Postoperative Metastasis Research Articles

Inhalable Chemotactic Liposome for Targeted Modulation of Pulmonary Pre‐Metastatic Niche

AbstractInhalation offers a non‐invasive method to administer drugs to lungs, but achieving selective delivery to pulmonary lesions while sparing normal lung tissues remains challenging. Here, the development of an inhalable chemotactic liposome designed for targeted modulation of pulmonary pre‐metastatic niche (PMN) is reported. The inhaled liposome can migrate along chemokine gradients, preferentially accumulating in chemokine‐secreting PMNs within the lung. Upon localized drug release, the liposome mitigates fibrosis, and disrupts PMN evolution, thereby attenuating the pro‐metastatic role of PMN as a hospitable “soil” for residual tumor cell “seeding” post‐surgery. This approach further complements a sprayable hydrogel developed for immediate post‐surgical application within the tumor resection cavity. While this hydrogel alone reduces the metastatic potential of postoperative tumor residues, it proves insufficient in halting the spread to lungs. However, the integration of the inhalable liposome and sprayable hydrogel into a dual‐pronged strategy presents a patient‐friendly method that simultaneously targets both the pro‐metastatic PMN “soil” and metastatic tumor “seeds”, resulting in significant inhibition of postoperative lung metastasis.

Erythrocyte modified controlling nutritional status as a biomarker for predicting poor prognosis in post-surgery breast cancer patients

Nutrition and inflammation are closely related to prognosis in breast cancer patients. However, current nutritional and inflammatory measures predict disease free survival (DFS) of breast cancer are still different, and the most predictive measures remain unknown. This study aimed to compare the predictive effects of commonly used nutritional and inflammatory measures on DFS and to improve existing nutritional or inflammatory measures in order to develop a new model that is more effective for predicting postoperative recurrence and metastasis in breast cancer patients. The clinical data of 536 female breast cancer patients with invasive ductal carcinoma who underwent surgery at Shaoxing People’s Hospital from January 2012 to December 2018 were retrospectively evaluated. The predictive effects of nutritional and inflammatory indicators on DFS were evaluated. Machine learning was used to evaluate and rank laboratory indicators, select relatively important variables to modify nutritional or inflammatory indicators with the best predictive power, and evaluate their predictive role in patients’ postoperative recurrence and metastasis. Among various metrics predicting DFS, the CONUT score emerged paramount with an area under the curve (AUC) of 0.667. Interestingly, the combination of the erythrocyte levels with the CONUT score (ECONUT) achieved the highest AUC (0.722). The Kaplan-Meier survival analysis showed that the group exhibiting high ECONUT scores experiencing a notably poorer DFS. ECONUT was identified as an independent risk factor for postoperative DFS (P < 0.001). The ECONUT model could provide an effective assessment tool for predicting DFS in breast cancer patients.

High-risk habitat radiomics model based on ultrasound images for predicting lateral neck lymph node metastasis in differentiated thyroid cancer

BackgroundThis study aims to evaluate the predictive usefulness of a habitat radiomics model based on ultrasound images for anticipating lateral neck lymph node metastasis (LLNM) in differentiated thyroid cancer (DTC), and for pinpointing high-risk habitat regions and significant radiomics traits.MethodsA group of 214 patients diagnosed with differentiated thyroid carcinoma (DTC) between August 2021 and August 2023 were included, consisting of 107 patients with confirmed postoperative lateral lymph node metastasis (LLNM) and 107 patients without metastasis or lateral cervical lymph node involvement. An additional cohort of 43 patients was recruited to serve as an independent external testing group for this study. Patients were randomly divided into training and internal testing group at an 8:2 ratio. Region of interest (ROI) was manually outlined, and habitat analysis subregions were defined using the K-means method. The ideal number of subregions (n = 5) was determined using the Calinski-Harabasz score, leading to the creation of a habitat radiomics model with 5 subregions and the identification of the high-risk habitat model. Area under the curve (AUC) values were calculated for all models to assess their validity, and predictive model nomograms were created by integrating clinical features. The internal and external testing dataset is employed to assess the predictive performance and stability of the model.ResultsIn internal testing group, Habitat 3 was identified as the high-risk habitat model in the study, showing the best diagnostic efficacy among all models (AUC(CRM) vs. AUC(Habitat 3) vs. AUC(CRM + Habitat 3) = 0.84(95%CI:0.71–0.97) vs. 0.90(95%CI:0.80-1.00) vs. 0.79(95%CI:0.65–0.93)). Moreover, integrating the Habitat 3 model with clinical features and constructing nomograms enhanced the predictive capability of the combined model (AUC = 0.95(95%CI:0.88-1.00)). In this study, an independent external testing cohort was utilized to assess the model’s accuracy, yielding an AUC of 0.88 (95%CI: 0.78–0.98).ConclusionThe integration of the High-Risk Habitats (Habitat 3) radiomics model with clinical characteristics demonstrated a high predictive accuracy in identifying LLNM. This model has the potential to offer valuable guidance to surgeons in deciding the necessity of LLNM dissection for DTC.Clinical trial numberNot applicable.

