Background: Current evidence suggests that neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) alone is insufficient for magnetic resonance imaging (MRI)–suspected lateral lymph node metastasis (LLNM) in rectal cancer. However, whether upfront TME with lateral lymph node dissection (LLND) is adequate, and whether adding nCRT before planned LLND confers additional benefit, remains controversial. Methods: Between May 2021 and September 2022, a total of 342 patients from 20 Chinese centers were enrolled, of whom 293 were included in the final analysis and received either long-course nCRT plus TME with LLND or upfront TME+LLND. Groups were balanced by propensity score matching. The primary endpoint was 3-year recurrence-free survival (RFS). Findings: After matching, the nCRT group had significantly better 3-year RFS (HR 0.54; 95% CI. 0.32–0.92; P=0.023) and locoregional recurrence-free survival (HR 0.37; 95% CI, 0.19–0.74; P=0.005); distant metastasis-free survival did not differ (HR 0.74; 95% CI, 0.37–1.47; P=0.385). In patients with pretreatment positive lateral nodes (n=141), nCRT also improved RFS (HR 0.53; 95% CI, 0.28–0.99; P=0.049) and local control (HR 0.35; 95% CI, 0.15–0.77; P=0.010). Pathologic complete response in lateral nodes after nCRT was 44.7% (34/76). Overall postoperative complication rates were similar between groups (19.8% vs 16.0%; P=0.474), as were severe complications (grade III–V, 9.4% vs 8.5%; P=0.811). Interpretation: In MRI-suspected LLNM, adding nCRT to TME with LLND significantly improves RFS and local control without increasing morbidity. Upfront surgery alone is insufficient. These findings support a combined treatment paradigm and confirm the necessity of nCRT in these patients.

For patients with mismatch repair-proficient / microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC), the NECTAR (NEoadjuvant Chemoradiotherapy plus immunoTherapy for locally Advanced Rectal cancer) trial reported an encouraging pathological complete response (pCR) rate of 40.0%. Given that pMMR/MSS tumors are generally resistant to immunotherapy, this pCR rate highlights the potential of combination therapy to overcome primary resistance. Here, we report the 3-year survival outcomes of the NECTAR trial, using neoadjuvant chemoradiotherapy (NCRT) plus tislelizumab in pMMR/MSS LARC. In this phase 2, multi-center, single-arm trial, eligible pMMR/MSS LARC patients received three cycles of neoadjuvant programmed cell death protein 1 (PD-1) blockade, three cycles of chemotherapy, and long-course radiotherapy followed by total mesorectal excision (TME). This 3-year analysis evaluates disease-free survival (DFS) and safety. From June 2021 to November 2022, 50 patients were enrolled and 46 patients completed neoadjuvant therapy and TME. Of the 46 patients, 20 patients reached pCR. With a median follow-up of 44.2 months, the median DFS was not reached. The 3-year DFS rate was 89.1%. All patients who achieved pCR (20/46) remained DFS at 3 years. Patients with a low neoadjuvant rectal (NAR) score (<8) had the 3-year DFS rate of 100%, suggesting that overcoming therapeutic resistance in immunotherapy may translate into sustained survival benefits. No new grade ≥III treatment-related adverse events (trAEs) occurred during the 3-year follow-up. The 3-year survival outcomes demonstrate promising efficacy and safety of this NECTAR trial, which provides a promising therapeutic avenue for a patient population traditionally resistant to single-agent immunotherapy.

