Nutrition and continuous nursing intervention following radical resection of esophageal cancer in a patient after liver transplantation: a case report.

Background: Reasonable nutritional intervention is very important to promote wound healing and rehabilitation in patients with radical esophagectomy for esophageal cancer. This report aims to summarize the experience of nutritional and continuous nursing intervention in a patient who underwent radical resection of esophageal cancer after liver transplantation, by testing a comprehensive approach to optimize nursing plans in similar clinical practice. We hope that the implementation of home enteral nutrition can improve the nutrition status and quality of life of postoperative patients. Case Description: A patient with liver transplantation was admitted to The Fourth Hospital of Hebei Medical University for postoperative care. The nursing intervention were subsequently summarized and analyzed. In July 2023, the patient successfully underwent radical resection for esophageal cancer. Following the operation, the patient received regular medication and on-site nutritional intervention with the consent of her family. At discharge, the prealbumin, albumin, total protein and hemoglobin values of the patient were low, and body weight was 91 kg. The patient's nutritional risk screening (NRS2022) score was 5 points, and the Patient-Generated Subjective Global Assessment (PG-SGA) score was 4 points. After discharge, the patient continued to receive family enteral nutrition treatment, dietary guidance and psychological nursing. A follow-up review conducted 4 weeks after discharge showed improvements in the patient's NRS2022, albumin, total protein, hemoglobin, and body weight. Conclusions: Strengthening postoperative nutritional intervention are vital for promoting rehabilitation in patients who undergo radical resection of esophageal cancer after liver transplantation.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

A retrospective analysis of lymph node dissection in Siewert II adenocarcinoma of the esophagogastric junction.

BACKGROUND: Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access. METHODS: The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed. RESULTS: The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058). CONCLUSION: Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.

FAM189A2 plays a tumour suppressor role in lung adenocarcinoma by influencing cell apoptosis, CXCR4 expression and tight junction proteins.

Transmembrane proteins play key roles in the development of lung cancer. The family with sequence similarity 189 member A2 (FAM189A2) gene encodes a transmembrane structural protein, yet its involvement in lung adenocarcinoma remains largely unexplored. This study elucidated its role in lung adenocarcinoma and its possible molecular mechanism. Our findings revealed diminished expression levels of FAM189A2 in LUAD tissues. Additionally, the activity of LUAD cells was significantly inhibited by overexpression of FAM189A2. Following FAM189A2 overexpression, the expression of OCLN and TJP2 was upregulated in LUAD cells, while CXCR4 expression experiences a notable decrease. Moreover, the coimmunoprecipitation experiment confirmed the direct interaction between FAM189A2 and CXCR4. The infiltration levels of T cells (CD4+ memory resting, CD8+, regulatory), NK cells, B memory cells, endothelial cells and cancer-associated fibroblasts were significantly correlated with FAM189A2 expression. These results indicate FAM189A2 may act as a tumour suppressor in LUAD through tight junction protein (TJP) and CXCR4 regulation. Moreover, FAM189A2 is significantly correlated with the immune microenvironment of LUAD, which may be involved in prognosis and immunotherapeutic efficacy.

Wilms' Tumor 1-Associating Protein Promotes Nonsmall-Cell Lung Cancer Through the Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5.

OBJECTIVES: This study aimed to analyze the functional roles and molecular mechanism of Wilms' tumor 1-associating protein (WTAP) in the tumorigenesis of nonsmall-cell lung cancer (NSCLC). METHODS: Retrospective analysis was used. Tumor tissues and surrounding nontumor tissues of 150 patients with NSCLS who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2016 to January 2018 were selected. The expression of WTAP in NSCLC tissues was detected by immunohistochemistry. Clinicopathologic parameters were then subjected to univariate and multivariate Cox regression analysis in purpose of uncovering the independent risk factors for overall survival time. MTS (3-[4,5-dimethylthiazol-zyl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazoliuzolium, inner salt) assay, colony formation assay, and transwell assays were performed to estimate cell proliferation, migration, and invasion. Meanwhile, the relationship between WTAP and the cell migration and invasion marker-related proteins were evaluated by Western blot analysis and RT-qPCR. WTAP expression was knocked-down in cell lines by shRNA, and RNA-Seq was performed to investigate the pathways regulated by WTAP. RESULTS: In NSCLC patients, WTAP was highly expressed in tumor tissues and the higher expression was significantly associated with poor overall survival (OS) (P<0.01). Compared with the control group in vitro, the overexpression of WTAP could significantly promote cell proliferation, migration, and invasion (P<0.01), while knock-down WTAP significantly reduces the above effects (P<0.01). In a mouse orthotopic implantation model, higher WTAP abundance could significantly promote tumor enlargement compared with the control group (P<0.01). Compared with the control group, the knock-down of WTAP significantly inhibit the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in cell lines (P<0.01). Besides, in NSCLC, knocked-down CEACAM5 significantly reduced the impact of WTAP on cell proliferation, migration, and invasion compared with the control group (P<0.05). CONCLUSIONS: This study suggests that high expression of WTAP was associated with poor clinical outcomes. CEACAM5 may play a synergistic role with WTAP to jointly promote NSCLC progression by enhancing cell proliferation, invasion, and migration.

Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Mechanistic Study of CRABP2: Accelerating Lung Cancer Migration and Metastasis through Regulation of the ROS/Src Signaling Pathway.

Objective: This study aims to establish a theoretical foundation for the clinical treatment of lung cancer by investigating the regulatory role of CRABP2 in the ROS/Src signaling pathway, specifically in accelerating the migration and metastasis of lung cancer. Methods: Lung cancer mouse models were established using BALB/c-nu mice, randomly assigned to the control group (NC group) and the experimental group (mimic group). Tumor volume was precisely observed. The impact of CRABP2 on lung cancer migration and metastasis was analyzed through hematoxylin and eosin (H&E) staining and histochemical staining observation. Protein expression analysis was employed to assess CRABP2, ESR1, NOX1, NOX4, p-Src, and p-FAK levels, shedding light on the underlying mechanism. CRABP2's influence on lung cancer migration and metastasis was further investigated using scratch and Transwell experiments. Results: The findings revealed that the mimic group, with enhanced CRABP2 expression, exhibited a higher proliferation rate and increased migration and metastasis capabilities in lung cancer. Protein expression analysis demonstrated that CRABP2 and ESR1 positively influenced the ROS/Src pathway, promoting lung cancer migration and metastasis. Scratch and Transwell's experiments supported the fact that CRABP2 significantly accelerated lung cancer migration and metastasis. Conclusions: CRABP2 plays a crucial role in expediting lung cancer migration and metastasis by upregulating ESR1 expression, consequently activating the ROS/Src pathway. This study introduces a novel therapeutic avenue for the clinical treatment of lung cancer, offering a theoretical framework for advancing lung cancer treatment strategies.

Oblique conformal anastomosis decreased the risks of cervical anastomotic leakage after totally minimally invasive esophagectomy.

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

Smart colloidal photonic crystal sensors.

Smart colloidal photonic crystals (PCs) with stimuli-responsive periodic micro/nano-structures, photonic bandgaps, and structural colors have shown unique advantages (high sensitivity, visual readout, wireless characteristics, etc.) in sensing by outputting diverse structural colors and reflection signals. In this review, smart PC sensors are summarized according to their fabrications, structures, sensing mechanisms, and applications. The fabrications of colloidal PCs are mainly by self-assembling the well-defined nanoparticles into the periodical structure (supersaturation-, polymerization-, evaporation-, shear-, interaction-, and field-induced self-assembly process). Their structures can be divided into two groups: closely packed and non-closely packed nano-structures. The sensing mechanisms can be explained by Bragg's law, including the change in the effective refractive index, lattice constant, and the order degree. The sensing applications are detailly introduced according to the analytes of the target, including solvents, vapors, humidity, mechanical force, temperature, electrical field, magnetic field, pH, ions/molecules, and so on. Finally, the corresponding challenges and the future potential prospects of artificial smart colloidal PCs in the sensing field are discussed.

Using molecular characteristics to distinguish multiple primary lung cancers and intrapulmonary metastases.