Pleural metastases from differentiated thyroid cancer: clinical features and long-term outcomes.

Pleural metastasis (PM) is rare in patients with differentiated thyroid cancer (DTC). Radioiodine (131I) therapy has been the main treatment for postoperative metastasis and recurrence of DTC. However, clinical data on PM from DTC are limited. This study investigated the clinicopathological characteristics of patients with PM from DTC that was treated surgically and with 131I therapy and evaluated their long-term prognosis and prognostic factors. Review of the Shanghai Sixth People's Hospital medical records for 2010-2023 identified PM in 27 of 14,473 patients with DTC. Overall survival (OS) was assessed by the Kaplan-Meier method. The prevalence of PM in DTC was 1.87‰ (27/14,473). The median age at the time of initial diagnosis of PM was 59 years (range 34-79). At the end of follow-up, eight patients (29.63%) had disease progression (PD), four (14.81%) had partial response (PR), and the remainder had stable disease (SD); no patient achieved complete response (CR). Twelve patients (44.44%) died and 15 (55.56%) survived. Thirteen patients (48.15%) did not show 131I avidity, and 16 (59.26%) had radioiodine-refractory DTC (RR-DTC). Twenty patients (74.07%) had malignant pleural effusion (MPE), which was large in 11 cases (40.74%), moderate in two. More than moderate MPE (P=0.031), lack of 131I avidity (P=0.041), and RR-DTC (P=0.030) were significantly associated with worse 5-year OS in patients with PM of DTC. PM is rare in DTC. Lack of 131I avidity, RR-DTC, and more than moderate MPE are associated with a poor OS in patients with DTC and PM.

The expression and clinical significance of serum exosomal-long non-coding RNA DLEU1 in patients with cervical cancer

Background Accumulating evidence has demonstrated that the long non-coding RNA (lncRNA) lymphocytic leukaemia deletion gene 1 (DLEU1) is abnormally overexpressed in many cancer types, including cervical cancer (CC). However, the potential clinical significance of DLEU1 in serum exosomes of patients with CC remains unclear. Methods The expression of serum exosomal DLEU1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to evaluate the clinical diagnostic efficacy of DLEU1. The Kaplan–Meier survival curve and Cox proportional hazards model were used to assess the effect of DLEU1 on postoperative recurrence, metastasis and prognosis among patients with CC. Results Our research showed that DLEU1 expression in the serum exosomes of patients with CC was significantly upregulated compared to that in patients with cervical intraepithelial neoplasia (CIN) and healthy controls (HCs) (both p < .001). DLEU1 relative expression was significantly correlated with tumour size, cervical invasion depth, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis among patients with CC (p < .01 all). The combined detection of DLEU1, carbohydrate antigen 125 (CA-125) and squamous cell carcinoma (SCC) exhibited significantly higher diagnostic efficiency (p < .01). Furthermore, the overall survival (OS) and disease-free survival (DFS) of CC patients in the high DLEU1 expression group were markedly lower than those in the low DLEU1 expression group (both p < .01). Cox univariate and multivariate regression analyses indicated that DLEU1 was an independent risk factor for postoperative recurrence and metastasis in CC patients. Conclusions Our findings suggest that serum exosome DLEU1 has certain clinical value for diagnosing, monitoring recurrence and metastasis, and evaluating CC prognosis.

