Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and highly aggressive mesenchymal neoplasm that is frequently associated with anaplastic lymphoma kinase (ALK) gene fusion. Surgical resection remains the cornerstone of treatment for patients with early- and intermediate-stage EIMS; however, a standardized therapeutic approach for advanced-stage EIMS has yet to be established. Primary pulmonary EIMS is exceedingly rare, with only a limited number of cases reported in the literature. While treatment with ALK-tyrosine kinase inhibitors (TKIs) is considered a viable therapeutic option, and clinical outcomes with monotherapy using ALK-TKIs have frequently been suboptimal. This study presents a case of advanced primary pulmonary EIMS with a TPM3-ALK fusion. The patient received first-line targeted therapy with the second-generation ALK-TKI Ensartinib, in conjunction with radiotherapy for residual and metastatic lesions. This treatment regimen resulted in significant tumor reduction and sustained disease control. The progression-free survival (PFS) exceeded 32 months, with no significant treatment-related adverse events observed. This study investigates the feasibility of combining targeted therapy with local radiotherapy, guided by genetic testing, to offer novel treatment strategies for patients with advanced primary pulmonary EIMS.
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Tumor metastasis is the leading cause of cancer-related mortality. Disseminated tumor cells (DTCs), serving as the critical 'seeds' in the metastatic cascade, hold the key to determining the success or failure of metastasis. Following dissemination from the primary tumor and colonization of distant organs, DTCs often enter a prolonged state of dormancy. Their subsequent escape from immune surveillance through sophisticated mechanisms enables them to transition from this dormant state to a proliferative one, ultimately culminating in clinically detectable metastatic lesions. A profound understanding of DTCs immune evasion is therefore essential for unraveling the fundamental biology of metastasis and developing effective anti-metastatic strategies. This article systematically reviewed the latest advances in the mechanisms underlying DTCs immune evasion, focusing on three core aspects: defects in antigen presentation, formation of an immunosuppressive microenvironment, and metabolism reprogramming-mediated immunosuppression. Specifically, DTCs achieve 'immune invisibility' by downregulating major histocompatibility complex class-I (MHC-I) molecule expression; they actively construct a local 'protective shield' by recruiting immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs); and they impair effector immune cell function at the energetic and metabolic levels by remodeling glucose, amino acid, and lipid metabolism. Building upon this, we innovatively integrate the traditional Chinese medicine (TCM) theories of 'hidden toxicity due to vital qi deficiency' and the 'metastatic state' to elucidate the dynamic pathogenic relationship between the body's systemic 'Zhengqi' (vital energy) status and the dormancy-awakening switch of DTCs, offering a novel holistic perspective for comprehending the metastatic process. Finally, we discussed the prospects of multi-target combination therapeutic strategies against DTCs immune evasion and highlight the potential of emerging technologies, such as single-cell sequencing and spatial transcriptomics, aiming to provide valuable insights for future in-depth research and clinical translation in the field of anti-metastasis therapy.
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Leptomeningeal metastasis (LM) is a devastating complication of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), with a poor prognosis. While high-dose third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can enhance drug concentrations in the central nervous system, their efficacy as monotherapy remains limited. Intrathecal Pemetrexed (IP) offers a promising local treatment approach by bypassing the blood-brain barrier and acting directly within the cerebrospinal fluid. However, clinical data on the efficacy and safety of combining high-dose third-generation EGFR-TKIs Furmonertinib (160 mg/d) with IP in EGFR-mutant NSCLC-LM patients are still scarce. Therefore, this study aims to evaluate the efficacy and safety of this combination regimen in this population to provide real-world data support for clinical practice.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a newly defined type of epithelial tumor in the 2021 World Health Organization (WHO) fifth edition classification of thoracic tumors, with a low incidence. Currently, its treatment and prognosis remain unclear. Pathologically, it can be distinguished from SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) based on histological morphology and immunohistochemistry, yet whether there are differences in their clinical features, sensitivity to radiotherapy, and prognosis remains unknown. This study aimed to analyze the clinical characteristics of patients with SMARCA4-UT and SMARCA4-dNSCLC and to identify prognostic factors.

