Clinical significance of baseline Epstein-Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations.

OPINION STATEMENT: The MET exon 14 skipping mutation is found in approximately 3% of lung adenocarcinomas and slightly more than 2% of lung squamous cell carcinomas. In recent years, more and more evidence has shown that MET inhibitors have achieved good anti-tumor effect in patients with MET exon 14 skipping mutation, suggesting that MET exon 14 skipping mutation may be a new target for NSCLC patients. Patients with positive MET exon 14 skipping mutation are recommended to be administered MET inhibitors, and crizotinib is recommended by the NCCN guideline. Due to the presence of gene amplification, second site mutation, bypass activation, and pathological type transformation, one of the inevitable problems of targeted therapy is drug resistance. If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.

Mutation Profile of Resected EGFR-Mutated Lung Adenocarcinoma by Next-Generation Sequencing.

BACKGROUND: The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: Mutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with EGFR mutations using targeted next-generation sequencing. Co-mutation profiles were systematically analyzed. RESULTS: Rare EGFR alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in EGFR exon 20 that could confer resistance to first-generation TKIs. Ninety-one percent of patients harbored at least one co-mutation in addition to the major EGFR mutation. TP53 was the top mutated gene and was found more frequently mutated at later stage. Markedly, NF1 mutations were found only in stage II-III ADCs. Conversely, RB1 mutations were more frequent in stage I ADCs, whereas APC mutations were observed exclusively in this group. Thirty-four percent of patients with EGFR TKI-sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as PIK3CA, BRCA1, and NOTCH1. CONCLUSION: Operable lung ADCs with EGFR TKI-sensitizing mutations are associated with a high proportion of co-mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy. IMPLICATIONS FOR PRACTICE: The efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring EGFR mutation after surgical resection is still under debate. Next-generation sequencing of 416 cancer-relevant genes in 139 resected lung cancers revealed the co-mutational landscape with background EGFR mutation. Notably, the study identified potential EGFR TKI-resistant mutations in 34.71% of patients with a drug-sensitizing EGFR mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients.

Oxidized low density lipoprotein receptor 1 promotes lung metastases of osteosarcomas through regulating the epithelial-mesenchymal transition.

BACKGROUND: Oxidized low density lipoprotein receptor 1 (OLR1), a type II membrane protein, has been identified as receptor for oxidized low-density lipoprotein. The current study firstly provided evidence that OLR1 regulated EMT and thus promoted lung metastases in osteosarcoma (OS). METHOD: All relevant experiments were conducted according to the manufacturer's protocols. In vivo tumor xenograft experiments were carried out in 6- to 16-week-old mice, then maintained in our animal facility under pathogen-free conditions in accordance with the Institutional Guidelines and approval by local authorities. For the use of the clinical materials for research purposes, prior patient's consent and approval from the Institute Research Ethics Committee were obtained. All statistical analyses were performed using IBM SPSS Statistics 22.0 for Windows. RESULT: Microarrays were adopted to explore the underlying epigenetic mechanisms related to metastasis. 11 genes were identified among total 26,890 differentially expressed genes. After validated in paired primary and metastatic tissues, OLR1 was selected in the current study. The expression levels of OLR1 were tested in 4 widely used cell lines. Cell proliferation, migration and invasion could be enhanced when OLR1 was overexpressed. OLR1 overexpression also triggered G1 to S + G2 phases of cell cycle. Accordingly, cell proliferations, migration and invasion would be reduced when OLR1 was silenced. OLR1-silencing blocked G1 to S + G2 phases of cell cycle. Also, OLR1 silencing effectively suppressed local tumor carcinogenesis and lung metastases in vivo. Moreover, silencing OLR1 repressed the expression of mesenchymal markers (Snail, Twist, and N-cadherin), but induced an epithelial marker (E-cadherin). CONCLUSION: This study indicated a novel molecular mechanism involving the role of OLR1 in lung metastases of osteosarcoma, strengthened the correlation between OLR1 and lung metastases.

Label-free detection of DNA hybridization with a compact LSPR-based fiber-optic sensor.

A miniaturized, robust, localized surface plasmon resonance (LSPR)-coupled fiber-optic (FO) nanoprobe providing an integrated and portable solution for detection of DNA hybridization and measurement of DNA concentrations has been demonstrated. The FO nanoprobe was created by constructing arrays of metallic nanostructures on the end facets of optical fibers utilizing nanofabrication technologies, including electron beam lithography and lift-off processes. The LSPR-FO nanoprobe device offers real-time, label-free, and low-sample-volume quantification of single-strand DNA in water with high sensitivity and selectivity, achieving a limit of detection around 10 fM. These results demonstrate the feasibility of the LSPR-FO nanoprobe device as a compact and low-cost biosensor for detection of short-strand DNA.

