Esophageal cancer (EC) is one of the most common malignant tumors in China. EC is characterized by a poor clinical prognosis, with many patients being diagnosed at advanced stages. This study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical features, treatment, and prognostic factors of patients with distant metastatic EC were screened and analyzed, and a nomogram was drawn to construct a predictive model. Eligible patients with distant metastatic EC diagnosed from January 2004 to December 2015 were extracted from the SEER database. Propensity score matching (PSM) was used to eliminate group baseline differences.The data were divided into the training cohort (1116 cases) and validation cohort (426 cases) by using R software and random sampling function at the ratio of 7:3. The baseline table was plotted using Chi-square test or Fisher's exact test. Kaplan-Meier curve, log-rank test, and Cox regression were used for survival analysis. C-index and AUC were used to evaluate the performance of the prognosis model. The calibration curve was used to evaluate the calibration of the model. Using the data of the validation cohort, external validation is used to create a prediction model. After applying the inclusion and exclusion criteria and PSM, a total of 1542 cases diagnosed between 2004 and 2015 were included in the study. We analyzed the Kaplan-Meier survival of patients with metastatic EC before and after PSM, focusing on different treatment methods. The results indicated that radiotherapy, chemotherapy, and surgical treatment provided significant survival benefits to patients with metastatic EC(P < 0.05). Univariate and Multivariate regression analysis showed that T-stage, M-stage, primary site, surgery, chemotherapy, and radiotherapy were independent prognostic factors affecting the prognosis of distant metastatic EC (P < 0.05). Evaluating the predictive ability of the nomogram, the C index of the training cohort was 0.69 (95% CI 0.67-0.71), and the C-index of the validation cohort was 0.659 (95% CI 0.627-0.693)0.6606 patients met the inclusion criteria and were enrolled in the study's external validation group. In this group, the AUC values of our external validation model for 1-, 2-, and 3-year overall survival (OS) were 0.775 (95% CI 0.762-0.787), 0.790 (95% CI 0.744-0.807). The C-index was 0.726. The AUC values for both the training and validation cohorts for the 1-year OS ranged from 0.50 to 0.70, and the AUC for the rest of the training and validation cohort ranged from 0.70 to 0.90, which suggests that the model is moderately discriminating. The calibration curves of 1 year, 2 years, and 3 years in the two groups are very close to the 45° reference line, suggesting that the models exhibit a good degree of calibration. The C-index, the AUC, and calibration curves suggest that the models have good discriminating and calibration. The results reveal that the T stage, M stage, primary tumor site, surgery, chemotherapy, and radiotherapy play an important role in influencing the treatment effect and prognosis of patients. The nomogram prediction model, which is based on these independent risk factors, shows good discriminative ability and calibration.

PurposeThis study aimed to develop and validate a clinicopathological model to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and identify key prognostic factors.MethodsThis retrospective study analyzed data from 279 breast cancer patients who received NAC at Zhejiang Provincial People’s Hospital from 2011 to 2021. Additionally, an external validation dataset, comprising 50 patients from Lanxi People’s Hospital and Second Affiliated Hospital, Zhejiang University School of Medicine from 2022 to 2023 was utilized for model verification. A multivariate logistic regression model was established incorporating clinical, ultrasound features, circulating tumor cells (CTCs), and pathology variables at baseline and post-NAC. Model performance for predicting pCR was evaluated. Prognostic factors were identified using survival analysis.ResultsIn the 279 patients enrolled, a pathologic complete response (pCR) rate of 27.96% (78 out of 279) was achieved. The predictive model incorporated independent predictors such as stromal tumor-infiltrating lymphocyte (sTIL) levels, Ki-67 expression, molecular subtype, and ultrasound echo features. The model demonstrated strong predictive accuracy for pCR (C-statistics/AUC 0.874), especially in human epidermal growth factor receptor 2 (HER2)-enriched (C-statistics/AUC 0.878) and triple-negative (C-statistics/AUC 0.870) subtypes, and the model performed well in external validation data set (C-statistics/AUC 0.836). Incorporating circulating tumor cell (CTC) changes post-NAC and tumor size changes further improved predictive performance (C-statistics/AUC 0.945) in the CTC detection subgroup. Key prognostic factors included tumor size >5cm, lymph node metastasis, sTIL levels, estrogen receptor (ER) status and pCR. Despite varied pCR rates, overall prognosis after standard systemic therapy was consistent across molecular subtypes.ConclusionThe developed predictive model showcases robust performance in forecasting pCR in NAC-treated breast cancer patients, marking a step toward more personalized therapeutic strategies in breast cancer.

Purpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET. Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively. Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000). Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68-2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37-3.68, p = 0.799). 65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with aggressive clinicopathological features and more tend to have distant metastasis rather than nodal involvement or local relapse. ER+/PR-/HER2- early BC did not seem to benefit from adjuvant ET.

In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is downregulated in LUAD and downregulation of tRF-29-79 is associated with poorer prognosis. In vivo and in vitro assay reveal that tRF-29-79 inhibits proliferation, migration and invasion of LUAD cells. Mechanistically, we discovered that tRF-29-79 interacts with the RNA-binding protein PTBP1 and facilitates the transportation of PTBP1 from nucleus to cytoplasm, which regulates alternative splicing in the 3' untranslated region (UTR) of SLC1A5 pre-mRNA. Given that SLC1A5 is a core transporter of glutamine, we proved that tRF-29-79 mediate glutamine metabolism of LUAD through affecting the stability of SLC1A5 mRNA, thus exerts its anticancer function. In summary, our findings uncover the novel mechanism that tRF-29-79 participates in glutamine metabolism through interacting with PTBP1 and regulating alternative splicing in the 3' UTR of SLC1A5 pre-mRNA.

Background:Tracheo-carinal resection and reconstruction in cases of extensive malignant tumors present a significant surgical challenge, often complicated by high anastomotic tension and potential for incomplete anastomosis. Case Description:We report on a 45-year-old male with a primary adenoid cystic carcinoma. The tumor was about 3 cm in size and invaded about 1 cm of the lower trachea, 2 cm of the left main bronchus (LMB), and 1 cm of the right main bronchus (RMB), blocking about 70% of the tracheal lumen, 90% of the LMB, and 50% of the RMB. Resection of the lower trachea and part of the LMB and RMB was performed via the right chest. We used the right main bronchial flap as a bridge, suturing it separately to the lower tracheal segment and the LMB, thereby completing the carinal reconstruction. This technique was crucial for bridging the defect between the trachea and LMB, which was impossible to anastomose directly due to the tumor's extensive involvement. The elliptical-shaped lingual flap from the RMB provided a stable and tension-free foundation for the reconstruction, overcoming the limitations of conventional methods. Conclusions:The novel carinal reconstruction technique demonstrated a reliable alternative for complex tracheo-carinal defects, ensuring tension-free anastomosis and complete tumor resection with clear margins.

Complications often arose after polyacrylamide hydrogel (PAAG) injections for breast augmentation. This study aimed to explore the complications and clinical management of breast augmentation with PAAG. We retrospectively analyzed the data of 135 patients who underwent breast PAAG removal from January 2011 to December 2023 in our hospital. We also comprehensively analyzed the postoperative clinical results, subsequent complications, and clinical management after PAAG injections. Induration and nodules (60.0 www.springer.com/00266

The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold tumor categorization based on the abundance of intra-tumoral immune cells. By incorporating the spatial immune contexture, the tumor immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, the mechanisms underlying these different immune phenotypes are yet to be comprehensively elucidated. In this review, we discuss how tumor cells and the tumor microenvironment interact collectively to shape the immune landscape from the perspectives of tumor cells, immune cells, the extracellular matrix, and cancer metabolism, and we summarize potential therapeutic options according to distinct immunophenotypes for personalized precision medicine.

Tumor spread through air spaces (STAS) is a distinctive metastatic pattern affecting prognosis in lung adenocarcinoma (LUAD) patients. Several challenges are associated with STAS detection, including misdetection, low interobserver agreement, and lack of quantitative analysis. In this research, a total of 489 digital whole slide images (WSIs) were collected. The deep learning-based STAS detection model, named STASNet, was constructed to calculate semi-quantitative parameters associated with STAS density and distance. STASNet demonstrated an accuracy of 0.93 for STAS detection at the tiles level and had an AUC of 0.72-0.78 for determining the STAS status at the WSI level. Among the semi-quantitative parameters, T10S, combined with the spatial location information, significantly stratified stage I LUAD patients on disease-free survival. Additionally, STASNet was deployed into a real-time pathological diagnostic environment, which boosted the STAS detection rate and led to the identification of three easily misidentified types of occult STAS.

