The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

Number of lymph nodes dissected and upstaging rate of the N factor in robot-assisted thoracic surgery versus video-assisted thoracic surgery for patients with cN0 primary lung cancer.

PURPOSE: The accuracy of lymph node (LN) dissection in robotic surgery for lung cancer remains controversial. We compared the accuracy of LN dissection in robot-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS). METHODS: The subjects of this retrospective analysis were 226 patients with cN0 primary lung cancer who underwent robot-assisted or video-assisted thoracic lobectomy with LN dissection, in our department, between April, 2016 and February, 2021. We compared the numbers of all LNs and mediastinal LNs dissected, the time required for LN dissection, complications, and upstaging rates of the N factor between the groups. Furthermore, we performed an inverse probability of treatment weighting-adjusted analysis to reduce potential bias between the groups. RESULTS: The number of dissected LNs was higher in the RATS group in both the unweighted and weighted analyses. The time required for lymph node dissection was also longer in RATS. There was no significant difference in complications or in the upstaging rate of the N factor between the groups. CONCLUSION: More LNs were dissected with RATS. Thus, the usefulness of robot-assisted surgery for LN dissection needs to be investigated further.

Effects of histone deacetylase inhibitors Tricostatin A and Quisinostat on tight junction proteins of human lung adenocarcinoma A549 cells and normal lung epithelial cells.

Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for non-small cell lung cancer (NSCLC). However, more preclinical studies of HDAC inhibitors in NSCLC and normal lung epithelial cells are required to evaluate their antitumor activities and mechanisms. The bicellular tight junction molecule claudin-2 (CLDN-2) is highly expressed in lung adenocarcinoma tissues and increase the proliferation of adenocarcinoma cells. Downregulation of the tricellular tight junction molecule angulin-1/LSR induces malignancy via EGF-dependent CLDN-2 and TGF-ß-dependent cellular metabolism in human lung adenocarcinoma cells. In the present study, to investigate the detailed mechanisms of the antitumor activities of HDAC inhibitors in lung adenocarcinoma, human lung adenocarcinoma A549 cells and normal lung epithelial cells were treated with the HDAC inibitors Trichostatin A (TSA) and Quisinostat (JNJ-2648158) with or without TGF-ß. Both HDAC inhibitors increased anguin-1/LSR, decrease CLDN-2, promoted G1 arrest and prevented the migration of A549 cells. Furthermore, TSA but not Quisinostat with or without TGF-ß induced cellular metabolism indicated as the mitochondrial respiration measured using the oxygen consumption rate. In normal human lung epithelial cells, treatment with TSA and Quisinostat increased expression of LSR and CLDN-2 and decreased that of CLDN-1 with or without TGF-ß in 2D culture. Quisinostat but not TSA with TGF-ß increased CLDN-7 expression in 2D culture. Both HDAC inhibitors prevented disruption of the epithelial barrier measured as the permeability of FD-4 induced by TGF-ß in 2.5D culture. TSA and Quisinostat have potential for use in therapy for lung adenocarcinoma via changes in the expression of angulin-1/LSR and CLDN-2.

[Congenital Pericardial Defect Incidentally Found at Thoracoscopic Left Upper Lobe Resection:Report of a Case].

We report a rare case of a congenital pericardial defect that was incidentally found at thoracoscopic left upper lobe resection in a patient with lung cancer. A 75-year-old man with a left upper lobe lung cancer was referred to our hospital. We performed thoracoscopic left upper lobectomy and incidentally found a pericardial defect intraoperatively. Careful lymph node dissection was necessary to avoid injury of phrenic nerve and pulmonary artery. Surgery for lung cancer was completed without pericardial repair. After surgery, no complications associated with the pericardial defect has not been encountered.

[Spinal Cord Infarction after Right Upper Lobectomy Combined with Chest Wall Resection].