Aim To evaluate the value of trans-anal multipoint full-layer puncture biopsy (TMFP) in guiding organ preservation strategies and prognostic stratification for locally advanced rectal cancer (LARC) after neoadjuvant therapy. Method This prospective multicenter study was conducted across four tertiary centers in China. Sixty-one LARC patients after neoadjuvant chemoradiotherapy (± immunotherapy) who underwent in vivo TMFP were enrolled. Primary outcomes were TMFP-guided changes in treatment strategy (Watch-and-Wait, W&W, vs. surgery) and overall survival (OS). Results Among 61 patients, 20 achieved clinical complete response (cCR) and 41 were non-cCR. TMFP results significantly altered treatment decisions in non-cCR patients, with 48.8% (20/41) being TMFP-negative; half of these (10/20) successfully adopted a W&W strategy. The postoperative pCR rate in non-cCR but TMFP-negative patients who underwent surgery was 70% (7/10). TMFP demonstrated superior prognostic stratification compared to cCR: the OS of TMFP-negative patients was significantly better than that of TMFP-positive patients (P = 0.04), whereas no significant difference was found between cCR and non-cCR groups (P = 0.58). Among TMFP-negative patients, no survival difference was observed between the W&W and surgery groups (P = 0.40). The procedure was well-tolerated with a low complication rate. Conclusions TMFP serves as a pivotal clinical decision-making tool that safely expands organ preservation opportunities to a significant subset of non-cCR patients and provides powerful prognostic stratification, outperforming traditional cCR assessment. Integrating TMFP into the post-neoadjuvant workflow optimizes the balance between oncological safety and functional preservation.

Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation–immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled. The patients were randomly assigned to receive neoadjuvant chemoradiation + concurrent/sequential PD-1 blockade (experiment groups A/B) or neoadjuvant chemoradiation alone (control group). Radical surgeries were scheduled after neoadjuvant treatments. The primary endpoint was the pCR rate. The pCR rates were 27.1 NCT05245474 ). In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

PURPOSE:The clinical benefit of incorporating oxaliplatin into conventional neoadjuvant chemoradiotherapy (nCRT) for patients with high-risk locally advanced rectal cancer (LARC) remains controversial. METHODS AND MATERIALS:This multicenter, open-label, randomized controlled trial enrolled 505 patients with high-risk LARC, defined by the presence of at least 1 of the following adverse features: clinical T4 stage, clinical N2 stage, high tumor grade, extramural vascular invasion, involvement of the mesorectal fascia, or perianal musculature involvement. Enrollment took place between August 2017 and April 2022. Patients were randomly assigned to receive long-course radiation therapy combined with a 3-cycle chemotherapy regimen of capecitabine and oxaliplatin (CapeOX group; n = 248) or capecitabine alone (Cape group; n = 257). The primary endpoint was 3-year disease-free survival (3y-DFS). RESULTS:Following nCRT, radical surgery was performed in 91.5% of the CapeOX group and 92.2% in the Cape group (P = .778). Pathologic complete response rates were comparable between the CapeOX and Cape groups (25.5% vs 25.3%; P = .954). A significantly greater proportion of patients in the CapeOX group achieved marked tumor regression (College of American Pathologists (CAP 0-1)) compared with the Cape group (58.6% vs 46.8%; P = .011). The incidence of grade 3 to 4 treatment-related toxicities was similar between the groups (CapeOX: 14.1% vs Cape: 9.3%; P = .095). After a median follow-up of 37 months, 3y-DFS and 3-year overall survival rates were comparable between the groups (both P > .050). Overall, patients who achieved CAP 0 to 1 had significantly better 3y-DFS than those with CAP 2 to 3 (89.0% vs 80.9%; P = .018). CONCLUSIONS:The addition of oxaliplatin to conventional nCRT may enhance pathologic tumor regression in patients with high-risk LARC without a significant increase in severe adverse events. However, this intensified 3-cycle chemotherapy regimen did not translate into a long-term survival benefit.

