Lung Resection Research Articles

Drainless Uniportal VATS Wedge Resection for Early Non-Small Cell Lung Cancer: Propensity Analysis of the Effect of Polyglycolic Acid Sheet (NeoveilTM)

Objectives: Absorbable biomaterials as adjuvant therapy after thoracoscopy are sometimes used in clinical scenarios. With the prevalence of enhanced rapid recovery in thoracic surgery, drainless video-assisted thoracoscopy surgery (VATS) is often adopted by thoracic surgeons. Here, we discuss utilizing an absorbable biomaterial, NeoveilTM (Polyglycolic Acid sheet), for drainless VATS to treat early lung cancer. Methods: This single-center retrospective study was conducted from January 2018 to December 2022 at the National Taiwan University Hospital. We included patients who underwent drainless VATS for early-stage non-small cell lung cancer (NSCLC) in our institute. Propensity analysis was used to minimize selection bias. Outcome measurements were in-hospital stay, operation time, rate of thoracocentesis or chest drain re-insertion, complication rate, and perioperative course. Results: During the study period, 158 lung cancer patients were performed with drainless VATS wedge resection. Among them, Neoveil for stapling line coverage was done in 72 patients, while 86 patients did not receive Neoveil. After propensity analysis, we had 58 patients using Neoveil after drainless thoracoscopic lung resection, compared fairly with 58 patients without Neoveil after the same procedure. The basic characteristics are comparable regarding age, gender, BMI, operation methods, and lung cancer stage after propensity matching. The in-hospital stay (3.2 days in the Neoveil group and 5.6 days in the non-Neoveil group) and operation time (95.7 min in the Neoveil group and 59.3 min in the non-Neoveil group) are significantly different (p = 0.0001). One versus four patients was noted for postoperative conversion chest drainage insertion in each group (p = 0.17). Neither late complications nor recurrence/metastasis occurred in both groups during the following. Conclusions: Based on our 5-year retrospective study, which is balanced with propensity analysis, drainless thoracoscopic surgery treating early lung cancer can be enhanced by Neoveil with faster recovery by reducing the hospital stay, though with longer operation time.

Abstract C025: Identification of cell-cell signaling programs across the tumor-tumor microenvironment ecosystem and associated with clinical status in neoadjuvant osimertinib treated patient samples revealed by spatial profiling

Abstract Lung cancer is the leading cause of cancer mortality, and despite improvements in treatment, tumors typically respond incompletely and resume growth after acquisition of drug resistance. Recent completion of a neoadjuvant osimertinib Phase II trial treating patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) (NCT03433469) (Blakely et. Al, JCO 2024) has highlighted the importance of further identifying non-genomic mechanisms of persistence and resistance to targeted therapy. Here we analyzed these patient samples to identify transcriptionally regulated signaling patterns enriched at Residual Disease (RD) after neoadjuvant osimertinib treatment compared to treatment naïve samples (TN), as well as signaling patterns enriched at RD in patients who ultimately develop disease recurrence after surgical resection compared to those who remain disease-free. Spatially resolved transcriptomic sequencing was performed, using the 10X Genomics Visium platform, on 36 tissue sections (n=9 TN, n=19 RD, n=4 Progressive Disease (PD), n=4 Tumor Adjacent Normal), from 25 patients. TN and PD samples were from standard-of-care surgical resections. 18 of 19 RD samples were from NCT03433469. The Visium array spots that tile the sequencing capture area are 55 µm in diameter, and thus can contain an estimated 1-10 cells within each array spot. After quality control, 91,582 array spots remained for downstream analysis. We identified high confidence tumor array spots annotated both as “Cancer” by a board-certified pathologist and with tumor characteristic copy number variations. Through dimensionality reduction clustering, we identified 10 major array spot clusters, including the high confidence tumor array spot cluster. These clusters were further subset into 44 high resolution clusters of array spot niches, 32 of which were shared across at least nine patients. Because array spots are not single-cell resolution, these niches represent spots with similar mixed cell type composition and transcriptional signatures. We identified significant increases in the CCL14+ Endothelial Cell Niche, CXCL2+ Endothelial Cell Niche, Lymphocytes + Endothelial Niche, and CXCL12+ Fibroblast Niche in RD samples compared to TN. We identified a cell signaling program defined by spatially co-expressed ligand-receptor pairs associated with focal adhesion, enriched in PD samples. This same pattern was enriched in RD samples from patients who had recurrent disease after surgical resection compared to RD samples from patients who remained disease free. These data describe an increase in immune trafficking in RD samples, as well as identify an EGFR- alternative signaling pathway correlating with osimertinib resistance. Identification of spatially resolved, differential architectural organization and signaling patterns in RD and PD states will expand our understanding of targeted therapy resistance in EGFRm NSCLC, with the potential to identify additional clinically actionable targets. Citation Format: Whitney Tamaki, Daniel L. Kerr, Wei Wu, Grant Eilers, Anatoly Urisman, Yu-Ting Chou, Philippe Gui, Shigeki Nanjo, Johannes R. Kratz, David M. Jablons, Trever G. Bivona, Collin M. Blakely. Identification of cell-cell signaling programs across the tumor-tumor microenvironment ecosystem and associated with clinical status in neoadjuvant osimertinib treated patient samples revealed by spatial profiling [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C025.

