e23514 Background: Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal neoplasm of the gastrointestinal tract. While radical resection is the gold-standard treatment for localized GIST, the 5-year recurrence rate of high-risk GIST exceeds 50%, posing a major clinical challenge. Whether ctDNA-based detection of postoperative molecular residual disease (MRD) can reliably predict recurrence in high-risk locally advanced GIST patients remains a key question in translational oncology. Methods: This prospective study enrolled patients with high-risk locally advanced GIST who underwent R0 resection. Surgical tissue specimens were obtained for genomic profiling. Blood samples were collected at baseline (pre-surgery), at a landmark time point within one month after surgery, and serially thereafter at 3- to 6-month intervals during follow-up. Tumor-derived variants were identified through whole-exome sequencing of resected tumors. A personalized tumor-informed assay was designed by selecting up to 50 top-ranked variants with a variant allele frequency ≥3.0% to monitor MRD status. Results: As of Jan 2026 (cutoff), 44 eligible patients were enrolled. 44 tumor samples, 42 pre-surgical plasma samples, and 330 post-surgical blood samples were analyzed, with a median follow-up of 21 months. Tumor sequencing detected mutations in KIT and PDGFRA in 39 (88.6%) and 4 (9.1%) patients. Prior to surgery, MRD was detected in 57.1% (24/42) of plasma samples, and positivity correlated with larger tumor volume, higher Ki-67 index, mitotic count, and TMB (all P < 0.05). Multivariable logistic regression identified the Ki-67 index as an independent predictor of pre-surgical MRD positivity (OR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024). In landmark analysis, ctDNA was detectable in 4 patients (4/41, 9.8%). These patients had worse DFS trend vs. MRD-negative patients (HR=3.48, 95% CI=0.70–17.35, P =0.11). To date, 8 patients had radiologically confirmed recurrence via CT. Among 4 patients with both MRD positivity and recurrence, one had longitudinal MRD positivity at 9 months post-op (3-month lead before CT relapse), and 2 had simultaneous detection by both methods. Notably, none of these 4 patients received regular adjuvant therapy. Additionally, multivariable Cox regression (adjusted for sex, age, TNM stage, and adjuvant therapy) showed longitudinal MRD positivity was associated with inferior DFS (HR=4.59, 95% CI=1.00–20.98, P =0.05). Patients with sustained negative MRD (n=29) had better survival than those with MRD conversion to negative (n=2), positive (n=8), or persistent positivity (n=2) (P=0.1). Conclusions: This study indicates that personalized tumor-informed ctDNA may predict recurrence in high-risk locally advanced GIST patients, particularly those not receiving regular adjuvant therapy. Clinical follow-up is ongoing. Clinical trial information: NCT05408897 .

Microsatellite-stable/proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC) is characterized by a cold tumor microenvironment, with limited CD8⁺ T cell infiltration and poor responsiveness to immune checkpoint inhibitors (ICIs). Here, using an in vivo CRISPR/Cas9 screen in a CMT93 cell-derived murine tumor model, we identify Arid3b as a key negative regulator of CD8⁺ T cell infiltration and antitumor activity. Genetic ablation of Arid3b in CD8⁺ T cells significantly enhances their intratumoral accumulation and promotes robust tumor control. Mechanistically, Arid3b deficiency upregulates Runx3, driving a tissue-resident memory-like phenotype and effector function. Notably, the benefits conferred by Arid3b deficiency are abrogated upon Runx3 deletion, indicating a RUNX3-dependent mechanism. Together, targeting ARID3B could offer a promising strategy to reshape the tumor microenvironment and sensitize MSS CRC to immunotherapy.