BACKGROUND:Accurate risk stratification is essential to optimize neoadjuvant therapy for locally advanced rectal cancer (LARC) in the era of precision medicine. This study assessed the feasibility and safety of a circulating tumor DNA (ctDNA)-guided neoadjuvant strategy. METHODS:This interim analysis included patients with mid-low rectal adenocarcinoma (cT3-4N0M0 or cT1-4N1-2M0) from the multicenter, randomized CINTS-R trial using a 2:1 allocation to an experimental or control group. The control group received conventional nCRT (long-course radiotherapy with concurrent capecitabine followed by one XELOX cycle). In the experimental group, treatment was stratified as follows: (1) ctDNA-defined high-risk patients received TNT, consisting of the same nCRT followed by five additional XELOX cycles (six in total); (2) ctDNA-defined low-risk patients proceeded directly to surgery after nCRT; and (3) patients with dMMR/MSI-H/TMB-H tumors received neoadjuvant tislelizumab (≥6 cycles). The analysis focuses on feasibility and safety outcomes. RESULTS:Between February 2023 and September 2024, 349 patients were randomized and 316 included in analysis (experimental: 210; control: 106). Among the experimental group, 115 were ctDNA-high-risk and 89 ctDNA-low-risk. High-risk patients were significantly older and more often male, with larger tumors, longer tumor-to-anal verge distance, greater circumferential involvement, and higher EMVI rates (all p ＜0.05). Serious adverse events (SAEs, CTCAE v5.0, grade 3-4) occurred in 10.0 % vs. 6.6 % of patients in the experimental and control groups (p = 0.316). Notably, 15.7 % of TNT-treated patients discontinued chemotherapy due to SAEs, whereas all nCRT recipients completed treatment. CONCLUSION:This interim analysis demonstrates the feasibility and safety of a ctDNA-guided, risk-adapted neoadjuvant strategy for LARC. Final outcomes will further clarify its clinical efficacy. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05601505.

Purpose:This study aimed to measure the precise distance from the lowest boundary of a rectal tumor to the anal verge (DTAV) in patients with rectal cancer. Materials and Methods:A retrospective analysis was performed on clinical data from 70 rectal cancer patients. DTAV measurements were collected using transrectal biplane ultrasound, MRI, and colonoscopy. Results:The difference in DTAV measurements between the mean DTAV value obtained by ultrasound (US mean ) and colonoscopy exhibited a difference of 0.22 cm. In contrast, the difference between US mean and MRI was 0.48 cm, while the difference between MRI and colonoscopy was -0.26 cm. The ICC for DTAV measurements demonstrated excellent agreement, with values of 0.948 between US mean and MRI, 0.942 between US mean and colonoscopy, and 0.943 between MRI and colonoscopy. The minimum DTAV value obtained by ultrasound (US min ) was 5.05 cm, the middle DTAV value obtained by ultrasound (US mid ) was 5.10 cm, and the maximum DTAV value obtained by ultrasound (US max ) was 5.30 cm. Notably, the median values of the differences in DTAV measurements between US max and US min , US max and US mid , as well as US mid and US min , were 0.2 cm, 0.1 cm, and 0.1 cm, respectively. Furthermore, the consistency of DTAV measurements between US min and US mid , US max and US mid , as well as US min and US max was excellent, with all ICC values reaching 0.999. Additionally, the radiologist's reassessment of MRI DTAV data showed excellent consistency with the original results, with an ICC value of 0.985. Conclusion:Transrectal biplane ultrasound utilizing EFOV imaging technology exhibited both accuracy and reproducibility for measuring DTAV. This approach provided a highly efficient and practical clinical tool for DTAV measurement.

Introduction: An accurate staging diagnosis of rectal cancer holds crucial importance in determining the appropriate treatment plan for patients. Aim: To evaluate the application of transrectal biplane ultrasonography combined with Sound Touch Elastography (STE) technology in preoperative uT stage of rectal cancer. Methods: A retrospective analysis was conducted on the ultrasonographic data of 32 patients. The STE values within the tumor and the adjacent peritumoral fat tissue were recorded, and the ratio of STE values between adjacent and distant peritumoral fat tissues was defined as the Stiffness Ratio (SR). Results: The STE values were not statistically significantly different between the high and low pT stage groups within tumors (P > 0.05). However, there were statistically significant differences in the STE values of the adjacent peritumoral fat tissue and the SR between the two groups (P < 0.05). Binary logistic regression analysis showed that the SR was a relevant factor in distinguishing high and low pT stages of rectal cancer. The optimal cut-off value of the SR was 1.915, with a sensitivity of 95.7% and a specificity of 88.9% in predicting high pT stages of rectal cancer. The consistency observed between traditional TRUS and pathological staging in differentiating between high and low pT stages of rectal cancer was moderate. However, the incorporation of SR had enhanced this consistency to a favorable level. Conclusion: The combination of TRUS and STE technology enhanced the accuracy of pT stage in rectal cancer, with SR serving as a critical indicator for predicting high pT stages and constituting a valuable supplement to traditional TRUS.