Unique structural configuration of EV-DNA primes Kupffer cell-mediated antitumor immunity to prevent metastatic progression.

Extracellular vesicles (EVs) transport biomolecules that mediate intercellular communication. We previously showed that EVs contain DNA (EV-DNA) representing the entire genome. However, the mechanism of genomic EV-DNA packaging and its role in cancer remain elusive. We now demonstrate that EV-DNA is predominantly localized on the vesicle surface and associated with uniquely modified and cleaved histones. Moreover, a genome-wide clustered regularly interspaced short palindromic repeats knockout screen revealed that immune developmental pathways and genes, including apoptotic peptidase activating factor 1 (APAF1) and neutrophil cytosolic factor 1 (NCF1), regulate EV-DNA packaging. Furthermore, in colorectal cancer models, uptake of EV-DNA by pre-metastatic liver Kupffer cells (KCs) activated DNA damage responses. This activation rewired KC cytokine production and promoted the formation of tertiary lymphoid structures, thereby suppressing liver metastasis. Conversely, loss of APAF1 decreased EV-DNA packaging and promoted liver metastasis. Importantly, colorectal cancer biopsy EV-DNA secretion could serve as a predictive biomarker for postoperative metastasis. Taken together, our findings indicate that uniquely chromatinized EV-DNA induces antitumor immunity.

Impact of Lymphatic and Venous Invasion Patterns on Postoperative Prognosis and Distant Metastasis in Esophageal Squamous Cell Carcinoma After Preoperative Chemotherapy.

Lymphovascular invasion (LVI) is reported to correlate with postoperative prognosis in esophageal squamous cell carcinoma (ESCC). However, reports analyzing lymphatic and venous invasion separately are rare, and no studies have examined the correlation in resected specimens after neoadjuvant chemotherapy (NAC). This study evaluated the postoperative prognosis and distant metastatic recurrence patterns in ESCC patients who underwent esophagectomy after NAC. This retrospective study analyzed 427 ESCC patients who underwent radical esophagectomy after NAC. The study examined the association of LVI patterns with postoperative overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). The study also evaluated the correlation with postoperative distant metastasis patterns. Multivariate analyses showed that patients with venous invasion (VI) alone had significantly worse OS (HR, 2.99; p < 0.001), RFS (HR, 2.92; p < 0.001), and DMFS (HR, 3.63; p < 0.001) than patients without LVI. Patients with both lymphatic invasion (LI) and VI had the worst OS (HR, 4.23; p < 0.001), RFS (HR, 3.38; p < 0.001), and DMFS (HR, 4.59; p < 0.001) among all groups. For the ypN0 patients, VI positivity was the only independent risk factor for DMFS (HR, 5.33; p < 0.001). Regarding distant organ metastasis, liver, brain, and bone metastasis were more frequently detected in patients with both LI and VI than in patients with other LVI patterns. The study showed that ESCC patients treated with NAC who have resected specimens positive for VI, especially those also with positive lymphatic invasion, have a worse postoperative prognosis and a higher risk for postoperative distant metastases than those without LVI. More aggressive postoperative adjuvant therapy may be suitable for improving the prognosis of such patients.

Vagus Nerve Preservation for Early Distal Gastric Cancer With Monitoring and Indocyanine Green Labeling

