Kun-Hao Bai

Background: Immunotherapy has improved outcomes in metastatic colorectal cancer (mCRC), but benefits remain largely restricted to the minority with specific biomarkers like microsatellite instability-high (MSI-H). This study aims to develop and validate a revised tumor burden score (rTBS) as a prognostic model to stratify survival outcomes in mCRC patients receiving immunotherapy. Methods: We analyzed a retrospective cohort of 339 immunotherapy-treated mCRC patients (2019–2024). Univariable and multivariable Cox regression analysis were employed to identify independent prognostic factors and construct a model for progression-free survival (PFS). rTBS was developed by integrating CEA, metastatic organ count, and target lesion count. rTBS prognostic performance was validated via bootstrapping, internal and external dataset, ROC curves, and Kaplan-Meier analysis across MSI/TMB subgroups. Results: Independent risk factors included TMB level, CEA, metastatic organ count, and target lesion count. The integrated rTBS outperformed TMB (AUC = 0.768 vs 0.656) and traditional metrics. Low rTBS patients showed superior PFS and overall survival (Both P < 0.0001), higher objective response rate (ORR: 37% vs 21.4%, P = 0.002) and disease control rate (DCR: 73.6% vs 51.1%, P < 0.0001). rTBS also stratified outcomes in both MSI-H/TMB-High and MSI-L/MSS/TMB-Low subgroups (both P < 0.0001). Moreover, split-sample testing, external validation, and bootstrap analysis collectively demonstrated the model’s robust validity. Conclusions: The rTBS is a robust, cost-effective prognostic model that stratifies survival in immunotherapy-treated mCRC across subtypes, particularly in the MSI-L/MSS/TMB-Low subgroup lacking reliable biomarkers. It bridges molecular heterogeneity and clinical practice, and warranting further multicenter validation.

BACKGROUND The technical complexity and potential for complications associated with endoscopic submucosal dissection (ESD) pose limitations on the widespread use of this procedure for stage 1 rectal neuroendocrine tumors (NETs), despite its high success rate in achieving complete resection (R0). AIM To examine the results of ESD and hybrid ESD, a simpler adaptation of the ESD technique, for stage 1 rectal NETs. METHODS Seventy-nine patients with 84 lesions of clinical stage 1 rectal NETs who received treatment at Sun Yat-sen University Cancer Center from January 2010 to June 2021 were reviewed retrospectively. RESULTS Sixty-one lesions in 58 patients were treated with ESD, while 23 in 21 patients were treated with hybrid ESD. The 84 rectal NETs had a median diameter of 8 (5) mm (range, 3-20 mm), with the median lesion size 8 (5) mm for ESD and 8 (4) mm for hybrid ESD (P = 0.359). For ESD, the median duration of procedure was 46.00 (14.00) minutes, while for hybrid ESD, it was 32.00 (15.00) minutes (P < 0.001). Both the ESD and hybrid ESD groups had identical rates of en bloc resection (100.00% vs 100.00%, P = 1.000), R0 resection (86.89% vs 86.96%, P = 1.000), perforation (1.64% vs 0.00%, P = 1.000), and delayed bleeding (1.64% vs 4.35%, P = 0.475). After a median of 27.50 (30.00) months of observation, neither group had recurrence. CONCLUSION For endoscopic excision of stage 1 rectal NETs, both ESD and hybrid ESD were well tolerated and produced positive results, with similar efficacy and safety.

Background: Immunotherapy for metastatic colorectal cancer (mCRC) leads to varying patient outcomes owing to the heterogeneity of metastatic organs. However, whether the metastatic organ count influences prognosis in mCRC patients receiving immunotherapy remains unclear. Therefore, this retrospective study aimed to investigate this issue to derive a clear conclusion to facilitate clinical treatment. Methods: This retrospective cohort study included 208 patients with mCRC receiving immunotherapy at the Sun Yat-sen University Cancer Center. Cox regression analysis was conducted to determine variables independently associated with immunotherapy response and progression-free survival (PFS). The Kaplan–Meier curve analysis and log-rank test were used to evaluate PFS across varying metastatic organ counts. Subsequently, a nomogram was constructed for PFS prediction. Results: Patients with varying metastatic organ counts exhibited significantly different objective response rates (ORRs) (1 to ≥4 organs: 49.3%, 30.0%, 19.6%, 5.9%, respectively, P < 0.001). Multivariable Cox analysis identified low tumor mutational burden (hazard ratio [HR]=2.49, 95% confidence interval [CI]: 1.60–3.88, P< 0.001), second-or-higher-line immunotherapy (HR = 2.83, 95% CI: 1.81–4.44, P< 0.001), and high metastatic organ counts (3 organs: HR = 2.21, 95% CI: 1.40–3.51, P= 0.001; ≥4 organs: HR = 3.85, 95% CI: 2.06–7.22, P< 0.001) as independent factors associated with low PFS time. Additionally, patients with lung metastasis had a markedly lower ORR (14.6%) than did others (distant lymph node [30.7%], liver [30.3%], peritoneum [29.5%]; P< 0.001). Conclusions: Increased metastatic organ count in patients with mCRC was associated with decreased immunotherapy ORR and worse prognosis, with a particularly pronounced effect observed in patients with lung metastasis.

BACKGROUND Stage 1 rectal neuroendocrine tumors (NETs) are best treated with endoscopic submucosal dissection (ESD) or transanal endoscopic microsurgery (TEM) for local resection. AIM To investigate the safety and efficacy of ESD and TEM for local resection of stage 1 rectal NETs. METHODS This retrospective observational analysis included patients with clinical stage 1 rectal NETs (cT1N0M0, less than 20 mm) who underwent ESD or TEM. The ESD and TEM groups were matched to ensure that they had comparable lesion sizes, lesion locations, and pathological grades. We assessed the differences between groups in terms of en bloc resection rate, R0 resection rate, adverse event rate, recurrence rate, and hospital stay and cost. RESULTS Totally, 128 Lesions (ESD = 84; TEM = 44) were included, with 58 Lesions within the matched groups (ESD = 29; TEM = 29). Both the ESD and TEM groups had identical en bloc resection (100.0% vs 100.0%, P = 1.000), R0 resection (82.8% vs 96.6%, P = 0.194), adverse event (0.0% vs 6.9%, P = 0.491), and recurrence (0.0% vs 3.4%, P = 1.000) rates. Nevertheless, the median hospital stay [ESD: 5.5 (4.5-6.0) vs TEM: 10.0 (7.0-12.0) days; P < 0.001], and cost [ESD: 11.6 (9.8-12.6) vs TEM: 20.9 (17.0-25.1) kilo-China Yuan, P < 0.001] were remarkably shorter and less for ESD. CONCLUSION Both ESD and TEM were well-tolerated and yielded favorable outcomes for the local removal of clinical stage 1 rectal NETs. ESD exhibits shorter hospital stay and fewer costs than TEM.

Purpose: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. Methods: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. Results: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn’t reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3–4 adverse events (AEs) compared with others. Conclusion: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.