11522 Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Radical resection is the standard treatment of localized GIST, yet the 5-year recurrence rate for high-risk GIST is more than 50%. It remains unclear whether detecting post-surgery molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can predict the recurrence of high-risk locally advanced GIST. Methods: Patients with high-risk locally advanced stage GIST who underwent R0 surgery were enrolled prospectively. Surgical tissue samples were collected. Blood samples were collected pre-surgery, within 1-month post-surgery, and every 3–6 months thereafter. Tumor-derived variants were identified by whole-exon sequencing of the surgical tissues. Up to 50 highly ranked variants with allele frequency 3.0% were selected for the personalized panel design, which was subsequently used to assess MRD status. Results: As date cutoff of December 2024, 44 eligible patients were enrolled, among whom 42 tissue samples, 41 pre- and 166 post-surgical blood samples were collected and analyzed, and the median follow-up time was 21 months. Tissue-based sequencing identified variants in KIT and PDGFRA in 37 (84.1%) and 4 (9.1%) patients, respectively. Positive MRD was detected in 56.1% (23/41) of all pre-surgical plasma samples. Pre-surgical MRD positivity was associated with tumor volume, mitoses and Ki-67 (P < 0.05). Landmark analysis within 1 month post-surgery showed that 4 patients (4/41, 9.8%) were positive for ctDNA. Patients with positive MRD at landmark showed marginally worse DFS compared with those with negative MRD (HR = 4.24, 95% CI = 0.81-22.26, P = 0.07).To date, 7 patients have been detected recurrence by CT scan. Among the 4 patients with both radiological and MRD positivity, longitudinal ctDNA detected recurrence with lead-time of 3 months compared with CT scan for 2 patients. The other 2 cases are simultaneously. Notably, these 4 patients didn’t receive regular adjuvant therapy. Furthermore, the longitudinal MRD positivity was associated with inferior DFS after adjusting sex, age, TNM stages and whether receiving adjuvant therapy in the multivariable cox regression (HR = 5.63, 95% CI = 1.09-28.99, P = 0.04). Additionally, 30 patients with consistent negative MRD during surveillance exerted significantly superior survival compared with patients whose MRD status converted to negative (n = 2), converted positive (n = 7) and remained consistently positive (n = 2) from landmark to longitudinal monitoring (P = 0.04). Conclusions: The present study suggests that personalized tumor-informed ctDNA has the potential to inform recurrence in high-risk locally advanced stage GIST patients, especially for patients who have not received regular adjuvant therapy. Clinical enrollment is still ongoing. Clinical trial information: NCT05408897 .

BACKGROUND:Radical lymphadenectomy is essential for the long-term outcomes of colorectal cancer (CRC). However, the exact distribution and drainage patterns of central lymph nodes in left-sided colon cancer and rectal cancer remain unclear. This study aimed to map apical lymph node distribution using intraoperative Indocyanine green (ICG) fluorescence imaging and to evaluate the superiority of fluorescence-guided lymph node dissection in CRC surgery. METHODS:We conducted a prospective, propensity score-matched comparative study involving patients who underwent laparoscopic surgery for left-sided colon cancer and rectal cancer. The patients were assigned to either ICG fluorescence-guided or conventional laparoscopic surgery. Lymph node yield, short-term perioperative outcomes, and long-term survival were compared between groups. The central lymph node distribution patterns in the ICG group were analyzed. RESULTS:After propensity score matching, a total of 180 patients were enrolled, with 60 and 120 patients in the ICG and control groups, respectively. The ICG group had a significantly higher median number of retrieved lymph nodes [20.8 (7.9) vs 16.3 (7.1), P < 0.001] and a significantly lower postoperative complication rate (11.7% vs 17.5%, P = 0.01). Importantly, ICG-guided surgery was associated with a reduced risk of inadequate lymph nodes retrieval and was identified as an independent prognostic factor of overall survival (hazard ratio = 2.544, 95% CI: 1.088-5.948, P = 0.031). ICG imaging revealed that central lymphatic drainage patterns were highly personalized. Over 95% of apical lymph nodes located within 2.2 cm on the left side of the IMA, 1.3 cm on the right side and 0.9 cm from the root of the IMA, and additional atypical drainage pathways - including to the iliac region - were observed in select cases. CONCLUSIONS:ICG fluorescence-guided surgery improves the accuracy and extent of lymph node dissection in left-sided colon cancer and rectal cancer, reduces the risk of inadequate retrieval, and is independently associated with improved long-term survival. These findings support the integration of ICG-guided lymphadenectomy as a promising procedure for CRC.

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

11534 Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Radical resection is the standard treatment of localized GIST, yet the 5-year recurrence rate for high-risk GIST is more than 50%. It remains unclear whether detecting post-surgery molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can predict the recurrence of high-risk locally advanced GIST. Methods: Patients with high-risk stage II-III GIST who underwent R0 surgery and following adjuvant imatinib/avapritinib were enrolled prospectively. Surgical tissue samples were collected. Blood samples were drawn pre-surgically, and at 7 days, 1 month, and every 3–6 months post-surgically. Tumor-derived variants were identified by whole-exon sequencing of the surgical tissues. Up to 50 highly ranked variants with a variant allele frequency 3.0% were selected for the personalized panel design, which was subsequently used to assess MRD status. Results: A total of 36 patients with a median age of 65 years were included in the current analysis (data cutoff on January 16, 2024). Most tumors (17/36, 47%) were located at the stomach or gastroesophageal junction, and 94.4% of patients (34/36) did not receive neoadjuvant treatment. The mean maximum diameter of tumors was 7.87 ± 2.87 cm. At present, 36 tissue samples, 34 pre- and 161 post-surgical blood samples were collected and analyzed. Tissue sample-based sequencing identified variants in KIT and PDGFRA in 31 (86%) and 4 (11%) patients, respectively. 98.4% (1003/1019) of tumor variants included in personalized panels were patient-specific. ctDNA was detected in 64.7% (22/34) of pre-surgical plasma samples. The ctDNA-positive rate at baseline was associated with tumor mutation burden (p < 0.05), rather than tumor size (p = 0.6). Landmark analysis at 1 week post-surgery showed that 12.1% of patients were positive for ctDNA. Up to now, 4 patients were identified with tumor recurrence based on imaging results. Among these patients, 3 patients (3/4) exhibited ctDNA positivity preceding radiological recurrence. Notably, a 71-year-old patient was ctDNA-positive at 1 week post-surgery. Longitudinal analysis revealed that his ctDNA became negative after adjuvant treatment but turned positive at 9 months post-surgery, with a lead time of 2 months prior to his radiological recurrence. Additionally, a patient tested positive for ctDNA at 3 months post-surgery but had negative imaging results. Follow-up visits are ongoing for this patient. Conclusions: The present study suggests that personalized tumor-informed ctDNA has the potential to inform recurrence in high-risk stage II-III GIST patients. Clinical enrollment is still ongoing.