Objective: To investigate risk factors for postoperative lymph node metastasis in patients with intrahepatic cholangiocarcinoma (ICC) after curative resection. Methods: This retrospective case-series study consecutively enrolled 230 patients who underwent initial curative hepatectomy and were pathologically confirmed as ICC at Peking University People's Hospital between January 2015 and September 2025. The cohort comprised 120 men (52.2%) and 110 women (47.8%), with an age (M(IQR)) of 59 (14) years (range:31 to 83 years). Multivariable logistic regression was performed to identify independent risk factors for lymph node metastasis. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method and Cox proportional hazards models. Subgroup analyses based on lymph node status (N0, N1, and Nx) were conducted to explore the impact of lymphadenectomy extent and postoperative adjuvant therapy on prognosis across subgroups. Restricted cubic spline (RCS) analysis was used to assess the association between lymph node ratio (LNR) and survival outcomes. Results: Among the 230 ICC patients, 144 underwent lymphadenectomy, with a lymph node metastasis rate of 38.9% (56/144). Multivariable logistic regression identified carcinoembryonic antigen >4.7 μg/L (OR=5.895, P=0.030), preoperative radiological lymphadenopathy (OR=11.822, P=0.006), and large duct type histological subtype (OR=18.224, P=0.001) as independent risk factors for lymph node metastasis. Survival analyses showed that lymph node metastasis was associated with shortened OS and RFS (both P<0.01). In subgroup analyses of lymphadenectomy, retrieval of ≥6 lymph nodes prolonged RFS in the N1 group (P=0.004) but did not improve OS; in the N0 group, retrieval of <6 lymph nodes was associated with better OS and RFS compared with ≥6 nodes (both P<0.05). RCS analysis demonstrated a significant linear association between LNR and RFS (P=0.006), whereas no association was observed between LNR and OS (P=0.451). Regarding adjuvant therapy, adjuvant treatment improved OS in the overall cohort (P=0.039) but did not prolong RFS (P>0.05). In the N1 group, adjuvant therapy improved OS (P=0.031); in the N0 group, it improved RFS (P=0.031); however, no survival benefit was observed in the Nx group (both P>0.05). Conclusions: Elevated carcinoembryonic antigen, preoperative lymphadenopathy, and large duct type histological subtype are independent risk factors for postoperative lymph node metastasis in ICC. Lymph node status significantly affects prognosis. Patients with lymph node-positive disease may benefit from retrieval of ≥6 lymph nodes and postoperative adjuvant therapy, whereas excessive lymphadenectomy should be avoided in lymph node-negative patients, in whom adjuvant therapy mainly contributes to delaying recurrence.

Objective: To develop and validate a nomogram model based on CT imaging features for predicting the very early recurrence (VER) of patients with intrahepatic mass-forming cholangiocarcinoma (IMCC) after radical resection. Methods: This is a retrospective multicenter case series study. Retrospective analysis of clinic data was conducted in IMCC patients who underwent curative resection and contrast-enhanced CT at three independent institutions from Jiangsu province between January 2009 and December 2019 (institution 1: the First Affiliated Hospital with Nanjing Medical University; institution 2: Yancheng First People's Hospital; institution 3: Changzhou First People's Hospital). A total of 282 patients were included. A preoperative nomogram was developed based on a training cohort of 179 IMCC patients who were collected from institution 1. In the training cohort, univariate and multivariate Logistic regression analysis were used to construct the nomogram. The constructed model was validated in an independent external dataset (103 IMCC patients received surgical treatment at institution 2 and institution 3). The predictive efficacy of the nomogram model was evaluated using the receiver operating characteristic curve and its area under the curve (AUC), calibration curve, and decision curve analysis (DCA), and was compared with the AJCC 8th edition staging system. Results: The preoperative clinical-imaging prediction model was constructed based on the albumin-bilirubin grading and three CT imaging features (tumor size, multi-nodular type, and arterial phase enhancement pattern). In the training cohort, the predictive efficacy of the preoperative clinical-imaging model (AUC=0.819, 95%CI: 0.756 to 0.883) was significantly higher than that of the AJCC 8th edition staging system (AUC=0.707, 95%CI: 0.633 to 0.782)(P=0.006); in the external validation cohort, the predictive efficacy of the preoperative clinical-imaging model (AUC=0.766, 95%CI: 0.672 to 0.861) was slightly better than that of the AJCC 8th edition staging system (AUC=0.709, 95%CI: 0.611 to 0.808), but the difference was not statistically significant (P=0.370). The calibration curve indicated that the predicted probabilities of the clinical-imaging nomogram model were in good agreement with the actual observed values. The DCA showed that this model had better clinical net benefit compared to the AJCC 8th edition staging system. Conclusions: The preoperative albumin-bilirubin grading and three CT imaging features, including tumor size, multi-nodular type, and arterial phase enhancement pattern, are independent risk factors for postoperative VER in IMCC patients. The clinical-imaging nomogram model constructed based on the albumin-bilirubin grading and these three imaging features can accurately predict postoperative VER in IMCC patients before surgery, providing a reference for the selection of individualized treatment strategies.

