Surgical treatment for secondary spontaneous pneumothorax: a risk factor analysis.

PURPOSE: While surgery is an effective treatment for secondary spontaneous pneumothorax (SSP), it can be difficult, because affected patients are usually in a poor general condition. The present study investigated the risk factors of postoperative complications after surgery for SSP. METHODS: Eighty-eight patients with SSP who underwent surgery from January 2006 to March 2018 were investigated. Clinical data were reviewed, and a multivariate analysis was performed. RESULTS: Eighty-four patients (95%) were males, and the median patient age was 72 years. Underlying lung diseases were chronic obstructive pulmonary disease in 58 patients (65.9%), interstitial pneumonia in 26 (29.5%), and others in 4 (4.5%). Postoperative complications developed in 21 patients (24%). Hospital mortality/prolonged length of stay occurred in 6 patients (7%). A multivariate analysis showed that the preoperative performance status (performance status 0-2 vs. 3, hazard ratio: 6.570, 95% confidence interval: 1.980-21.800) was an independent predictor of postoperative complications. CONCLUSION: Surgery for SSP contributed to early chest tube removal and favorable outcomes. However, rare fatal events occurred, and the patient performance status was a risk factor for postoperative complications. A careful evaluation of each patient's performance status is needed to determine the need for surgical intervention for SSP.

Ex Vivo Expanded and Activated Natural Killer Cells Prolong the Overall Survival of Mice with Glioblastoma-like Cell-Derived Tumors.

Glioblastoma (GBM) is the leading malignant intracranial tumor and is associated with a poor prognosis. Highly purified, activated natural killer (NK) cells, designated as genuine induced NK cells (GiNKs), represent a promising immunotherapy for GBM. We evaluated the anti-tumor effect of GiNKs in association with the programmed death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint pathway. We determined the level of PD-1 expression, a receptor known to down-regulate the immune response against malignancy, on GiNKs. PD-L1 expression on glioma cell lines (GBM-like cell line U87MG, and GBM cell line T98G) was also determined. To evaluate the anti-tumor activity of GiNKs in vivo, we used a xenograft model of subcutaneously implanted U87MG cells in immunocompromised NOG mice. The GiNKs expressed very low levels of PD-1. Although PD-L1 was expressed on U87MG and T98G cells, the expression levels were highly variable. Our xenograft model revealed that the retro-orbital administration of GiNKs and interleukin-2 (IL-2) prolonged the survival of NOG mice bearing subcutaneous U87MG-derived tumors. PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.

[Effectiveness of Osimertinib for Postoperative Recurrence of Lung Cancer with L861Q Activating EGFR Mutation:Report of a Case].

A 69-year-old woman was referred to our hospital because of an abnormal shadow on a chest roentgenogram at a medical check-up. Chest computed tomography showed a 2.5 cm-diameter tumor in the right pulmonary lower lobe. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could not detect the other lesions. The patient underwent thoracoscopic right lower lobe lobectomy for lung adenocarcinoma. Pathological diagnosis was invasive adenocarcinoma (pT1cN0M0). EGFR status was positive for the L861Q mutation in exon 21. At 31 months after surgery, the recurrence appeared as vertebral and multiple pulmonary lesions, and the treatment with osimertinib showed satisfactory response seven months after starting the treatment.

Isolation and culture of pleural mesothelial cells.

Purpose: Although the isolation of rat and mouse mesothelial cells has previously been reported, most mesothelial cells used for experimental studies are obtained from peritoneal cells. Here, we describe an optimized method for the isolation and in vitro propagation of rodent pleural mesothelial cells without the requirement for specialized surgical techniques. Materials and Methods: To harvest pleural mesothelial cells, the pleural space of 8-9-week-old rats or older mice was filled with 0.25% trypsin in ethylenediaminetetraacetic acid (EDTA) buffer for 20 min at 37 °C. Cells were then harvested, and incubated at 37 °C in a humidified atmosphere with 5% CO2. Immunofluorescence analysis of plated pleural mesothelial cells was performed using Alexa 546 (calretinin). To investigate optimal proliferation conditions, medium enriched with various concentrations of fetal calf serum (FCS) was used for pleural mesothelial cell proliferation. Results: By day 10, confluent cell cultures were established, and the cells displayed an obvious cobblestone morphology. Immunofluorescence analysis of the cells demonstrated that all stained positive for Alexa 546 (calretinin) expression. Mesothelial cells grew better in medium containing 20% FCS than with 10% FCS. Conclusions: This is a simple procedure for the efficient collection of primary pleural mesothelial cells, which were obtained in defined culture conditions from the euthanized rodent thoracic cavity using trypsin-EDTA treatment. The ability to easily culture and maintain identifiable pleural mesothelial cells from rodents will be helpful for future experiments using these cells.