Objectives: Multiple lung cancers may present as multiple primary lung cancers (MPLC) or intrapulmonary metastasis (IPM) with variations in clinical stage, treatment, and prognosis. However, the existing differentiation criteria based on histology do not fully meet the clinical needs. Next-generation sequencing (NGS) may play an important role in assisting the identification of different pathologies. Here, we extended the relevant data by combining histology and NGS to develop detailed identification criteria for MPLC and IPM. Materials and Methods: Patients with lung cancer (each patient had ≥2 tumors) were enrolled in the training (n = 22) and validation (n = 13) cohorts. Genomic profiles obtained from 450-gene-targeted NGS were analyzed, and the new criteria were developed based on our findings and pre-existing Martini & Melamed criteria and molecular benchmarks. Results: The analysis of the training cohort indicated that patients identified with MPLC had no (or <2) trunk or shared mutations. However, 98.02% of mutations were branch mutations, and 69.23% of MPLC had no common mutations. In contrast, a higher percentage of trunk (33.08%) or shared (9.02%) mutations were identified in IPM, suggesting significant differences among mutated components. Subsequently, eight MPLC and five IPM cases were identified in the validation cohort, aligning with the independent imaging and pathologic distinction. Overall, the percentage of trunk and shared mutations was higher in patients with IPM than in patients with MPLC. Based on these results and the establishment of new determination criteria for MPLC and IPM, we emphasize that the type and number of shared variants based on histologic consistency assist in identification. Conclusion: Determining genetic alterations may be an effective method for differentiating MPLC and IPM, and NGS can be used as a valuable assisting tool.

SENP3 mediates the activation of the Wnt/ß-catenin signaling pathway to accelerate the growth and metastasis of oesophagal squamous cell carcinoma in mice.

As a common malignant tumor, esophageal squamous cell carcinoma (ESCC) is occasionally seen in clinical practice. This type of disease has low incidence rate and mortality. The post-translational modification of small ubiquitin like modifiers (SUMO) can play a crucial role in regulating protein function, and can significantly impact the occurrence and development of diseases. SUMO-specific peptidase (SENP) affects cell activity by regulating the biological function of SUMO. SENP3 belongs to the SENP family, and available data indicate that many malignancies are associated with SENPs, it is currently unclear its role in ESCC. This study indicates that there is a high level of SENP3 expression in ESCC tumor cells. If the expression level of this gene is high, it can have a significant impact on ESCC cell lines and affect physiological activities such as invasion of KYSE170 cells. If the gene is knocked out, this situation will not occur. There is also research data indicating that this gene can effectively activate related signaling pathways, thereby promoting the physiological activities of malignant tumor cells. In a nude mouse xenograft tumor model, KYSE170 cells with SENP3 expression knockdown induced a smaller volume and weight of tumor tissue. Therefore, it can be clearly stated that SENP3 can enable Wnt/ ß- The catenin signaling pathway is stimulated, which in turn affects the physiological activities of ESCC cells, including the invasion process. The results of this article lay the foundation for clinical staff to carry out clinical management.

Long Non-coding RNA X-Inactive Specific Transcript Promotes Esophageal Squamous Cell Carcinoma Progression via the MicroRNA 34a/Zinc Finger E-box-Binding Homeobox 1 Pathway.

BACKGROUND: The long non-coding RNA X-inactive specific transcript (XIST) plays a crucial role in transcriptional silencing of the X chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) regulation. AIMS: This study aimed to investigate the impact of XIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT pathway. METHODS: XIST and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. XIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm XIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse model. RESULTS: XIST and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. XIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to XIST and ZEB1. XIST knockdown suppressed xenograft tumor growth. CONCLUSION: XIST promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the XIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in ESCC.

Mitigating Effect of Matricin Against Benzo(a)pyrene-induced Lung Carcinogenesis in Experimental Mice Model.

BACKGROUND: Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. METHODS: Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. RESULTS: The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. CONCLUSION: The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kß pathway.

Heavy Metal Contamination Characteristics in Acid Soil-rice Systems and the Corresponding Human Health Risk in a Mining and Smelting Area in Jiangxi Province.

To understand the effects of mining activities on soil cadmium and rice, a typical mining area was selected. The Cd content in a considerable number of soils exceeded the standard limitation GB/T 36,783 - 2018, with a rate of 42.03%. Further analysis revealed soil total Cd content was strongly correlated with soil bioavailability of Cd (R2 0.721**), pH (R2 0.386**) and soil total content of lead(R2 0.678**). It suggests that soil total Cd content and soil pH significantly affect rice Cd levels, and that acid soil increases soil Cd bioavailability [Soil Cd (B)] and accumulation in rice grain. Furthermore, a mathematical dynamic fitting is developed to describe the relationship between rice Cd content, soil pH, and soil Cd bioavailability in acidic soil (pH 5-5.5). Rice Cd content (mg/kg) = - 179.2 + 67.24 × (Soil pH) - 12.81× [Soil Cd (B)] - 6.28 × 153(Soil pH) 2 + 65.79 × [Soil Cd (B)]2. This study identifies the main types of pollutants emitted by industrial activities and recommends Cd as the most concerning pollutant for rice planting and paddy soil.