Objective: To investigate the effects of visceral fat and subcutaneous fat distribution and the expression level of serum Takeda G protein-coupled receptor 5 (TGR5) on the clinicopathologic features and postoperative recurrence and metastasis of patients with endometrial cancer (EC). Methods: This was a retrospective cohort study. A total of 146 EC patients who underwent laparoscopic radical resection of EC at Northwest Women and Children's Hospital from March 2020 to March 2024 were enrolled as the EC group, and 153 concurrent patients with benign endometrial lesions were enrolled as the control group. The EC group was followed up for 1 year after the surgery to analyze the prognosis. Depending on whether recurrence and metastasis occurred, the EC group was further divided into the recurrence or metastasis subgroup (n=45) and the non-recurrence or metastasis subgroup (n=101). Age, obstetric history, body mass index (BMI), serum TGR5 level, visceral fat area (VFA) and subcutaneous fat area (SFA) were collected and compared between the recurrence or metastasis subgroup, non-recurrence or metastasis subgroup and the control group. The area under curve, sensitivity, specificity and the Youden index of the predictive value of TGR5 expression level, VFA level, SFA level, and BMI in patients in the EC group were analyzed using receiver operating characteristic (ROC) curves. Based on the cut-off value determined by the Youden index, the patients in the EC group were further classified into high-expression/high-level and low-expression/low-level groups. Univariate and multivariate Cox proportional hazards regression models were used to identify the risk factors for recurrence and metastasis of patients in the EC group in 1 year. The one-year recurrence and metastasis of EC patients with different serum TGR5 expression levels, VFA levels, SFA levels and BMI were analyzed, survival curves were plotted and data of recurrence-free survival (RFS) were obtained using the Kaplan-Meier method. ROC curves were constructed to evaluate the diagnostic efficacy of serum TGR5 expression level, VFA level, SFA level, BMI and their combined indicators. Results: The serum TGR5 expression level, VFA level, SFA level and BMI were significantly higher in the recurrence or metastasis subgroup compared to the non-recurrence or metastasis subgroup (all P<0.05). Furthermore, all four indicators in both the recurrence or metastasis subgroup and the non-recurrence or metastasis subgroup were significantly higher than those in the control group (all P<0.05). When the serum TGR5 expression level was 7.7 μg/L, the VFA level was 90.4 cm², the SFA level was 221.6 cm², and the BMI was 23.9 kg/m², the Youden index reached its maximum value for each respective parameter. Cox regression analyses revealed that serum TGR5≥7.7 μg/L (HR=6.382, 95%CI:2.151-18.939, P=0.001), VFA≥90.4 cm² (HR=6.914, 95%CI:2.279-20.979, P=0.001), SFA≥221.6 cm² (HR=7.520, 95%CI:2.414-23.421, P=0.001) and BMI≥23.9 kg/m² (HR=9.434, 95%CI:3.019-29.473, P<0.001) were risk factors for recurrence and metastasis within 1 year after surgery. The incidence of postoperative recurrence and metastasis in the high TGR5 expression group, high VFA level group and high SFA level group were significantly higher, while the RFS times were significantly shorter than those in the low TGR5 expression group, low VFA level group and low SFA level group (all P<0.05). ROC curve analysis showed that the above independent factors had good evaluation efficacy, and the combined detection was superior to single indicator detection. Conclusions: EC patients with high serum TGR5 expression level, VFA level and SFA level have a higher recurrence and metastasis rate. High serum TGR5 expression level, high VFA level, high SFA level and high BMI are risk factors for recurrence and metastasis within 1 year after radical resection of EC, and the diagnostic value of combined detection is superior to single indicator detection.