BACKGROUND:The addition of PD1 blockade to neoadjuvant chemoradiotherapy (CRT) has been shown to significantly increase pCR rates in locally advanced rectal cancer (LARC). Yet, its impact on total mesorectal excision (TME) remains unknown. METHODS:A post-hoc analysis of the randomized POLARSTAR trial, which enrolled patients with LARC at eight major colorectal cancer centres in Beijing to compare neoadjuvant CRT plus PD1 blockade with CRT alone, was undertaken. Patients received one of three combinations of neoadjuvant treatments before TME surgery: CRT plus concurrent PD1 blockade (concurrent group), CRT plus sequential PD1 blockade (sequential group), and CRT alone (control group). Several parameters related to TME surgery were studied. RESULTS:For the concurrent group, the sequential group, and the control group, 52, 46, and 45 patients respectively were included in this analysis. The proportion of patients undergoing sphincter-saving plus one-stage anastomosis surgery was 92% (48 of 52), 96% (44 of 46), and 87% (39 of 45) respectively. The proportion of patients without a stoma was 21% (11 of 52), 17% (8 of 46), and 11% (5 of 45) respectively. The grade 3/4 surgical complication rate was 4% (2 of 52), 7% (3 of 46), and 4% (2 of 45) respectively. Significant differences were observed between the sequential group and the control group with respect to the proportion of patients with TRG0 (37% versus 18% respectively; P = 0.040), ypT0/is ypN0 (39% versus 20% respectively; P = 0.046), and a low neoadjuvant rectal (NAR) score (54% versus 31% respectively; P = 0.025). CONCLUSIONS:Neoadjuvant CRT plus PD1 blockade enhances pathological tumour regression and is beneficial to the successful implementation of TME in patients with LARC. Validations with larger sample sizes are warranted.

AIM:Assessing tumour response following neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer is essential for selecting patients for the watch-and-wait procedure. The accuracy of clinical complete response (cCR) for predicting pathological complete response (pCR) is inadequate. The aim of this study was to assess the ability of transanal multipoint full-layer puncture biopsy (TMFP) to predict pCR following nCRT for rectal cancer. METHOD:This nonrandomized prospective multicentre trial enrolled 113 patients from four centres between April 2020 and June 2023. Of these, 63 were assigned to the in vitro TMFP group and 50 to the in vivo TMFP group. The primary outcome measured was the predictive accuracy of TMFP for pCR. RESULTS:All patients underwent total mesorectal excision. TMFP showed significantly higher accuracy for predicting pCR than cCR (87.6% vs. 68.1%, p = 0.016). The positive predictive value was higher for in vivo than for in vitro TMFP (90.0% vs. 64.5%, p = 0.018), and the predictive accuracy did not differ significantly between the two groups (94.0% vs. 82.5%, p = 0.066). In cCR patients, although with no significant difference between in vivo and in vitro TMFP regarding positive predictive value (95.0% vs. 86.7%, p = 0.794) and accuracy (96.0% vs. 92.9%, p = 1.000), the predictive accuracy of in vivo TMFP was as high as 96%. CONCLUSIONS:TMFP is safe and feasible for assessing the response of rectal cancer to nCRT. TMFP showed high sensitivity and accuracy for predicting pCR and could be a useful supplement to the current cCR standard.