Treatment of Lung Carcinosarcoma and Other Rare Histologic Subtypes of Non-small Cell Lung Cancer.

OPINION STATEMENT: Lung carcinosarcoma (PCS) and other histological subtypes of non-small cell lung cancer, such as primary pulmonary lymphoma (PPL), pulmonary carcinoid (PC), and primary pulmonary lymphoepithelioma-like carcinoma (LELC), are rare. For their low incidence, the diagnosis and treatment are still controversial. Some patients only need surgery, while others may need chemotherapy, radiotherapy, or targeted therapy. In this paper, we retrospectively reviewed the literature of some rare histological subtype of NSCLC for the recent 20 years, and try to get some conclusions.

[Design, synthesis of novel N, N'-bis-(halogenophenyl)-4- methoxybenzene-1, 3-disulfonamides and evaluation of their anti-platelet aggregation activity].

Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Esophageal carcinosarcoma: a unique entity with better prognosis.

BACKGROUND: Esophageal carcinosarcoma is a rare kind of malignancy, and how to identify the patients with poor prognosis is critical for improving treatment efficacy and survival outcome. METHODS: The clinical characteristics, pathologic features, treatments, and outcomes of esophageal carcinosarcoma were analyzed in 33 patients. Meanwhile, we hypothesized that elevated neutrophil to lymphocyte ratio (NLR) correlates with poor prognosis. RESULTS: Most patients had polypoid tumors, and the carcinomatous elements were squamous in all patients except one with adenosquamous carcinoma. Eight patients had elevated NLR (≥5). The median follow-up time was 39.1 (range, 0.5-178.2) months. The median overall survival time (OS) was 43.5 months, and the 1-, 3-, and 5-year OS rates were 74, 57, and 48%, respectively. Tumor recurrence occurred in 15 patients, and the median relapse-free survival time (RFS) was 23.9 months, and the 2-year RFS rate was 50%. For patients who received curative resection, OS and RFS were significantly associated with preoperative NLR. In the multivariate Cox regression model, higher NLR was an independent prognostic factor (P value was 0.001 for both OS and RFS). CONCLUSIONS: Our study identified the baseline NLR to be an independently prognostic factor for curatively resected esophageal carcinosarcoma.

Effects of CXCR4 gene silencing by lentivirus shRNA on proliferation of the EC9706 human esophageal carcinoma cell line.

CXCL12/CXCR4 has been studied as an important biomarker for many human malignancies, but studies are limited for esophageal squamous cell carcinoma (ESCC). In this study, an effective RNAi sequence targeting the CXCR4 gene was selected, a lentiviral shRNA vector was constructed to specifically silence CXCR4 expression in the EC9706 ESCC cell line, and the effects of CXCR4 silencing on cell growth in vitro and tumour growth in nude mice were then evaluated. The expression of CXCR4 in EC9706 was significantly downregulated after transfection with a lentiviral shRNA vector. The expression of the apoptosis-related gene Bcl-2 was decreased. In addition, after CXCR4 inhibition, cell growth was considerably inhibited, increased apoptosis in the EC9706 cells was found, the G0/G1 percentage was significantly increased, and the number of cells in S phase was reduced. Moreover, tumour growth in nude mice was inhibited. In conclusion, the downregulation of CXCR4 expression by transfection with a lentiviral shRNA vector in ESCC cells could inhibit tumour proliferation. Our data may provide an avenue for finding new ESCC treatments.

Fish oil-supplemented parenteral nutrition in patients following esophageal cancer surgery: effect on inflammation and immune function.

Our aim was to investigate whether adding ω-3 polyunsaturated fatty acids (PUFAs) to parenteral nutrition (PN) could reduce inflammation and improve immune function in patients following esophageal cancer surgery. In this pilot study, 60 patients with esophageal cancer were divided into 2 groups (30 patients in each group). All patients had total scores of more than or equal to 3 on the nutritional risk screening (NRS2002) test recommended by the European Society of Parenteral Enteral Nutrition, which showed that all patients had nutritional risk and should receive nutritional support. Both groups received isocaloric and isonitrogenous PN. One group received a ω-3 PUFAs supplement. Key indicators of inflammation [serum procalcitonin (PCT) level and the ratio of CD4(+) to CD8(+) (CD4(+)/CD8(+) ratio)] were determined intraoperatively and 24, 72, and 144 h postoperatively. PCT level was notably lower and CD4(+)/CD8(+) ratio was markedly higher in the ω-3 PUFAs group (P = 0.007 for PCT level and P = 0.012 for CD4(+)/CD8(+) ratio) on postoperative day 6 but not on postoperative days 1 and 3. ω-3 PUFAs supplemented PN can reduce inflammation and improve immune function in patients following esophageal cancer surgery. A larger trial is required to see whether ω-3 PUFAs supplementation of PN improves the clinical outcomes of patients following esophageal cancer surgery.