Divergent clinical and immunologic outcomes based on STK11 co-mutation status in resectable KRAS-mutant lung cancers following neoadjuvant immune checkpoint blockade.

Co-mutations of the KRAS and STK11 genes in advanced non-small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. While neoadjuvant chemoimmunotherapy is now a standard of care treatment for resectable NSCLC, the clinical and immunologic impact of KRAS andSTK11 co-mutations in this setting are unknown. We evaluated and compared recurrence-free survival of resectable KRAS-mutated NSCLC tumors, with or without co-occuring STK11 mutations, treated with neoadjuvant ICB. Single cell transcriptomics was performed on tumor-infiltrating T cells from 7 KRASmut/STK11wttumors and 6 KRASmut/STK11mut tumors. Relative to KRASmut/STK11wttumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased PGE-2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TIL from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT). These divergent T cell transcriptional fates suggest T cell maintenance and residence may be detrimental to anti-tumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning PGE-2 and IL-2 signaling as they relate to T cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB.

ASO Author Reflections: The Candidate Biomarkers for Predicting Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

ASO Author Reflections: The Candidate Biomarkers for Predicting Neoadjuvant Immunotherapy in Resectable Non-small Cell Lung Cancer.

Racial/ethnic differences in survival and treatment response with PD-1/PD-L1 inhibitors in resectable non-small cell lung cancer: a meta-analysis of randomized controlled trials.

The optimal treatment for resectable Non-Small Cell Lung Cancer (NSCLC) remains under investigation, particularly about its effectiveness across different ethnicities. This meta-analysis aims to investigate the potential benefits of adding PD1/PD-L1 inhibitors for treatment, stratified by ethnicity. We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) that investigated the use of PD1/PD-L1 inhibitors to treat patients with resectable NSCLC. The outcomes evaluated were disease-free survival/event-free survival (DFS/EFS), major pathological response (MPR), and pathological complete response (pCR). Hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were computed for all endpoints using DerSimonian and Laird random-effects models. Statistical analyses were performed with R Software, version 4.2.3. A total of six RCTs comprising 3,827 patients with NSCLC were included. In populations of Asian descent, PD1/PD-L1 significantly improved DFS/EFS (HR 0.59; 95% CI 0.44-0.78), MPR (RR 5.76; 95% CI 3.58-9.28), and pCR (RR 25.00; 95% CI 6.17-101.36). Similarly, patients of European ancestry experienced significantly improved DFS/EFS (HR 0.77; 95% CI 0.65-0.90), MPR (RR 2.75; 95% CI 2.00-3.77), and pCR (RR 4.53; 95% CI 2.69-7.6) with PD1/PD-L1 therapy. Notably, patients with mixed ethnicity also demonstrated significant improvement in MPR (RR 4.05; 95% CI 2.60-6.33) and pCR (RR 8.44; 95% CI 3.75-19.00) when receiving PD1/PD-L1 inhibitors. This comprehensive meta-analysis suggests that incorporating PD1/PD-L1 inhibitors into treatments offers a promising benefit for patients with resectable NSCLC, regardless of ethnicity. Future studies with in-depth molecular characterization of patients can further refine these findings and potentially guide the development of personalized treatment strategies based on individual ethnic backgrounds.