A 42-year-old man presented with a one-month history of back pain. Chest computed tomography revealed a mass (7.6×5.7 cm) in the right upper lobe, suspicious of chest wall invasion. We performed right upper lobectomy combined with chest wall resection. Partial dissections of the second to sixth ribs and the third and fourth vertebral bodies were conducted. Postoperatively, motor paralysis of the right lower extremity was observed and a diagnosis of spinal infarction was made. After cerebrospinal fluid drainage and administration of edaravone with early rehabilitation, he was able to walk with a brace and was discharged from the hospital.

[Left Upper Lobectomy Followed by Left Lower Pulmonary Vein Reconstruction after Miscutting the Common Trunk of the Left Pulmonary Veins].

A 65-year-old woman was diagnosed with lung cancer on the left upper lobe. During thoracoscopic left upper lobectomy, the common trunk of pulmonary vein was mistaken for the left upper pulmonary vein and divided incorrectly. Instead of left pneumonectomy, we successfully performed pulmonary vein reconstruction. As a result of anticoagulant therapy for 1 month, postoperative course was uneventful.

[Successful Robotic Resection of Left Upper Mediastinal Tumor].

A man was diagnosed with a left upper mediastinal mass. The mass was located near the left subclavian vein, phrenic nerve, vagus nerve, left subclavian artery, and left brachiocephalic vein. He underwent a robotic surgery without additional approaches such as cervical approach on transmanubrial approach. Robotic surgery enabled to remove the tumor safely due to the highly flexible robot forceps under a 3-dimensional visual field. Robotic surgery may be effective for tumors in the upper mediastinum, where important blood vessels and nerves are closely present.

Comparison of imaging changes in pulmonary artery diameter at the occlusion site using silk or metal clamps for pulmonary artery troubles.

OBJECTIVES: We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and safety. METHODS: We retrospectively reviewed the records of patients who underwent either of the above clamping techniques during anatomical lung resection at our hospital between April 2007 and August 2022. We measured the PA diameter at the occlusion site on computed tomography images acquired within 1 year pre- and postoperatively. The difference between pre- and postoperative diameters of the occlusion sites was calculated as the change in the PA diameter. We zoned the occlusion site of the PA to adjust for variation. PA deformation was evaluated as an adverse event caused by clamping. RESULTS: Ultimately, 27 and 26 patients who underwent the DLT and DeBakey clamp, respectively, were included. No additional injury due to the clamp procedure was found in either group. For zone R1/L1, defined as the main PA, the median changes in the PA diameter were 0.02 (-0.7 to 0.27) mm for the DLT and 0.36 (-0.28 to 0.89) mm for the DeBakey clamp. No significant differences were observed between the 2 groups (P = 0.106). Furthermore, no aneurysms, dissections, or stenoses were found in either group. CONCLUSIONS: The DLT and DeBakey clamp had only minimal effects on the occlusion site of the PA. The DLT is a practical thoracoscopic technique for PA bleeding when primary haemostasis has been achieved.

Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma A549 cells.

Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-ß type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-ß1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-ß1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-ß1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma.

Robot-assisted vs. video-assisted thoracoscopic surgery in lung cancer.

Background: The major advantages of robot-assisted surgery are the fine field of view provided by the high-precision three-dimensional (3D) images and the good operability provided by the robotic arms that enables precise movements. A growing number of retrospective studies have compared robotic-assisted thoracoscopic surgery (RATS) with video-assisted thoracoscopic surgery (VATS), but the number of cases is limited and the results are contradictory. Methods: We studied the medical records of primary lung cancer patients who underwent lobectomy with lymph node dissection between 2017 and 2020. Four hundred and eleven patients fulfilled the inclusion criteria in this study (RATS: 103; VATS: 308). We compared the perioperative factors and postoperative results of the VATS and RATS groups. Further, we adjusted background factors using propensity score matching (PSM) then compared the results of 200 patients (100 patients in each group). In this study, we matched interlobar fissure completeness, which affects operative difficulty and operative time; however, this has been superficially compared in previous studies. Results: After PSM, a significant difference was observed in the intraoperative blood loss (RATS: 53.3 mL, VATS: 120.3 mL, P=0.04). The rates of surgical complications were comparable between the groups (10.0% vs. 13.0%, P=0.66) with similar mean operation times (RATS: 215.0 min, VATS: 210.1 min, P=0.57). The mean postoperative stay in the RATS group was shorter than that in the VATS group (10.0 vs. 11.5 days, P=0.04). Conclusions: Initial experience of RATS had no obvious drawbacks when compared with that of VATS on propensity-matched analysis.

