Intratumor microbiome-derived butyrate promotes lung cancer metastasis.

Most recurrences of lung cancer (LC) occur within 3 years after surgery, but the underlying mechanism remains unclear. Here, we collect LC tissues with shorter (<3 years, recurrence group) and longer (>3 years, non-recurrence group) recurrence-free survival. By using 16S sequencing, we find that intratumor microbiome diversity is lower in the recurrence group and butyrate-producing bacteria are enriched in the recurrence group. The intratumor microbiome signature and circulating microbiome DNA can accurately predict LC recurrence. We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth. Mechanistically, bacteria-derived butyrate promotes LC metastasis by increasing expression of H19 in tumor cells through inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization. Depletion of macrophages partially abolishes the metastasis-promoting effect of butyrate. Our results provide evidence for the cross-talk between the intratumor microbiome and LC metastasis and suggest the potential prognostic and therapeutic value of the intratumor microbiome.

CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Multi-omics analysis reveals NNMT as a master metabolic regulator of metastasis in esophageal squamous cell carcinoma.

Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial-mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test.

BACKGROUND: Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath. METHODS: This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients' baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery). RESULTS: A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123. CONCLUSIONS: Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients' response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.

Clinical status and future prospects of single-incision robotic-assisted surgery: a review.

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.

Circular RNA P4HB promotes glycolysis and tumor progression by binding with PKM2 in lung adenocarcinoma.

BACKGROUND: Emerging evidence indicates that circular RNAs (circRNAs) play vital roles in tumor progression, including lung adenocarcinomas (LUAD). However, the mechanisms by which circRNAs promote the progression of LUAD still require further investigation. METHODS: Quantitative real-time PCR was performed to detect the expression of circP4HB in LUAD tissues and cells. Then, Kaplan-Meier analysis was used to determine the prognostic value of circP4HB expression. We employed RNA pull-down, RNA immunoprecipitation, mass spectrometry, cells fraction, glucose consumption, lactate production, pyruvate kinase M2 (PKM2) activity, and macrophage polarization assays to uncover the underlying mechanisms of circP4HB in LUAD. RESULTS: We found that circP4HB is upregulated in LUAD tissues and correlated with advanced TNM stages and lymph node metastasis. LUAD patients with high circP4HB expression had poor prognoses. Functionally, circP4HB promoted LUAD progression in vivo and in vitro. Upregulated circP4HB increased glucose consumption, lactate production and accelerated aerobic glycolysis in LUAD cells. Mechanically, circP4HB mainly accumulated in the cytoplasm of LUAD cells and bound with PKM2 and subsequently upregulating PKM2 enzymatic activity by increasing its tetramer formation. Additionally, circP4HB promoted M2 macrophage phenotype shift via targeting PKM2. Finally, rescue assays further confirmed that circP4HB could promote LUAD cell progression through its interaction with PKM2. CONCLUSION: These results demonstrate that circP4HB could promote LUAD progression, indicating circP4HB might be a potential therapeutic target of LUAD.

Thyroid dysfunction induced by immune checkpoint inhibitors and tumor progression during neoadjuvant therapy of non­small cell lung cancer: A case report and literature review.

Immune checkpoint inhibitors (ICIs) have a demonstrable treatment response in patients with resectable non-small cell lung cancer (NSCLC). However, immune-related adverse events and tumor progression in patients administered ICIs are of great concern. The present case study is of a 59-year-old male with NSCLC (squamous, stage IIIA) who received neoadjuvant immunotherapy combined with chemotherapy before surgery. The patient first developed hyperthyroidism and then hypothyroidism, indicating that ICI-related thyroid dysfunction had occurred. Furthermore, the patient suffered from tumor progression and could not undergo resection. The present case called attention to the prevention and management of irAEs, and the precaution that should be taken with regard to tumor progression. The case also suggested that the development of ICI-related thyroid dysfunction may not predict an improved response to ICI therapies, which needs further evidence to illustrate.

Single-incision robotic assisted surgery: a nonrandomized cohort pilot study on a novel surgical platform in colorectal surgery.

