[Effect of Japanese Traditional Medicine, Ninjin-Youei-To(TJ-108), on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy, and thus, it is very important to maintain the quality of life(QOL)of these patients. Ninjin-Youei-To(TJ-108), a Japanese traditional medicine, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-108 in patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate factors influencing the QOL of these patients, we administered a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 15 patients with non-small cell lung cancer. Factors related to the overall QOL scores and other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale" were analyzed. No significant decrease in each of the evaluated factors was observed in this study.

[Ciliated Muconodular Papillary Tumor of the Lung].

A ciliated muconodular papillary tumor (CMPT) has been reported to be a low-grade malignant tumor or benign tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation, occur in the peripheral lung. We present a case of CMPT in this report. A 42-year-old male was referred to our department due to a nodule detected in the peripheral left lower lobe of lung. The nodule was resected via wedge resection based on a suspected diagnosis of carcinoma. Intraoperative analysis of the frozen sections was suggestive of mucinous adenocarcinoma. A left lower lobectomy and mediastinal lymph node dissection were performed. The resected specimen was characterized as a papillary tumor with central fibrosis, proliferating along the alveolar walls, surrounded by mucous lakes, and consisting of ciliated columnar cells and goblet cells. Nuclear atypia was mild, and no mitotic activity was observed. Based on these findings, the tumor was finally diagnosed as CMPT. No recurrence has been noted for 24 months after surgery.

[A Retrospective Study Analyzing the Clinical Course of Patients with Non-Small Cell Lung Cancer Receiving Local or Systemic Therapy after Post-Operative Recurrence].

BACKGROUND: While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported. OBJECTIVE: We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy. METHODS: Clinical data were retrospectively analyzed and survival duration was compared using the logrank test. RESULTS: A total of 22 patients were included. Median progression-free survival in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies was 15.1 months, 6.3 months, and 13 months, respectively. Two patients receiving treatment with EGFR-TKI did not show disease progression at 41.3 months and 45.8 months(p=0.265). Median overall survivals in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies were 26.5 months, 20 months, and 37.9 months, respectively(p=0.510). After the treatment, 6 patients showed regrowth of the recurrent lesion, 8 patients showed remote metastases, and 2 patients showed both regrowth of the recurrent lesion and remote metastases. CONCLUSION: Patients who received treatment including local therapy showed longer survival duration, but statistical significance was not detected. Our study suggested that regrowth of the recurrent lesion and remote metastases can be equally observed after treatment.

Current topics in surgery for multiple ventricular septal defects.

In this review article, we describe several topics, including the sandwich technique, the transatrial re-endocardialization technique, the limited apical left ventriculotomy approach and device closure. The sandwich technique was introduced for the closure of muscular ventricular septal defects (VSD) by sandwiching the septum between two felt patches placed in the left and right ventricle. This technique requires neither the transection of muscular trabeculae nor ventriculotomy. Although the sandwich technique has resulted in the improvement of surgical outcomes, cases of postoperative cardiac dysfunction have been reported. Multiple smaller VSDs have been closed with transatrial re-endocardialization. Septal dysfunction may be avoided through this technique, in which the septal trabeculae are approximated in two layers of superficial, endocardial running sutures. Recently, a number of reports have recommended a limited apical left ventriculotomy approach. With this technique, a much shorter incision of around 1 cm at the apex of the left ventricle may be sufficient for achieving the complete closure of apical muscular VSDs. The transcatheter or perventricular device closure of muscular VSDs has increasingly been performed with good results. Although favorable early and mid-term results of device closure have been reported, this method is not always safer or less invasive than surgical closure. Long-term evaluations should be performed to determine whether the right and left ventricular functions are affected by treatment with relatively large devices in the heart.

Complete thoracoscopic diaphragm plication using carbon dioxide insufflation: report of a case.

Diaphragm plication has become the accepted treatment for major respiratory impairment caused by diaphragmatic eventration and paralysis. Various open and minimally invasive plication techniques have been described and while video-assisted thoracoscopic diaphragm plication appears to be a safe and effective alternative to open surgery, the workspace is limited. We describe how we performed complete thoracoscopic diaphragm plication using carbon dioxide (CO2) insufflation for a patient with unilateral diaphragmatic eventration. Using CO2 insufflation seems to dramatically improve the workspace.

Current topics in surgery for isolated total anomalous pulmonary venous connection.

Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains a challenge, with reported early mortality rates of up to 20%. In this review article, we describe several topics, including surgery for neonates, diagnoses with multidetector computed tomography (MDCT), and primary sutureless repair. Several studies have reported mortality rates of around 10%, and demonstrated unchanged hospital mortality in neonates, despite improvement of the overall mortality of cohorts including older patients. Previous reports identified a low body weight at the time of the operation, preoperative pulmonary venous obstruction (PVO), and a prolonged cardiopulmonary bypass time as risk factors for hospital mortality. With the development of new technologies, MDCT has become a good diagnostic modality for use in the pre- and post-operative evaluation. MDCT delineates the drainage site of the vertical vein and the atypical vessel into the systemic vein, and it can also evaluate the existence of obstruction in the vertical vein. Following favorable experiences with post-repair PVO, the indications for sutureless repair as a primary operation have been expanded for infants, including those at risk of developing PVO after the repair of TAPVC. Primary sutureless repair has proven especially useful for difficult patient groups, such as those with congenital PVO, infracardiac TAPVC with small pulmonary veins, or mixed-type TAPVC.

Predictive factors of early autologous blood pleurodesis for postoperative air leak.

BACKGROUND: The usefulness of autologous blood pleurodesis for air leak after pulmonary resection is well known; however, factors predicting the therapeutic efficacy are poorly understood. Herein, we aimed to examine the predictors of early autologous blood pleurodesis for air leak following pulmonary resection. METHODS: Patients who underwent pulmonary resection and autologous blood pleurodesis with thrombin for postoperative air leak between January 2016 and October 2022 were retrospectively analyzed. Patients received 50-100 mL of autologous blood and 20,000 units of thrombin on postoperative days 1-4. If necessary, the same procedure or pleurodesis with other chemical agents was repeated until the air leak stopped. Patients were divided into single-dose and multiple-dose groups based on the number of times pleurodesis had occurred before the air leak stopped and were statistically analyzed. Logistic regression analysis was performed to identify predictors of treatment efficacy. RESULTS: Of the 922 patients who underwent pulmonary resection, 57 patients (6.2%) were included and divided into single-dose (n = 38) and multiple-dose (n = 19) groups. The amount of air leaks was identified as a significant predictor of multiple dosing, with a cutoff of 60 mL/min, in multivariate logistic regression analyses (odds ratio 1.13, 95% CI 1.03-1.24, p = 0.0065). The multiple-dose group showed a significantly higher recurrence of air leak (p = 0.0417). CONCLUSIONS: The amount of air leaks after pulmonary resection is the only significant factor predicting whether multiple autologous blood pleurodesis is required, and the recurrence rate of pneumothorax is significantly higher in such cases.

Differential distribution of lymphatic clearance between upper and lower regions of the lung.

BACKGROUND AND OBJECTIVE: Many lung diseases arise as the consequence of inhalational injury. When pathogenic materials are inhaled, it is possible that their clearance routes become the main focus of injury in the lung. Lymphatic clearance is important in the removal from the lung of small inhaled particles. The leak of toxic agents from the lymphatic flow potentially explains the topographic distribution of diffuse lung diseases triggered by inhaled materials, for example asbestosis. The aim of this study was to evaluate the differences in lymphatic distribution across various craniocaudal levels of the lung by using carbon dust deposition (CDD) as a tracing marker. METHODS: We evaluated 61 HE-stained slides of the normal lung area from 61 lobectomy specimens. The intensity of CDD was scored into five degrees (0-4) in bronchiolovascular (BV) areas and subpleural/septal (SP) areas per slide. The distribution was highlighted by subtraction scores of SP areas from those of bronchiolovascular areas. RESULTS: The subtraction scores of the upper lung area were significantly greater than those in the lower area, whereas there was no significant difference in scores by pulmonary lobes. CONCLUSIONS: Our results indicated that the main lymphatic clearance routes vary according to the craniocaudal levels, and are predominant in BV areas of the upper areas and in SP areas of the lower areas of the lung. This may explain the histological variations in anatomical distribution observed in the biopsy specimens of some diffuse lung diseases.

[Endovascular stent-graft insertion followed by resection of a locally-advanced lung tumor that invaded the thoracic aorta].