Objective: To investigate the potential value of quantitative digital pathology analysis in predicting prognosis in micropapillary serous borderline ovarian tumor (MP-SBOT). Methods: Clinical and pathological data from 366 serous borderline ovarian tumor (BOT) patients who attended the First Affiliated Hospital of Nanjing Medical University between October 2012 and November 2023 were retrospectively reviewed. Patients were classified into MP-SBOT group and non-MP-SBOT group according to their pathological subtype. Within the MP-SBOT group, patients were further classified into recurrence and non-recurrence subgroups. Digital image analysis using QuPath was performed on 83 ovarian serous tumors with adequate tissue quality, including MP-SBOT (n=48), SBOT in the non-MP-SBOT group (n=9), serous cystadenoma (n=11), low-grade serous carcinoma (n=7) and high-grade serous carcinoma (n=8). Quantitative pathological features including nuclear area, cellular area, and nuclear-to-cytoplasmic ratio (N/C ratio) of tumor cells were extracted. Univariate and multivariate Cox regression analyses were used to identify factors associated with MP-SBOT recurrence. Kaplan-Meier method was applied to estimate progression-free survival (PFS) time. Results: (1) Compared with non-MP-SBOT group, MP-SBOT group patients exhibited higher median serum carbohydrate antigen 125 level (127.9 vs 36.5 kU/L), higher D-Dimer level (0.7 vs 0.3mg/L), higher proportion of bilateral ovarian tumors (60.4% vs 15.4%), higher proportion of invasive peritoneal implants (25.0% vs 3.1%), higher proportion of International Federation of Gynecology and Obstetrics (FIGO) stage Ⅱ-Ⅲ (54.1% vs 10.0%), higher proportion of mixed cystic-solid mass detected by imaging examination (88.1% vs 70.1%) and higher proportion of recurrence (33.3% vs 13.5%) with statistically significant differences (all P<0.001). (2) Quantitative digital pathology revealed the distinct cellular morphologic characteristics in MP-SBOT. The tumor cell N/C ratio was significantly higher in MP-SBOT group than non-MP-SBOT group (0.48 vs 0.41; P<0.05). The tumor cell N/C ratio increased progressively with tumor malignancy. (3) Univariate Cox analysis identified tumor cell N/C ratio>0.50 and conservative surgery as factors associated with recurrence in MP-SBOT group. Multivariate analysis confirmed that an elevated tumor cell N/C ratio was an independent risk factor for recurrence in MP-SBOT group (HR=7.278, 95%CI:1.940-27.307, P=0.003). (4) Kaplan-Meier survival analysis showed that patients with tumor cell N/C ratio>0.50 had a significantly shorter median PFS than those with the tumor cell N/C ratio≤0.50 (164.0 vs 35.0 months, P<0.001). Conclusions: MP-SBOT display more aggressive clinical features. The elevated tumor cell N/C ratio shows potential clinical value in predicting recurrence in MP-SBOT patients.

The adhesion of cancer cells to the vascular endothelium during hematogenous metastasis is a crucial first step, involving the interaction of multiple adhesion molecules between cancer cells and endothelial cells. Here, a parallel-plate flow chamber combined with fluorescence microscopy was used to observe the adhesion behavior and subsequent calcium response of MDA-MB-231 cells on different functionalized substrates under flows, revealing the underlying force-regulation mechanism by analyzing and extracting relevant characteristic parameters. Our results demonstrated that fluid shear stress positively regulated the rolling velocity of cells by affecting the dissociation rate constant of CD44/E-selectin, and rapidly activated integrin α5β1 at the sub-second level, slowing down the rolling velocity of cells, but not enough to firm adhesion. Force triggered the calcium response of MDA-MB-231 cells on E-selectin. Furthermore, the activated integrin α5β1 binding with fibronectin enhanced and quickened cellular calcium response with higher activation ratio and peak intensity, and shorter delay time. This study can deepen the understanding of the hematogenous metastasis process of breast cancer cells, and provide reference for relevant clinical treatment strategies and drug development.

Bacterial outer membrane vesicles (OMVs) have attracted widespread attention in the field of drug delivery due to their excellent biocompatibility, tumor penetration, and loading capacity. The anti-angiogenic peptide AP25 can block malignant tumor angiogenesis and has broad-spectrum anti-cancer activity. To achieve efficient delivery of AP25, we modified AP25 on the surface of OMVs through genetic engineering and explored their inhibitory effects on breast cancer and gastric cancer in vitro. The results indicated that the engineered OMVs had typical morphological characteristics of OMVs, and the particle size distribution conformed to the theoretical. Proteinase K digestion combined with Western blotting confirmed that AP25 was modified on the membrane surface of OMVs. Cell experiments showed that WAP25 OMVs significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 and HGC-27 cells, promoted the cell apoptosis, and downregulated the expression of tumor migration and angiogenesis-related proteins: integrin beta 1 (integrin β1), Homo sapiens inhibitor of DNA binding 1 (ID1), nuclear factor kappa-B (NF-κB), and vascular endothelial growth factor (VEGF). This study achieves effective delivery of protein drugs based on OMVs for the first time, providing new ideas for the anti-angiogenesis therapy for tumors and the functional development of bacterial OMVs.