Clinical characteristics and treatment patterns in early-stage resected non-small cell lung cancer patients: a descriptive retrospective study

Clinical characteristics and treatment patterns in early-stage resected non-small cell lung cancer patients: a descriptive retrospective study

Abstract 4112652: Impact of metabolic overweight/obesity phenotypes on clinical outcomes of patients with resectable non-small cell lung cancer in an Asian population

Background: Metabolic syndrome and obesity are known to increase the incidence of lung cancer. We investigated the association between metabolic health and overweight/obesity phenotypes and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC). Methods: This large retrospective cohort study included adult patients who underwent curative upfront surgery for their stage IA-IIIB NSCLC at a tertiary university hospital from January 2010 to December 2020. They were classified into four phenotypes based on the combination of metabolic health status and body mass index categories: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy overweight/obesity (MUO). The primary outcomes were disease recurrence and death. Results: Of the 1,513 patients (342 with MHNW, 585 with MUNW, 122 with MHO, and 464 with MUO), patients with the phenotype of MHO were less likely to experience recurrence (MHO [13.1%] vs. MHNW [16.1%] vs. MUNW [22.9%] vs. MUO [19.2%], p = 0.018) and death (MHO [15.6%] vs. MHNW [24.6%] vs. MHUW [31.3%] vs. MUO [24.8%], p < 0.001) compared to those with other 3 phenotypes. Similar results were observed in Kaplan-Meier curves for the primary outcomes according to the four phenotypes (all log-rank P < 0.05). In multivariate Cox regression analyses, both MHO and MUO phenotypes did not increase the risk of recurrence compared to the MHNW phenotype and were associated with improved survival (MHO: adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.36-0.98, p = 0.040; MUO: adjusted HR 0.76, 95% CI 0.60-0.96, p = 0.022). Conclusions: After curative resection for NSCLC, regardless of metabolic health, patients with overweight/obesity were not at an increased risk of recurrence and paradoxically, had favorable overall survival.

Robot-assisted laparoscopic hepatectomy for liver metastasis from clitoral malignant melanoma: a case report.

Malignant melanomas occur most commonly in the skin, mucous membranes, or choroid. Clitoral malignant melanomas are extremely rare. Stage IV malignant melanomas have a poor prognosis, and molecularly targeted agents or immune checkpoint inhibitors are recommended. However, surgical resection is reportedly a valid option for improving the prognosis of patients with oligometastases, defined as a small number of metastases that can be completely resected. In this report, we describe hepatic resection for a recurrent liver metastasis in a patient who had undergone removal of a clitoral malignant melanoma 9years previously. An 82year-old woman presented with a black nodule on her clitoris. Total resection of the nodule resulted in a diagnosis of clitoral malignant melanoma (pT4bN0M0, pStage IIC; UICC 8th edition). A follow-up computed tomography scan 4years later revealed a single 5mm mass in the lower lobe of the right lung, prompting partial resection of the right lung. Pathological examination of the operative specimen revealed a pulmonary metastasis of malignant melanoma. The patient was treated with pembrolizumab monotherapy as adjuvant chemotherapy for 1year. A follow-up computed tomography scan 9years after surgical removal of the primary lesion revealed an 18mm mass in segment II of the liver, prompting robot-assisted laparoscopic left lateral sectionectomy. The provisional diagnosis of metastatic malignant melanoma in the liver was confirmed by histopathological examination of the operative specimen. The patient was treated with pembrolizumab monotherapy as postoperative adjuvant chemotherapy for 1year. No further recurrence was detected at the 1.5year follow-up. We performed hepatectomy for oligometastasis of clitoral malignant melanoma, an extremely rare entity. Surgery has the potential to prolong the prognosis of patients with oligometastasis.

Video- assisted thoracoscopic lung resection with or without enhanced recovery after surgery: a single institution, prospective randomized controlled study

Video- assisted thoracoscopic lung resection with or without enhanced recovery after surgery: a single institution, prospective randomized controlled study

Causes of ventilatory inefficiency in lung resection candidates

Causes of ventilatory inefficiency in lung resection candidates

Phrenic nerve infiltration: a good practice to combine pulmonary expansion and pain control in patients with high-risk of prolonged air leak.