BACKGROUND: The technological barriers and steep learning curve of single-incision laparoscopic surgery had kept it from further applications. A literature review had reported that robotic technology could preserve its advantages while simplifying its difficulties. This nonrandomized cohort pilot study aims to evaluate the feasibility and safety of single-incision robotic assisted colorectal surgery based on a novel robotic surgical platform, the SHURUI Endoscopic Surgical Robotic System (SR-ENS-600). METHOD: This study enrolled 7 patients with colorectal malignancy who underwent single-incision robotic assisted surgery (SIRAS) at a tertiary general surgery center, and retrospectively included 23 patients who underwent robotic assisted surgery from September 2015 to June 2016 and 35 patients who underwent single-incision laparoscopic surgery from June 2017 to March 2018, which were labeled as the initial in-learning-curve attempts from the same surgical team. The technological feasibility and safety of SIRAS were evaluated. Perioperative outcomes, short-term postoperative outcomes, clinicopathologic outcomes, and follow-up were reported. RESULTS: Six SIRAS operations were completed successfully without eventful intraoperative complications, except for one operation that encountered a large-volume of intraoperative hemorrhage. Two SIRAS cases were converted to multiport laparoscopic surgery because of intraoperative hemorrhage and difficulty in retraction. Postoperative pathology reported satisfactory specimen qualities. There were no short-term postoperative complications, no short-term mortality, no tumor recurrence, or metastasis reported. There was one incisional hernia reported half a year after operation. Patients with advanced staging were sent to standard evaluation and chemotherapy, and follow-up is still on-going. CONCLUSIONS: SIRAS can be feasibly performed by a skilled surgical team via the SR-ENS-600 platform for strictly-selected patients, which provides preferable instrument maneuverability and stability in confined surgical fields and overcomes the technical difficulty of multisite dissection through a single-incision. Large-volume investigations and high-level evidences are required to further validate its safety and superiority.

Systemic inflammation influences the prognosis of patients with radically resected non-small cell lung cancer and correlates with the immunosuppressive microenvironment.

The impact of host condition on prognosis of non-small cell lung cancer (NSCLC) and the interaction between host and NSCLC remain unclear. This study investigated the association between systemic inflammation and prognosis and characteristics of radically resected NSCLC. This study consisted of a cohort study and an exploratory study of institutional prospective databases. All participants underwent video-assisted thoracoscopic lobectomy as the primary treatment. Systemic inflammation was assessed before surgery using the advanced lung cancer inflammation index and the systemic inflammation response index. Next-generation sequencing and multiplex immunofluorescence analysis were conducted to delineate tumor characteristics. In the cohort study including 1507 participants, high inflammation was associated with poor disease-free survival and overall survival before and after propensity score matching and in multivariable analysis. Systemic inflammation showed good prognostic value for stage IA-IB NSCLC, and the prognostic value diminished with upstaging of NSCLC. In the exploratory study including 217 adenocarcinomas, tumor microenvironment of high inflammation group showed a greater abundance of PDL1+ tumor cells and immune cells, which were independent from driver gene mutations and clinicopathological characteristics. Spatial analysis demonstrated a higher frequency of immune-suppressed cellular neighborhood, increased avoidance between immune cells and PDL1- tumor cells and compromised immune killing and presentation in tumor microenvironment of high inflammation group. Systemic inflammation showed limited association with genomic mutations. Systemic inflammation may influence the prognosis of NSCLC at both the systematic level and the local immune response. The correlation between high inflammation and immunosuppressive microenvironment indicates a novel thread for anticancer treatment.

Chemical fingerprints and implicated cancer risks of Polycyclic aromatic hydrocarbons (PAHs) from fine particulate matter deposited in human lungs.

Exposure to fine particles (PM2.5) and associated PAHs are frequently linked with lung cancer, which makes the understanding of their occurrence and health risk in human lungs urgently important. Using the ultrasonic treatment and sequencing centrifugation (USC) extraction method coupled with gas chromatography-tandem mass spectrometry (GC - MS/MS) analysis, we revealed the molecular fingerprints of PM-accumulated PAHs in human lungs from a cohort of 68 patients with lung cancer in a typical air-polluted region, China. Sixteen priority PAHs can be grouped by concentrations as âˆ¼ 1 × 104 ng/g (ANT/BkF/ACE/DBA/BgP/PHN/PYR), 2-5 × 103 ng/g (BaP/FLE/NaP/BbF), and âˆ¼ 1 × 103 ng/g (IND/Acy/CHR/FLT/BaA). The sum concentration of 16 PAHs was approximately equaled to 13% of those in atmospheric PM2.5, suggesting significant pulmonary leaching of PAHs deposited in lungs. Low- and high-molecular weight PAHs accounted for âˆ¼ 41.8% and âˆ¼ 45.1% of the total PAHs, respectively, which indicated that atmospheric PM2.5, tobacco and cooking smoke were likely to be important sources of pulmonary PAHs. The evident increasing concentrations of NaP and FLE in pulmonary PM were significantly correlated with smoking history among smokers. The implicated carcinogenic potency of PM-accumulated PAHs among the participants aged 70-80 was 17 times that among participants aged 40-50 on the basis of BaP equivalent concentration (BaPeq) evaluation. The particulate enrichment factor (EFP), the PAH content in pulmonary PM relative to the bulk lung tissue, was equaled to 54 âˆ¼ 835 and averaged at 436. The high value of EFP suggested that PAHs were essentially accumulated in pulmonary PM and exhibited a pattern of "hotspot" distribution in the lungs, which would likely increase the risk of monoclonal tumorigenesis. The chemical characteristics of PM-accumulated PAHs in human lungs together with their implicated lung cancer risks could provide significant information for understanding health effects of particulate pollution in the human body.

