Emergent ultrasmall multiferroics in paraelectric perovskite oxide by hole polarons.

Ultimately small multiferroics with coupled ferroelectric and ferromagnetic order parameters have drawn considerable attention for their tremendous technological potential. Nevertheless, these ferroic orders inevitably disappear below the critical size of several nanometers in conventional ferroelectrics or multiferroics. Here, based on first-principles calculations, we propose a new strategy to overcome this limitation and create ultrasmall multiferroic elements in otherwise nonferroelectric CaTiO3 by engineering the interplay of oxygen octahedral rotations and hole polarons, though both of them are generally believed to be detrimental to ferroelectricity. It is found that the hole doped in CaTiO3 spontaneously forms a localized polaronic state. The lattice distortions associated with a hole polaron interacting with the intrinsic oxygen octahedral rotations in CaTiO3 effectively break the inversion symmetry and create atomic-scale ferroelectricity beyond the critical size limitation. The hole polaron also causes highly localized magnetism attributed to the associated spin-polarized electric state and thus manifests as a multiferroic polaron. Moreover, the hole polaron exhibits high hopping mobility accompanied by rich switching of polarization and magnetic directions, indicating strong magnetoelectric coupling with a mechanism dissimilar from that of conventional multiferroics. The present work provides a new mechanism to engineer inversion symmetry and opens avenues for designing unusual multifunctional materials.

Outcomes and pathologic response of primary lung cancer treated with tyrosine kinase inhibitor/immune checkpoint inhibitor before salvage surgery.

PURPOSE: Advances in primary lung cancer drug therapy have extended patients' survival, including patients with stage IV disease. This study assessed the safety and effectiveness of salvage surgery following tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapy in primary lung cancer. METHODS: A retrospective chart review was conducted of 2050 primary lung cancer surgeries performed at our institution between 2012 and 2022. The study included patients who underwent salvage surgery for unresectable lesions that became resectable or localized residual lesions after treatment. We investigated patients' clinicopathological characteristics, therapeutic responses, and survival outcomes. RESULTS: We identified eight cases of salvage surgery after TKI treatment and eight cases after ICI treatment. Five patients experienced early recurrence after surgery; however, the long-term outcome in the post-TKI group was favorable, with a median overall survival (OS) of 66 (range: 28-80) months. Postoperative recurrence was confined to local lymph node recurrence in one patient in the post-ICI group. Despite the relatively short observation period, the long-term prognosis remained promising, with a median OS of 18.7 (range: 9.7-55.8) months. CONCLUSIONS: Salvage surgery after TKI or ICI treatment can be safely performed, and the OS may be favorable.

Prognostic impact of circulating tumor cells detected with the microfluidic "universal CTC-chip" for primary lung cancer.

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression-free survival (P = .037) and cancer-specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression-free survival was worse in CTC-positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM-chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.

Surgical strategy for malignant pleural mesothelioma: the superiority of pleurectomy/decortication.

PURPOSE: Both extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are used for the surgical treatment of malignant pleural mesothelioma (MPM). This study aimed to compare the operative and clinical outcomes and survival between EPP and P/D. METHODS: We performed a retrospective analysis of the surgical and clinical data of 40 patients who underwent either EPP (n = 18) or P/D (n = 22) for MPM at our institution between January 2000 and December 2018. RESULTS: In comparison to EPP, P/D was associated with a higher intraoperative bleeding volume (1175 vs 1805 ml, p = 0.0020) and greater duration of postoperative thoracic drainage (3 vs 16 days, p < 0.0001). Adjuvant chemotherapy was more common after P/D (81.8%) than after EPP (33.3%; p = 0.0024). For epithelioid-type MPM, overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients who underwent P/D in comparison to those who underwent EPP (p = 0.040 and p = 0.015, respectively), with no difference for the biphasic and sarcomatoid types of MPM. A Cox proportional hazards regression model identified P/D as a significant favorable prognostic factor for OS [hazard ratio (HR), 0.391; 95% confidence interval (CI), 0.175-0.871; p = 0.022] and RFS (HR, 0.418; 95% CI, 0.190-0.920; p = 0.030). CONCLUSIONS: Based on our findings, P/D may be superior to EPP for improving the prognosis of patients with resectable epithelioid-type MPM.

