Spatiotemporal Nitric Oxide Modulation via Electrochemical Platform to Profile Tumor Cell Response.

Nitric oxide (NO) is a gaseous molecule intricately implicated in oncologic processes, encompassing the modulation of angiogenesis and instigating apoptosis. Investigation of the antitumor effects of NO is currently underway, necessitating a detailed understanding of its cellular-level reactions. Regulating the behavior of radical NO species has been a significant challenge, primarily due to its instability in aqueous environments by rapid O2-induced degradation. In this study, we devised an electrochemical platform to investigate the cellular responses to reactive gaseous molecules. Our designed platform precisely controlled the NO flux and diffusion rates of NO to tumor cells. COMSOL Multiphysics calculations based on diffusion and reaction kinetics were conducted to simulate the behavior of electrochemically generated NO. We discerned that the effective distance, NO flux, and electrolysis duration are pivotal factors governing cellular response by NO.

Different modifiable risk factors for the development of non-advanced adenoma, advanced adenomatous lesion, and sessile serrated lesions, on screening colonoscopy.

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20-2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05-2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.

Improvement of Therapeutic Effect via Inducing Non-Apoptotic Cell Death Using mRNA-Protection Nanocage.

Necroptosis, a cell death mechanism with the characteristics of both apoptosis and necrosis, is proposed as a promising therapeutic approach for cancer therapy. Induction of necroptosis for cancer therapy may be possible through the regulation of the expression of a key factor gene receptor-interacting protein kinase-3 (RIPK3) via in vitro transcription (IVT) mRNA delivery. However, mRNA is susceptible to degradation and has a low delivery efficiency, which highlights the requirement of a proper delivery vehicle for intracellular delivery. Therefore, a new mRNA delivery system based on the nanostructured silica nanoparticles, termed mRNA-protective nanocage (mPN) has been developed. High-efficiency expression of RIPK3 and induction of necroptosis is achieved through delivery of RIPK3 IVT mRNA with mPN in vitro and in vivo models. Importantly, the mPN carrying RIPK3 mRNA distributed locally in tumors upon intravascular injection, and successfully induced necroptosis and immune cell infiltration, a hallmark of necroptosis. the suppression of tumor growth in a murine cancer model, demonstrating the synergistic effect of RIPK3 mRNA- and immune cell-mediated therapy is also observed. These findings suggest the potential for anticancer therapy through necroptosis induction and provide a strategy for the development of mRNA-based nanomedicine.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

SUZ12 inhibition attenuates cell proliferation of glioblastoma via post-translational regulation of CDKN1B.

BACKGROUND: Human gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. Differential expression of Polycomb repressive complex 2 (PRC2) has been reported in various subtypes of glioma. However, the role of PRC2 in uncontrolled growth in glioma and its underlying molecular mechanisms remain to be elucidated. OBJECTIVE: We aimed to investigate the functional role of PRC2 in human glioblastoma cell growth by silencing SUZ12, the non-catalytic core component of PRC2. METHODS: Knockdown of SUZ12 was achieved by infecting T98G cells with lentivirus carrying sequences specifically targeting SUZ12 (shSUZ12). Gene expression was examined by quantitative PCR and western analysis. The impact of shSUZ12 on cell growth was assessed using a cell proliferation assay. Cell cycle distribution was analyzed by flow cytometry, and protein stability was evaluated in cycloheximide-treated cells. Subcellular localization was examined through immunofluorescence staining and biochemical cytoplasmic-nuclear fractionation. Gene expression analysis was also performed on human specimens from normal brain and glioblastoma patients. RESULTS: SUZ12 knockdown (SUZ12 KD) led to widespread decrease in the PRC2-specific histone mark, accompanied by a slowdown of cell proliferation through G1 arrest. In SUZ12 KD cells, the degradation of CDKN1B protein was reduced, resulting from alterations in the MYC-SKP2-CDKN1B axis. Furthermore, nuclear localization of CDKN1B was enhanced in SUZ12 KD cells. Analysis of human glioblastoma samples yielded increased expression of EZH2 and MYC along with reduced CDKN1B compared to normal human brain tissue. CONCLUSION: Our findings suggest a novel role for SUZ12 in cell proliferation through post-translational regulation of CDKN1B in glioblastoma.

Effect of preoperative patient education and simulated mouth breathing training on opioid requirements in the post-anesthesia care unit after nasal surgery: a randomized controlled study.