Objective: To investigate the safety and effectiveness of the transanal eversion technique using double purse-string forceps in laparoscopic anterior resection of middle-low rectal cancer. Methods: Clinical data of patients with middle-low rectal cancer undergoing laparoscopic anterior resection at the General Surgery Department of Henan Cancer Hospital from August 2015 to December 2018 were analyzed retrospectively. According to the inclusion and exclusion criteria, 238 patients were enrolled, including 36 patients in the double purse-string forceps method group and 202 patients in the traditional double-staplers method group. Propensity score matching (1∶3) was performed based on age, gender, body mass index (BMI), tumor size, distance from the tumor's lower margin to the anus, preoperative clinical stage, and neoadjuvant chemoradiotherapy. This resulted in 23 patients in the double purse-string forceps group and 69 in the double-staplers group. Surgical outcomes, pathological indicators, and postoperative complications were compared between the two groups. Results: Compared with the double-staplers method group, the double purse-string forceps group had a lower protective stoma rate [2/23 vs 18/69, P=0.049], a shorter incision length [(1.6±1.5) cm vs (4.7±1.1) cm, P＜0.01], and less postoperative pain [(3.9±1.9) points vs (4.8±1.5) points, P=0.024]. There were no significant differences in the length of specimen, distal margin length, number of lymph nodes dissected, number of positive lymph nodes and pTNM stage between the two groups (P＞0.05). There was no significant difference in complications including anastomotic leakage between the two groups (P＞0.05). Conclusions: The transanal eversion technique using double purse-string forceps in laparoscopic anterior resection of middle-low rectal cancer is safe and feasible by eliminating the ischemic area. This method can significantly reduce the ratio of protective stoma, shorten surgical incision length, and relieve postoperative pain.

Objective: To investigate the impact of lymph node dissection (LND) and its extent on long-term survival outcomes in patients with cN0M0 renal cell carcinoma (RCC) undergoing radical nephrectomy.Methods: A total of 1 109 patients with RCC who underwent radical nephrectomy at Sun Yat-sen University Cancer Center between March 1999 and January 2022 were retrospectively analyzed. Clinical and pathological data as well as follow-up information were collected. Patients were grouped according to whether LND was performed: the LND group (n=512) and the NLND group (n=597). Propensity score matching (PSM) was applied at a 1∶1 ratio, yielding 340 matched pairs. Cox proportional hazards models were used to evaluate the associations between LND and overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Among patients who underwent LND, the relationships of the number of removed lymph nodes, extended LND, and lymph-node status with OS, CSS, and PFS were also assessed. Results: Among the 1 109 patients, 512 received LND, with a median of 4 lymph nodes removed. Fifty-eight patients underwent extended LND, and 35 patients (6.8%) were pathologically lymph-node positive (pN+). After a median follow-up of 77.8 months, 234 of the 1 109 patients developed recurrence or metastasis, and 201 died. After PSM, the 5-year OS, CSS, and PFS rates in the LND group were 90.8%, 91.7%, and 82.4%, respectively, compared with 89.9%, 91.2%, and 83.7% in the NLND group, with no statistically significant differences between the two groups (P=0.89, 0.56, and 0.16, respectively). Multivariable Cox analyses showed that LND was not associated with OS, CSS, or PFS in patients with cN0M0 RCC undergoing radical nephrectomy (OS: HR=0.97, 95% CI: 0.66-1.41; CSS: HR=1.03, 95% CI: 0.67-1.59; PFS: HR=1.16, 95% CI: 0.82-1.63). Subgroup multivariable analyses indicated that LND was not an independent prognostic factor for OS, CSS, or PFS among patients with pT3-4 disease, grade G3-4 tumors, non-clear cell RCC, or adverse pathological prognostic features (all P＞0.05). Pathological lymph-node positivity was an independent predictor of OS, CSS, and PFS among patients who underwent LND (OS: HR=3.16, 95% CI: 1.68-5.96; CSS: HR=3.27, 95% CI: 1.67-6.39; PFS: HR=2.23, 95% CI: 1.30-3.83). Conclusions: LND and its extent do not confer survival benefits in patients with cN0M0 RCC undergoing radical nephrectomy. However, LND provides accurate pathological staging, which is valuable for prognostic assessment and for guiding decisions regarding adjuvant therapy.