Abstract Background Pneumatosis cystoides intestinalis (PCI) is a special type of pneumatosis intestinalis (PI), however, its clinical features and prognosis distinguished from necrotizing PI (NPI) have not been elucidated sufficiently. Methods Clinical data of patients diagnosed with PCI and NPI from January 2011 to December 2020 in Peking University People's Hospital were reviewed. The clinical characteristics, treatment strategy, and prognosis of PCI and NPI were compared. Results A total of 25 patients diagnosed with PCI and 21 patients diagnosed with NPI were involved in this study. Patients in PCI group were accompanied by lighter inflammatory responses than NPI group. In the CT examination, patients in PCI group were observed with higher proportion of cystic gas (100.0% vs 0.0%, P < 0.001) and free peritoneal air (68.0% vs 14.3%, P < 0.001), and lower proportion of peritoneal irritation sign (0.0% vs 61.9%, P < 0.001), bowel effusion (0.0% vs 66.7%, P < 0.001) and ascites (0.0% vs 90.5%, P < 0.001) compared to NPI group. All patients in PCI group were cured after conservative treatment. However, 18 (85.7%) patients in NPI group had enterectomy, and 8 (38.1%) patients died in the hospital. Conclusion PCI is a special type of PI with benign prognosis. Early identification of PCI and differentiation from NPI is the prerequisite to avoid overtreatment.

Background: The relationships between the pelvimetry and technical difficulties in performing rectal surgery for mid-low rectal cancer remain unclear.Methods: Two hundred and twenty-one cases of mid-low rectal cancer patients who underwent sphincter-preserved total mesorectum excision (TME) were analyzed. The data of the pelvimetry and the relative position between trocar site and tumor were measured with magnetic resonance imaging (MRI).Results: Univariate analysis showed that the interspinous diameter, the sacrococcygeal distance, and the angle of sacral promontory inclination were significantly associated with the technical difficulty during laparoscopic surgery, but only the interspinous diameter remained an independent risk factor in multivariate analysis. The simulated trocar angle q was an independent risk factor affecting the operation time during laparoscopic surgery, simulated trocar angle h was significantly related to intraoperative blood loss in both laparoscopic surgery and transanal TME (taTME) surgery groups. Conclusion: Interspinous diameter can predict difficulty in laparoscopic surgery and may provide useful information for preoperative planning and consideration of approach.(c) 2021 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Objective: To investigate the capability of a radiomics model, which was designed to identify histopathologic growth pattern (HGP) of colorectal liver metastases (CRLMs) based on contrast-enhanced multidetector computed tomography (ceMDCT), to predict early response and 1-year progression free survival (PFS) in patients treated with bevacizumab-containing chemotherapy. Methods: Patients with unresectable CRLMs who were treated with bevacizumab-containing chemotherapy were included in this multicenter retrospective study. For each target lesion, the radiomics-diagnosed HGP (RAD_HGP) of desmoplastic (D) pattern or replacement (R) pattern was determined. Logistic regression and receiver operating characteristic (ROC) curves were used to assess lesion- and patient-based responses according to morphologic response criteria. One-year PFS was calculated using Kaplan-Meier curves. Hazard ratios for 1-year PFS were obtained through Cox proportional hazard regression analysis. Results: Among 119 study patients, 206 D pattern and 140 R pattern lesions were identified. In patients with multiple lesions, 52 had D pattern, 31 had R pattern, and 36 had mixed (D + R) pattern. The area under the curve value for RAD_HGP in predicting early response was 0.707 for lesion-based analysis and 0.720 for patient-based analysis. Patients with D pattern had a significantly longer PFS than patients with R pattern or mixed pattern (P < 0.001). RAD_HGP was the only independent predictor of 1-year PFS. Conclusions: HGP diagnosed using a radiomics model could be used as an effective predictor of PFS for patients with CRLMs treated with bevacizumab-containing chemotherapy.