BACKGROUND: A simulated education, prior to surgery about postoperative nasal stuffiness and ease of breathing through the mouth may help patients tolerate discomfort after nasal surgery. This study aimed to investigate the effect of preoperative simulated education on immediate postoperative opioid requirements in patients undergoing elective nasal surgery. METHODS: This randomized controlled trial of 110 patients undergoing nasal surgery randomly allocated patients into either a control (group C) or an education group (group E). One day before surgery, patients in group E were intensively trained to breathe through the mouth by using a nasal clip, with informative explanations about inevitable nasal obstruction and discomfort following surgery. Patients in group C were provided with routine preoperative information. Total intravenous anesthesia (TIVA) with propofol and remifentanil was used for anesthesia. No further opioid was used for analgesia intraoperatively. The primary outcome was index opioid (fentanyl) requirements at the post-anesthesia recovery unit (PACU). Secondary outcomes were emergence agitation, pain scores at the PACU, and postoperative recovery using the Quality of Recovery-15 (QoR15-K). RESULTS: The rate of opioid use in the PACU was 51.0% in the group E and 39.6% in the group C (p = 0.242). Additional request for analgesics other than index opioid was not different between the groups. Emergence agitation, postoperative pain severity, and QoR15-K scores were comparable between the groups. CONCLUSION: Preoperative education with simulated mouth breathing in patients undergoing nasal surgery did not reduce opioid requirements. TRIAL REGISTRATION: KCT0006264; 16/09/2021; Clinical Research Information Services ( https://cris.nih.go.kr ).

Patient-derived glioblastoma cell lines with conserved genome profiles of the original tissue.

Glioblastoma (GBM) is the most lethal intracranial tumor. Sequencing technologies have supported personalized therapy for precise diagnosis and optimal treatment of GBM by revealing clinically actionable molecular characteristics. Although accumulating sequence data from brain tumors and matched normal tissues have facilitated a comprehensive understanding of genomic features of GBM, these in silico evaluations could gain more biological credibility when they are verified with in vitro and in vivo models. From this perspective, GBM cell lines with whole exome sequencing (WES) datasets of matched tumor tissues and normal blood are suitable biological platforms to not only investigate molecular markers of GBM but also validate the applicability of druggable targets. Here, we provide a complete WES dataset of 26 GBM patient-derived cell lines along with their matched tumor tissues and blood to demonstrate that cell lines can mostly recapitulate genomic profiles of original tumors such as mutational signatures and copy number alterations.

Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice.

Chemotherapies are used for treating retinoblastoma; however, numerous patients suffer from recurrence or symptoms due to chemotherapy, which emphasizes the need for alternative therapeutic strategies. The present study demonstrated that protein arginine deiminase Ⅱ (PADI2) was highly expressed in human and mouse retinoblastoma tissues due to the overexpression of E2 factor (E2F). By inhibiting PADI2 activity, the expression of phosphorylated AKT was reduced, and cleaved poly (ADP­ribose) polymerase level was increased, leading to induced apoptosis. Similar results were obtained in orthotopic mouse models with reduced tumor volumes. In addition, BB­Cl­amidine showed low toxicity in vivo. These results suggested that PADI2 inhibition has potential clinical translation. Furthermore, the present study highlights the potential of epigenetic approaches to target RB1­deficient mutations at the molecular level. The current findings provide new insights into the importance of retinoblastoma intervention by managing PADI2 activity according to the treatment of specific inhibitors and depletion approaches in vitro and in orthotopic mouse models.

Development of three-dimensional canine hepatic tumor model based on computed tomographic angiography for simulation of transarterial embolization.

Introduction: Transarterial embolization (TAE) is one of the treatment options for liver masses that are not suitable for surgery and they have been applied in veterinary medicine for about 20 years, but surgical resection is considered as the first treatment option, and only a few case reports and articles about TAE in dogs have been published. Although understanding of vascular anatomy for the procedure is important, previous studies lack of the information about hepatic artery anatomy in small and toy-breed dogs. Due to the introduction of 3D print in veterinary medicine, it is now possible to make 3D models for preoperative planning. The purpose of this study is to understand the hepatic arterial vascular structure of various sizes and breeds of dogs, and to develop 3D-printed canine artery models with and without hepatic tumors to simulate TAE procedure. Methods: CT images of a total of 84 dogs with normal hepatic arteries were analyzed, and the mean value and standard deviation of body weight, celiac artery size, and hepatic artery size were 6.47 ± 4.44 kg, 3.28 ± 0.77 mm, and 2.14 ± 0.43 mm, respectively. Results: It was established that type 2-2-1, which has two separate hepatic branches-the right medial and left branch and the right lateral branch that runs to the right lateral lobe and caudate process-is the most prevalent of the hepatic artery branch types, as it was in the previous study. The review of 65 CT images of dogs with hepatic tumors showed that 44.6% (29/65) had multifocal lesions in multiple lobes, for which TAE can be recommended. Discussion: Based on the result, a 3D model of the normal canine hepatic artery and the hepatic tumor was made using one representative case from each group, and despite the models having some limitations in reflecting the exact tactile and velocity of blood vessels, TAE procedure was successfully simulated using both models.

