Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy.

BACKGROUND: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. METHODS: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. RESULTS: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. CONCLUSIONS: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Simultaneous uniportal video-assisted thoracic surgery for pulmonary nodules and synchronous mediastinal lesions.

INTRODUCTION: Video-assisted thoracic surgery (VATS) has been widely accepted in the diagnosis and treatment of thoracic diseases for the past three decades due to its small incision, minimal trauma, and rapid recovery after surgery. A growing number of patients with concurrent pulmonary nodules and mediastinal lesions have been detected. Simultaneous ipsilateral resection of coexisting lesions is a preferred procedure. AIM: To introduce our technique and preliminary experience in performing uniportal video-assisted thoracic surgery (VATS) for the simultaneous resection of pulmonary and mediastinal lesions. MATERIAL AND METHODS: We retrospectively analysed 8 consecutive patients who underwent simultaneous uniportal VATS resection of coexisting lesions of the lung and mediastinum in our centre. The clinical data were recorded and analysed. RESULTS: A total of 8 patients were enrolled, and all patients successfully underwent surgery through a single incision; no perioperative deaths occurred. The average single incision length was 3.9 ±0.3 cm, the operative time was 102.3 ±54.4 min, and the bleeding volume was 27.5 ±17.9 ml. The thoracic drainage time was 3.0 ±2.3 days, with a mean volume of 390.6 ±361.3 ml. The length of postoperative hospital stay was 4.0 ±1.9 (range: 3-9) days. No serious complications were observed in the hospital or during postoperative follow-up. CONCLUSIONS: Uniportal VATS is feasible and safe for the simultaneous resection of pulmonary and mediastinal lesions in selected patients and offers cosmetically pleasing incisions and promising clinical application prospects.

Exploration of Prognostic Biomarkers for Lung Adenocarcinoma Through Bioinformatics Analysis.

With the development of computer technology, screening cancer biomarkers based on public databases has become a common research method. Here, an eight-gene prognostic model, which could be used to judge the prognosis of patients with lung adenocarcinoma (LUAD), was developed through bioinformatics methods. This study firstly used several gene datasets from GEO database to mine differentially expressed genes (DEGs) in LUAD tissue and healthy tissue via joint analysis. Later, enrichment analysis for the DEGs was performed, and it was found that the DEGs were mainly activated in pathways involved in extracellular matrix, cell adhesion, and leukocyte migration. Afterward, a TCGA cohort was used to perform univariate Cox, least absolute shrinkage and selection operator method, and multivariate Cox regression analyses for the DEGs, and a prognostic model consisting of eight genes (GPX3, TCN1, ASPM, PCP4, CAV2, S100P, COL1A1, and SPOK2) was established. Receiver operation characteristic (ROC) curve was then used to substantiate the diagnostic efficacy of the prognostic model. The survival significance of signature genes was verified through the GEPIA database, and the results exhibited that the risk coefficients of the eight genes were basically congruous with the effects of these genes on the prognosis in the GEPIA database, which suggested that the results were accurate. Finally, combined with clinical characteristics of patients, the diagnostic independence of the prognostic model was further validated through univariate and multivariate regression, and the results indicated that the model had independent prognostic value. The overall finding of the study manifested that the eight-gene prognostic model is closely related to the prognosis of LUAD patients, and can be used as an independent prognostic indicator. Additionally, the prognostic model in this study can help doctors make a better diagnosis in treatment and ultimately benefit LUAD patients.

Uniportal video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery are feasible approaches with potential advantages in minimally invasive mediastinal lesions resection.

BACKGROUND: This study aims to identify the feasibility of uniportal video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) compared with multiportal VATS in the resection of mediastinal lesions. METHODS: Patients who underwent mediastinal lesion resection were enrolled and allocated to the uni-VATS, tri-VATS, and RATS groups according to the surgical approach. Propensity score-matched (PSM) analysis was performed between the VATS and RATS groups as well as the uni-VATS and tri-VATS groups. The operative and recovery parameters were compared. RESULTS: Totally, 274 patients were enrolled. There was no difference in the operative parameters among the groups. Compared with multiportal VATS, uniportal VATS and RATS had a significantly shorter chest tube placement time (2.43±0.88 vs. 1.78±1.22 vs. 2.21±1.11 days, P<0.001) and hospital length of stay (LOS) (4.07±1.75 vs. 3.27±1.05 vs. 3.62±1.21 days, P=0.001) without increasing the incidence rate of complications (5.6% vs. 7.2% vs. 5.7%, P=0.864). After PSM, the RATS group showed a significantly lower unplanned conversion rate than the VATS group (0.0% vs. 8.2%, P=0.041), while the uni-VATS group had a shorter chest tube placement time (1.83±1.20 vs. 2.35±0.86 days, P=0.013) and hospital LOS (3.23±1.03 vs. 3.95±2.00 days) than the tri-VATS group. CONCLUSIONS: Compared with multiportal VATS, uniportal VATS and RATS are technically safe and feasible with potential advantages for mediastinal lesion resection.