This case report presents an incident of spontaneous migration of a peripherally inserted central catheter (PICC) into the azygos vein, leading to accidental transection during surgery. A patient with esophageal cancer had a PICC placed in the left upper arm one day prior to surgery, with the catheter tip confirmed by intracavitary electrocardiogram (IC-ECG) and anterior/lateral chest X-ray imaging. However, during the surgery, the PICC was unintentionally cut when the surgeon isolated and clamped the azygos vein. The surgical team removed the catheter and re-sutured the azygos vein remnant, introducing avoidable risks. This report analyzes the spontaneous migration of the PICC to the azygos vein and explores possible contributing factors to this incident.

Despite being the leading cause of lung cancer-related deaths, the underlying molecular mechanisms driving metastasis progression are still not fully understood. Transfer RNA-derived fragments (tRFs) have been implicated in various biological processes in cancer. However, the role of tRFs in lung adenocarcinoma (LUAD) remains unclear. Our study identified a tRF, tRF-Val-CAC-024, associated with the high-risk component of LUAD, through validation using 3 cohorts. Our findings demonstrated that tRF-Val-CAC-024 acts as an oncogene in LUAD. Mechanistically, tRF-Val-CAC-024 was revealed to bind to aldolase A (ALDOA) dependent on Q125/E224 and promote the oligomerization of ALDOA, resulting in increased enzyme activity and enhanced aerobic glycolysis in LUAD cells. Additionally, we provide preliminary evidence of its potential clinical value by investigating the therapeutic effects of tRF-Val-CAC-024 antagomir-loaded lipid nanoparticles (LNPs) in cell-line-derived xenograft models. These results could enhance our understanding of the regulatory mechanisms of tRFs in LUAD and provide a potential therapeutic target.

Hormone receptor-positive breast cancer (HR+ BC) is known to be relatively insensitive to chemotherapy, and since chemotherapy has remained the major neoadjuvant therapy for HR+ BC, the undetermined mechanism of chemoresistance and how chemotherapy reshapes the immune microenvironment need to be explored by highthroughput technology. By using single-cell RNA sequencing and multiplexed immunofluorescence staining analysis of HR+ BC samples (paired pre- and post-neoadjuvant chemotherapy (NAC)), the levels of previously unrecognized immune cell subsets, including CD8+ T cells with pronounced expression of T-cell development (LMNA) and cytotoxicity (FGFBP2) markers, CD4+ T cells characterized by proliferation marker (ATP1B3) expression and macrophages characterized by CD52 expression, were found to be increased post-NAC, which were predictive of chemosensitivity and their antitumor function was also validated with in vitro experiments. In terms of immune checkpoint expression of CD8+ T cells, we found their changes were inconsistent post-NAC, that LAG3, VSIR were decreased, and PDCD1, HAVCR2, CTLA4, KLRC1 and BTLA were increased. In addition, we have identified novel genomic and transcriptional patterns of chemoresistant cancer cells, both innate and acquired, and have confirmed their prognostic value with TCGA cohorts. By shedding light on the ecosystem of HR+ BC reshaped by chemotherapy, our results uncover valuable candidates for predicting chemosensitivity and overcoming chemoresistance in HR+ BC.

Table. S4. Characteristics of the patient samples and basic information.

Table. S3. List of primers used in this study.

Fig. S3. CD24hiCD27+ Bregs induce epithelial-mesenchymal transition and stemness of BC cells.

Small extracellular vesicles (sEVs) are essential mediators of intercellular communication within the tumor microenvironment (TME). Although the biological features of sEVs have been characterized based on in vitro culture models, recent evidence indicates significant differences between sEVs derived from tissue and those derived from in vitro models in terms of both content and biological function. However, comprehensive comparisons and functional analyses are still limited. Here, we collected sEVs from breast cancer tissues (T-sEVs), paired normal tissues (N-sEVs), corresponding plasma (B-sEVs), and tumor organoids (O-sEVs) to characterize their transcriptomic and proteomic profiles. We identified the actual cancer-specific sEV signatures characterized by enriched cell adhesion and immunomodulatory molecules. Furthermore, we revealed the significant contribution of cancer-associated fibroblasts in the sEV network within the TME. In vitro model-derived sEVs did not entirely inherit the extracellular matrix- and immunity regulation-related features of T-sEVs. Also, we demonstrated the greater immunostimulatory ability of T-sEVs on macrophages and CD8+ T cells compared to O-sEVs. Moreover, certain sEV biomarkers derived from noncancer cells in the circulation exhibited promising diagnostic potential. This study provides valuable insights into the functional characteristics of tumor tissue-derived sEVs, highlighting their potential as diagnostic markers and therapeutic agents for breast cancer.