Radical gastric cancer surgery can cause functional and physiological disorders due to the resection of perigastric vagus nerves. Few studies have used intraoperative neurophysiological monitoring and indocyanine green (ICG) labeling to preserve the perigastric vagus nerve and to evaluate the corresponding effects. To assess the feasibility and effects of vagus nerve preservation using neurophysiologic monitoring and ICG labeling during laparoscopic distal gastrectomy in patients with early distal gastric cancer. This open-label, prospective randomized clinical trial initially enrolled 285 patients with clinical stage cT1N0M0 distal gastric cancer from May 2022 to May 2023. This trial was conducted at Qilu Hospital of Shandong University in Jinan, China, and enrolled patients aged 18 to 80 years with histologically proven gastric adenocarcinoma scheduled for distal gastrectomy. The final follow-up examination was performed May 1, 2024. Eligible participants were randomly assigned 1:1 to vagus nerve preservation distal gastrectomy (VPG) or vagus nerve resection distal gastrectomy (VRG). The primary outcome was the incidence of postsurgical gastroparesis. Secondary outcomes included postoperative gallstone formation, quality of life, morbidity, mortality, overall survival, and disease-free survival up to 12 months postoperatively. All analyses were based on both intention-to-treat and per-protocol analyses. Of 264 patients included in the intention-to-treat analysis, the median (IQR) patient age was 58.0 (52.0-67.0) years, and 67 patients (25.4%) were female. Both the VPG and VRG groups included 132 patients. Postoperative gastroparesis occurred in 1 patient (0.8%) in the VPG group and in 10 patients (7.6%) in the VRG group. Gallstones developed in 0 patients in the VPG group and in 9 patients (6.8%) in the VRG group. As assessed by mean (SD) score on the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, the VRG group experienced more nausea and vomiting at 6 months postsurgery (19.38 [7.62]) than the VPG group (17.15 [9.21]) (P = .03) and had significantly higher rates of persistent appetite loss, reflux symptoms, and eating difficulties at both 6 months and 12 months than the VPG group. Differences in postoperative complications and metastasis were not significant. Neurophysiologic monitoring and ICG labeling during distal laparoscopic gastrectomy for vagus nerve preservation in patients with early distal gastric cancer are safe and feasible. Preserving the perigastric vagus nerve may retain the function of the remnant stomach and improve quality of life. Chictr.org.cn Identifier: ChiCTR2200059489.

ASO Author Reflections: Prediction of Postoperative Liver Metastasis Risk in Resectable Gastroenteropancreatic Neuroendocrine Tumors Based on Readily Available Clinical Features.

ASO Author Reflections: Prediction of Postoperative Liver Metastasis Risk in Resectable Gastroenteropancreatic Neuroendocrine Tumors Based on Readily Available Clinical Features.

RBIO-06. STEREOTACTIC RADIOSURGERY ENHANCES T-CELL RECEPTOR REPERTOIRES AND INDUCES IMMUNOGENICITY IN BRAIN METASTASIS

Abstract BACKGROUND Brain metastasis is a frequent and deadly complication of systemic malignancy. The incidence rate is increasing and the prognosis remains poor, in contrast to recent advances in the management of systemic malignancy. Our previous work revealed an immunosuppressive microenvironment in brain metastasis and correlation between T-cell status and patient outcomes, shared across the primary tumor histologies. Therefore, we hypothesize that induction of immunogenicity has potential to improve brain metastasis patient outcome. METHODS Pre-operative stereotactic radiosurgery (SRS) (n = 44) and post-operative SRS (n = 47) brain metastasis specimens were collected from an ongoing clinical trial (MDACC protocol 2018-0552) designed to determine optimal timing of SRS for the treatment of brain metastasis. The patient materials were extracted DNA and RNA, and subjected to T-cell receptor (TCR) repertoire sequencing and mRNA-seq to interrogate radiation-induced immunogenicity. RESULTS In a preliminary analysis of the first 21 specimens, Gene Set Enrichment Analysis revealed that SRS significantly enhanced multiple immune-related signaling pathways including interferon response, along with apoptotic pathways, in brain metastasis. We also found that TCR signaling and PD-1 signaling was upregulated by radiotherapy. TCR repertoire analysis further identified increased density and diversity of TCRs induced by SRS treatment. Profiling of the remaining sample set is currently ongoing. CONCLUSIONS In light of our previous finding regarding the correlation between immune status and outcomes of patients with brain metastases, reversing immunosuppression in brain metastasis could be a key factor on patient prognosis and treatment. Our TCR repertoire and mRNA sequencing analyses with pre-operative and post-operative SRS brain metastasis cohorts support a role for radiation-induced immunogenicity, pointing to a prospective therapeutic approach for brain metastasis management.