OBJECTIVE:While laparoscopic sleeve gastrectomy (LSG) is an established bariatric procedure for obesity, postoperative gastroesophageal reflux disease (GERD) remains a significant complication. This study evaluates the short-term efficacy of a novel technique combining LSG with acute angle of His reconstruction (LSG-His) versus conventional LSG. METHODS:This is a single center retrospective observation cohort study. Among 83 patients undergoing bariatric surgery, 39 receiving conventional LSG and 44 undergoing LSG-His (with diaphragmatic fundopexy using 2-0 Prolene sutures) were analyzed. GERD symptoms were assessed using the Reflux Diagnostic Questionnaire (RD-Q) and GERD Questionnaire (GERD-Q) at baseline and at 3-, 6-, 12-, 24-month postoperatively. Weight loss outcomes included percentage of excess weight loss (%EWL) and total weight loss. RESULTS:Postoperative follow-up showed a sustained reduction in GERD symptoms for the LSG-His group across all time points using both scoring systems (all p<0.001 vs LSG). The results demonstrated that, when assessed using the GERD-Q at the 24-month follow-up, the prevalence of GERD symptoms was 14% (95% CI: 6.3% - 25.7%) among LSG-His patients versus 46% (95% CI: 32.1% - 60.7%) among LSG patients (p<0.001). As evaluated via the RD-Q at the same 24-month follow-up, GERD symptom prevalence was 7% (95% CI: 2.3%- 17.9%) in the LSG-His group compared with 41% (95% CI: 27.3% - 56.3%) in the LSG group (p<0.001).%EWL was higher in the LSG-His group at 3 months (54.7% vs 46.5%, p=0.033), 6 months (73.8% vs 64%, p=0.047), 12 months (82.9% vs 72.2%, p=0.042) and 24 months (84.1% vs 75.4%, p=0.038) follow-up compared to LSG group. CONCLUSION:In this retrospective observational study, LSG-His was associated with lower rates of GERD symptoms and higher %EWL compared to standard LSG, but with comparable %TWL in 24 month outcomes. However, these preliminary results are limited to short-term follow-up, and long-term prospective studies with objective reflux assessment are warranted.

Recent advancements in the understanding of lower rectum anatomy, rectal cancer biology, and surgical techniques have emphasized the importance of radical surgery for low rectal cancer that balances oncological safety and anal function preservation. After total mesorectal excision (TME) and coloanal anastomosis, participants face high risks of anastomotic leakage and infection, often requiring a protective ileostomy. However, ileostomies themselves lead to significant complications, such as dehydration and chronic renal failure, and many participants cannot have their stomas reversed as planned. The Turnbull-Cutait procedure, involving delayed transanal pull-through rectal resection, has emerged as a safer alternative, reducing leakage complications and avoiding the need for a protective stoma. Recent studies support its use in challenging rectal cases, showing comparable or better outcomes than standard techniques. Despite these promising results, limited data exists on its application to intersphincteric resection (ISR) or intersphincteric dissection (ISD), which itself has higher complication rates. Therefore, further research is needed to evaluate this Turnbull-Cutait anastomosis procedure (delayed transanal pull-through) in ISR, comparing its complications, oncological outcomes, and functional results to those of traditional methods (direct anastomosis). This study is a prospective, multicenter, 1:1, non-inferiority, randomized controlled trial with 110 participants, divided into two groups: the staged Turnbull-Cutait pull-through anastomosis group (n = 55) and the direct anastomosis group (n = 55). The control group will undergo ISR with traditional anastomosis plus protective ileostomy, while the experimental group will receive the transanal pull-through and delayed anastomosis without ileostomy. The primary outcome is the 30-day overall postoperative complication rate, including anastomotic leakage, infection, and other complications. Secondary outcomes include long-term complications, total surgery time, anorectal function (measured by LARS and Wexner scores), urinary and sexual function, quality of life (EORTC QLQ–CR29 and FIQL), and 3-year disease-free survival (DFS) and overall survival (OS). Currently, there is a lack of systematic studies exploring the use of delayed pull-through anastomosis in intersphincteric resection (ISR) procedures. Existing research on this technique in low rectal cancer is limited to small, single-center, retrospective studies with low levels of evidence. Therefore, a multicenter, prospective, randomized controlled trial is needed to determine whether delayed pull-through anastomosis can serve as a viable alternative to ISR-coloanal anastomosis, offering comparable or lower rates of postoperative complications, as well as similar oncological outcomes and defecatory function. This study aims to provide higher-quality evidence through a larger, well-designed trial, which could significantly inform clinical practice in this under-explored area. ClinicalTrials.gov NCT06662643. Registered on October 29, 2024.