The role of heparin bridging in lung cancer surgery: a nationwide database analysis.

PURPOSE: There is little evidence to demonstrate the impact of heparin bridging (HB) in major surgery. This study aimed to evaluate the benefits and risks of HB in lung cancer surgery by comparing HB and non-HB (NHB) groups. METHODS: We extracted patients who were taking an anticoagulant, were diagnosed with lung cancer, and underwent lung resection between April 2014 and March 2018 from a nationwide database in Japan. We compared the HB and NHB groups to determine the benefits and risks of HB. The proportion of postoperative thromboembolism and bleeding events between the HB and NHB groups was the primary outcome. We performed propensity score matching to remove any HB assignment bias. RESULTS: We selected 2416 patients, and among these, 1068 patients had HB and 1348 did not. Propensity score matching extracted 1500 patients: 750 with HB and 750 without HB. After matching, a Chi-square test showed no significant difference in the incidence of postoperative thromboembolism (1.5% vs 0.9%, p value = 0.343) and bleeding events (5.9% vs 4.0%, p value = 0.124) between the two groups. CONCLUSIONS: There was no significant difference in the incidence of postoperative thromboembolism and bleeding in the patients with and those without HB.

The surgical technique for complete resection of lung cancer invading the intrapericardial pulmonary vein and left atrium.

In patients with lung cancer invading the left atrium, performing complete resection is difficult. In many cases of complete resection, pneumonectomy is performed. We herein report two techniques in which complete resection with negative margins at the intrapericardial pulmonary vein and left atrium was achieved without pneumonectomy. In the first technique, the groove of the pericardium between the right and left atrium was dissected and an atrial cuff was made in a manner that elongated the intrapericardial pulmonary vein. In the second technique, traction was applied to the atrial cuff, and only the middle lobe vein of the elongated pulmonary vein was resected, to perform atrial cuff plasty. The upper lobe vein and inferior pulmonary vein could be preserved. These techniques of PV elongation and atrial cuff plasty are suitable for both achieving complete resection and lung preservation for lung cancer patients with invasion of the left atrium.

[The Outcome of Multiple Lung Cancer Cases with Two-stage Surgery].

BACKGROUNDS: There is an increasing number of cases of two-stage surgery for synchronous or metachronous lung cancer. We discuss the surgical treatment strategy for multiple lung cancers. METHODS: We retrospectively reviewed the clinicopathological factors and prognosis of 105 patients (210 surgeries) who underwent two-stage surgery for lung cancer during the period from 2010 to 2019 in our department. RESULTS: A total of 105 cases were reviewed;58 males and 47 females, 67 were synchronous and 38 were metachronous. Long-term prognosis of death from other diseases due to respiratory diseases was found in eight patients (7.6%). Recurrence of lung cancer was observed in 29 (27.6%), and cancer death was found in 9 of them. The overall three-year and five-year survival rates were 85.3% and 71.3 %, respectively. The absence of ground-glass opacity components in the tumor( p=0.036) and advanced pathological stage( p=0.048) were significantly associated with postoperative recurrence. CONCLUSIONS: The recurrence rate was high in cases of solid tumors and advanced pathological stage, even in multiple lung cancers. Thus, an appropriate combination of limited surgery and standard surgery should be used, taking into account the nature of the tumor and the patient's ability to tolerate the surgery.

Perioperative pirfenidone treatment for lung cancer patients with idiopathic pulmonary fibrosis.