A 52-year-old man with fever and dyspnea was admitted to our hospital. Chest computed tomography showed a mass measuring 3.5×3.0 cm in the S(1+2) segment of the left lung with involvement of the aorta. Although cytological examination using broncho fiberscopy did not show any malignancy, we suspected the mass to be T4N0M0 lung cancer. The tumor was diagnosed as having invaded the aorta using intravascular ultrasound. First, an endovascular graft was inserted, and then, a left upper lobectomy with resection of the infiltrated aortic wall was performed without cardiopulmonary bypass. The patient had an uneventful recovery without any complications. Pathological examination revealed the tumor to be a large-cell carcinoma. We think that an aortic endograft can be useful for resection of an infiltrated aortic wall, although further studies are necessary.

[Immunoglobulin G4-related inflammatory pseudotumor of the lung].

A 61-year-old man was pointed out a solitary nodule located in the left lung (S9) measuring 18 × 29 mm in size along with lymphadenopathy by chest computed tomography (CT). Positron emission tomography( PET) scan showed a positive sign corresponding to the nodule[ standardized uptake value (SUV) max 5.8]. No diagnostic material was obtained from the transbronchial tumor biopsy, since it was difficult to rule out malignancy, surgical biopsy was performed with sampling of mediastinal lymph nodes. Histopathological examination showed marked infiltration of inflammatory cells, many of which were demonstrated to be immunoglobulin (Ig) G4-positive plasma cells by immunohistochemical staining. Hence, IgG4-related inflammatory pseudotumor of the lung was diagnosed.

[Lung biopsy by video-assisted thoracic surgery in patient with untreated Evans syndrome].

A 78-year-old man referred to our hospital with the chief complaints of anorexia, general malaise, rash, and weight loss. Laboratory examination revealed pancytopenia, hyperglobulinemia, generalized adenopathy, and multiple pulmonary nodules. Video-assisted thoracic surgery (VATS) was performed to diagnose pulmonary nodules. After operation, it was difficult to achieve hemostasis for a while. Finally, the patient was diagnosed as pulmonary cryptococcosis and Evans syndrome.

[Synchronous pulmonary hamartoma and lung cancer in a young patient].

A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.

Inducible capillary formation in lymphatic endothelial cells by blocking lipid phosphate phosphatase-3 activity.

Lymphangiogenesis plays critical roles under normal and/or pathological conditions; however, the molecular contributors to this event were unknown until recently. In the present study, we first employed gene chip analysis and confirmed that lipid phosphate phosphatase-3 (LPP3) expression was increased until capillary formation in the conditionally immortalized rat lymphatic endothelial cell line. Signaling responses occur when several lipids induce acute biological functions; further, lipid phosphate phosphatases (LPPs) control their functions via dephosphorylation; however, there is no report on the association between LPP3 and lymphangiogenesis. siRNA-targeted LPP3 significantly increased capillary formation of human lymphatic endothelial cells; in contrast, it decreased cell adhesion to the basement membrane matrix. Furthermore, the inducible effect of the LPP inhibitor on capillary formation was observed. For the first time, we report that LPP3 abolishes accelerated abnormal lymphangiogenesis. Blocking LPP3 activities may aid in the development of novel therapy for lymph vessel defects.

Efficacy of 50 mg pregabalin for prevention of postoperative neuropathic pain after video-assisted thoracoscopic surgery and thoracotomy: a 3-month prospective randomized controlled trial.

BACKGROUND: This study analyzed the preventive effect of 50 mg/day pregabalin on postoperative neuropathic pain, and any additional benefits related to sleep and respiratory function. METHODS: This prospective randomized controlled study included lung resection patients 20-89 years of age. Patients were randomly assigned to the treatment (pregabalin; initial dose, 50 mg/day) or control (non-steroidal anti-inflammatory drugs) group. Pregabalin patients received non-steroidal anti-inflammatory drugs and pregabalin (25 mg, twice daily) from the second postoperative day. Pain scores, neuropathic pain, analgesic use, respiratory function, and insomnia scale scores for 3 months after surgery were evaluated. RESULTS: This study included 46 patients who received pregabalin and 46 control patients. Pregabalin patients had significantly less postoperative neuropathic pain than control patients (19.6% vs. 41.3%; P=0.0404), and their duration of neuropathic pain was significantly shorter (30 vs. 90 days; P=0.024). The onset of postoperative neuropathic pain, insomnia scale scores, and respiratory function were similar between groups. No pregabalin-related adverse events were reported. CONCLUSIONS: Pregabalin (50 mg/day) had a significant preventive effect on postoperative neuropathic pain after thoracic surgery, without side effects. Early postoperative administration of pregabalin would help prevent neuropathic pain and provide better pain control after thoracic surgery.

Risk factors of neuropathic pain after thoracic surgery.