Interlobar division using vessel-sealing system in robot-assisted pulmonary lobectomy.

Objective: We investigated the safety of a novel interlobar fissure division technique using the da Vinci vessel sealing system in robot-assisted pulmonary lobectomy. Methods: The medical records of patients who underwent robotic pulmonary lobectomy with node dissection for primary lung cancer between 2018 and 2020 were reviewed. The inclusion criteria were fulfilled by 111 patients, whose perioperative factors and postoperative results were compared with those previously reported. Furthermore, the new robotic lung interlobar division technique using the da Vinci vessel sealing system without a robotic stapler was evaluated in patients with low-grade incomplete fissure. We considered the Craig and Walker classification of lung fissures grades 1 and 2 as a good adaptation for the vessel sealing system interlobar fissure division. Results: The vessel sealing system group had shorter mean operative and console times (P = .03 and P = .01, respectively) and lesser median intraoperative blood loss (20 mL vs 50 mL; P = .01). The vessel sealing system group had lower surgical complication rates (2.2% vs 20.0%; P = .01). The incidence of persistent postoperative air leak was lower (0% vs 10.0%; P = .06), and fewer robotic stapler cartridges were used during surgery (3.4 vs 5.6; P < .001) in the vessel sealing system group than in the stapler group. Conclusions: We report the safety of using the da Vinci vessel sealing system as an alternative to the use of robotic staples for interlobar fissure division in robot-assisted pulmonary lobectomy. This technique seems easy and feasible though limited to the low-grade incomplete fissure.

Causes and management of intraoperative complications in robot-assisted anatomical pulmonary resection for lung cancer.

Background: To perform safe robot-assisted anatomical lung resections, the details of intraoperative complications need to be shared among thoracic surgeons. However, only limited data are available. Methods: This retrospective, single-institutional study evaluated 134 patients who underwent robot-assisted anatomical lung resection. We examined the causes, management, and outcomes of all intraoperative complications. Results: Of the 134 eligible patients, 118 (88%) underwent lobectomy and 16 (12%) underwent segmentectomy. Intraoperative complications occurred in 17 (12.7%) patients. These complications included pulmonary artery (PA) injuries in seven patients, pulmonary vein (PV) injuries in three, azygos vein (AV) injury in one, superior vena cava (SVC) injury in one, bronchial injuries in three, and lung injuries in four. Most PA injuries were at a distal side and controlled by pressure, fibrin sealant, or stapling of the proximal side. In the three PV injuries, right upper PV was sandwiched by robotic instruments, V6 was punctured by the tip of the Maryland bipolar forceps, and the distal side of V2t was injured during tunneling of a minor interlobar fissure. These were controlled the same way as the PA injuries. The AV injury occurred during hilar lymph node (LN) dissection and was controlled by suturing. The SVC injury was caused by interference of the robotic forceps and the suction tube outside the field of view during upper mediastinal LN dissection. The injury was controlled by continuous pressure while layering polyglycolic acid sheets and fibrin glue. In the three bronchial injuries, B10 was injured during subcarinal LN dissection, right main bronchus was injured during upper bronchus dissection and the stapling failure of the bronchus occurred by strong traction. They were all repaired by suturing. All lung parenchymal injuries were caused by manipulation of robotic instruments outside the field of view. The lung injuries were repaired by suturing with pledgets. No cases were converted to thoracotomy. The 30-day mortality rate was 0.7%. The cause of mortality was pneumonia. Conclusions: In robot-assisted anatomical pulmonary resection for lung cancer, most major intraoperative complications can be safely managed robotically without conversion to thoracotomy.