ObjectiveProlonged air leak (PAL) due to residual air space after lung resection is a main challenge. To date, few surgical options have been described to prevent this complication. The aim of this study is to investigate the safety and the efficacy of intra-operative phrenic nerve infiltration with long-acting anaesthetics in producing transient hemidiaphragm paralysis in patients at high risk for PAL, thus improving pulmonary expansion after surgery, and reducing air leaks, while controlling post-operative pain. MethodsBetween January 2021-2023, 65 consecutive patients at risk for PAL (defined in accordance with “2019 Society of Thoracic Surgery score-criteria of PAL”) who underwent lung resection (lobectomy or anatomical segmentectomy) for malignancy were prospectively included in the study. They have been randomly (1:2 ratio) assigned to receive (group A, 22 patients) intra-operative phrenic nerve infiltration with Ropivacaine 10 mg/ml in the peri-neurotic fat on the pericardium or not to receive intra-operative phrenic nerve infiltration (group B, 43 patients). Five patients of Group B have been excluded because they did not undergo anatomical resection. Data on pulmonary re-expansion, prolonged air leaks, pain at 24- and 72-hours post-surgery, referred shoulder pain, length of hospital stay, length of chest tube permanence, were collected and compared. ResultsHemidiaphragm elevation (p=0.006) and pulmonary expansion (p=0.000) were significantly higher in Group A. Patients in Group A showed lower pain at 24 and 72 hours compared to Group B (p=0.004). Shoulder pain (0.001) and prolonged air leak (0.000) were higher in Group B. Length of chest tube was longer in group B. No difference in hospital stay length was observed. ConclusionThis is the first study to investigate two combined effects of phrenic nerve anaesthetic infiltration (hemidiaphragm elevation and pain control), with potential enhancement of patient’s recovery after surgery. Intraoperative phrenic nerve infiltration in patients with risk for PAL appears a safe and effective clinical practice to improve pulmonary expansion in this set of patients, reducing post-operative air leak. This result is associated with an additional improvement in pain control, especially for shoulder pain.

Risk of Financial Toxicity Among Adults Undergoing Lung and Esophageal Resections for Cancer

Although financial toxicity, defined as the harmful financial burden experienced by patients undergoing cancer treatment, has been of growing interest, data in thoracic oncology are lacking. We aimed to examine the risk of financial toxicity among patients undergoing surgical resection of thoracic malignancies. Adults undergoing lobectomy, pneumonectomy, or esophagectomy for cancer were identified in the 2012-2021 National Inpatient Sample (NIS). Risk of financial toxicity was defined as health expenditure (total hospitalization costs for the uninsured and maximum out-of-pocket costs for the insured) exceeding 40% of post-subsistence income. Multivariable logistic regressions were used to identify factors associated with financial toxicity risk. Of 384,340 patients, 69.5% had government-funded insurance, 27.2% private insurance, and 1.0% were uninsured. Compared to those with insurance, uninsured patients were more commonly Black and Hispanic and less commonly electively admitted. Mortality, complications, LOS, and costs were comparable regardless of insurance status. Approximately 68.9% of uninsured and 17.3% of insured patients were at risk of financial toxicity, and incidence of financial toxicity remained stable over time. After risk adjustment, complications were associated with over 2-fold increased risk of financial toxicity among uninsured (AOR 2.21, 95% CI 1.38-3.55). Among the insured, Black, Hispanic, and publicly insured patients demonstrated greater risk of financial toxicity, while minimally invasive operations and metropolitan hospitals exhibited lower risk of financial toxicity. Concordant with prior work examining financial toxicity in abdominal oncologic surgery, thoracic surgery demonstrates a comparable burden of financial toxicity. Referral policies and care subsidization may be considered in patients undergoing thoracic malignancy resections at risk for financial toxicity.

What Is Best Liquid Remnant for Resected Early-Stage Non-small Cell Lung Cancer?

What Is Best Liquid Remnant for Resected Early-Stage Non-small Cell Lung Cancer?

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021.

Living on the Edge: Role of Adjuvant Therapy After Resection of Primary Lung Cancer Within 2 Millimeters of a T-Stage Cutoff

ObjectivesWe evaluated the use of systemic therapy and overall survival in patients with resected non-small cell lung cancer (NSCLC) whose pathologic tumor size was within 2mm of a T-stage cutoff. MethodsRetrospective cohort study using the National Cancer Database of patients who underwent resection of tumors within 2mm of the T1c/T2a, T2a/T2b, and T2b/T3 T-stage cutoffs. Patients with nodal involvement or whose T-stage was based on pathologic features other than tumor size were excluded. A multistate model compared the primary outcomes of systemic therapy and overall survival. ResultsFrom the NCDB, 18,490 patients were identified: 9,966 at the T1c/T2a cutoff, 5,593 at the T2a/T2b cutoff, and 2,931 at the T2b/T3 cutoff. Peaks in tumor size distribution occurred at 5mm intervals. Based on an expected normalized curve, 2,050 patients (11.1%) may have been under-staged. Use of systemic therapy was higher among patients with larger tumors at the T1c/T2a cutoff (7.1% vs. 8.9%; p<0.001), the T2a/T2b cutoff (20.0% vs. 25.5%; p<0.001), and the T2b/T3 cutoff (31.2% vs. 41.8%; p<0.001). In a multistate model, mortality was higher above the T1c/T2a cutoff (Hazard Ratio [HR] 1.10; p=0.01), T2a/T2b cutoff (HR 1.17; p<0.01), and T2b/T3 cutoff (HR 1.13; p=0.03). In patients who received systemic therapy, this trend was eliminated (HR 1.24; p=0.14, HR 0.79; p=0.07, and HR 1.23; p=0.09, respectively). ConclusionsRounding of tumor size for pathologic staging is common. While seemingly trivial, rounding may downstage patients and is associated with decreased rates of adjuvant therapy use and potentially worse overall survival.