Complete mediastinal lymph node dissection in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

BACKGROUND: Although video-assisted thoracic surgery (VATS) lobectomy has been used more and more frequently for the treatment of patients with early-stage lung cancer, controversies are mainly focused on whether the complete mediastinal lymph node dissection (MLND) can be achieved by VATS. This retrospective study aimed to compare the validity of MLND between VATS and open thoracotomy. METHODS: Patients with lung cancer were matched from a pool of pulmonary lobectomies performed by one surgeon. Patients undergoing VATS were matched with those undergoing thoracotomy in terms of gender, age, clinical tumor stage, tumor location, and surgical procedure. RESULTS: After matching, 31 patients in VATS group and 31 patients in open group were eligible for analysis. In the VATS and open groups, the mean total number of dissected lymph nodes was 28.2 ± 8.4 and 29.8 ± 11.6 (p = 0.517), respectively. In the VATS and open groups, the number of N1 nodes was 9.5 ± 4.1 and 8.4 ± 4.7 (p = 0.333), respectively. And the number of N2 nodes was also similar between the VATS and open group (18.6 ± 7.0 vs 21.4 ± 10.0, p = 0.211). No significant differences were observed between the two groups in the operating time, the blood loss, the length of chest tube drainage, the length of hospital stay, and the rate of specific complications. CONCLUSION: Our early experience suggests that, with regard to the number of the dissected lymph nodes, VATS lobectomy can achieve complete MLND, compared with the traditional approach. MLND by VATS is technically feasible and safe for early-stage lung cancer.

Rapid Identification of Three Gram-Negative Bacteria by Surface-Enhanced Raman Spectroscopy.

Gram-negative bacteria had been regarded as several important sources of lethal infection. Rapid identification of pathogenic bacteria is extremely important for the diagnosis and clinical treatment of diseases. In current study, three gram-negative bacteria, including Klebsiella aerogenes, Enterobacter cloacae and Escherichia coli, were used to access the feasibility of characterizing Gram-negative bacteria by surface-enhanced Raman Spectroscopy (SERS). Bacterial samples were from Escherichia coli isolates (n=1000), Klebsiella aerogenes isolates (n=1000) and Enterobacter cloacaeand isolates (n=1000). The differences of three Gram-negative bacteria were characterized by SERS spectra. Furthermore, four multivariate statistical algorithms based on the combination of principal component analysis (or partial least squares) and linear discriminant analysis (or support vector machine) were used to discriminate the spectra of three gram-negative bacteria.

"Capsule drape wrap"-a new technology for iridoschisis management during phacoemulsification.

AIM: To introduce a new technique for iridoschisis management during phacoemulsification: "capsule drape wrap". METHODS: "Capsule drape wrap" technique was used for an 80-year-old man with idiopathic iridoschisis in the right eye during phacoemulsification. The inserted flexible nylon iris hooks to hold anterior capsule in place, the margin of the anterior capsule could act as drape wrap, tracking the fibrillary iris strands firmly from free floating and stabilizing the capsular bags simultaneously. RESULTS: The eye with iridoschisis was successfully treated. Iris fibrils remained immobile during the procedure, and despite the severity of iridoschisis, there were no intraoperative complications such as tear of the iris, hyphema, iris prolapse, loss of mydriasis, or rupture of the posterior lens capsule during phacoemulsification. The best-corrected visual acuity was increased by 0.1 (logMAR) 6mo after the surgery. CONCLUSION: "Capsule drape wrap" for iridoschisis is easily manageable, prevents further disruption to the loose iris fibers and ensures the stability of capsule-iris complex simultaneously, consequently minimizing the risk of surgical complications in phacoemulsification.

CNS efficacy of afatinib as first-line treatment in advanced non-small cell lung cancer patients with EGFR mutations.