Rare atypical type a thymoma: a case report and literature review

BackgroundAn atypical type A thymoma variant was recently added to the World Health Organization classification of type A thymoma in 2015. This novel form of type A thymoma presents with hypercellularity, increased mitotic activity, and necrosis. In particular, necrosis seems to be related to postoperative recurrence and metastasis, but the clinical significance of these changes still needs to be studied.Case presentationA 76-year-old man underwent thoracoscopic surgery for tumour resection due to an anterior mediastinal mass. Pathological examination revealed that the tumour invaded the surrounding thymic tissue. Cells were arranged in nest-like and whirl-like patterns, accompanied by prominent comedo-like necrosis, increased cell density, mild atypia, and a mitotic count of 4–6 per 10 high-power fields. Immunohistochemistry revealed positive expression of cytokeratin 19 and P63 in the tumour cells. Lymphocytes in the background were positive for CD3 and CD5, did not express terminal deoxynucleotide transferase, CD20, or CD117, and had an MIB-1 labelling index(LI) value of 15%. On the basis of these findings, the tumour was finally diagnosed as an atypical type A thymoma variant.ConclusionsWe report a case of atypical type A thymoma and review the literature to enhance our understanding of and provide accumulated pathological data on this rare disease.

Clinicopathological analysis of sclerosing haemangiomatoid nodular transformation of the spleen: analysis of three cases and a literature review

ObjectiveTo examine the clinicopathological features, immunohistochemical profiles, and differential diagnosis of sclerosing angiomatiod nodular transformation (SANT).MethodsThree cases of SANT of the spleen, diagnosed between 2014 and 2023 at the Affiliated Hospital of Zunyi Medical University, were analysed. Pathological features were assessed using haematoxylin and eosin staining, followed by immunohistochemistry with the EnVision system. Additionally, a review of relevant literature was conducted.ResultsThe study included one male and two female patients aged 40–55 years, with a median age of 47.5 years. All lesions were solitary, with tumour diameters ranging from 4 to 7.4 cm (mean 5.7 cm). Gross examination demonstrated that the masses were well-demarcated from the surrounding splenic tissue, with no evident capsule. The cut surfaces of the masses exhibited irregular, porcelain-white nodules that were tough in consistency, with some areas intermingling with splenic tissue. Microscopic examination revealed round or circular nodules comprising multiple slit-like or sinusoidal capillaries, separated by concentric collagen fibres. The nodules exhibited chronic inflammatory cell infiltration, calcification, haemosiderin deposition, and fibrous connective tissue with hyaline or mucoid changes. Immunohistochemical analysis demonstrated differential expression of markers, including cluster of differentiation (CD) 34, CD31, and CD8, within the sinusoidal nodule areas. Periodic acid-Schiff staining was positive for perinodular collagen deposits, while reticulin staining highlighted nodule profiles and intranodular vessels. None of the patients experienced postoperative recurrence or metastasis, and one patient was on aspirin for thrombocytosis.ConclusionSANT of the spleen is generally considered a rare, benign lesion with angioma-like characteristics. It exhibits exhibiting distinctive histomorphological features within the red pulp. Understanding the differential diagnosis is crucial to prevent missed or incorrect diagnoses.

CT assessment of liver fat fraction and abdominal fat composition can predict postoperative liver metastasis of colorectal cancer

ObjectiveThe aim of this study is to investigate the clinical value of liver fat fraction assessed by CT(CT-LFF) and abdominal fat components. We focus on predicting liver metastasis (LM) after colorectal cancer (CRC) surgery. MethodsClinical and imaging data from 79 patients who underwent radical CRC surgery between January 2019 and December 2021 were retrospectively collected. Semi-automatic software was used to quantify the area of different body tissues at the level of the third lumbar vertebra, and liver fat fraction was calculated based on the CT values. Patients were grouped according to BMI, tumor grade, T stage, N stage, vascular invasion (VI), perineural invasion (PNI), and preoperative levels of CEA and CA199. A multivariate logistic regression model was used to identify independent risk factors for early LM after surgery. The diagnostic performance was assessed using the receiver operating characteristic analysis with 5-fold cross-validation. The Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. ResultsThe study found that the occurrence of LM after CRC surgery was significantly associated with CA199 positivity, VI, PNI, N1-2 stage, CT-LFF, VAT index (VATI). Multivariate logistic regression analysis showed that CA199 positivity (OR = 7.659), N1-2 stage (OR = 6.394), CT-LFF (OR = 1.271), VATI (OR = 1.043) were independent risk factors for predicting LM after CRC surgery. The multivariate logistic regression model, constructed using these independent risk factors, demonstrated robust predictive performance across 5-fold cross-validations, with an average AUC of 0.898 (95 % CI: 0.828–0.969). Survival analysis showed a significant difference in liver metastasis-free survival rates between the high-risk and low-risk groups (P < 0.001). ConclusionCT-LFF and VATI assessed by CT are independent risk factors for predicting LM after CRC surgery. The multivariate prediction model combining CA199 and N stage shows high predictive performance.