Prognostic impact of underlying lung disease in pulmonary wedge resection for lung cancer.

BACKGROUND: Pulmonary wedge resection is an option for lung cancer patients with limited cardiopulmonary preservation. As the impact of underlying lung status on the prognosis of such patients remains unclear, we assessed this issue. METHODS: A total of 149 borderline surgical candidates with localized lung cancer who had undergone wedge resection were retrospectively investigated. Clinical variables related to perioperative morbidity, local control rate, and oncological outcomes based on underlying lung disease were analyzed. RESULTS: According to the risk analysis of postoperative complications, underlying lung disease did not influence the surgical morbidity. Postoperative recurrence occurred in 65 patients (locoregional recurrence in 36, distant metastasis in 12, and both simultaneously in 17). Multivariate analysis revealed that emphysema on computed tomography (CT) [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.21-0.99] was an independent indicator of locoregional recurrence. Forty-four patients died of lung cancer and 29 of other causes. Multivariate analysis demonstrated that interstitial lung disease on CT (HR 1.98; 95% CI 1.01-3.89) was a predictor of poor prognosis. CONCLUSION: Pulmonary wedge resection can be safely undergone by lung cancer patients regardless of pulmonary comorbidity, although underlying lung disease may influence the prognosis after wedge resection.

[Preoperative Detection of Pleural Adhesions Using Transthoracic Ultrasonography].

Recently, there has been an increase in the experience of lung surgery in cases with a history of thoracotomy or pneumonia. In these cases, pleural adhesion is often seen and makes the surgery to be difficult. Especially in thoracoscopic surgery, lung damage must be care at the 1st port insertion. In this report, the usefulness of the extent of pleural adhesion to the chest wall before surgery by using a transthoracic ultrasonography was assessed. Between April 2017 and September 2018, 32 patients underwent preoperative ultrasound examination, and 128 ports were evaluated whether had adhesions or not using lung sliding sign. All patients of 128, 24 adhesions were found at surgery, resulting in 14 true positive, 10 false negative, 0 false positive, and 104 true negative findings [sensitivity:58.3% (14/24), specificity: 100.0% (104/104), accuracy:92.2% (118/128)]. Especially, about the 1st port, accuracy was 93.8 % (30/32). In Conclusion, preoperative transthoracic ultrasonography could provide useful information on the pleural adhesion leading safe initial thoracoscopic access without lung injury.

[Prognostic Significance of Mode of Nodal Involvement in Pulmonary pN1 Squamous Cell Carcinoma].

According to the tumor, node, metastasis (TNM) classification of the Union for International Cancer Control (UICC) and the International Association for the Study of Lung Cancer (IASLC), N factor is defined by the anatomic extent of the metastatic lymph nodes, but is not related to the metastatic pattern. N1 is defined as "metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension". Lymph node involvement is one of the most important prognosistic factors in non-small cell lung cancer patients. Squamous cell carcinoma (SCC) arises in the central airway and directly invades adjacent lymph nodes more frequently compared to the other histologic types. We retrospectively evaluated the prognostic impact of lymph node involvement patterns in pulmonary pN1 squamous cell carcinoma (SCC) patients. The clinical records of 23 patients with pN1 SCC who underwent complete resection and systematic lymph node dissection at our institute were retrospectively reviewed. We classified the patient into 2 N1 groups based on the nodal involvement pattern:metastatic N1 nodes involved directly by the main tumor (direct group) and metastatic N1 nodes not directly involved by the main tumor (separate group). The direct group consisted of 10 patients, and the separate group comprised 13 patients. There were no significant difference in the gender, tumor size, surgical procedure, and number of metastatic lymph nodes. Overall survival and disease-free survival curves were plotted using the Kaplan-Meier method, and the statistical differences between both groups was determined by the log-rank test. P values <0.05 were considered statistically significant. The direct group had a much better 5-year overall survival rate of 100.0% compared with 55.9% for the separate group (p=0.037). The N factors in TNM classification are defined only by anatomical location. However, our results suggest that the mode of nodal involvement in pulmonary pN1 SCC might be a prognostic factor. Accordingly, it is likely that biological behaviors are different between direct metastasis and separate metastasis. Since there are some limitations in this study:its retrospective design and small sample size, the clinical implication of direct extension to N1 lymph nodes needs to be confirmed by a large scale prospective study in the future.