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration.

Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basolateral organization of the AT2s and their establishment during development and remodeling after injury repair remain unknown. Thick tissue imaging and electron microscopy revealed that a single AT2 can have multiple apical domains that enface multiple alveoli. AT2s gradually establish multi-apical domains post-natally, and they are maintained throughout life. Lineage tracing, live imaging, and selective cell ablation revealed that AT2s dynamically reorganize multi-apical domains during injury repair. Single-cell transcriptome signatures of residual AT2s revealed changes in cytoskeleton and cell migration. Significantly, cigarette smoke and oncogene activation lead to dysregulation of multi-apical domains. We propose that the multi-apical domains of AT2s enable them to be poised to support the regeneration of a large array of alveolar sacs.

The telomere maintenance mechanism spectrum and its dynamics in gliomas.

BACKGROUND: The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. METHODS: Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. RESULTS: We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. CONCLUSIONS: This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.

Subcellular progression of mesenchymal transition identified by two discrete synchronous cell lines derived from the same glioblastoma.

Glioblastomas (GBM) exhibit intratumoral heterogeneity of various oncogenic evolutional processes. We have successfully isolated and established two distinct cancer cell lines with different morphological and biological characteristics that were derived from the same tissue sample of a GBM. When we compared their genomic and transcriptomic characteristics, each cell line harbored distinct mutation clusters while sharing core driver mutations. Transcriptomic analysis revealed that one cell line was undergoing a mesenchymal transition process, unlike the other cell line. Furthermore, we could identify four tumor samples containing our cell line-like clusters from the publicly available single-cell RNA-seq data, and in a set of paired longitudinal GBM samples, we could confirm three pairs where the recurrent sample was enriched in the genes specific to our cell line undergoing mesenchymal transition. The present study provides direct evidence and a valuable source for investigating the ongoing process of subcellular mesenchymal transition in GBM, which has prognostic and therapeutic implications.

Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma.

The tumor immune microenvironment (TIME) in high-grade glioma (HGG) exhibits high spatial heterogeneity. Though the tumor core and peripheral regions have different biological features, the cause of this spatial heterogeneity has not been clearly elucidated. Here, we examined the spatial heterogeneity of HGG using core and peripheral regions obtained separately from the patients with HGG. We analyzed infiltrating immune cells by flow cytometry from 34 patients with HGG and the transcriptomes by RNA-seq analysis from 18 patients with HGG. Peripheral region-infiltrating immune cells were in vitro cultured in hypoxic conditions and their immunophenotypes analyzed. We analyzed whether the frequencies of exhausted CD8+ T cells and immunosuppressive cells in the core or peripheral regions are associated with the survival of patients with HGG. We found that terminally exhausted CD8+ T cells and immunosuppressive cells, including regulatory T (TREG) cells and M2 tumor-associated macrophages (TAMs), are more enriched in the core regions than the peripheral regions. Terminally exhausted and immunosuppressive profiles in the core region significantly correlated with the hypoxia signature, which was enriched in the core region. Importantly, in vitro culture of peripheral region-infiltrating immune cells in hypoxic conditions resulted in an increase in terminally exhausted CD8+ T cells, CTLA-4+ TREG cells, and M2 TAMs. Finally, we found that a high frequency of PD-1+CTLA-4+CD8+ T cells in the core regions was significantly associated with decreased progression-free survival of patients with HGG. The hypoxic condition in the core region of HGG directly induces an immunosuppressive TIME, which is associated with patient survival.

Genome-wide perturbations of Alu expression and Alu-associated post-transcriptional regulations distinguish oligodendroglioma from other gliomas.