Objective: To investigate the diagnostic value of multimodal blood flow imaging in differentiating benign and malignant small renal masses (SRMs). Methods: A total of 170 patients with renal tumors (172 lesions) who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from January 2020 to December 2023 were enrolled.The maximum diameter of the tumors was ≤4 cm. All patients received Color Doppler flow imaging (CDFI), Power Doppler imaging (PDI), Microflow imaging (MFI), and Contrast-enhanced ultrasound (CEUS) examinations before surgery. Two sonologists were responsible for grading the blood flow and evaluating the vascular morphology to make a diagnosis of whether the tumors were benign or malignant. Taking the postoperative pathological diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the four ultrasound examination methods. Results: Among the 172 lesions, 141 were malignant and 31 were benign. In the MFI imaging mode, the Kappa value for the evaluation of SRMs blood flow grading by two independent sonologists was 0.819, and the Kappa value for vascular morphology was 0.806.The detection rate of MFI for lesions with blood flow grading of 2-3 and vascular morphology of types Ⅳ-Ⅴ was 77.9% (134/172), which was higher than that of CDFI [36.6% (63/172)] and PDI [43.0% (74/172)]. Blood flow grading of 2-3 and vascular morphology of types Ⅳ-Ⅴ in the MFI mode could serve as independent predictors for malignant SRMs (P＜0.001). In the CEUS mode, malignant SRMs mainly manifested as fast wash-in (75.9%), fast wash-out (70.9%), and high enhancement (85.1%). In contrast, benign SRMs mainly showed slow wash-in (51.6%), slow wash-out (45.2%), and low enhancement (45.2%). Ring enhancement was observed in 37.6% of malignant SRMs, while no ring enhancement was detected in any of the benign SRMs. All these differences were statistically significant (P＜0.001).The accuracy of CDFI, PDI, MFI, and CEUS in diagnosing malignant SRMs was 0.500, 0.552, 0.855, and 0.901, respectively; the sensitivity was 0.418, 0.489, 0.887, and 0.986, respectively; the specificity was 0.871, 0.839, 0.710, and 0.516, respectively; and the area under the curve (AUC) was 0.645, 0.664, 0.798, and 0.751, respectively. Overall, MFI and CEUS demonstrated more superior diagnostic efficacy for SRMs. Conclusions: MFI exhibits high sensitivity in detecting the microvascular flow signals of SRMs. It shows comparable diagnostic performance to CEUS in differentiating the benign and malignant SRMs. It is a non-invasive, safe, cost-effective, and highly repeatable examination method.

Objective: To investigate the expression differences of smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAF) in different regions of lung squamous carcinoma and lung adenocarcinoma, as well as to analyze their prognostic value. Methods: Data of a total of 243 non-small cell lung cancer patients who underwent radical surgery from January 1, 2014 to December 31, 2018 at Shandong Cancer Hospital were retrospectively collected. Tissue microarrays containing the tumor center (TC) and invasive margin (IM) regions were constructed using patients' postoperative paraffin specimens, and the densities of SMA+ CAF within the total, epithelial, and stromal regions were detected using multiplex immunofluorescence. The recurrence-free survival time (RFS) of patients was obtained by the electronic case system or telephone follow-up, and univariate and multivariate Cox regression analyses were used to clarify the factors influencing the postoperative recurrence of patients. Results: Of the 243 patients, there were 83 cases of lung squamous carcinoma, with 30 (36.1%) recurrences during the follow-up period, and 160 cases of lung adenocarcinoma, with 46 (28.8%) recurrences during the follow-up period. In the TC and IM regions, the differences between the lung squamous carcinoma group and the lung adenocarcinoma group in total, epithelial, and stromal SMA+ CAF were not statistically significant (all P＞0.05). Multifactorial Cox regression analysis showed that IM SMA+ CAF/TC SMA+ CAF was an independent risk factor for RFS in patients with lung squamous carcinoma (HR=2.833, 95% CI: 1.187-6.671, P=0.019), and adjuvant chemotherapy was an independent risk factor for RFS in patients with lung adenocarcinoma (HR=2.682, 95% CI: 1.178-6.006, P=0.019). Conclusions: There was no difference in the spatial distribution of SMA+ CAF between lung squamous carcinoma and lung adenocarcinoma. Patients with higher IM SMA+ CAF/TC SMA+ CAF ratios were more prone to postoperative recurrence in lung squamous carcinoma.