BACKGROUND: This study aimed to clarify the incidence and risk factors of neuropathic pain after thoracic surgery, focusing especially on patients who underwent complete video-assisted thoracoscopic surgery (VATS). METHODS: We retrospectively identified 185 patients who underwent thoracic surgery at our hospital over a 2-year period. Logistic regression analysis was used to analyze the association of various factors with postoperative neuropathic pain. RESULTS: Forty-eight (25.9%) patients developed postoperative neuropathic pain, and 9 (18.8%) of these patients reported persistent pain 1 year postoperatively. The median interval from surgical treatment to the onset of neuropathic pain was 7 days, and the duration was 50 days. Multivariate logistic regression analysis revealed a significant positive correlation between postoperative neuropathic pain and preoperative use of hypnotic medication [odds ratio (OR), 5.45; 95% confidence interval (CI); 2.52-12.17] and duration of surgery ≥2.5 hours (OR, 2.72; 95% CI, 1.27-6.09), and a significant negative association with the complete VATS approach (OR, 0.18; 95% CI, 0.073-0.42). CONCLUSIONS: Preoperative use of hypnotic medication, the thoracotomy approach, and duration of surgery ≥2.5 hours are associated with increased risk of neuropathic pain after thoracic surgery. The complete VATS approach could decrease the incidence of postoperative neuropathic pain, regardless of the duration of surgery.

CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro.

To develop new therapy strategies for lung cancer, we established an animal model, which reflects the clinical features of mediastinal lymph node metastasis of lung cancer. This study was designed to determine whether CCL21 induced biological functions associated with the metastasis of highly lymph node metastatic human non-small cell lung cancer (NSCLC) selected by our model. Orthotopic intrapulmonary implantation of human NSCLC (Lu-99 and A549) was performed to analyze the metastatic characteristics of these cells. The expression of CCR7, which is a receptor of CCL21, was detected using CCL19 [also called EBI1-ligand chemokine (ELC)]-Fc chimera by flow cytometric analysis. The effects of CCL21 on the migration, adhesion and growth of human NSCLC were investigated. After orthotopic implantation of human NSCLC cell lines, Lu-99, but not A549, metastasized to mediastinal lymph nodes, forming large size nodules, and expressed CCR7 on the surface. Accordingly, its ligand CCL21 induced chemotactic migration and alpha4beta1-mediated adhesion to VCAM-1 of Lu-99. The expression of CCR7 and vigorous responses to its ligand CCL21 potentially account for lymph node metastasis of a human NSCLC line Lu-99.

Survival of Lung Adenocarcinoma Patients Predicted from Expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on Tumor Cells and Tumor-Infiltrating T Cells.

The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I-IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival. The difference in survival of the clusters was confirmed separately for pStage I and pStage II-IIIA patients. Cluster A patients who also had CD4 and CD8 T-cell infiltration showed even better survival, as expected. The findings were confirmed by examining an independent validation cohort of 68 pStage I lung adenocarcinoma patients. Our data showed that PD-L1 expression was a positive indicator, whereas Galectin-9 and XAGE1 expression was negative. In vitro analyses suggested that PD-L1 expression was upregulated by IFNγ secreted from activated T cells in the tumor and Galectin-9 expression was counteracting those T cells. Thus, use of these immune markers enables the creation of a discriminant function with which to classify tumors and predict survival. Cancer Immunol Res; 4(12); 1049-60. ©2016 AACR.

Spontaneous Hemothorax Caused by Pulmonary Micro-Venous Hemangioma.

Various etiologies of spontaneous hemothorax have been reported, though the cause remains unidentified in some patients despite an exploratory thoracotomy. We report on an 89-year-old man with spontaneous hemothorax resolved by partial resection of the lung using complete video-assisted thoracoscopic surgery. The histopathologic findings revealed a ruptured micro-venous hemangioma located just below the bleeding visceral pleura. To the best of our knowledge, this is the first report of spontaneous hemothorax caused by a pulmonary micro-venous hemangioma.

Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-ß-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.

Complete port-accessed lobectomy by the muscle-sparing method.

We report the case of a 53-year-old woman who underwent complete port-accessed middle lobectomy by a new technique that preserves all muscles, including the extracostal and intercostal muscles. The operation was performed by using only thoracovideoscopy, and the resected lobe was withdrawn in a pouch through a subxiphoid incision through the substernal route. This complete port-accessed lobectomy is a new technique and is thought to be less invasive than video-assisted lobectomy with minithoracotomy.