Multicenter evaluation of CT deep radiomics model in predicting Leibovich score risk groups for non-metastatic clear cell renal cell carcinoma

BackgroundNon-metastatic clear cell renal cell carcinoma (nccRCC) poses a significant risk of postoperative recurrence and metastasis, underscoring the importance of accurate preoperative risk assessment. While the Leibovich score is effective, it relies on postoperative histopathological data. This study aims to evaluate the efficacy of CT radiomics and deep learning models in predicting Leibovich score risk groups in nccRCC, and to explore the interrelationship between CT and pathological features. Patients and MethodsThis research analyzed 600 nccRCC patients from four datasets, dividing them into low (Leibovich scores of 0–2) and intermediate to high risk (Leibovich scores exceeding 3) groups. Radiological model was developed from CT subjective features, and radiomics and deep learning models were constructed from CT images. Additionally, a deep radiomics model using radiomics and deep learning features was developed, alongside a fusion model incorporating all feature types. Model performance was assessed by AUC values, while survival differences across predicted groups were analyzed using survival curves and the log-rank test. Moreover, the research investigated the interrelationship between CT and pathological features derived from whole-slide pathological images. ResultsWithin the training dataset, four radiological, three radiomics, and thirteen deep learning features were selected to develop models predicting nccRCC Leibovich score risk groups. The deep radiomics model demonstrated superior predictive accuracy, evidenced by AUC values of 0.881, 0.829, and 0.819 in external validation datasets. Notably, significant differences in overall survival were observed among patients classified by this model (log-rank test p < 0.05 across all datasets). Furthermore, a correlation and complementarity were observed between CT deep radiomics features and pathological deep learning features. ConclusionsThe CT deep radiomics model precisely predicts nccRCC Leibovich score risk groups preoperatively and highlights the synergistic effect between CT and pathological data.

Serum non-high-density lipoprotein cholesterol predicts distant metastases following resection of stages I to III colorectal cancer.

The aim of this study was to examine the relationship between levels of non-high-density lipoprotein cholesterol (non-HDL-C) and postoperative distant metastasis for stages I to III colorectal cancer (CRC). Demographic, clinicopathological, and lipid data were collected from 588 patients, who were subsequently grouped according to their non-HDL-C levels. The primary endpoint was distant metastasis, survival without distant metastasis-free survival (DMFS). The association between non-HDL-C and pathological features, as well as postoperative distant metastasis, was assessed using a chi-square test, Mann-Whitney U test, and Cox proportional hazard regression model. The correlation between DMFS and non-HDL-C levels was analyzed employing the Kaplan-Meier method and log-rank test. The incidence of postoperative distant metastasis was significantly higher in the high non-HDL-C group (34.8%) compared to the low non-HDL-C group (18.2%) (P < .001). Non-HDL-C levels were significantly higher in the metastasis group than in the nonmetastasis group (P = .001). Multivariate Cox proportional hazards identified non-HDL-C ≥ 4.1mmol/L(HR: 2.604; 95% CI: 1.584-4.282; P = .001) as independent risk factors for postoperative distant metastasis. The high non-HDL-C group exhibited a higher rate of distant metastasis and a shorter duration of DMFS (HR: 2.133; 95% CI: 1.404-3.240; P < .001). Our study suggests that high levels of non-HDL-C (≥4.1 mmol/L) may potentially serve as predictors for postoperative distant metastasis in stages I to III CRC.

Mechanotransduction-Piloted Whole-Cell Vaccines for Spatiotemporal Modulation of Postoperative Antitumor Immunity.