Clinical effect of soft coagulation for air leak treatment during pulmonary lobectomy.

BACKGROUND: Soft coagulation using the VIO soft coagulation system is used to treat minor lung air leaks during pulmonary resection in Japan. We previously reported that it has a similar effect as the air leak treatment with fibrin glue. We evaluated the efficacy of soft coagulation using the VIO soft coagulation system for lung air leakage during pulmonary resection. METHODS: Intraoperative air leaks from the interlobar lung parenchyma were observed in 42 of the 283 patients who underwent video-assisted thoracoscopic surgery lobectomy between 2016 and 2018. We retrospectively reviewed these 42 patients who were treated using the VIO soft coagulation system for air leaks. We classified the air leaks in to grades using the Macchiarini scale score and evaluated the surgical outcomes of air leak treatment. RESULTS: Air leaks from the interlobar lung parenchyma having Macchiarini scale scores 1, 2, and 3 occurred in 8, 17, and 17 patients, respectively. In all the 8 patients with score 1 air leaks (100%), the air leaks could be controlled using the VIO soft coagulation system alone, and none had delayed pneumothorax requiring intervention. Of the score 2 and 3 air leaks, 52.9% and 35.3% were controlled using the VIO soft coagulation system alone, respectively. CONCLUSIONS: Macchiarini scale score 1 air leaks from the interlobar lung parenchyma could be well controlled using the VIO soft coagulation system. Therefore, soft coagulation with this system may be an alternative method for treating minor air leaks during pulmonary resection surgery.

Robot-assisted and video-assisted thoracoscopic surgery for thymoma: comparison of the perioperative outcomes using inverse probability of treatment weighting method.

Background: Minimally invasive surgery is the standard treatment for early-stage thymoma. We compared the perioperative outcomes between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) for thymoma. Methods: Between April 2011 and August 2021, patients with thymoma who underwent thymectomy by RATS (n=20) or VATS (n=37) at our hospital were retrospectively reviewed. We evaluated the postoperative quality of life (QOL), surgical outcomes, complications, mortality, and pain grade. Postoperative QOL was assessed according to the time to achieve "B duration" and "CIII duration" based on the Nursing Dependency Score and Nursing Criteria, respectively. Results: After the inverse probability of treatment weighting (IPTW), the B duration and CIII duration were significantly shorter with RATS than with VATS (P<0.001 and P=0.037, respectively). These superior results of RATS group compared to those of the VATS group were confirmed with logistic regression analysis (OR 0.25, 95% CI: 0.10-0.63, P=0.003; and OR 0.31, 95% CI: 0.12-0.76, P=0.011, respectively). After the IPTW, the VATS group had significantly fewer patients with epidural analgesia than the RATS group (P=0.018). In contrast, additional regular analgesics (including those for wound pain and neuralgia) were prescribed significantly more often during postoperative hospitalization in the VATS group (P=0.033). Patients in both groups had no myasthenic crisis or mortality. The postoperative pain grade at the first and second follow-ups did not significantly differ between the two groups after the IPTW (P=0.376 and P=0.109, respectively). Conclusions: RATS offered the advantages of improved postoperative QOL according to nursing care systems compared to VATS.

Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma.

BACKGROUND: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. METHODS: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). RESULTS: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. CONCLUSIONS: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.

Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells.

Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells.

Two cases of left recurrent laryngeal nerve paralysis after right superior mediastinal node dissection.