Objective Postoperative bowel obstruction was one of the most severe complications in patients who received colorectal surgeries. This study aimed to explore risk factors of early postoperative obstruction and to construct a nomogram to predict the possibility of occurrence. Methods The records of 1437 patients who underwent elective colorectal surgery in Peking University People’s Hospital from 2015 to 2020 were retrospectively collected. Risk factors of early postoperative bowel obstruction were identified by logistic regression analysis and a nomogram was then constructed. Bootstrap was applied to verify the stability of the model. Results COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were identified as independent risk factors and were put into a nomogram for predicting early postoperative bowel obstruction. The nomogram showed robust discrimination, with the area under the receiver operating characteristic curve was 0.894 and was well-calibrated. Conclusion A nomogram including independent risk factors of COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were established to predict the risk of early postoperative bowel obstruction.

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.

在胃肠道恶性肿瘤根治性手术中，淋巴结清扫效力和吻合口血供是影响患者远期生存期和近期有无严重手术并发症的关键因素，也是术者的关注要点。近年来，吲哚菁绿荧光显像技术逐步应用于胃肠手术中，在术中淋巴结定位和吻合口处血管造影等方面效果明显。本文对吲哚菁绿荧光显像技术在胃肠道手术中的应用价值和前景作一综述。

Objective:To investigate the role of indocyanine green(ICG) fluorescence imaging in laparoscopic anterior resection for rectal cancer.Methods:A retrospective analysis was performed on 7 patients who had undergone laparoscopic anterior resection with the use of ICG fluorescence imaging at Peking University People′s Hospital between Oct 2018 and Mar 2019. The clinicopathological variables, surgical factors, short-term outcome and complications were analyzed.Results:The median operation time was 185 min. The median estimated blood loss was 50 ml. The median time from ICG injection to anastomotic perfusion was 45 s. One patient received extended proximal resection of bowel due to poor perfusion as suggested by ICG imaging. The median time to soft diet was 4 days, and the median hospital stay was 8 days. The median number of lymph nodes harvested was 16. There were no major complications in all these patients. No adverse events related to ICG were recorded.Conclusions:ICG fluorescence imaging was safe and effective in detecting insufficient blood supply around newly established bowel anastomsis, hence potentially reducing the anastomotic leakage rate.

Radical resection is one of the most important treatment for rectal cancer, which requires not only removal of adequate bowel and mesorectum around the tumor, but also thorough lymphadenectomy. Besides, postoperative complications are surgeons' concerns as well. According to different ways to manage inferior mesenteric artery, procedures could be divided into two groups: inferior mesenteric artery (IMA) high ligation and low ligation, which lead to various outcomes of the extent of lymph nodes dissection, survival, preservation of intestinal blood supply, incidence of anastomotic leakage, and postoperative functions including defecation function, urinary function and sexual function. Author believes that for those patients with clinical stage T1, low ligation and D2 lymph nodes dissection could be considered. However, for patients with locally advanced carcinomas (clinical stage T2+or N+), especially suspicious metastasis of lymph nodes around IMA root, high ligation and D3 lymph node dissection is suggested to ensure en bloc resection. As for those patients with high risks for compromised intestinal blood supply, preservation of left colic artery plus D3 lymph nodes dissection might be a feasible way. Intraoperative indocyanine green fluorescent imaging might play a role in quality control of lymphadenectomy.

BACKGROUND:Transanal total mesorectal excision (taTME) is a novel sphincter-preserving procedure for low rectal cancer. This "bottom to up" approach is unfamiliar to colorectal surgeons and the crucial anatomical landmarks also remain unclear. METHODS:Two hundred and five cases of pelvic magnetic resonance imaging (MRI) from 2015 to 2016 were reviewed. Curvature of posterior mesorectal fascia, distal mesorectal angle, length of posterior mesorectal fascia, main structures around the mesorectum were measured and analyzed. The landmarks identified on MRI were verified in taTME procedures of five rectal cancer patients. RESULTS:The most of acute angles of posterior mesorectal fascia located at the joint of anococcygeal ligament-coccyx. Degree of distal mesorectal angle was independently correlated with gender and degree of angle of anococcygeal ligament-coccyx. Candidate landmarks evaluated by MRI with verification during taTME procedures included: anterior: seminal vesicle for male while cervix for female. And peritoneal reflection was a substitute landmark when cervix was hardly confirmed in operation; posterior: the joint of anococcygeal ligament-coccyx. The area between the joint of anococcygeal ligament-coccyx and S3S4 was a "transitional zone", the level of S3S4 could be the as the terminal landmark of transanal posterior dissection during taTME. CONCLUSIONS:Preoperative MRI geometrical measurement of mesorectum might play an important role in evaluating the difficulty of taTME procedure before operation, as well as standardizing landmarks during taTME procedure.