Whole tumor cell vaccines hold promise by presenting a broader spectrum of autologous-origin tumor antigens to combat postoperative recurrence and metastasis. However, challenges such as intractable adjuvant modification and obscure interactions with antigen-presenting cells in the postoperative microenvironment impede their translation into effective personalized immunotherapies. In this study, we propose cancer vaccines derived from manganese oxide-immobilized resected tumor cells, featuring whole tumor antigens and adjustable stiffness to modulate interactions with antigen-presenting cells in the postoperative microenvironment. These vaccines effectively stimulate dendritic cell phagocytosis and function through sequential stiffness-mediated mechanotransduction and interferon signaling. We evaluated their efficacy using an orthotopic triple-negative breast cancer mouse model and found that combining the vaccines with radiotherapy effectively inhibits postoperative tumor recurrence and metastasis. Our study underscores the potential of utilizing mechanotransduced adjuvants alongside directly inactivated whole-cell vaccines as a universal solution for preventing postoperative tumor recurrence.

Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma

Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.

Pachymic acid promotes ferroptosis and inhibits gastric cancer progression by suppressing the PDGFRB-mediated PI3K/Akt pathway

Gastric cancer (GC) is a common malignant tumour with high incidence and mortality rates worldwide. Despite current treatment modalities, including surgical resection and chemotherapy, challenges such as postoperative recurrence, metastasis and drug resistance persist. Therefore, investigating the feasibility and mechanism of traditional Chinese medicine in treating gastric cancer is crucial for discovering new anti-gastric cancer drugs or adjuvant therapies. Pachymic acid (PA) is a natural triterpenoid found in the traditional Chinese medicinal herb Poria cocos (PC) (Schw. Wolf). Recent studies have reported its inhibitory effects on various cancer cells, including liver, cervical, breast and gastric cancer. Our in vitro and in vivo experiments confirmed that PA inhibits the proliferation, migration and invasion of gastric cancer cells. The treatment of gastric cancer cells with various death inhibitors revealed that PA may suppress gastric cancer progression by inducing ferroptosis. Malondialdehyde, Fe2+, reactive oxygen species and glutathione assays were performed to validate the effects of PA on ferroptosis in gastric cancer. High-throughput sequencing combined with analysis of the TCGA database identified PDGFRB as a potential downstream target of PA. In vivo experiments indicated that the PDGFRB overexpression could counteract the antitumour effects of PA, while ferroptosis induced by the PI3K/Akt signalling pathway may play a key role in this process. This study provides initial evidence that PA, through its interaction with PDGFRB, alters the PI3K/Akt signalling pathway, leading to ferroptosis in gastric cancer cells, thus manifesting its antitumour properties. This discovery holds promise for the development of novel therapeutic strategies for gastric cancer patients.

99mTc-FAPI-04 SPECT/CT outperforms contrast-enhanced CT in detecting metastasis in postoperative patients with colorectal cancer.

To compare the performance of 99mTc-FAPI-04 SPECT/CT and contrast-enhanced CT (CECT) in the detection of postoperative metastasis in patients with colorectal cancer (CRC). The postoperative patients with CRC were consecutively recruited from January 2023 to June 2023, and the enrolled patients completed 99mTc-FAPI-04 SPECT/CT imaging and CECT examination within two weeks. Histopathological analysis and the follow-up results were used as the reference criteria. The location and number of metastatic sites and the detection accuracy between the two imaging methods were compared. The tumor-to-background ratio (TBR) of liver metastasis and lymph node metastasis in 99mTc-FAPI-04 SPECT/CT imaging were also calculated for comparison. In total, 19 postoperative CRC patients, including 15 patients with metastasis, were included in this study. In the patient-based analysis, 99mTc-FAPI-04 SPECT/CT showed a significantly higher sensitivity for the detection of metastasis than CECT (93.3% vs. 80.0%, p = 0.038), but both techniques had the same specificity (100%, 4/4). For the lesion-based analysis, the detection rates of metastatic sites were 92.2% (47/51) and 72.5% (37/51) for 99mTc-FAPI-04 SPECT/CT and CECT, respectively, and the difference between them was statistically significant. In the diagnosis of liver metastasis and lymph node metastasis, 99mTc-FAPI-04 SPECT/CT both exceeded CECT. Additionally, the TBR in lymph node metastasis was higher than that in liver metastasis. The findings suggested that 99mTc-FAPI-04 SPECT/CT could detect metastasis more effectively than CECT, especially liver and lymph node metastases, in postoperative CRC patients.

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.