Background: Afatinib is a potent, irreversible second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has demonstrated efficacy in advanced non-small cell lung cancer (NSCLC) patients harboring either common or uncommon EGFR mutations. However, data on its activity against brain metastases are limited. This study aimed to retrospectively evaluate the efficacy and safety of afatinib as first-line treatment for EGFR-mutant NSCLC patients with brain metastases. Methods: Treatment-naive advanced NSCLC patients harboring EGFR mutations and brain metastases treated with afatinib were retrospectively reviewed to assess the central nervous system (CNS) efficacy and also the systematic benefits. Results: Totally 43 patients with measurable or non-measurable brain metastases were enrolled in the CNS full analysis (cFAS) set. Among them, 23 patients with measurable brain metastases were included in the CNS evaluable for response (cEFR) set. The CNS ORR was 48.8% (95% CI, 33.3 - 64.5%) in the cFAS set and 82.6% (95% CI, 61.2 - 95.0%) in the cEFR set, respectively. CNS mDoR was 8.9 months (95% CI, 4.7 - 13.1 months) and CNS mPFS was 12.7 months (95% CI, 6.9 - 18.5 months) in the cFAS set. In the subgroup analysis stratified by EGFR mutation types, CNS ORR of cEFR set in the common mutation cohort was 100% (95% CI, 75.3 - 100%) and 60% (95% CI, 26.2 - 87.8%) in the uncommon mutation cohort (p = 0.024); CNS ORR of cFAS set was 57.7% (95% CI, 36.9 - 76.6%) and 35.3% (95% CI, 14.2 - 61.7%), respectively (p = 0.151). CNS mPFS was 14.4 months in patients with common mutations and 6.1 months in patients with uncommon mutations (hazard ratio, 0.47; 95% CI, 0.22 - 1.00; p = 0.045). Patients with common mutations showed a significantly lower cumulative incidence of CNS failure than uncommon mutation cohort (p = 0.0026). Most of patients experienced grade 1/2 treatment-related adverse events. Conclusions: First-line afatinib demonstrated encouraging efficacy on brain metastases in NSCLC patients harboring either common or major uncommon EGFR mutations in a real-world setting, with manageable toxicities. Patients with common mutations showed better CNS outcomes than those with uncommon mutations.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods: Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results: A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions: This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

The independent prognostic effect of marital status on non-small cell lung cancer patients: a population-based study.

Background: Previous studies had demonstrated that marital status was an independent prognostic factor in multiple cancers. However, the impact of marital status on non-small cell lung cancer (NSCLC) patients was still highly controversial. Method: All NSCLC patients diagnosed between 2010-2016 were selected from the Surveillance, Epidemiology and End Results (SEER) database. To control the confounding effect of related clinicopathological characteristics, propensity score matching (PSM) was conducted between married and unmarried groups. In addition, independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression. Moreover, nomograms were established based on the clinicopathological characteristics, and the predictive accuracy was assessed by calibration curves. Furthermore, decision curve analysis (DCA) was used to determine the clinical benefits. Results: In total, 58,424 NSCLC patients were enrolled according to the selection criteria. After PSM, 20,148 patients were selected into each group for further analysis. The married group consistently demonstrated significantly better OS and CSS compared to unmarried group [OS median survival (95% CI): 25 (24-26) vs. 22 (21-23) months, p < 0.001; CSS median survival (95% CI): 31 (30-32) vs. 27 (26-28) months, p < 0.001]. Moreover, single patients were associated with the worst OS [median survival (95% CI): 20 (19-22) months] and CSS [median survival (95%CI): 24 (23-25) months] among unmarried subgroups. Besides, unmarried patients had a significantly worse prognosis compared to married patients in both univariate and multivariate Cox proportional hazard regressions. Furthermore, married group was associated with better survival in most subgroups. To predict the 1-, 3- and 5-year OS and CSS probabilities, nomograms were established based on age, race, sex, gender, marital status, histology, grade, TNM stage. The C-index for OS and CSS were 0.759 and 0.779. And the calibration curves showed significant agreement between predictive risk and the observed probability. DCA indicated nomograms had consistently better predict performance. Conclusion: This study demonstrated that unmarried NSCLC patients were associated with significantly worse OS and CSS compared to married NSCLC patients. Therefore, unmarried patients need not only closer surveillance, but also more social and family support, which may improve patients' adherence and compliance, and eventually improve the survival.

Invasiveness assessment by artificial intelligence against intraoperative frozen section for pulmonary nodules ≤ 3 cm.

PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Background: Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Methods: Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. Results: A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). Conclusions: L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.