PURPOSE: To assess the efficacy and feasibility of perioperative pirfenidone treatment (PPT) in lung cancer patients with idiopathic pulmonary fibrosis (IPF). METHODS: The subjects of this retrospective review were 100 patients diagnosed with IPF, who underwent surgical resection for primary lung cancer between January 2011 and April 2018 at our institution. We compared the clinical outcomes of patients treated with pirfenidone (PPT group; n = 28) and those of patients not treated with pirfenidone (non-PPT group; n = 72). RESULTS: The Japanese Association for Chest Surgery (JACS) risk score was significantly higher in the PPT group (p = 0.020, 10.9 vs. 9.4); therefore, we subdivided the groups based on JACS risk score. In the low-risk group, the incidence of postoperative acute exacerbation (AE) both within the postoperative day (POD) 30 and 90 was 0.0% (0/6) and 6.5% (2/31) in the PPT and non-PPT groups, respectively (p = 0.522). In the intermediate/high-risk group, the incidence of postoperative AE was 4.5% (1/22) and 19.5% (8/41) within POD 30 (p = 0.106) and 4.5% (1/22) and 24.4% (10/41) within POD 90 (p = 0.048) in the PPT and non-PPT groups, respectively. No serious pirfenidone-related complications were observed. CONCLUSIONS: Based on our findings, PPT is an effective and feasible prophylactic treatment to reduce postoperative AE.

[Carinal Resection with Lung Resection and Perioperative Management].

Carinal resection with lung resection is a rare surgical procedure with high risk. In-hospital mortality rates for carinal reconstruction and sleeve pneumonectomy were 6.5% and 16.7%, respectively. Thus, thoracic surgeons need to learn the procedure for patients who need the surgery. This time, we will account for preoperative evaluation, intraoperative advice, and postoperative management in carinal resection with right upper lobectomy presenting 2 cases in our hospital. Case 1 had a high caliber mismatch of bronchial stumps because of partial carinal resection, which was corrected by simple sutures of the anterior cartilage. That allowed us to perform sleeve right upper lobectomy avoiding carinal reconstruction. Case 2 was a case in which lung and bronchial tissue sticking to mediastinum due to obstructive pneumonia prevented us from anastomosing intermediate bronchus to the trachea or left main bronchus. We had to choose sleeve right pneumonectomy, and a fistula on the anastomotic site occurred later resulting in a bad course. We hope our experiences aid future patients who need the carinal resection.

Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma.

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated. The CTC-chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell-detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC-chip showed superior CTC-detection performance over CellSearch in experimental models (sensitivity, 63.3%-64.5% vs 0%-1.1%; P < .001) and in clinical samples (CTC-positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC-chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer.

BACKGROUND: Consolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies. METHODS: To examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy. RESULTS: PD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival (P = 0.019). CONCLUSION: Tumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

VAB-10 spectraplakin acts in cell and nuclear migration in Caenorhabditis elegans.

Cytoskeletal regulation is important in cell migration. The Caenorhabditis elegans gonadal distal tip cells (DTCs) offer a simple model with which to investigate the mechanism of cell migration in organogenesis. Here, we report that one of the spectraplakin isoforms, VAB-10B1, plays an essential role in cell and nuclear migration of DTCs by regulating the actin and microtubule (MT) cytoskeleton. In the vab-10(tk27) mutant, which lacks VAB-10B1, alignment of filamentous (F)-actin and MTs was weakly and severely disorganized, respectively, which resulted in a failure to translocate the DTC nucleus and a premature termination of DTC migration. An MT growing-tip marker, EBP-2-GFP, revealed that polarized outgrowth of MTs towards the nuclei of migrating DTCs was strikingly impaired in tk27 animals. A vab-10 mini-gene encoding only the actin- and MT-binding domains significantly rescued the gonadal defects, suggesting that VAB-10B1 has a role in linking actin and MT filaments. These results suggest that VAB-10B1/spectraplakin regulates the polarized alignment of MTs, possibly by linking F-actin and MTs, which enables normal nuclear translocation and cell migration of DTCs.