Brief Report: Prognostic impact of adjuvant immunotherapy in patients with resectable non-small cell lung cancer following neoadjuvant chemoimmunotherapy

ObjectiveThe potential survival benefits of adjuvant immunotherapy for resectable non-small cell lung cancer (NSCLC) following neoadjuvant chemoimmunotherapy, as well as the optimal number of adjuvant immunotherapy cycles, remain uncertain. This study aims to evaluate the prognostic impact of adjuvant immunotherapy and determine the optimal number of cycles. MethodsA total of 438 patients who received neoadjuvant chemoimmunotherapy between August 2019 and June 2022 across four hospitals were enrolled in this study, with a median follow-up time of 31.3 months. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier methods and tested by log-rank test. Unstratified Cox proportional hazards models were fitted to the subgroups. ResultsIn this multi-center cohort, 29.7% of patients (n=130) achieved a pathologic complete response (pCR). Patients who received adjuvant immunotherapy experienced significant survival benefits compared to those who did not (RFS: hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.41-0.98, P = 0.037; OS: HR 0.27, 95% CI 0.13-0.57, P < 0.001). Subgroup analyses showed that patients with a squamous histologic type, positive PD-L1 expression, and those with a major pathologic response (MPR) particularly benefited from adjuvant immunotherapy. Additionally, we found that six cycles of adjuvant immunotherapy served as a threshold for better prognostic differentiation, suggesting that six or more cycles may be more beneficial. ConclusionsOur study demonstrated that the addition of adjuvant immunotherapy to neoadjuvant chemoimmunotherapy is significantly associated with improved RFS and OS in patients with resectable NSCLC. We also identified that six cycles of adjuvant immunotherapy may be the optimal regimen for these patients.

Outcomes of patients with COVID-19 pneumonia requiring lung resections in a third-level hospital

IntroductionCurrently, there is little evidence on the surgical management of pulmonary complications of COVID-19 pneumonia. This study aimed to give insight into common complications arising in patients with COVID-19 pneumonia that require lung resections.MethodsThis is a retrospective single-center study looking at conditions arising in patients with COVID-19 pneumonia who required lung resection for resolution between March 2020 and March 2021. Clinical presentation, indications to undergo surgery, and factors associated with increased mortality were analyzed. Analysis of nominal variables was performed using nonparametric statistical tests.ResultsTwelve men (92.3%) and one woman (7.7%) were included in the analysis; the age of included participants ranged from 27 to 72 years, with the mean age being 52. The most common presenting signs and symptoms were dyspnea and tachypnea, which were present in all patients, most common cause for surgery was pneumatocele with 6 cases, followed by lung abscess; patients who underwent surgery because of persistent air leak were more likely to require surgical reintervention (p = 0.005). The overall mortality in our sample was 23%. Increasing age (p = 0.014), myalgias (p = 0.035), elevated D-dimer (p = 0.007), and pulmonary embolism (p = 0.014) were associated with increased mortality.ConclusionsLung resections to treat pulmonary complications in patients with COVID-19 pneumonia appear to be safe, with a survival rate of 77%. Recognizing clinical characteristics such as age, myalgias, elevated D-dimer and pulmonary embolism can aid in identifying those at increased risk.

Cost-consequence analysis of the enhanced recovery after surgery protocol in major lung resection with minimally invasive technique (VATS).