AI-based chest CT semantic segmentation algorithm enables semi-automated lung cancer surgery planning by recognizing anatomical variants of pulmonary vessels.

Background: The recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)-based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons' performance. Methods: The semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons' judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT. Results: A total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons. Conclusion: The semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.

Sarcopenic obesity and therapeutic outcomes in gastrointestinal surgical oncology: A meta-analysis.

Background: Sarcopenic obesity (SO) has been indicated as a scientific and clinical priority in oncology. This meta-analysis aimed to investigate the impacts of preoperative SO on therapeutic outcomes in gastrointestinal surgical oncology. Methods: We searched the PubMed, EMBASE, and Cochrane Library databases through March 4th 2022 to identify cohort studies. Endpoints included postoperative complications and survival outcomes. Newcastle Ottawa Scale was used for quality assessment. Heterogeneity and publication bias were assessed. Subgroup analyses and sensitivity analyses were performed. Results: Twenty-six studies (8,729 participants) with moderate to good quality were included. The pooled average age was 65.6 [95% confidence interval (CI) 63.7-67.6] years. The significant heterogeneity in SO definition and diagnosis among studies was observed. Patients with SO showed increased incidences of total complications (odds ratio 1.30, 95% CI: 1.03-1.64, P = 0.030) and major complications (Clavien-Dindo grade ≥ IIIa, odds ratio 2.15, 95% CI: 1.39-3.32, P = 0.001). SO was particularly associated with the incidence of cardiac complications, leak complications, and organ/space infection. SO was also predictive of poor overall survival (hazard ratio 1.73, 95% CI: 1.46-2.06, P < 0.001) and disease-free survival (hazard ratio 1.41, 95% CI: 1.20-1.66, P < 0.001). SO defined as sarcopenia in combination with obesity showed greater association with adverse outcomes than that defined as an increased ratio of fat mass to muscle mass. A low prevalence rate of SO (< 10%) was associated with increased significance for adverse outcomes compared to the high prevalence rate of SO (> 20%). Conclusion: The SO was associated with increased complications and poor survival in gastrointestinal surgical oncology. Interventions aiming at SO have potentials to promote surgery benefits for patients with gastrointestinal cancers. The heterogeneity in SO definition and diagnosis among studies should be considered when interpreting these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255286], identifier [CRD42021255286].

Colorectal cancer vaccines: The current scenario and future prospects.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Current therapies such as surgery, chemotherapy, and radiotherapy encounter obstacles in preventing metastasis of CRC even when applied in combination. Immune checkpoint inhibitors depict limited effects due to the limited cases of CRC patients with high microsatellite instability (MSI-H). Cancer vaccines are designed to trigger the elevation of tumor-infiltrated lymphocytes, resulting in the intense response of the immune system to tumor antigens. This review briefly summarizes different categories of CRC vaccines, demonstrates the current outcomes of relevant clinical trials, and provides particular focus on recent advances on nanovaccines and neoantigen vaccines, representing the trend and emphasis of CRC vaccine development.

Short- and long-term outcomes of robotic- versus laparoscopic-assisted right hemicolectomy: A propensity score-matched retrospective cohort study.

BACKGROUND: This study aimed to retrospectively compare the short- and long-term outcomes of robotic- and laparoscopic-assisted right hemicolectomies. MATERIALS AND METHODS: Patients who underwent right hemicolectomy with either robotic (46 patients) or laparoscopic (186 patients) surgery between January 2016 and December 2018 were analyzed retrospectively using propensity score matching (PSM). RESULTS: After matching, the robotic group included 45 patients (out of 46) and the laparoscopic group included 100 patients (out of 186). Compared to the laparoscopic group, the robotic group had shorter median times to first flatus (2 vs. 4 days; p < 0.01) and a liquid diet (4 vs. 5 days; p < 0.01) and shorter median postoperative hospital stays (7 vs. 8 days; p < 0.01). There were no significant differences in other short-term or oncological outcomes between the two groups. The 3-year overall survival and disease-free survival rates were equivalent. CONCLUSIONS: Robotic-assisted right hemicolectomy had the advantages of a quick recovery of bowel functions and an earlier postoperative discharge and was non-inferior to laparoscopic-assisted right hemicolectomy in all other outcomes.