Background Neoadjuvant chemoradiotherapy (nCRT) is the standard for locally advanced rectal cancer (LARC). However, distant metastasis remains the primary cause of treatment failure. Early identification of high-risk individuals for personalized treatment may offer a solution. Circulating tumour DNA (ctDNA) could assist in this process. Methods From September 2017 to June 2019, the study prospectively recruited 113 patients with LARC (cT3-4N0M0 or cTanyN + M0) who underwent nCRT followed by radical surgery across 8 tertiary centers. ctDNA was analysed using large-panel targeted sequencing at baseline, during nCRT, pre-surgery, post-surgery, post-adjuvant chemotherapy (ACT), and during annual follow-ups for 3 years. Findings We analysed 103 tissue and 669 plasma samples from 103 patients. With a median 53-month follow-up, significantly worse progression-free survival (PFS) and overall survival (OS) were observed if median variant allele frequency (mVAF) of baseline ctDNA per patient was >= 0.5% (PFS, HR 4.39, p < 0.001; OS, HR 5.61, p = 0.004) or ctDNA was still detectable two weeks into nCRT (PFS, HR 7.63, p < 0.001; OS, HR 5.08, p < 0.001). Furthermore, when compared to the low-risk (C1) group (characterized by " ctDNA undetected during nCRT with baseline mVAF <0.5%" or " ctDNA undetected during nCRT with TMB (tumour mutational burden) >= 20/Mb " ), the high-risk (C2) group (characterized by " ctDNA detected during nCRT" or " baseline mVAF >= 0.5% with TMB <20/Mb") showed significantly worse long-term outcomes (3 y-PFS, 55.9% vs. 94.2%; 3 y-OS, 79.4% vs. 100%). The ctDNA clearance during nCRT, baseline mVAF, and TMB may be effective prognostic indicators. Interpretation Our findings reaffirm the clinical monitoring value of ctDNA and demonstrate the strong prognostic value of baseline ctDNA and its early clearance status in patients with LARC undergoing nCRT. This highlights the potential of dynamic ctDNA monitoring as actionable stratified indicators to guide personalized neoadjuvant treatment strategies. Copyright (c) 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

BackgroundTo improve the prognosis of patients with obstructive colon cancer, performing neoadjuvant chemotherapy after self-expanding metallic stent (SEMS) placement followed by elective surgery is currently one of the treatment methods for obstructive colon cancer. However, the oncological risks of this treatment approach are currently unclear. To evaluate the oncological risks of this treatment model by detecting changes in circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) during the stent placement combined with neoadjuvant chemotherapy process.MethodsFrom January to December 2023, 10 patients with obstructive colon cancer who received neoadjuvant chemotherapy after SEMS placement, followed by surgical treatment, were included in this study. Blood samples were collected one day before stent placement, 3 days after stent placement, one day before surgery, and one day after surgery. cfDNA and ctDNA in the blood were detected and analyzed.ResultsThe stent placement success rate was 100%, with no cases of perforation, displacement, or re-obstruction, and no perioperative deaths. After neoadjuvant chemotherapy, peripheral ctDNA decreased compared to before stent placement. There were no statistically significant differences in cfDNA and ctDNA changes at the four time points during the treatment process.ConclusionsThis study did not find an increase in ctDNA after stent placement combined with chemotherapy, suggesting that the model of stent placement combined with neoadjuvant chemotherapy for obstructive colon cancer may be a safe and reliable therapy.

Since self-expanding metal stents (SEMS) were first introduced in acute colon cancer obstruction, the increased rate of primary anastomosis and improved quality of life following SEMS placement have been clearly shown. However, it was demonstrated that SEMS are associated with higher recurrence rates. Although several trials have shown that overall and disease-free survival in patients following SEMS placement is similar with patients undergoing emergency surgery, obstruction and a high incidence of recurrence imposed many concerns. The optimal time interval from SEMS to surgery is still a matter of debate. Some studies have recommended a time interval of ~2 weeks between SEMS insertion and elective surgery. A prolonged interval of time from SEMS insertion to elective surgery and the administration of neoadjuvant chemotherapy (NAC) has been proposed. SEMS-NAC might have advantages for improving the surgical and long-term survival outcomes of patients with acute colon cancer obstruction, which is an optional approach in the management of acute colon cancer obstruction.