ERAS is an evidence-based multimodal perioperative protocol focused on stress reduction and promoting a return to function. The aim of this work is to perform a cost-consequence analysis for the implementation of ERAS in major lung resection by means of minimally invasive surgery (VATS) from the public health service perspective, evaluating resource consumption and clinical outcomes with respect to a control group of past patients, which did not adopt an ERAS protocol. Outcome differences (re-intervention rates, major and minor intraoperative and postoperative complications, readmissions, and mortality) as well as the costs of preoperative, operative, and postoperative care were estimated. The sample consisted of 64 consecutive patients enrolled in the ERAS programme between April 2021 and August 2022, compared to a control group (historical cohort) comprising 31 patients treated from April 2020 to December 2020, prior to the implementation of the ERAS programme. The study sample comprises patients who fulfil the established ERAS protocol inclusion criteria, including general criteria (acceptance of the protocol, proximity of residence, absence of contraindications to physiotherapy and early mobilisation), surgical criteria (anatomical lung resection up to lobectomy, absence of extensive resection, good possibility of conducting the operation in VATS) and anaesthesiologic criteria (ASA ≤2). Costs were quantified using the national health system perspective. The average length-of-stay was at least one day shorter in the ERAS group [<0.001. Average total costs including entire pathway healthcare costs were substantially reduced for ERAS-VATS patients (mean: € 5,955.71 vs. €6,529.41 Δ = -573.70 p = 0.018)]. Specifically, the median costs of the admission phase were significantly different between the two groups (median: €4,648.82 vs. €5,596.58, p = 0.008), with a reduction in hospital stay expenditure in the ERAS-VATS group (median: €1,599.62 vs. €2,399.43, p = 0.025). No significant differences were found regarding major clinical outcomes. The implementation of an ERAS programme is a dominant strategy, representing an intervention capable of reducing overall costs in the context of elective anatomical lung resection with VATS without any significant differences in major complications and re-intervention rates.

Comprehensive strategies for preoperative pulmonary risk evaluation and management.

Postoperative pulmonary complications (PPCs) significantly increase morbidity and mortality in surgical patients, particularly those with pulmonary conditions. The incidence of PPCs varies widely, influenced by surgery type, patient age, smoking status, and comorbidities like chronic obstructive pulmonary disease (COPD) and congestive heart failure. Preoperative pulmonary function tests and chest radiographs, while critical for lung resection surgery, should be selectively used based on individual risk factors. Effective risk stratification models, including ASA classification, Arozullah Respiratory Failure Index, Gupta Calculators, and ARISCAT model, aid in predicting PPCs. Key strategies to reduce PPCs involve preoperative optimization of pulmonary conditions, smoking cessation, and respiratory rehabilitation. In COPD and asthma patients, maintaining optimal disease control through inhaled therapies, systemic corticosteroids, and preoperative respiratory exercises is crucial. Anemia and hypoalbuminemia are notable predictors of PPCs, warranting careful management. The type and duration of anesthesia significantly impact PPC risk, with regional anesthesia preferred over general anesthesia when feasible. Comprehensive preoperative evaluation and tailored interventions are essential to improve surgical outcomes and reduce PPC incidence. Further study involving domestic patients is needed to refine national guidelines for managing patients at risk of PPCs.

Histopathological Correlation Between High Endothelial Venule Neogenesis and the Tumor Microenvironment in Lung Adenocarcinoma.

The dynamic interplay between cancer cells and the microenvironment involves a wide range of intricate relationships that evolve during different stages of tumor progression. Recent attention has focused on high endothelial venules (HEVs), specialized endothelial cells in tumors with a unique cuboidal shape similar to those in lymph nodes. Previous animal studies have shown that normalization of tumor angiogenesis through anti-VEGFR2 therapy promotes HEV formation. However, few reports exist regarding the relationship between HEVs and preexisting blood vessels or interstitial fibers. In this study, we histologically examined whether tumor vascular structure correlates with HEV neogenesis. A total of 109 patients with pathological stage I lung adenocarcinoma who had undergone curative lung resection at our Institute between 2012 and 2016 were included. HEVs were identified by anti-peripheral node addressin (PNAd) staining. Immunostaining and Elastica-Masson-Goldner staining were performed on tumor sections and quantified. PNAd-positive cells were identified in 102 (93.6%) patients. Nearly all PNAd-positive cells were located within or near immune cell clusters. We investigated the correlation between microvessel structures or interstitial fibers and the number/density of PNAd-positive vessels, but no significant correlation was found. Since PNAd-positive cells were concentrated in immune cell aggregates, we focused our analysis specifically on these regions. Immune cell aggregates with abundant PNAd-positive vessels had a greater microvessel density along with by rich collagen fiber production, and displayed a more mature morphological phenotype of HEVs. The generation of PNAd-positive cells in tumors is governed by an angiogenetic mechanism distinct from that of broader tumor microenvironment. Furthermore, the accumulation of immune cells is associated with increased HEV maturation.