[Resection of a Posterior Mediastinal Tumor Using Intraoperative Motor Evoked Potential Monitoring;Report of a Case].

A 20-year-old man with a posterior mediastinal tumor incidentally found on a chest X-ray was referred to our hospital. Chest computed tomography showed a 3 cm nodule located on the left side of the 10-11th thoracic vertebra, where the artery of Adamkiewicz is presumed to arise. He underwent left thoracotomy to remove the lesion. The tumor was safely resected with the assistance of intraoperative motor evoked potential(MEP) monitoring. The postoperative diagnosis was a benign schwannoma. In thoracic surgery for posterior mediastinal tumors, intraoperative MEP monitoring is useful for preventing paraplegia.

[Primary Pulmonary Synovial Sarcoma Confirmed by Demonstration of SYT-SSX Fusion Gene Translocation by Fluorescence In Situ Hybridization].

A 58-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Chest computed tomography showed a 3 cm nodule in the left lung. Thoracoscopic left upper lobectomy was performed to remove the lesion, and the postoperative diagnosis was primary pulmonary synovial sarcoma according to the histology and SYT-SSX gene analysis.

Effects of anesthetics on early postoperative cognitive outcome and intraoperative cerebral oxygen balance in patients undergoing lung surgery: a randomized clinical trial.

PURPOSE: One-lung ventilation (OLV) may impair cerebral oxygen balance and induce postoperative cognitive dysfunction (POCD). It is unclear whether the type of anesthetic influences the incidence of POCD in patients undergoing OLV. This prospective study compared the incidence of POCD and intraoperative cerebral oxygen desaturation in OLV patients anesthetized with propofol vs sevoflurane during lung surgery. METHODS: There were 148 participants enrolled in this study and randomized equally to either the propofol or the sevoflurane group. Anesthesia was maintained with either propofol or sevoflurane combined in both groups with fentanyl and epidural anesthesia. Regional cerebral oxygen saturation (rSO2), jugular bulb venous oxygen saturation (SjO2), and the incidence of cerebral oxygen desaturation (rSO2 or SjO2 < 50% or rSO2 < 80% of baseline) were measured during anesthesia. Cognitive function was assessed using seven neurocognitive tests two days preoperatively, five days postoperatively (primary outcome), and three months postoperatively. Bivariable and multivariable regression analyses were conducted to identify factors associated with POCD. RESULTS: Rates of POCD did not differ statistically between groups five days postoperatively (propofol, 16/72 patients; sevoflurane, 24/72 patients; RR, 0.67; 95% CI, 0.39 to 1.15; P = 0.14) or three months postoperatively (propofol, 9/60 patients; sevoflurane, 12/58 patients; RR, 0.73; 95% CI, 0.33 to 1.59; P = 0.42). Only three subjects per group showed intraoperative cerebral oxygen desaturation. Multivariable regression analysis revealed older age as an independent predictor of POCD. CONCLUSIONS: No statistically significant difference in the incidence of POCD could be detected between the sevoflurane and propofol anesthesia groups. Postoperative cognitive dysfunction was relatively frequent following OLV in both groups. ( REGISTRATION NUMBER: UMIN 000002826).