ObjectiveWe aim to explore the clinicopathological features associated with axillary node response and recurrence in breast cancer patients undergoing neoadjuvant treatment (NAT).MethodsWe retrospectively reviewed the medical records of 486 stage I to III breast cancer patients who received NAT and surgery between 2016 and 2021.ResultsA total of 486 cases were reviewed and 154 (31.7%) patients achieved breast pathological complete response (pCR) (ypT0/Tis). Of the 366 cases with initially cN+, 177 (48.4%) cases reach ypN0. Breast pCR is in high accordance to axillary pCR (81.5%). Hormone receptor (HR)-/HER2+ breast cancer patients have the highest axillary pCR rate (78.3%). Patients achieve axillary pCR have a significantly better disease-free survival (DFS) (P=0.0004). Further analysis reveals that the DFS of ypN0 and ypN1 cases are similar (P=0.9049). Moreover, DFS in patients with ypN0 (P<0.0001) and ypN1 (P<0.0001) is significantly better than that in patients with ypN2-3. For post-mastectomy ypN0 cases, radiation could only improve DFS in patients with initially cN+ stage (P=0.0499). Multivariate Cox regression analysis shows that radiation is an independent factor to improve DFS (Hazard ratio (HR): 0.288(0.098-0.841), P=0.0230). Radiation does not improve DFS in pre-cN0/ypN0 patients (P=0.1696).ConclusionAxillary pCR rate is higher than breast pCR rate. HR-/HER2+ patients have the highest axillary pCR rate. Axillary pCR is associated with better DFS. Radiation could further improve DFS in ypN0 patients with initially positive nodal disease.

Classification of histological patterns in lung adenocarcinoma (LUAD) is critical for clinical decision‐making, especially in the early stage. However, the inter‐ and intraobserver subjectivity of pathologists make the quantification of histological patterns varied and inconsistent. Moreover, the spatial information of histological patterns is not evident to the naked eye of pathologists.

Fig. S12. The addition of anti-PD1/PD-L1 to neoadjuvant chemotherapy improves the pCR rate of patients with mLNs.

According to the diverse cellular morphology, lung adenocarcinoma (LUAD) was classified into five pathological subtypes, referred to as follows: High-risk group (micropapillary and solid), intermediate-risk group (acinar and papillary) and low-risk group (epidic). Nevertheless, little is known about the biological function of long non-coding RNA (lncRNA) in the molecular determination of LUAD histologic patterns. Screening the transcriptional expression data from TCGA-LUAD, the differentially expressed lncRNA across the divergent pathological subtypes were explored. Pan-cancer analysis revealed the characteristic of FAM83A-AS1, which was also confirmed in the LUAD tissues. The function of FAM83A-AS1 was uncovered through the in vitro assays. RNA immunoprecipitation and dual-luciferase reporter assays were performed to explore the molecular mechanisms of FAM83A-AS1. In the present study, it was identified that the expression of FAM83A-AS1 was increased from the low-risk group to the high, which was associated with a poorer prognosis and higher risk of recurrence. Pan-cancer analysis revealed that FAM83A-AS1 was positively correlated with high tumor mutational burden. Additionally, FAM83A-AS1 promoted cell migration, invasion and growth of LUAD cancer cells. Mechanistically, FAM83A-AS1 sponged miR-202-3p to regulate the expression of hexokinase II (HK2) in post-transcription, which facilitated the malignancy and glycolysis. The present study uncovered the biological roles of FAM83A-AS1/miR-202-3p/HK2 axis in regulating malignancy and glycolysis of LUAD, which provided novel avenues to addressing the determination of histologic patterns.

Fig. S11. Anti-PD-L1 treatment attenuates the activation of B cells and improves the treatment response rate of mLNs.