Objective: To investigate the mutation status of breast cancer susceptibility genes (BRCA) in colorectal cancer and the relationship between BRCA and the clinical-pathological characteristics and prognosis of colorectal cancer. Methods: A total of 132 colorectal cancer tissue specimens surgically resected at Shanxi Cancer Hospital from 2018 to 2021 were collected. Second-generation sequencing was used to detect BRCA mutations. Immunohistochemical staining assessed the infiltration density of CD3+, CD4+, and CD8+ T cells, and CD20+ B cells. The association between BRCA mutations and clinical-pathological features, immune cell infiltration density, and prognosis of colorectal cancer was analyzed. Results: Among 132 colorectal cancer cases, the overall BRCA mutation rate was 9.09% (12/132), with BRCA1 mutation rate at 3.03% (4/132) and BRCA2 mutation rate at 6.06% (8/132). Compared with the BRCA wild-type group, the BRCA mutation group exhibited smaller tumors (P=0.036), less vascular or nerve invasion (P=0.041), and lower tumor budding grades (P=0.013). Tumor microenvironment analysis revealed that the infiltration densities of CD3+, CD4+, and CD8+ T cells in the BRCA mutation group were 1 729.66 (652.91, 3 065.98)/mm², 438.36 (97.37, 718.43)/mm², and 1 017.86 (506.19, 2 257.35)/mm², respectively, all higher than those in the BRCA wild-type group [555.72 (304.58, 933.26)/mm², 89.34 (58.15, 178.35)/mm², and 354.23 (157.78, 752.37)/mm², respectively, all P＜0.05]. Molecular feature analysis revealed five cases of TMB-H in the BRCA-mutant group and three cases in the BRCA-wild group, with a statistically significant difference between the two groups (P＜0.001). Survival analysis revealed no association between BRCA mutation status and overall survival in colorectal cancer patients (P＞0.05). Multivariate Cox regression analysis identified clinical stage as an independent predictor of overall survival, with patients at stages Ⅲ-Ⅳ exhibiting poorer prognosis (HR=5.359, 95% CI: 1.124-25.546). Conclusion: BRCA-mutated colorectal tumors exhibit lower invasiveness, higher TMB-H rates, and abundant immune cell infiltration in the tumor microenvironment, suggesting that patients with BRCA-mutated colorectal cancer are more likely to benefit from immunotherapy.

Objective: To explore a novel strategy for treating immunologically "cold" lung tumors by combining neoantigen-pulsed dendritic cell (DC) vaccines with CpG. Methods: LLC1 cells were analyzed by whole-exome sequencing and RNA sequencing. Tumor-specific nonsynonymous mutations were identified using RNA sequencing data, and candidate neoantigens were screened by predicting their binding affinity to major histocompatibility complex molecules using NetMHCpan v4.0 and NetMHCⅡpan v3.2. Neoantigens LLC1-M01, LLC1-M02, LLC1-M03, LLC1-M04, and LLC1-M05 were synthesized via Fmoc solid-phase peptide synthesis. Candidate neoantigens were subcutaneously inoculated into C57BL/6 mice. Neoantigen immunogenicity was assessed using flow cytometry, and interferon-gamma (IFN-γ) secretion by effector T cells was measured via enzyme-linked immunospot assay. A neoantigen-pulsed DC vaccine was prepared. Changes in immune cells and cytokines within the tumor microenvironment were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA). In a lung cancer LLC1 cell tumor-bearing mouse model, treatments included unpulsed DC vaccine, CpG, LLC1-M02-DC, LLC1-M02-WT-DC, and LLC1-M02-DC+CpG. The percentages of CD3+CD4+ and CD3+CD8+ T cells, perforin and granzyme expression in CD3+ or CD8+ T cells in tumor tissues, as well as tumor volume, mouse body weight changes, and survival time were monitored. Results: The percentages of CD3+IFN-γ+ T cells induced by neoantigens LLC1-M01 and LLC1-M02 were (4.80±1.00)% and (13.81±3.00)%, respectively, which were higher than that induced by the irrelevant peptide VSV-NP43-69 [(1.00±0.30)%; both P＜0.001]. The IFN-γ secretion capacity of effector splenocytes induced by LLC1-M01 was (200.00±45.00) spot-forming units (SFU)/105 cells, showing no significant difference from LLC1-M01-WT [(193.00±42.00) SFU/105 cells; P=0.753]. In contrast, IFN-γ secretion induced by LLC1-M02 was (820.00±200.00) SFU/105 cells, significantly higher than that induced by LLC1-M02-WT [(430.00±100.00) SFU/105 cells; P＜0.001]. At an effector-to-target ratio of 50:1, the specific killing rate of LLC1 cells by effector T cells induced by LLC1-M02-DC was (35.02±8.00)%, which was higher than the rates of killing against MC38 and B16-F10 cells (P＜0.001), and also higher than that induced by M02-WT against LLC1 cells [(20.01±4.00)%; P＜0.001]. Compared with the no-CpG group, the CpG group showed increased percentages of CD3+CD8+, CD3+perforin+, CD3+granzyme+, CD8+perforin+, and CD8+granzyme+ T cells in tumor tissue (all P＜0.01), downregulated expression of tumor necrosis factor-alpha (TNF-α), IFN-γ, interleukin (IL)-2, and IL-12 (all P＜0.01), and upregulated expression of IL-10 and IL-13 (all P＜0.01). In tumor-bearing mice treatment experiments, compared with the unpulsed DC vaccine group, CpG group, and LLC1-M02-WT-DC group, tumor growth was significantly inhibited in the LLC1-M02-DC group. The LLC1-M02-DC+CpG group exhibited stronger tumor growth inhibition than the LLC1-M02-DC group (P＜0.001), while no significant differences in body weight were observed among groups. The median survival times of tumor-bearing mice in the unpulsed DC vaccine, CpG, LLC1-M02-DC, LLC1-M02-WT-DC, and LLC1-M02-DC+CpG groups were 28.0, 30.5, 55.0, 37.5, and 79.0 days, respectively. Survival time in the LLC1-M02-DC group was significantly longer than that in the LLC1-M02-WT-DC group (P=0.045) but significantly shorter than that in the LLC1-M02-DC+CpG group (P=0.008). Conclusions: The neoantigen LLC1-M02 from the murine LLC1 cell line exhibits strong immunogenicity. The LLC1-M02-DC vaccine combined with CpG enhances the inhibitory effect on lung "cold" tumors.