Case report: Pathological complete response of pregnancy associated pulmonary enteric adenocarcinoma to chemoradiotherapy.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological features similar to those of primary and metastatic colorectal adenocarcinoma. To date, only a few studies have reported the therapeutic effects of chemoradiotherapy on PEAC. This report describes the case of a 28-year-old woman with pregnancy-related PEAC who presented with left shoulder pain. A superior sulcus tumor was identified in the left thoracic cavity, and the biopsy indicated more than 50% intestinal differentiation components. Moreover, immunohistochemical staining revealed positive CDX2 and CK7 expression. Positron emission tomography-computed tomography, upper endoscopy, colonoscopy, and small intestinal capsule endoscopy revealed no gastrointestinal malignancies. The patient was diagnosed with locally advanced PEAC (clinical stage T4N0M0; stage IIIA). Therefore, the patient was treated with preoperative chemoradiotherapy and underwent gross total resection during surgery. Pathological evaluation of the specimen revealed no residual tumor, indicating that the chemoradiotherapy for PEAC was highly effective. One subsequent brain metastasis was also resected, and the patient has not experienced recurrence in 28 months since this resection and continues to be monitored regularly. This is the first pathologically confirmed report of the use of chemoradiotherapy (carboplatin [CBDCA] and paclitaxel [PTX]) for PEAC and its clinical efficacy. Unlike previous reports, the efficacy of this treatment is attributed to the use of PTX in preoperative chemotherapy and the p21- status of the patient, which may have increased sensitivity to chemoradiation therapy. Therefore, chemoradiotherapy (CBDCA + PTX) may be a viable treatment option for advanced intestinal lung adenocarcinoma.

Salvage pleurectomy/decortication following immunotherapy for malignant pleural mesothelioma.

Salvage surgery following immunotherapy is a promising treatment option for advanced malignant tumour. However, only a few cases of salvage surgery for malignant pleural mesothelioma (MPM) have been reported. This retrospective study was conducted to assess the feasibility of salvage surgery following immunotherapy for initially unresectabele MPM. Among 61 patients who received pleurectomy/decortication (P/D) for MPM, 7 patients received salvage P/D after immunotherapy. Surgical indication of salvage P/D was conversion to resectability in 5 patients and local relapse in 2 patients, and macroscopic complete resection was achieved in all patients. Although salvage P/D was associated with longer operation time (median, 507 min), higher intraoperative blood loss (median, 2573 mL) and higher morbidity (≥ grade 3, 29%), no patient died after surgery. Radiographic response to immunotherapy was well correlated with pathologic response, as all 4 patients with partial response showed significant pathologic response (viable cells, ≤50%). With the median postoperative follow-up duration of 9.0 months, all patients were alive mostly without tumour recurrence as local recurrence developed in 1 patient. To conclude, salvage P/D after immunotherapy may be a feasible treatment option for selected patients with advanced MPM, which should be validated in future multi-institutional studies. In addition, a long-term follow-up is essential to reveal the clinical benefit achieved with salvage P/D following immunotherapy.

Sarcomatoid malignant pleural mesothelioma: a case of long-term recurrence-free survival following curative intent surgery alone.

BACKGROUND: Curative intent surgery may be indicated for some patients with resectable early stage malignant pleural mesothelioma (MPM). However, sarcomatoid MPM is a highly aggressive subtype for which curative intent surgery is generally not recommended. CASE PRESENTATION: We present the case of a 63-year-old man who presented with dyspnea and chest tightness. Computed tomography revealed pleural thickening and nodular lesions. A pleural biopsy confirmed lymphohistiocytoid MPM (cT1N0M0, stage IA), prompting surgical intervention. The patient underwent left extrapleural pneumonectomy (EPP), and the final diagnosis was sarcomatoid MPM (pT2N0M0, stage IB). Although post-operative chemotherapy was planned, the patient refused additional treatment, because of the introduction of home oxygen therapy, and has remained recurrence-free for 10 years after the surgery. CONCLUSIONS: This case presents a noteworthy instance of achieving long-term recurrence-free survival solely through curative intent surgery for sarcomatoid MPM. It highlights the potential efficacy of surgical intervention in managing this aggressive subtype, offering a glimmer of hope for improved outcomes. Further research is warranted to better define the role of surgery in the treatment of sarcomatoid MPM.