[Study on the Application of A New Type of Anhydrous Thoracic Negative Pressure Drainage Device in Patients after Thoracic Surgery].

BACKGROUND: After general thoracic surgery, a chest tube is usually placed for closed drainage to expel gas accumulation in the thoracic cavity and fluid accumulation to promote lung re-expansion. It can also be observed whether there is active bleeding after the operation and whether there is a pulmonary leak. The conventional drainage of the chest cavity is connected with a water-sealed drainage bottle, and the patient condition is judged by observing the drainage situation and the fluctuation of the water column, which is a very classic method. However, the water-sealed bottle has the disadvantages of being easy to overturn and inconvenient to carry, which is not conducive to the early activities of patients. Under the concept of accelerated rehabilitation, our center applied a new type of anhydrous thorax negative pressure drainage device and achieved good results. The purpose of this study was to observe the effect of a new type of anhydrous thoracic negative pressure drainage device in patients after thoracic surgery. METHODS: Retrospective analysis of patients who underwent lung surgery in the First Affiliated Hospital of Zhejiang University Medical College from January 2018 to December 2019, patients were divided into two groups. One group of patients used a traditional closed-chest drainage water-sealed bottle as a control group, and the other group used a new type of anhydrous negative-pressure drainage bottle as an experimental group. Patients' gender, age, hypertension, diabetes, smoking history, surgical incisions and surgical methods, and the length of hospital stay and postoperative hospital stay were calculated. RESULTS: There were no statistical differences in age, gender, comorbidities (hypertension, diabetes, smoking history), scope of surgery, and duration of surgery between the two groups of patients, but there were statistical differences in surgical incisions between the two groups of patients (P=0.01). We found that patients using the new waterless negative pressure drainage device were shorter than patients with water negative pressure drainage device in terms of postoperative hospital stay and total hospitalization time, and the difference was statistically significant (P=0.02, P=0.04). CONCLUSIONS: The new type of anhydrous thoracic negative pressure drainage device has a good effect on the rapid recovery and advancement after thoracic surgery.

LTB4 and montelukast in transplantation-related bronchiolitis obliterans in rats.

BACKGROUND: Lung transplantation is the only effective treatment for end-stage lung diseases. Bronchiolitis obliterans, which is known as non-infectious chronic lung allograft dysfunction (CLAD) in the new classification, is the greatest threat to long-term survival after lung transplantation. This study investigated the role of leukotriene B4 (LTB4) and montelukast in transplantation-related bronchiolitis obliterans and discussed the pathophysiological significance of LTB4 in chronic rejection. METHODS: Rats were randomly divided into an experimental group (montelukast), a positive control group (dexamethasone), and a blank control group (normal saline solution; NS). Each piece of trachea removed from a F344 rat was transplanted into a Lewis rat through a 5-mm incision at the episternum by subcutaneous embedding. The recipients were treated with gastric lavage with 3 mg/kg · d montelukast suspension, 1 mg/kg · d dexamethasone, and 1 mL/kg · d NS, respectively, in each group. On Day 28, peripheral blood was drawn to measure the white blood cell counts and plasma LTB4 levels. The donor specimens were stained by H-E and Masson, and their organizational structure and extent of fibrosis were visually assessed. The measurement data were compared using one-way analysis of variance, and the categorical data were compared using the chi-square test. A P value of less than 0.05 was considered to indicate statistical significance. RESULTS: The white blood cell counts of the montelukast, dexamethasone, and NS groups were (16.0 ± 4.2) × 109/L, (19.5 ± 11.6) × 109/L, and (25.8 ± 3.6) × 109/L; no statistical significance was found (P = 0.101). The concentrations of LTB4 were 2230 ± 592 pg/mL, 1961 ± 922 pg/mL, and 3764 ± 1169 pg/mL, and statistical significance was found between the NS group and each of the others (P = 0.009). The percentages of tracheal occlusion were 73.6% ± 13.8%, 23.4% ± 3.2%, and 89.9% ± 11.3%, and statistical significance was found among the three groups (P = 0.000). CONCLUSIONS: The study established a model to simulate bronchiolitis obliterans after clinical lung transplantation. Oral administration of montelukast reduced plasma LTB4 levels in rats and played a preventive role against tracheal fibrosis after transplantation. This suggests that LTB4 may be involved in bronchiolitis obliterans after pulmonary transplantation. This study indicates a new direction for research into the prevention and treatment of bronchiolitis obliterans after lung transplantation.