Alu is a primate-specific repeat element in the human genome and has been increasingly appreciated as a regulatory element in many biological processes. But the appreciation of Alu has been limited in tumorigenesis, especially for brain tumor. To investigate the relevance of Alu to the gliomagenesis, we studied Alu element-associated post-transcriptional processes and the RNA expression of the element by performing RNA-seq for a total of 41 pairs of neurotypical and diverse glioma brain tissues. We find that A-to-I editing and circular RNA levels, as well as Alu RNA expression, are decreased overall in gliomas, compared to normal tissue. Interestingly, grade 2 oligodendrogliomas are least affected in A-to-I editing and circular RNA levels among gliomas, whereas they have a higher proportion of down-regulated Alu subfamilies, compared to the other gliomas. These findings collectively imply a unique pattern of Alu-associated transcriptomes in grade 2 oligodendroglioma, providing an insight to gliomagenesis from the perspective of an evolutionary genetic element.

Association between cardiologist evaluation and mortality in myocardial injury after non-cardiac surgery.

OBJECTIVE: Myocardial injury after non-cardiac surgery (MINS) is strongly associated with mortality, but few studies assessed treatment strategies. This study aimed to identify whether evaluation by cardiologists could reduce mortality in MINS patients. METHODS: From a single-centre retrospective cohort, we enrolled a total of 5633 adult patients diagnosed with MINS between January 2010 and June 2019. The patients were divided into two groups based on evaluation by cardiologist, which was defined as a cardiology consultation or transfer to the cardiology department. For the outcome, 30-day mortality was compared in crude and propensity-score matched populations. RESULTS: Of a total of 5633 patients, 2120 (37.6%) were evaluated by cardiologists and 3513 (62.4%) were not. Mortality during the first 30 days after surgery was significantly lower in MINS patients who were evaluated by cardiologists compared with those who were not (5.8% vs 8.3%; HR, 0.64; 95% CI 0.51 to 0.80; p<0.001 for all-cause mortality and 1.6% vs 2.0; HR 0.62; 95% CI 0.40 to 0.96; p=0.03 for cardiovascular mortality). The propensity score matched analysis showed similar results (5.6% vs 8.6%; HR 0.64; 95% CI 0.50 to 0.81; p<0.001 for all-cause mortality and 1.3% vs 2.2%; HR 0.58; 95% CI 0.35 to 0.95; p=0.03 for cardiovascular mortality). CONCLUSIONS: Cardiologist evaluation was associated with lower mortality in patients diagnosed with MINS. Further studies are needed to identify effective treatment strategies for MINS. TRIAL REGISTRATION NUMBER: KCT0004244.

Association between preoperative neutrophil-lymphocyte ratio and mortality after plastic and reconstructive surgery.

Predictive factors associated with postoperative mortality have not been extensively studied in plastic and reconstructive surgery. Neutrophil-lymphocyte ratio (NLR), a systemic inflammation index, has been shown to have a predictive value in surgery. We aimed to evaluate association between preoperative NLR and postoperative outcomes in patients undergoing plastic and reconstructive surgery. From January 2011 to July 2019, we identified 7089 consecutive adult patients undergoing plastic and reconstructive surgery. The patients were divided according to median value of preoperative NLR of 1.84. The low NLR group was composed of 3535 patients (49.9%), and 3554 patients (50.1%) were in the high NLR group. The primary outcome was mortality during the first year, and overall mortality and acute kidney injury were also compared. In further analysis, outcomes were compared according to quartile of NLR, and a receiver operating characteristic curve was constructed to estimate the threshold associated with 1-year mortality. This observational study showed that mortality during the first year after plastic and reconstructive surgery was significantly increased in the high NLR group (0.7% vs. 3.5%; hazard ratio, 4.23; 95% confidence interval, 2.69-6.63; p < 0.001), and a graded association was observed between preoperative NLR and 1-year mortality. The estimated threshold of preoperative NLR was 2.5, with an area under curve of 0.788. Preoperative NLR may be associated with 1-year mortality after plastic and reconstructive surgery. Further studies are needed to confirm our findings.

Intraoperative Hyperglycemia May Be Associated with an Increased Risk of Myocardial Injury after Non-Cardiac Surgery in Diabetic Patients.

