BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

As a new therapeutic strategy for esophageal cancer, immunotherapy has attracted more and more attention. The completed and ongoing clinical trials of immunotherapy for esophageal cancer confirm the great potential of immune checkpoint inhibitors in esophageal cancer. Future research will focus on the combination of immunotherapy with existing or new therapeutic modalities and the identification of populations likely to benefit from immunotherapy.

Objective:To evaluate the efficacy of unilateral biportal endoscopy (UBE) in the treatment of central lumbar spinal stenosis.Methods:The retrospective case-control study was conducted. 36 patients with central lumbar spinal stenosis were treated by unilateral dual channel spinal endoscopy who underwent Beijing Mentougou District Hospital from November 2019 to September 2021 were collected. There were 19 males and 17 females, including 11 cases of L 5-S 1, 19 cases of L 4-L 5 and 6 cases of L 3-L 4; The age was (70.0±3.9) years old, and ranged from 55 to 82 years old. The observation indicators: the changes of dural sac area in lumbar magnetic resonance cross-section before and after surgery, and the improvement of visual analogue of pain (VAS) score and Oswestry dysfunction index (ODI) before and after surgery in 1, 3, 6, and 12 months, as well as the occurrence of complications. Measurement data with normal distribution were represented as mean±standard deviation ( ± s), and comprison between groups was conducted using the t test; Comprison between groups of count data was conducted using the chi-square test or Fisher exact probability. Results:Postoperative MRI showed that the area of the transverse dural sac increased from (65.5±6.7) mm 2 before operation to (173.5±5.5) mm 2 after operation after the removal of the ligamentum flavum ( P<0.05). The follow-up of 36 patients for 12 months after operation showed that the VAS score decreased from (8.5±2.0) scores to (1.3±0.8) scores, and the ODI decreased from (59.3±12.3)% to (13.6±1.6)%( P<0.05). No complications such as nerve injury, cerebrospinal fluid leakage and infection related to operation occurred in 36 patients. Conclusions:Unilateral biportal endoscopy is one of the safe and effective treatment methods in the treatment of central lumbar spinal stenosis, with obvious improvement in symptoms, and the increase in the area of the spinal dural sac. It can obtain good early clinical effects.

Objective:To establish an in vivo model of acute radiation esophagitis in Wistar rats based on a small animal precision radiotherapy platform (SARRP). Methods:Thirty-six Wistar rats were randomly divided into control group, 40, 60 and 75 Gy groups. Based on MRI images, the esophageal target area of rats was outlined and the radiotherapy plan was formulated. The rats were respectively irradiated with 0, 8, 12 and 15 Gy per day for 5 consecutive days. The changes of body weight, food intake, esophageal pathology and magnetic resonance imaging were observed.Results:The body weight of rats in 75 Gy group decreased significantly on the 6th day after irradiation (IR) ( P<0.05). The esophageal tissue of rats in each IR group was thicker than that in control ( F = 14.20, P < 0.05). HE staining showed that the formation rate of radiation-induced esophagitis in 40 Gy and 60 Gy groups were 4/5 and 5/5, respectively, mainly mild. In 75 Gy group, the incidence of radiation-induced esophagitis approached to 5/5, of which 3/5 was severe at 9 d post-IR. The pathological injury scores [ M( Q1, Q3)] of rats in each group were 0, 1.0 (0.5, 2.5), 1.0 (1.0, 2.5) and 4.0 (1.5, 6.0) on the 9th day after IR. There was significant difference between the 75 Gy group and the control group ( H=12.69, P<0.05). After dynamic monitoring of neck MRI images, it was found that the esophageal signal of rats in each IR group increased and widened at 9 d post-irradiation. Conclusions:The animal model of acute radiation-induced esophagitis in rats was successfully established based on a small animal precision radiotherapy platform combined with MRI. 75 Gy was the best irradiation dose and the 9th day was the best observation time point.