Objective: To explore the appropriate extent of No.12a lymph node dissection in locally advanced distal gastric cancer patients. Methods: This study utilized a prospective observational research design, The inclusion criteria were: (1) age 18-75 years, and Eastern Cooperative Oncology Group score ≤2; (2) histologically confirmed gastric adenocarcinoma, and tumor extending from the lower-middle of the gastric body to the antrum; (3) underwent totally laparoscopic or laparoscopy-assisted distal gastrectomy with D2 lymphadenectomy; (4) postoperative pathological examination confirmed stage pT2-4aNxM0 with negative margin; (5) intraoperative separate pathological examination of No.12a lymph nodes; (6) complete clinicopathological and follow-up data. Exclusion criteria were: (1) Multiple malignant lesions in the stomach; (2) previous upper abdominal surgery (except laparoscopic cholecystectomy); (3) history of intestinal obstruction; (4) combined organ resection; (5) invasion of the superior part of duodenum. A prospective single-center study enrolled 191 local advanced distal gastric cancer patients who underwent laparoscopic radical distal gastrectomy at Tianjin Medical University Cancer Institute & Hospital from January 2023 to April 2025. The No. 12a lymph nodes were categorized into two groups: No. 12a1 (lymph nodes located on the anterior and left wall surfaces of the proper hepatic artery) and No. 12a2 (lymph nodes located between the proper hepatic artery and the portal vein, and along the left wall of the portal vein). The lymph node metastasis rate of different groups was recorded. The relationship between No.12a lymph node metastasis and clinicopathological features, regional lymph node metastasis was analyzed. Results: A total of 191 patients were included, with 139 males (72.8%) and 52 females (27.2%), with median age of 61 years. A total of 7536 lymph nodes were dissected with a median of 37 (range: 17-89) nodes per case, including 1046 metastatic lymph nodes (median: 3, range: 0-40).The No.12a lymph node metastasis rate was 7.9% (15/191). The No.12a1 lymph node metastasis rate was 6.8% (13/191), and the metastasis rate of No.12a2 lymph node was 3.7% (7/191). Correlation analysis indicated that No.12a2 lymph node metastasis was correlated with pN3 (χ2=6.217,P=0.013) and pathological stageⅢ(χ2=6.475, P=0.011). The regional lymph nodes (No.6, No.7, No.8a, No.9, and No.12a1) metastasis was significant associated with No.12a2 lymph node metastasis (all P<0.05). Multivariate analysis indicated that only No.12a1 lymph node metastasis was an independent risk factor of No.12a2 lymph node metastasis. Conclusions: The metastasis rate of No.12a2 lymph node was relatively low in locally advanced distal gastric cancer, the clinical value of No.12a2 lymph node dissection needs further investigation. For patients with clinical stage cN3 or clinical stage III, as well as No.12a1 group of lymph node metastasis was detected during operation, systematic dissection of No.12a2 group lymph node may be more meaningful.

While endoscopic techniques have propelled the development of early gastric cancer (EGC) treatment, surgical intervention remains irreplaceable due to its thoroughness in lymph node dissection. The limitations of preoperative staging, the risk of lymph node metastasis, and technical constraints of endoscopy collectively establish surgery as the cornerstone of EGC therapy. Furthermore, it plays a critical role in managing post-endoscopic complications and non-curative resections. Concurrently, continuous innovations in surgical technology and life sciences, particularly the refinement of function-preserving gastrectomy, continue to consolidate the role of surgery. With the development of predictive models of early gastric cancers for lymph node metastasis, the synergy between surgery and endoscopy is poised to achieve precise and individualized treatment for patients with EGC.