Apatinib: A Novel Antiangiogenic Drug in Monotherapy or Combination Immunotherapy for Digestive System Malignancies.

Digestive system malignancies are one of the primary causes of cancer-related death. Meanwhile, angiogenesis has been proved to play an important role in the process of cancer neovascularization. Apatinib, a novel targeted antiangiogenic molecule, could generate highly selective competition in the vascular endothelial growth factor receptor-2, involved in tumor progression and metastasis. It has been implied as a promising cancer treatment agent that can prevent tumor cell proliferation meanwhile inhibit tumor angiogenesis. Furthermore, completed clinical trials demonstrated that apatinib could prolong the progression-free survival and overall survival in advanced gastric cancer and primary liver cancer. Recent studies revealed that apatinib had a synergistic effect with immunotherapy as a second-line and third-line treatment regimen for some other cancers. In this review, we summarize the pharmacological properties of apatinib and the latest clinical application in chemotherapy-refractory patients with advanced digestive system cancer. Based on the comparable survival results, the molecular mechanisms of apatinib are prospective to include the antiangiogenic, apoptosis-inducing, and autophagy-inducing properties in the corresponding signaling pathway. Treatment of apatinib monotherapy or combination immunotherapy remains the optimal option for patients with digestive system malignancies in the future.

Identification of lung cancer breath biomarkers based on perioperative breathomics testing: A prospective observational study.

Background: Breathomics testing has been considered a promising method for detection and screening for lung cancer. This study aimed to identify breath biomarkers of lung cancer through perioperative dynamic breathomics testing. Methods: The discovery study was prospectively conducted between Sept 1, 2020 and Dec 31, 2020 in Peking University People's Hospital in China. High-pressure photon ionisation time-of-flight mass spectrometry was used for breathomics testing before surgery and 4 weeks after surgery. 28 volatile organic compounds (VOCs) were selected as candidates based on a literature review. VOCs that changed significantly postoperatively in patients with lung cancer were selected as potential breath biomarkers. An external validation was conducted to evaluate the performance of these VOCs for lung cancer diagnosis. Multivariable logistic regression was used to establish diagnostic models based on selected VOCs. Findings: In the discovery study of 84 patients with lung cancer, perioperative breathomics demonstrated 16 VOCs as lung cancer breath biomarkers. They were classified as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan. In the external validation study including 157 patients with lung cancer and 368 healthy individuals, patients with lung cancer showed elevated spectrum peak intensity of the 16 VOCs after adjusting for age, sex, smoking, and comorbidities. The diagnostic model including 16 VOCs achieved an area under the curve (AUC) of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. The diagnostic model including the top eight VOCs achieved an AUC of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%. Interpretation: Perioperative dynamic breathomics is an effective approach for identifying lung cancer breath biomarkers. 16 lung cancer-related breath VOCs (aldehydes, hydrocarbons, ketones, carboxylic acids, and furan) were identified and validated. Further studies are warranted to investigate the underlying mechanisms of identified VOCs. Funding: National Natural Science Foundation of China (82173386) and Peking University People's Hospital Scientific Research Development Founds (RDH2021-07).

A fully automated noncontrast CT 3-D reconstruction algorithm enabled accurate anatomical demonstration for lung segmentectomy.

BACKGROUND: Three-dimensional reconstruction of chest computerized tomography (CT) excels in intuitively demonstrating anatomical patterns for pulmonary segmentectomy. However, current methods are labor-intensive and rely on contrast CT. We hereby present a novel fully automated reconstruction algorithm based on noncontrast CT and assess its performance both independently and in combination with surgeons. METHODS: A retrospective pilot study was performed. Patients between May 2020 to August 2020 who underwent segmentectomy in our single institution were enrolled. Noncontrast CTs were used for reconstruction. In the first part of the study, the accuracy of the demonstration of anatomical variants by either automated or manual reconstruction algorithm were compared to surgical observation, respectively. In the second part of the study, we tested the accuracy of the identification of anatomical variants by four independent attendees who reviewed 3-D reconstruction in combination with CT scans. RESULTS: A total of 20 cases were enrolled in this study. All segments were represented in this study with two left S1-3, two left S4 + 5, one left S6, five left basal segmentectomies, one right S1, three right S2, 1 right S2b + 3a, one right S3, two right S6 and two right basal segmentectomies. The median time consumption for the automated reconstruction was 280 (205-324) s. Accurate vessel and bronchial detection were achieved in 85% by the AI approach and 80% by Mimics, p = 1.00. The accuracy of vessel classification was 80 and 95% by AI and manual approaches, respectively, p = 0.34. In real-world application, the accuracy of the identification of anatomical variant by thoracic surgeons was 85% by AI+CT, and the median time consumption was 2 (1-3) min. CONCLUSIONS: The AI reconstruction algorithm overcame defects of traditional methods and is valuable in surgical planning for segmentectomy. With the AI reconstruction, surgeons may achieve high identification accuracy of anatomical patterns in a short time frame.