Bilateral thoracotomy for removal of uncommon postmediastinal multi-schwannomas.

Postmediastinal schwannoma is a kind of neurogenic tumor originating from the neuron sheath in the posterior mediastinum. In the majority of cases these tumors are located in the paravertebral sulcus and the incidence is similar in both sides of the thorax as single or multiple; however, multi-schwannomas involved in the bilateral postmediastinum are rare. We report a case of postmediastinal multi-schwannomas and discuss the clinical and surgical treatment. We are aware of no previously published reports on this rare condition.

Primary cardiac synovial sarcoma.

Synovial sarcomas are rare tumors and account for only 3% of cardiac malignancies. In this report, we present a case of a primary synovial sarcoma of the left ventricle.

Study of telomerase activity in pleural lavage fluid specimens in patients with non-small-cell lung cancer and its clinical significance.

OBJECTIVE: To detect telomerase activity in pleural lavage fluid specimens in patients with non-small-cell lung cancer (NSCLC) and to evaluate its clinical value. METHODS: From July 2005 to May 2007, 167 pleural lavage fluid specimens were obtained from 135 patients with NSCLC and 32 patients with benign lung tumour during operation. Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in these specimens. Pleural lavage cytology (PLC) analysis of the pleural lavage fluid specimens was used for comparison. All the above specimens were examined within 3h. RESULTS: The positive rate of telomerase activity and PLC in pleural lavage fluid from patients with NSCLC was 25.2% (34/135) and 8.1% (11/135), respectively, with a significant difference (P<0.05). Telomerase activity was detected in all 11 specimens with positive cytological examination. Telomerase activity was negative in all 32 patients with benign lung tumour. There was a significant relationship between telomerase activity and pleural extension, T level, N level as well as the clinical TNM (tumour, node, metastasis) stage of lung cancer. A significant association was found between positive telomerase activity and overall survival rate, even stage I survival rate. Multivariate Cox regression analysis demonstrated that telomerase activity, as well as PLC and the TNM stage were independent predictors of prognosis. CONCLUSION: Telomerase activity is a useful adjunct for cytological method in the diagnosis of pleural micro-metastasis and was related to prognosis in a patient with NSCLC.

Severe mitral valve insufficiency after transcatheter atrial septal defect closure with the amplatzer septal occluder: a device-related complication.

Atrial septal defect (ASD) is the one of the most common congenital cardiac diseases. Percutaneous device closure of the ASD has developed as an alternative to traditional surgical closure with a similar outcome, decreased surgical trauma, and shorter hospital stay. However, several complications have been reported. We now report a rare complication of late severe mitral insufficiency (MI) after a successful closure of a secundum ASD with an Amplatzer device. The potential mechanisms may be the continual traction of the oversized mismatched device on the root of the mitral annulus and the insufficient rim to the mitral annulus. The patient was sent for a surgical operation to remove the device, and the defect was closed. No MI was found at the one-year follow-up.

[Value of serum-vascular endothelial growth factor in the differential diagnosis of solitary pulmonary nodule].

OBJECTIVE: To evaluate serum-vascular endothelial growth factor (S-VEGF) in the differentiation of solitary pulmonary nodule (SPN). METHODS: Serum level of VEGF of 68 patients with SPN was measured by ELISA kit, and compared with the control group of 20 normal subjects. The nodules were diagnosed by operation and pathology. RESULTS: The median level of S-VEGF was 42.5 (range from 10 to 170) pg/ml in the control, 44 (range from 18 to 360) pg/ml in benign nodule group and 75 (range from 18 to 890) pg/ml in lung cancer group, with significant difference observed between the nodule group and control (P < 0.01), and between the lung cancer group and the benign nodule group (P < 0.05), but not between the benign nodule group and the control. In addition, when S-VEGF in different pathologic types of the limited number of lung cancer patients were compared, no significant difference was observed. CONCLUSION: S-VEGF is valuable in the differential diagnosis of solitary pulmonary nodule. An elevated S-VEGF level >or= 100 pg/ml in patients with SPN may strongly speak for a malignant nodule. Operation is suggested.