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

BACKGROUND:The National Comprehensive Cancer Network guidelines recommend adjuvant chemotherapy (ACT) for patients with stage II colon cancer who have undergone curative surgery when fewer than 12 lymph nodes (LNs) are retrieved. This study seeks to further examine the requirement for ACT in individuals who had 12 or more LNs harvested. AIM:To investigate if stage II colon cancer patients with 12 or more LNs retrieved benefit from ACT. METHODS:This retrospective cohort study included individuals diagnosed with stage II colon cancer who underwent surgery between 2008 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) registry and a Chinese multicenter database. All patients had at least 12 LNs retrieved. The key endpoint was overall survival (OS). Cox regression analysis was performed to assess independent OS predictors. Propensity score matching controlled for confounders, and Kaplan-Meier analysis evaluated the impact of ACT on survival. RESULTS:A total of 32742 patients with stage II colon cancer from the SEER cohort and 3153 patients from the Chinese cohort were included. The average number of LNs retrieved was 20.0 (15.0, 26.0) in the SEER cohort and 18.0 (15.0, 22.0) in the Chinese cohort. No-ACT remained an independent risk factor in both cohorts (hazard ratio = 1.589, 95% confidence interval: 1.485-1.700 and hazard ratio = 1.865, 95% confidence interval: 1.465-2.375, respectively). In the SEER cohort, patients in the ACT group consistently demonstrated better 5-year OS rates both before and after propensity score matching (79.4% vs 66.1% and 79.4% vs 69.4%, both P < 0.0001). Similarly, these findings were further validated in the Chinese cohort (91.2% vs 82.1% and 90.0% vs 82.8%, both P < 0.0001). ACT improved prognosis even in T3 and grade 1/2 patients. CONCLUSION:This research, based on two large population-based cohorts, demonstrates that stage II colon cancer patients with 12 or more LNs retrieved can still benefit from ACT.

Portal vein tumor thrombus (PVTT) is a major contributor to recurrence, metastasis, and poor prognosis in hepatocellular carcinoma (HCC). Effective early detection and therapeutic strategies for PVTT are lacking. In our ongoing investigation, we identified cell surface vimentin-positive (CSV+) CTCs as a key subpopulation enriched in HCC patients with PVTT, whereas conventional EpCAM+ CTCs exhibited limited clinical relevance. Integrated multi-omics analyses further revealed that tumor cells within the primary lesion exhibiting both epithelial-mesenchymal transition (EMT) and ferroptosis-associated signatures are more likely to intravasate and contribute to PVTT formation. Notably, G6PD was identified as a ferroptosis-related marker specifically enriched in this EMT-like tumor cell subset, suggesting its functional involvement in PVTT pathogenesis. Clinically, elevated levels of G6PD+CSV+ CTCs were associated with poor responses to targeted immunotherapy. Importantly, the identification of CSV also provides a rationale for developing CSV-guided delivery systems, enabling targeted silencing of PVTT-associated molecular drivers such as G6PD. Collectively, our findings highlight G6PD+CSV+ CTCs as a dual-function biomarker for both PVTT risk stratification and treatment response monitoring, offering a novel strategy for the precision management of advanced HCC with PVTT involvement.

BACKGROUND:The therapeutic efficacy and mode of combining immunotherapy with neoadjuvant chemoradiotherapy in proficient mismatch repair (pMMR)/microsatellite stable (MSS) locally advanced rectal cancer (LARC) remain uncertain. METHODS:In this multicenter, randomized, seamless phase 2/3 trial (ClinicalTrials.gov: NCT05484024), eligible participants were randomly assigned (1:1) to receive short-course radiotherapy (SCRT) (5 Gy × 5), followed by 4 cycles of capecitabine and oxaliplatin or 6 cycles of leucovorin, oxaliplatin, and fluorouracil, with (iTNT group) or without (total neoadjuvant therapy [TNT] group) 4 cycles of sintilimab. Following neoadjuvant therapy, participants underwent surgery or a watch-and-wait strategy based on clinical complete response. The primary endpoints were the complete response (CR) rate for phase 2 and the 3-year disease-free survival (DFS) rate for phase 3. FINDINGS:218 patients were randomized to the iTNT group (n = 110) and the TNT group (n = 108). All patients completed SCRT, with 88.2% in the iTNT group and 93.5% in the TNT group completing 4 cycles of neoadjuvant treatment. The CR rate was significantly higher in the iTNT group (45.5% vs. 25.0%; p = 0.003). Grade 3-4 treatment-related adverse events were reported in 34.5% of the iTNT group and 19.4% of the TNT group (p = 0.012), with thrombocytopenia, diarrhea, leukopenia, and neutropenia being the most frequently observed. Grade 3-4 immune-related adverse events occurred in 5.5% of patients in the iTNT group. CONCLUSIONS:The addition of the PD-1 inhibitor sintilimab significantly enhances the CR rate compared to SCRT-based TNT, with favorable tolerability in patients with pMMR/MSS LARC. FUNDING:This work was funded by the National Natural Science Foundation of China (82473248) and the Shenzhen Medical Research Fund (C2301001).

BACKGROUND:Laparoscopic colorectal resection (LCR) has increasingly been performed as an ambulatory procedure. However, whether ambulatory surgery is comparable to inpatient surgery remains uncertain. This systematic review and meta-analysis aim to provide a comprehensive review of the literature comparing the outcomes of LCR in ambulatory and inpatient settings. MATERIALS AND METHODS:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search strategy was developed and used to search the PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library, Web of Science, and Google Scholar before October 2024. The outcome measures included overall postoperative complications, anastomotic leak (AL), ileus, surgical site infection (SSI), 30-day readmission, reoperation, and mortality. Pooled risk ratio (RR) with 95% confidence intervals (CIs) were calculated for outcomes using fixed- or random-effects models. RESULTS:Seven studies were included, involving 1546 patients who underwent ambulatory surgery and 56 279 who underwent inpatient surgery. No significant differences were observed in the rates of ileus (RR = 0.55, 95% CI = 0.26-1.15, P = 0.11), SSI (RR = 0.71, 95% CI = 0.48-1.06, P = 0.10), or overall postoperative complications (RR = 0.99, 95% CI = 0.32-3.06, P = 0.98). However, the incidence of AL was significantly lower in the ambulatory group (RR = 0.42, 95% CI = 0.22-0.81, P = 0.01). No significant differences were found in 30-day readmission, reoperation, or mortality. CONCLUSION:Ambulatory LCR appears to be a safe and feasible option, with comparable short-term outcomes to inpatient surgery in selected patients. Further randomized studies are warranted to validate these findings.