Segmentectomy and Wedge Resection for Elderly Patients with Stage I Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Considerable controversies exist regarding the efficacies of segmentectomy and wedge resection for elderly patients with early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to solve these issues. METHODS: We searched the online databases PubMed, Web of Science, EMBASE, and Cochrane Library to identify eligible studies. Elderly patients were defined as ≥65 years. Early-stage NSCLC was defined as stage I based on TNM systems. The primary endpoints were survival outcomes (overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS)) and recurrence patterns. The second endpoints were perioperative morbidities. The hazard rate (HR) and odds ratio (OR) were effect sizes. RESULTS: Sixteen cohort studies (3140 participants) and four database studies were finally included. Segmentectomy and lobectomy showed no significant difference in OS (cohort studies HR 1.00, p = 0.98; database studies HR 1.07, p = 0.14), CSS (HR 0.91, p = 0.85), or DFS (HR 1.04, p = 0.78) in elderly patients with stage I NSCLC. In contrast, wedge resection showed inferior OS (HR 1.28, p < 0.001), CSS (HR 1.17, p = 0.001) and DFS (HR 1.44, p = 0.042) compared to lobectomy. Segmentectomy also showed comparable local recurrence risk with lobectomy (OR 0.98, p = 0.98), while wedge resection showed increased risk (OR 5.46, p < 0.001). Furthermore, sublobar resections showed a decreased risk of 30/90-day mortality, pneumonia, and leak complications compared to lobectomy. CONCLUSION: Segmentectomy is promising when applied to elderly patients with stage I NSCLC, while wedge resection should be limited. Randomized controlled trials are warranted to validate these findings.

Skeletal muscle wasting during neoadjuvant therapy as a prognosticator in patients with esophageal and esophagogastric junction cancer: A systematic review and meta-analysis.

BACKGROUND: Considerable controversies exist regarding the severity of skeletal muscle wasting (SMW) during neoadjuvant therapy (NAT) and its impact on therapeutic outcomes in patients with esophageal or esophagogastric junction cancer (EC/EGJC). This systematic review and meta-analysis aimed to resolve these issues. Particularly, the prognostic value of SMW during NAT was compared to pre-NAT and pre-surgery sarcopenia status. METHODS: We searched PubMed, Embase, and Cochrane Library databases through October 13th, 2021 to identify cohort studies focusing on SMW during NAT and therapeutic outcomes in EC/EGJC patients. Both neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy were studied. A meta-analysis was conducted to quantify SMW and increased sarcopenia during NAT. Therapeutic outcomes include perioperative morbidities and survival profiles. A separate meta-analysis investigating the impacts of pre-NAT/pre-surgery sarcopenia on therapeutic outcomes was synchronously performed. RESULTS: Twenty-five studies with 2706 participants were included in this review. The pooled SMW during NAT were -2.47 cm2/m2 in skeletal muscle index and -0.23 cm2/m2 in psoas muscle index, with wasting proportion reaching 4.44%. The pooled prevalence rate of sarcopenia increased from 53.1% before NAT to 65.8% before surgery. Neoadjuvant chemoradiotherapy, advanced age, and being male were identified as risk factors for severe SMW during NAT. Notably, severe SMW during NAT showed a greater hazard ratio (HR) than pre-NAT and pre-surgery sarcopenia in predicting overall survival (HR 1.92, P < 0.001; HR 1.17, P = 0.036; and HR 1.28, P = 0.011, respectively) and recurrence-free survival (HR 1.51, P = 0.002; HR 1.27, P = 0.008; and HR 1.38, P = 0.006, respectively). However, severe SMW during NAT was not significantly associated with perioperative morbidities. CONCLUSIONS: SMW during NAT is a novel prognosticator that is different from sarcopenia for poor survival in EC/EGJC patients. Interventions aiming at maintaining skeletal muscle during NAT are anticipated to promote therapeutic outcomes.