RéSUMé: OBJECTIF: La ventilation unipulmonaire (VUP) pourrait avoir un impact négatif sur l'équilibre d'oxygène cérébral et induire une dysfonction cognitive postopératoire (DCPO). Nous ne savons pas si le type d'agent anesthésique influence l'incidence de DCPO chez les patients recevant une VUP. Cette étude prospective a comparé l'incidence de DCPO et de désaturation peropératoire en oxygène cérébral chez les patients sous VUP anesthésiés avec du propofol vs du sévoflurane pendant une chirurgie pulmonaire. MéTHODE: Au total, 148 patients ont participé à cette étude et ont été randomisés en deux groupes égaux à recevoir du propofol ou du sévoflurane. L'anesthésie a été maintenue à l'aide de propofol ou de sévoflurane, et l'agent de choix a été combiné à du fentanyl et à une anesthésie péridurale dans les deux groupes. La saturation en oxygène cérébral régional (rSO2), la saturation en oxygène veineux au bulbe de la veine jugulaire (SjO2) et l'incidence de désaturation en oxygène cérébral (rSO2 ou SjO2 < 50 % ou rSO2 < 80 % par rapport aux valeurs de base) ont été mesurées pendant l'anesthésie. La fonction cognitive a été évaluée à l'aide de sept tests neurocognitifs deux jours avant l'opération, cinq jours après l'opération (critère d'évaluation principal) et trois mois après l'opération. Des analyses de régression bivariée et multivariée ont été réalisées afin d'identifier les facteurs associés à une DCPO. RéSULTATS: D'un point de vue statistique, les taux de DCPO n'étaient pas différents entre les groupes à cinq jours postopératoires (propofol, 16/72 patients; sévoflurane, 24/72 patients; RR, 0,67; IC 95 %, 0,39 à 1,15; P = 0,14) ou à trois mois postopératoires (propofol, 9/60 patients; sévoflurane, 12/58 patients; RR, 0,73, IC 95 %, 0,33 à 1,59; P = 0,42). Seuls trois patients par groupe ont manifesté une désaturation peropératoire en oxygène cérébral. L'analyse de régression multivariée a révélé qu'un âge avancé était un prédicteur indépendant de DCPO. CONCLUSION: Aucune différence significative d'un point de vue statistique n'a été observée en ce qui a trait à l'incidence de DCPO entre les groupes anesthésiés au sévoflurane ou au propofol. La dysfonction cognitive postopératoire était relativement fréquente après une VUP dans les deux groupes. (Numéro d'enregistrement: UMIN 000002826).

A new minimally invasive technique of combined chest wall resection for lung cancer.

We describe our technique of minimally invasive chest wall resection for primary lung cancer. We used this technique to perform two lobectomies combined with chest wall resection using thoracoscopic assistance. The intercostal muscles and vessels were divided using a vessel-sealing device, which was easy to maneuver through the access incision, achieving reliable hemostasis. In one patient, adding the utility port just over the dorsal edge of the chest wall proved useful for dissecting the distal area of the chest wall. This approach required only minimal incision without cutting the uninvolved extrathoracic musculature of the chest.

[Non Small Cell Lung Cancer with Mycosis Fungoides].

77-year-old man having a history of mycosis fungoides was admitted to our hospital with abnormal shadow in his chest computed tomography(CT). Chest CT showed a 1 cm nodule in the left lung. Left lung wedge resection was performed to remove the lesion, and the postoperative histological diagnosis was adenocarcinoma, primary lung cancer. After surgery, the patch and plaque on his skin disapperered within a month.

[Application of Curved Stapler for Pulmonary Wedge Resection].

End stapler is one of the indispensable devices for pulmonary resections. Various surgical staplers are now available and appropriate types are selected to dissect pulmonary parenchyma, vessel, or bronchus. In this study, we retrospectively reviewed the patients who received pulmonary wedge resections using newly released curved stapler (Endo GIA Radial Reload with Tri-Staple technology). Between April 2013 and October 2014, 10 lesions from the 9 patients were resected using the curved staplers. The reasons for the application of the staplers were pleuro-pulmonary adhesion in 3 lesions and centrally location in 7 lesions. There was no intraoperative complication. After the operations, temporary residual lobe congestion caused by the pulmonary vein stenosis was developed in 1 patient.

[Intercostal Lung Hernia after Video-assisted Thoracoscopic Lobectomy].

A 52-year-old woman had undergone video-assisted thoracoscopic right upper lobectomy for primary lung cancer. Although her postoperative course was uneventful progressive subcutaneous emphysema of the thorax and neck was developed 6 weeks after the lobectomy. Her chest computed tomography revealed intercostal lung herniation and subcutaneous emphysema. Surgical repair was performed via thoracoscopic assistance. The damaged portion of the lung was resected and the ribs were fixed using a wire for sternal suturing.