A Drug-Drug Interaction Study to Evaluate the Impact of Simvastatin and Itraconazole on Erlotinib Pharmacokinetics in Rats by UPLC-MS/MS.

Aim: The goal of our study was to investigate the effects of single-dose simvastatin and itraconazole application on the pharmacokinetics of erlotinib in rats. Methods: Twenty-one male Sprague-Dawley rats were randomly divided into 3 groups, including erlotinib combined with simvastatin, erlotinib combined with itraconazole and erlotinib alone groups. The rats were given a single dose of 2 mg/kg simvastatin, 15 mg/kg itraconazole or 0.5% sodium carboxymethyl cellulose followed by 12 mg/kg erlotinib. The concentration of erlotinib in rat plasma was determined by UPLC-MS/MS. As internal standard, tinidazole was used for chromatographic analysis on the Kinetex C18 column (100×2.1 mm, 2.6 µm). Results: Erlotinib was validated in the calibration range of 5-1000 ng/mL. The lower limit of quantification (LLOQ) was 5 ng/mL. The inter- and intra-day precisions for erlotinib were less than 10.56%, and the accuracies were in the range of 98.61-104.99%. The validated UPLC-MS/MS method was successfully applied to this study. Compared with the erlotinib alone group, the values of AUC0-t, AUC0-∞, Cmax, Vz/F and t1/2 in the simvastatin group showed no statistical differences among pharmacokinetic parameters (P>0.05). However, the values of AUC0-t, AUC0-∞ and Cmax, in the itraconazole group were approximately 1.32-fold, 1.32-fold and 1.34-fold higher, and the CL/F was lower than those in the erlotinib alone group; the difference was statistically significant (P<0.05). Conclusion: Simvastatin had no significant effect on the pharmacokinetics of erlotinib, whereas co-administration of itraconazole considerably increased the exposure of erlotinib. Therefore, we should pay more attention to the potential drug-drug interaction to ensure safety in cancer patient treatment.

PCSK9 promotes tumor cell proliferation and migration by facilitating CCL25 secretion in esophageal squamous cell carcinoma.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves an important role in maintaining plasma cholesterol levels, and fatty acid metabolism is involved in the progression of various types of cancer. In the present study, the role of PCSK9 in the development of esophageal squamous cell carcinoma (ESCC) was investigated. PCSK9 expression was compared between ESCC and normal esophageal epithelial tissues using reverse transcription-quantitative PCR. In addition, the association between PCSK9 expression and clinical staging and prognosis was assessed by immunohistochemistry. The effects of PCSK9 overexpression or knockdown on cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. The invasion and migration of cancer cells was assessed using wound healing and Transwell assays. Western blotting was performed to evaluate changes in the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. ELISA was performed to detect the effects of PCSK9 on chemokine (C-C motif) ligand 25 (CCL25) secretion. The results revealed that PCSK9 was highly expressed in ESCC tissues compared with that in normal esophageal tissues, and the high expression of PCSK9 was associated with a poor prognosis. Furthermore, PCSK9 could promote the proliferation, migration and invasion of ESCC cells in vitro. Mechanistically, PCSK9 could promote EMT by secreting CCL25. In conclusion, patients with ESCC may benefit from a novel therapeutic strategy based on these findings.

Prediction model using risk factors associated with anastomotic leakage after minimally invasive esophagectomy.

Objective: To explore the risk factors of anastomotic leakage after minimally invasive esophagectomy (MIE) and to build a prediction model of the probability of postoperative anastomotic leakage. Methods: Clinical data of patients undergoing MIE, admitted in the Fourth Hospital of Hebei Medical University from March 2018 to March 2022, were retrospectively selected, and risk factors of anastomotic leakage after MIE were analyzed by univariate and multivariate logistic regression. A prediction nomogram model was established based on the independent risk factors, and its prediction effect was evaluated. Results: A total of 308 patients were included. Thirty patients had postoperative anastomotic leakage, with an incidence of 9.74%. Logistic regression analysis showed that age, postoperative delirium, pleural adhesion, postoperative pulmonary complications, high postoperative white blood cell count and low lymphocyte count were risk factors for postoperative anastomotic leakage. A nomograph prediction model was constructed based on these risk factors. The predicted probability of occurrence of the nomograph model was consistent with the actual probability of occurrence. The calculated C-index value (Bootstrap method) was 0.9609, indicating that the nomograph prediction model had a good discrimination ability. By drawing the receiver operating characteristic (ROC) curve, we showed that the area under the curve (AUC) of the nomograph prediction model was 0.9609 (95%CI: 0.937-0.985), which indicated a good prediction efficiency of the model. Conclusions: The nomograph prediction model based on the independent risk factors of anastomotic leakage after MIE can accurately predict the probability of postoperative anastomotic leakage.