BACKGROUND: Ipsilateral recurrent laryngeal nerve paralysis is one of the rare complications during the superior mediastinal node dissection for lung cancer. However, very few reports of contralateral recurrent laryngeal nerve paralysis during the procedure are available. CASE PRESENTATION: Two women aged 74 and 80 years developed hoarseness after undergoing right upper lobectomy and right superior mediastinal node dissection for primary lung cancer. Postoperative laryngoscopy in the two patients confirmed left vocal cord paralysis. CONCLUSION: Node dissection is performed in the standard procedure for right upper lobe lung cancer. At this time, care must be taken not to cause damage not only to the recurrent laryngeal nerve on the ipsilateral side but also to the recurrent laryngeal nerve on the contralateral side.

The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma.

Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.

The left main bronchus transected incorrectly during video-assisted thoracoscopic lobectomy: a case report.

BACKGROUND: Several severe intraoperative complications of lung cancer surgery have been reported, but the incorrect transection of the main bronchus is a very rare and serious complication. We report a surgical case of a patient with left lower lobe lung cancer invading the inferior segment of the lingula, with fused interlobar fissure and dense pleural adhesion, in which the left main bronchus was mistaken for the left lower lobe bronchus and was transected. CASE PRESENTATION: A 64-year-old woman with lung adenocarcinoma was referred to our hospital for surgical treatment. Chest computed tomography (CT) scan showed a 30-mm nodule with a clear border and irregular margins in the center of the anterior (S8) segment of the lower lobe of the left lung and another similar 30-mm nodule in the lateral (S9) segment of the same lobe. Metastasis within the same lobe was suspected. A thoracoscopic left lower lobectomy was scheduled for the patient. As the patient had a moderately, fused fissure, dense pleural adhesion, and suspicious tumor invasion from the left S8 segment to the left S5 segment, and the interlobar node tightly adhered to the main PA at the site of basilar artery origin of the LLL, we performed left lower lobectomy and a left S5 segmentectomy using the fissureless fissure-last technique. During surgery, the left main bronchus was mistaken for the left lower lobe bronchus and was transected. After transecting the left main bronchus, we performed a sleeve bronchoplasty to prevent pneumonectomy. CONCLUSIONS: We experienced the rare and serious intraoperative complication of the incorrect transection of the main bronchus. There are few reports of this intraoperative complication, and it should not be overlooked by surgeons.

HMGB1 enhances epithelial permeability via p63/TGF-ß signaling in lung and terminal bronchial epithelial cells.

High mobility group box 1 (HMGB1) is involved in the induction of airway inflammation and injury in patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). HMGB1 increased by transforming growth factor-ß1 (TGF-ß1), impairs airway epithelial barrier function in the lung. In the present study, to investigate how HMGB1 affects the barrier of normal human lung epithelial (HLE) cells, monolayer cells (2D culture) and bronchial-like spheroid cells (2.5 D Matrigel culture), which have lumen formation, were pretreated with TGF-ß type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. In 2D culture, treatment with HMGB1 decreased expression of angulin-1/LSR, TRIC and CLDN-1, -4, -7 and increased that of CLDN-2. Pretreatment with EW-7197 prevented the changes of all tight junction molecules induced by HMGB1. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen, whereas pretreatment with EW-7197 prevented the hyperpermeability of FD-4 into the lumen caused by HMGB1. In 2.5D Matrigel culture, knockdown of transcription factor p63 prevented the hyperpermeability induced by HMGB1 as well as pretreatment with EW-7197. In the 2D culture of HLE cells with HMGB1, knockdown of p63 increased the level of angulin-1/LSR and CLDN-4, while pretreatment with EW-7197 enhanced the increase of CLDN-4 induced by knockdown of p63. Immunohistochemical analysis of IPF, CLDN-2, HMGB1 and p63 revealed that their levels were higher in the regenerative epithelium of the terminal bronchial region than in normal epithelium. HMGB1 induces epithelial permeability of HLE cells via p63/TGF-ß signaling in normal lung and IPF.