Synthesis and evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting Janus kinase 3.

Janus kinases (JAKs) have been known to play crucial roles in modulating a number of inflammatory and immune mediators. Here, we describe a series of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting JAK3 for use in treating immune diseases such as organ transplantation. In the chemical modification of compound 6, the introduction of a carbamoyl group to the C5-position and substitution of a cyclohexylamino group at the C4-position of the 1H-pyrrolo[2,3-b]pyridine ring led to a large increase in JAK3 inhibitory activity. Compound 14c was identified as a potent, moderately selective JAK3 inhibitor, and the immunomodulating effect of 14c on interleukin-2-stimulated T cell proliferation was shown. Docking calculations and WaterMap analysis of the 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives were conducted to confirm the substituent effects on JAK3 inhibitory activity.

[Temporary Middle Lobe Congestion after Wedge Resection].

A 55-year-old woman, who had undergone laparoscopic resection for colorectal cancer, detected a solitary pulmonary nodule on her surveillance chest computed tomography. The lesion located in the right middle lobe, and she received thoracoscopic resection for metastasis from the colorectal cancer. The lesion was removed by wedge resection. During the operation we noticed the middle pulmonary vein was partially stapled because the nodule located close to the vein. There was no macroscopic and hemodynamic problem after the wedge resection, therefore, we decided to complete the operation without resection of the residual middle lobe. After the operation, pulmonary congestion localized to the residual middle lobe progressed within a few days. Because she had no severe symptom nor hemodynamic instability, we continued observation without additional intervention. The congestion gradually improved, and then she discharged from our hospital on 20 days after operation.

Preoperative low-dose steroid can prevent respiratory insufficiency after thymectomy in generalized myasthenia gravis.

BACKGROUND: Postoperative respiratory insufficiency (PRI) in myasthenia gravis (MG) often occurs within several days after thymectomy and remains problematic. In limited studies reporting that preoperative steroids prevented PRI in patients with MG, high doses of steroids were used and detailed information on the use of steroids is limited. Because high-dose steroids significantly increase the risk of adverse effects, we studied 37 patients with generalized MG to investigate whether low-dose steroids might prevent PRI. METHODS: The low-dose steroids were started orally, and the dose was gradually increased to the maximum level (30 mg/day). Immediately before thymectomy, patients received the maximum dose of oral steroids daily. PRI was defined as the development of restrictive dysfunction requiring mechanical ventilation within 3 days after thymectomy and total postoperative mechanical ventilation support time of >24 h. RESULTS: The rate of PRI in the low-dose steroid use group was significantly lower than that in the no-steroid use group. The postoperative stay in the intensive care unit was shorter in the steroid use group. CONCLUSIONS: Extended thymectomy is a well-accepted surgical treatment for selected patients with MG. However, PRI remains problematic. Our results suggest that not only preoperative high-dose steroid treatment, but also low-dose steroid treatment can prevent PRI.

Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment.

Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although we previously identified a compound (2) with potent VAP-1 inhibitory activity in rats, the human activity was relatively weak. Here, to improve the human VAP-1 inhibitory activity of compound 2, we first evaluated the structure-activity relationships of guanidine bioisosteres as simple small molecules and identified a 1H-benzimidazol-2-amine (5) with potent activity compared to phenylguanidine (1). Based on the structure of compound 5, we synthesized a highly potent VAP-1 inhibitor (37b; human IC50=0.019 µM, rat IC50=0.0051 µM). Orally administered compound 37b also markedly inhibited ocular permeability in streptozotocin-induced diabetic rats after oral administration, suggesting it is a promising compound for the treatment of diabetic macular edema.

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema.

Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema: part 2.

Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP-1 inhibitory activity, the activity differed between humans and rats. This issue was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was found by high-throughput screening (HTS), a docking study of a human VAP-1 homology model, and an analysis of sequence information for humans and rats. As a result, we identified compound 35c, which showed strong VAP-1 inhibitory activity (human IC(50) of 20 nM; rat IC(50) of 72 nM) and significant inhibitory effects in the ex vivo test.