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT 3-4a N 0 M 0 and cT 1-4a N 1-2 M 0 ) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850–1000 mg/m2, bid, po, day1–14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6–12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61–53.82%], while 15 (30.0%, 95% CI: 19.1–43.75%), 9 (18.0%, 95% CI: 9.77–30.8%), 2 (4.0%, 95% CI: 1.10–13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Background: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). Methods: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. Findings: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. Conclusions: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. Funding: This research was funded by the China National Natural Science Foundation (82202884).

3611 Background: Several single-arm trials have reported pathological complete response (pCR) rates of 23-50% after combining neoadjuvant radiotherapy with immune checkpoint inhibitors in locally advanced rectal cancer (LARC). We aim to further clarify the efficacy and safety of adding PD1 inhibitors to the neoadjuvant long-course chemoradiation of LARC patients with this phase 2, randomized, controlled trial. Methods: Patients with mid-low, locally advanced rectal cancer were randomly allocated to receive neoadjuvant chemoradiation plus concurrent Tislelizumab (experiment group A), or neoadjuvant chemoradiation plus sequential Tislelizumab (experiment group B), or neoadjuvant chemoradiation only (control group). Patients of all three groups are scheduled to receive radical surgery after neoadjuvant treatment. The primary endpoint is pCR rate. Results: A total of 186 patients were enrolled. In the modified intention-to-treat population, which consist of patients having received chemoradiation and at least 1 cycle of PD1 blockade for the experiment groups and patients having received chemoradiation only for the control group, the pCR rates were 33.9% and 34.5% for experiment group A and B respectively, both significantly higher than the pCR rate of 15.5% in the control group (p=0.021 and 0.019). There were no significant differences between either one of the experiment groups and the control group regarding disease progression rate, grade 3-4 treatment-related adverse event rate and grade 3-4 surgical complication rate. Conclusions: For patients with mid-low locally advanced rectal cancer, the addition of PD1 inhibitors to neoadjuvant long-course chemoradiation, whether concurrently or sequentially, increases pCR rate, meanwhile raises no significant safety concerns. For the next step, phase 3 trials with larger sample sizes are encouraged. Clinical trial information: NCT05245474 .

Background and purpose For patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT), there is currently limited research on the optimal level of inferior mesenteric artery (IMA) ligation during surgery. We carried out a retrospective cohort study to analyze the impact of IMA ligation level on surgical outcomes and long-term patient prognosis. Methods The data originated from a multicenter randomized controlled trial conducted across six tertiary referral hospitals in Beijing, involving LARC patients undergoing nCRT followed by radical surgery. Patients were divided into high (HL) and low ligation (LL) groups based on the ligation level of IMA. Evaluation parameters included surgical outcomes, complications, long-term survival, and quality of life questionnaires. Results From August 2017 to April 2022, a total of 337 patients were included in the analysis. The number of lymph nodes retrieved was higher in the LL group compared to the HL group. There were no significant differences between the two groups in terms of operation time, intraoperative blood loss, and other factors. Conclusion For LARC patients undergoing nCRT, the level of IMA ligation during radical surgery does not significantly impact complications or long-term prognosis. The selection of ligation pattern should be based on a comprehensive assessment of factors including metastatic risk, vascular anatomy, comorbidity (such as atherosclerosis), and surgical skills of the surgeons.

Currently, the standard of clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) for local advanced rectal cancer generally lacks pathological examination, the cCR judged by the current standard is still far from the real pathological complete response. After nCRT, due to the presence of tissue edema and fibrosis, MRI is highly uncertain in determining the staging of local lesions. The precision of colonoscopy biopsy is generally low because residual cancer foci exist primarily in the muscular layer, which limits the determination of cCR by colonoscopy biopsy. Local excision through the anus can resect the whole intestinal wall tissue, which is relatively accurate and close to the real state of remission of the lesion, but there are many problems, such as affecting anal function, high rate of complications, and increased difficulty of following radical surgery. Based on the present diagnosis of cCR, the authors put forward the concept of modified cCR (m-cCR) which combined with the pathological standard of transanal multipoint full-layer puncture biopsy (TMFP). It is possible to improve the accuracy of cCR, and improve the safety of cCR patients who receive wait-and-watch therapy without increasing complications or affecting anal function. The exact conclusion needs to be confirmed by further studies.