Enhanced capture system for mesenchymal­type circulating tumor cells using a polymeric microfluidic device 'CTC­Chip' incorporating cell­surface vimentin.

CellSearch, the only approved epithelial cell adhesion molecule (EpCAM)­dependent capture system approved for clinical use, overlooks circulating tumor cells (CTCs) undergoing epithelial­mesenchymal transition (EMT­CTCs), which is considered a crucial subtype responsible for metastasis. To address this limitation, a novel polymeric microfluidic device 'CTC­chip' designed for the easy introduction of any antibody was developed, enabling EpCAM­independent capture. In this study, antibodies against EpCAM and cell surface vimentin (CSV), identified as cancer­specific EMT markers, were conjugated onto the chip (EpCAM­chip and CSV­chip, respectively), and the capture efficiency was examined using lung cancer (PC9, H441 and A549) and colon cancer (DLD1) cell lines, classified into three types based on EMT markers: Epithelial (PC9), intermediate (H441 and DLD1) and mesenchymal (A549). PC9, H441 and DLD1 cells were effectively captured using the EpCAM­chip (average capture efficiencies: 99.4, 88.8 and 90.8%, respectively) when spiked into blood. However, A549 cells were scarcely captured (13.4%), indicating that EpCAM­dependent capture is not suitable for mesenchymal­type cells. The expression of CSV tended to be higher in cells exhibiting mesenchymal properties and A549 cells were effectively captured with the CSV­chip (72.4 and 88.4% at concentrations of 10 and 100 µg/ml, respectively) when spiked into PBS. When spiked into blood, the average capture efficiencies were 27.7 and 46.8% at concentrations of 10 and 100 µg/ml, respectively. These results suggest that the CSV­chip is useful for detecting mesenchymal­type cells and has potential applications in capturing EMT­CTCs.

C/EBP homologous protein-10 (CHOP-10) limits postnatal neovascularization through control of endothelial nitric oxide synthase gene expression.

BACKGROUND: C/EBP homologous protein-10 (CHOP-10) is a novel developmentally regulated nuclear protein that emerges as a critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. In the present study, we analyzed the role of CHOP-10 in postnatal neovascularization. METHODS AND RESULTS: Ischemia was induced by right femoral artery ligation in wild-type and CHOP-10(-/-) mice. In capillary structure of skeletal muscle, CHOP-10 mRNA and protein levels were upregulated by ischemia and diabetes mellitus. Angiographic score, capillary density, and foot perfusion were increased in CHOP-10(-/-) mice compared with wild-type mice. This effect was associated with a reduction in apoptosis and an upregulation of endothelial nitric oxide synthase (eNOS) levels in ischemic legs of CHOP-10(-/-) mice compared with wild-type mice. In agreement with these results, eNOS mRNA and protein levels were significantly upregulated in CHOP-10 short interfering RNA-transfected human endothelial cells, whereas overexpression of CHOP-10 inhibited basal transcriptional activation of the eNOS promoter. Using a chromatin immunoprecipitation assay, we also showed that CHOP-10 was bound to the eNOS promoter. Interestingly, enhanced postischemic neovascularization in CHOP-10(-/-) mice was fully blunted in CHOP-10/eNOS double-knockout animals. Finally, we showed that induction of diabetes mellitus is associated with a marked upregulation of CHOP-10 that substantially inhibited postischemic neovascularization. CONCLUSIONS: This study identifies CHOP-10 as an important transcription factor modulating vessel formation and maturation.

Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy.

We investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.0%, p = 0.000), whereas that of CD155 did not significantly differ (40.0% vs 60.0%, p = 0.131). The PD-1 expression was not significantly different between the cCRT and drug therapy groups (51.1% vs 42.9%, p = 0.076), while the TIGIT was significantly higher in the cCRT group (41.5% vs 34.0%, p = 0.008). The patients who received cCRT resulted in elevated PD-L1and TIGIT values had a worse prognosis (p = 0.008). The PD-L1 and TIGIT expression after cCRT was significantly higher than after drug treatment. The cCRT population with high expression of both had a significantly poorer prognosis, indicating elevation of PD-L1 and TIGIT after cCRT as a negative prognostic factor. Combination therapy with anti-PD-L1 and anti-TIGIT antibodies after cCRT may contribute to an improved prognosis.

Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses.

BACKGROUND: The processes of arteriosclerosis, including atherosclerosis and vascular remodeling, are affected by interactions among numerous biological pathways such as responses to inflammation, oxidative stress, and endoplasmic reticulum stress. C/EBP homologous protein (CHOP), which is well known to induce cellular apoptosis in response to severe endoplasmic reticulum stress, is reportedly upregulated in plaque lesions. METHODS AND RESULTS: We examined the effects of CHOP deficiency on 2 types of arteriosclerosis: cuff injury-induced neointimal formation and hypercholesterolemia-induced atherosclerosis. Cuff injury-induced neointimal formation was markedly inhibited in CHOP(-/-) mice with suppressed aortic expression of inflammatory factors and smooth muscle cell proliferation-related proteins. A CHOP deficiency also inhibited aortic plaque formation in hypercholesterolemic apolipoprotein E(-/-) mice with suppressed aortic expression of inflammatory factors and oxidative stress markers. Bone marrow transplantation experiments revealed that recipient CHOP deficiency significantly suppressed both cuff injury-induced neointimal formation and hypercholesterolemia-induced atherosclerotic plaque formation to a greater extent than donor CHOP deficiency, suggesting the importance of CHOP in vascular cells for arteriosclerosis progression. Furthermore, in our in vitro experiments, in not only macrophages but also endothelial and smooth muscle cell lines, endoplasmic reticulum stress inducers upregulated inflammation-, adhesion-, or smooth muscle cell proliferation-related proteins, whereas decreased CHOP expression remarkably suppressed endoplasmic reticulum stress-induced upregulation of these proteins. CONCLUSIONS: In addition to the well-known signaling for apoptosis induction, CHOP may play important roles in augmenting potentially pathological biological stress responses. This noncanonical role of CHOP, especially that expressed in vascular cells, may contribute to the progression of vascular remodeling and atherosclerosis.

Dislocation of a middle lobe torsion-preventing bridging structure with an absorptive sheet and fibrin glue: a case report.

BACKGROUND: Middle lobe torsion is a rare complication of right upper lobectomy. Middle lobe torsion can be critical; thus, various preventive measures are used. CASE PRESENTATION: A 77-year-old man underwent thoracoscopic right upper lobectomy with partial middle resection and S6 segmentectomy for right upper lobe lung cancer located at the confluence of the three lobes and lower lobe lung cancer. Inversion of the middle lobe was observed during lung expansion before chest closure. A bridging structure with an absorptive sheet and fibrin glue was placed in the basal section of the middle lobe under lung expansion to prevent torsion. On postoperative day 1, the patient was tachycardic and was found to have decreased lung field permeability. The patient underwent emergency surgery for suspected middle lobe torsion. Dislocation of the bridging structure between the basal segments of the middle lobe was confirmed, and the middle lobe was deviated cephalad. In addition, pulmonary congestion in S4 due to pressure stenosis of V4 caused by the deviation of the middle lobe was observed, and middle lobe resection was performed. The postoperative course was uneventful. CONCLUSIONS: This case suggested that the reinforcement method with an absorptive sheet and fibrin glue lacked sufficient strength to prevent middle lobe torsion. Stronger fixation should be considered if the middle lobe rotation is thought to be sufficiently strong when the lung is reinflated before chest closure.