Objective: To analyze the effect of epigallocatechin-3-gallate (EGCG) in radiation induced esophagitis of model rabbit. Methods: Thirty male New Zealand rabbits were randomly divided into EGCG group, saline group, blank group. The rabbits in EGCG and saline groups were irradiated with 6 MV X-rays. The blank group did not receive radiation. After irradiation, rabbits were given with 440 μmol/L EGCG or saline three times a day in continuous 5 days. The scores of pathological changes of esophagus were observed by optical microscope.The serum levels of interleukine-1 beta (IL-1β), interleukine-6 (IL-6), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay. The expression levels of 67KD laminin receptor (67LR) was detected by immunohistochemistry. Results: After treatment, the scores of pathological changes of esophagus in blank group, saline group, EGCG group were 0, 3.9±1.10 and 2.80±0.92, respectively. At different time points after drug treatment, the levels of serum inflammatory factors among three groups were significantly different (F=23.66-236.32, P<0.05). The expressions of 67LR in esophageal tissue of 3 groups were also significantly different (F=585.38, P<0.05). Conclusions EGCG reduced radiation-induced esophagitis in rabbits by decreasing the levels of serum inflammatory factors, which may be related to the expression of 67LR protein.

Radiation therapy and immune checkpoint inhibitors(ICI) have a synergistic effect on anti-tumor,which involves a series of complex mechanisms of effects with the immune system,and can improve the clinical outcomes of cancer patients.However,the mechanism by which radiation therapy combined with ICI synergistically modulates the immune response may also trigger treatment-related adverse events.In view of the increasing number of clinical studies and practices of combination therapy,it is necessary to pay attention to the risk of adverse events in combination therapy of radiotherapy and ICI,so as to evaluate the safety of combination therapy.

Objective To investigate the influence of enteral nutrition on body weight,nutritional status,treatment toxicities,and short-term outcomes in esophageal carcinoma patients treated with concurrent chemoradiotherapy(CCRT). Methods Eligible esophageal carcinoma patients were randomly assigned(2:1) to receive either CCRT combined with enteral nutrition (study group) or CCRT alone (control group). The primary endpoint was changes in the body weight during and after radiotherapy. The secondary endpoints were nutrition-related hematological parameters,the toxicities of chemoradiotherapy,the completion rate of treatment,and short-term outcomes. The differences was using χ2 or t-test. Results Between September 2014 and June 2017,203 patients were included in the study,consisting of 139 patients in the study group and 64 patients in the control group. Compared with the control group,the study group had significantly less body weight loss during and after radiotherapy (P<0.05) and significantly less decreases in serum albumin and hemoglobin (P<0.05),but there was no significant difference in the reduction in total lymphocyte count between the two groups (P>0.05).The study group had significantly lower incidence rates of grade ≥3 myelosuppression and infection and a significantly higher completion rate of chemoradiotherapy compared with the control group (P<0.05).The incidence of radiation pneumonitis and esophagitis showed no significant difference between the two groups (P>0.05).The study group had an insignificantly higher objective response rate than the control group (P>0.05). Conclusions For esophageal carcinoma patients treated with CCRT,enteral nutrition can reduce body weight loss during and after radiotherapy,improve nutritional status and treatment tolerance,and reduce toxicities.

Radiotherapy is one of the important cancer therapy methods that can lead to tissue damage including radiation lung injury,radiation esophageal injury,radiation skin damage and abnormal changes in hemopoietic system and immune system.Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea.It has been demonstrated that EGCG has biological effects of antiinflammatory,antioxidant,anti-apoptosis and regulating immunity.Recently some studies of cell and animal models suggest that EGCG has radioprotective effect,but few clinical research was reported.In this review,the studies about EGCG in preventing and treating radiation injury were summarized from antiradiation mechanism in order to enhance the understanding of the potential clinical application of EGCG.

The microorganism in human body is related to human health and disease,which plays a significant role in the exclusion of pathogen invading,participation of immune regulation and occurrence and development of the tumors.Studies have indicated that dysbacteriosis is often detected in cancer patients;especially,enteric dysbacteriosis can promote the occurrence and development of the tumors by influencing homeostatic balance of intestinal tract,gut metabolite and immunological function.Moreover,proportion detection of intestinal flora can be used as a non-invasive screening method and a diagnostic indicator for early detection of the malignant neoplasms.This review summarizes the recent studies on the associations of intestinal flora with human diseases and the possible mechanisms causing tumorigenesis,which may provide a novel research paradigm for cancer prevention and treatment.