Comparison of neoadjuvant immunotherapy versus routine neoadjuvant therapy for patients with locally advanced esophageal cancer: A systematic review and meta-analysis.

Background: The neoadjuvant use of immune checkpoint inhibitor combined with chemotherapy (nICT) or chemoradiotherapy (nICRT) in locally advanced esophageal cancer (EC) is currently an area of active ongoing research. Therefore, we carried out a comprehensive meta-analysis to compare the efficacy and safety of the new strategy with routine neoadjuvant strategy, which included neoadjuvant chemotherapy (nCT) and neoadjuvant chemoradiotherapy (nCRT). Patients and methods: MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library were included. And, all of them were searched for eligible studies between January, 2000 and February, 2023. The pathological complete response (pCR) and major pathological response (MPR) were primary outcome of our study. The second outcome of interest was R0 resection rate. Odds ratio (OR) and associated 95% CI were used as the effect indicators comparing the safety and efficiency of the neoadjuvant immunotherapy with the routine neoadjuvant therapy. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity. Results: There were eight trials with 652 patients were included in our meta-analysis. The estimated pCR rate was higher in the neoadjuvant immunotherapy group (OR =1.86; 95% CI, 1.25-2.75; I2 = 32.8%, P=0.166). The different results were found in the esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) subgroups, the estimated OR was 2.35 (95%CI, 1.00-2.72; I2 = 30.9%, P=0.215) in the EAC subgroup, and 2.35 (95% CI, 1.20-4.54; I2 = 45.3%, P=0.161) in the ESCC subgroup, respectively. The neoadjuvant immunotherapy also showed the advantage in the MPR rates (OR =2.66; 95% CI, 1.69-4.19; I2 = 24.3%, P=0.252). There was no obvious difference between the neoadjuvant immunotherapy and routine neoadjuvant therapy with respect to surgical resection rate, R0 resection rate, surgical delay rate; while more treatment-related adverse events were observed for the neoadjuvant immunotherapy for pneumonitis/pneumonia (OR=3.46, 95% CI, 1.31-9.16; I2 = 67.3%, P=0.005) and thyroid dysfunction (OR=4.69, 95% CI, 1.53-14.36; I2 = 56.5%, P=0.032). Conclusion: The pooled correlations indicated that the neoadjuvant immunotherapy (both nICT and nICRT) could significantly increase the rates of pCR and MPR, compared with routine neoadjuvant therapy (both nCT and nCRT) in the treatment of locally advanced EC. The neoadjuvant immunotherapy and routine neoadjuvant therapy were with acceptable toxicity. However, randomized studies with larger groups of patients need to performed to confirm these results. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020155802.

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC.

BACKGROUND: A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1-84.0% vs. 42.4-78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1-60.9% vs. 13.5-47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature. CONCLUSIONS: The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates. TRIAL REGISTRATION: Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. REGISTRATION NUMBER: NCT04460066.

CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma.

We aimed to explore the effect of CD39 expression on CD8+ T cells and on the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). The independent prognostic factors for the surgical specimens of the 95 ESCC patients were screened by multivariate Cox regression analysis. Differential gene expression analysis was performed by the NetworkAnalyst platform based on data from the Gene Expression Omnibus (GEO). The expression of CD39 on CD8+ T cells in the CK+ region was higher in cancer tissue than in paracancerous tissue (p = 0.011), and high CD39-expressing CD8+ T cells in the CK+ region (HR, 2.587; p = 0.033) and high CD39-expressing CD8+ T cells in the CK- region (HR, 3.090; p = 0.008) were independent risk factors for prognosis in ESCC patients; the expression of ENTPD1 was upregulated in ESCC tissues compared to normal tissues (adjusted p < 0.001; log2 fold change = 1.99), and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. High CD39-expressing CD8+ T cells can be used as a new molecular marker for the diagnosis and prognosis of ESCC, and the restoration of partially exhausted CD8+ T cells by inhibiting CD39 may be a new strategy for treating ESCC.