BACKGROUND: Hyperglycemia in surgical candidates is associated with increased mortality and morbidity. We aimed to evaluate the effect of intraoperative blood glucose level on the incidence of myocardial injury after non-cardiac surgery (MINS) in diabetic patients. METHODS: Diabetic patients with available intraoperative blood glucose measurement during non-cardiac surgery were enrolled in this study. Based on the highest intraoperative blood glucose level, patients were stratified into two groups: the blood sugar glucose (BST) < 180 group (intraoperative peak glucose < 180 mg/dL) and BST ≥ 180 group (intraoperative peak glucose ≥ 180 mg/dL). The primary outcome was the incidence of MINS, and secondary outcomes were in-hospital and 30-day mortalities. RESULTS: Of the 11,302 diabetic patients, 8337 were in the BST < 180 group (73.8%) and 2965 in the BST ≥ 180 group (26.2%). After adjustment with inverse probability weighting, MINS was significantly higher in the BST ≥ 180 group (24.0% vs. 17.2%; odds ratio (OR), 1.26; 95% confidence interval (CI), 1.14-1.40; p < 0.001). In addition, in-hospital and 30-day mortalities were also higher in the BST ≥ 180 group compared to the BST < 180 group (4.2% vs. 2.3%, hazard ratio (HR), 1.39; 95% CI, 1.07-1.81; p = 0.001, and 3.1% vs. 1.8%; HR, 1.76; 95% CI, 1.31-2.36; p < 0.001, respectively). Receiver-operating characteristic plots showed that the threshold of glucose level associated with MINS was 149 mg/dL. CONCLUSION: Intraoperative hyperglycemia was associated with an increased MINS incidence and postoperative mortality in diabetic patients. Close monitoring of intraoperative blood glucose level may be helpful in detection and management of MINS.

Association between Intraoperative Hyperlactatemia and Myocardial Injury after Noncardiac Surgery.

BACKGROUND: Oxygen demand-supply mismatch is supposed to be one of the major causes of myocardial injuries after noncardiac surgery (MINS). Impaired tissue oxygenation during the surgery can lead to intraoperative hyperlactatemia. Therefore, we aimed to evaluate the relationship between intraoperative lactate level and MINS. METHODS: A total of 1905 patients divided into groups according to intraoperative hyperlactatemia: 1444 patients (75.8%) into normal (≤2.2 mmol/L) and 461 patients (24.2%) into hyperlactatemia (>2.2 mmol/L) groups. The primary outcome was the incidence of MINS, and all-cause mortality within 30 days was compared. RESULTS: In the crude population, the risks for MINS and 30-day mortality were higher for the hyperlactatemia group than the normal group (17.7% vs. 37.7%, odds ratio [OR]: 2.83, 95% confidence interval [CI]: 2.24-3.56, p < 0.001 and 0.8% vs. 4.8%, hazard ratio [HR]: 5.86, 95% CI: 2.9-12.84, p < 0.001, respectively). In 365 propensity score-matched pairs, intraoperative hyperlactatemia was consistently associated with MINS and 30-day mortality (21.6% vs. 31.8%, OR: 1.69, 95% CI: 1.21-1.36, p = 0.002 and 1.1% vs. 3.8%, HR: 3.55, 95% CI: 1.71-10.79, p < 0.03, respectively). CONCLUSION: Intraoperative lactate elevation was associated with a higher incidence of MINS and 30-day mortality.

Comparison of Positive End-Expiratory Pressure versus Tidal Volume-Induced Ventilator-Driven Alveolar Recruitment Maneuver in Robotic Prostatectomy: A Randomized Controlled Study.

BACKGROUND: We evaluated the pulmonary effects of two ventilator-driven alveolar recruitment maneuver (ARM) methods during laparoscopic surgery. METHODS: Sixty-four patients undergoing robotic prostatectomy were randomized into two groups: incrementally increasing positive end-expiratory pressure in a stepwise manner (PEEP group) versus tidal volume (VT group). We performed each ARM after induction of anesthesia in the supine position (T1), after pneumoperitoneum in the Trendelenburg position (T2), and after peritoneum desufflation in the supine position (T3). The primary outcome was change in end-expiratory lung impedance (EELI) before and 5 min after ARM at T3, measured by electrical impedance tomography. RESULTS: The PEEP group showed significantly higher increasing EELI 5 min after ARM than the VT group at T1 and T3 (median [IQR] 460 [180,800] vs. 200 [80,315], p = 0.002 and 280 [170,420] vs. 95 [55,175], p = 0.004, respectively; PEEP group vs. VT group). The PEEP group showed significantly higher lung compliance and lower driving pressure at T1 and T3. However, there was no significant difference in EELI change, lung compliance, or driving pressure after ARM at T2. CONCLUSIONS: The ventilator-driven ARM by the increasing PEEP method led to greater improvements in lung compliance at the end of laparoscopic surgery than the increasing VT method.