(Pro)renin Receptor Down-regulation Is Associated With a Higher Risk of Recurrence in Lung Adenocarcinoma.

BACKGROUND/AIM: The (pro)renin receptor [(P)RR] plays a role not only in cardiovascular and renal diseases, but also in tumorigenesis. (P)RR contributes to the activation of the Wnt/ß-catenin signaling pathway, independent of the renin-angiotensin system. Accumulating evidence has shown that (P)RR is expressed in various human cancers. However, its clinical impact in lung carcinomas remains unclear. This study aimed to clarify the associations between (P)RR expression and clinical outcomes in patients with non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We analyzed the data of 913 patients with NSCLC who underwent resection between 1999 and 2016. Tissue microarrays were constructed and the expression of (P)RR and ß-catenin was investigated using immunohistochemistry. Recurrence-free probability and overall survival were analyzed using a log-rank test and Cox proportional hazards model. RESULTS: In adenocarcinomas, (P)RR down-regulation correlated significantly with high-grade tumors (p=0.026) and a higher risk of recurrence in all patients (p=0.001). Among patients with (P)RR-positive tumors, the nuclear expression of ß-catenin was associated with a higher risk of recurrence (p=0.001). Multivariate analysis revealed that (P)RR down-regulation was an independent predictor of disease recurrence (p=0.031). Conversely, in squamous cell carcinoma, (P)RR was not associated with patient outcomes. CONCLUSION: (P)RR down-regulation is associated with a higher risk of recurrence in lung adenocarcinomas, thereby characterizing a prognostic subset within high-grade tumors.

[Esophagectomy for Bronchogenic Cyst within the Esophageal Muscle Layer with Dysphagia:Report of a Case].

A 26-year-old man referred to our hospital because of dysphagia and a mediastinal tumor detected on chest computed tomography (CT). A contrast-enhanced CT revealed a 12 cm long cystic tumor along the right thoracic esophagus. An upper gastrointestinal endoscopy showed no abnormalities in the esophageal mucosa, and an unclear boundary between the tumor and the esophageal wall was observed by echography. In surgery, the tumor and the esophagus were in one lump, and esophagectomy was performed. On the fourth postoperative day, esophagogastric anastomosis was performed with poststernal reconstruction, and the patient was discharged home on the 38th postoperative day. Pathological examination revealed that the mass was a cystic lesion within the esophageal muscular layer, and the cyst wall was coated with airway-like multi-lineal hairy epithelium, which led to the diagnosis of a bronchogenic cyst. Even if the cyst is within the esophageal muscularis layer, bronchogenic cyst should be considered in the differential.

[Pulmonary Herniation Requiring Reconstructive Surgery Caused by Minimally Invasive Cardiac Surgery:Report of a Case].

A 72-year-old man who underwent aortic valve replacement by a minimally invasive cardiac surgery (MICS) approach two years ago was visited our hospital complaining of swelling and pain in the right anterior chest. A chest computed tomography (CT) scan showed that the right upper lobe protruded beyond the right second intercostal space and outside the thorax. He was diagnosed as a right intercostal lung hernia and underwent chest wall reconstruction with a substitute method. Postoperative course was uneventful without any evidence of recurrence. Postoperative intercostal lung hernias in MICS may increase with the increment in MICS, and it is necessary to accumulate cases as one of the complications.

Segmentectomy Provides Comparable Outcomes to Lobectomy for Stage IA Non-small Cell Lung Cancer with Spread through Air Spaces.

This study aimed to compare the recurrence-free survival (RFS) and overall survival (OS) among wedge resection (non-anatomical resection), segmentectomy and lobectomy for pathological stage IA non-small cell lung cancer (NSCLC) with spread through air spaces (STAS). Patients underwent surgical treatment for pathological stage IA NSCLC between January 1, 2005, and March 31, 2016, at our hospital. Surgical procedures were classified as lobectomy, segmentectomy, and wedge resection. Among the 555 analyzed cases, STAS was observed in 148 patients (26.7%). STAS was correlated with worse RFS (P < 0.001) and OS (P < 0.001) and was an independent poor prognostic factor for RFS (hazard ratio: 2.37, P < 0.001) and OS (hazard ratio: 2.02, P < 0.001) in the multivariate analysis. In patients with STAS, the RFS and OS in the segmentectomy group were comparable to those in the lobectomy group. However, the RFS and OS in the wedge resection group were significantly lower than those in the lobectomy group (RFS, P < 0.001; OS, P = 0.001). Wedge resection was an independent prognostic factor for poor RFS (hazard ratio [HR] = 3.87; 95% confidence interval [CI] = 1.84 - 8.12, P < 0.001), and poor OS (hazard ratio [HR] = 3.39; 95% confidence interval [CI] = 1.33 - 8.76, P = 0.011) in the multivariate analysis. Segmentectomy is an adequate operation for patients with stage IA NSCLC with or without STAS. However, wedge resection is associated with a higher risk of recurrence in this patient population.

Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma.

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p < 0.001) and worse OS (hazard ratio [HR]: 1.75, p = 0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.

Safe pneumonectomy for locally advanced lung cancer after induction therapy.

PURPOSE: To assess the safety and long-term outcomes of pneumonectomy after IT (IT-Pn) versus upfront pneumonectomy without IT (U-Pn) for locally advanced non-small-cell lung cancer (NSCLC). METHODS: We reviewed the clinical records of 69 patients who underwent pneumonectomy as U-Pn (n = 30) or IT-Pn (n = 39) between 2000 and 2019 at our institution, RESULTS: U-Pn included patients with pathological N0 (n = 13), N1 (n = 11) and N2 (n = 6). Among the patients treated with IT-Pn, 18 had pathological N0 (including 7 with complete responses), 5 had N1, 14 had N2, and 2 had N3. It was suggested that 22 cases could be down-staged after IT. The 5-year overall survival (OS) was 28.1% in the U-Pn group and 43.1% in the IT-Pn group (p = 0.275), being 40.2% for IT-Pn with p-N2,3, but not reached for U-Pn with N2 (p = 0.307). The 90-day mortality was 6.7% for the U-Pn group and 5.1% for the IT-Pn group (p = 0.646). Major complications occurred in 25 patients (64.1%) treated with IT-Pn and 18 patients treated with U-Pn (60.0%; p = 0.602). CONCLUSIONS: Pneumonectomy for NSCLC can be performed safely after IT with favorable results. For patients with N2 disease, induction therapy followed by surgery may warrant further study.

[Prolonged Air Leaks after Right Upper Lobectomy Successfully Treated with Administration of Blood Coagulation Factor :Report of a Case].

A 80-year-old man who underwent right S1 segmentectomy three years ago was pointed out a mass shadow in the right upper lobe by chest computed tomography( CT). Because the mass was suspected of 2nd lung cancer, right upper lobectomy was performed. Air leakage from the chest tube appeared the day after the operation did not improve with the autologous blood patch pleurodesis. Since neither surgery nor invasive pleurodesis was thought to be possible because of the risk of acute respiratory failure due to the severe pulmonary emphysema, the administration of factor was challenged based on the result of its reduced activity. After the administration, the air leaks ceased promptly. Blood coagulation factor supplement may be effective in the treatment for intractable air leaks after lobectomy.

Tumor-associated macrophage infiltration is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas.

OBJECTIVE: Lung cancer can spread in numerous ways, one of which has been suggested to be spread through air spaces (STAS). The tumor immune microenvironment appears to play a significant role in this spread. Particularly, tumor-associated macrophages (TAMs) can create a favorable microenvironment for tumor progression. In this study, we analyzed data from 709 patients with stage 0-IIIA lung adenocarcinoma, resected between 1999 and 2016, and investigated whether immune cell infiltration was associated with the occurrence of STAS and clinical outcome of the disease. MATERIALS AND METHODS: Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, and CD68. The three tumor areas with the highest density of immune cells were photographed, and the immune cells were quantified. Associations between variables were analyzed using chi-square tests and Mann-Whitney U tests. Recurrence-free probability and overall survival were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: After analyzing the associations between STAS and each type of immune cell infiltration, high density of CD68 + TAMs was identified as an independent predictor of a high STAS rate (p =  0.014) and was found to be associated with a high risk of recurrence, using univariate analysis (p =  0.008). After adjusting for CD68+ TAMs, pathological stage, and lymphovascular invasion, STAS remained significantly associated with a high risk of recurrence (HR = 3.50, p < 0.001). CONCLUSION: We demonstrated that a high density of CD68 + TAMs is an independent predictor of an increased STAS rate. Additionally, STAS is correlated with aggressive tumor behavior characteristics.

Current status and perspectives of spread through air spaces in lung cancer.

According to the World Health Organization classification of 2015, spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. Many researchers have reported that STAS is recognized in all histological subtypes, and there is a strong association between STAS and prognosis in lung cancer. However, there are several technical issues associated with STAS, such as distinction between the actual in vivo phenomenon and an artifact, difficulty in assessing STAS in frozen specimens, and establishing the relationship between morphological and molecular properties of STAS. This review focuses on the current state of knowledge and the outlook of the STAS phenomenon from the perspective of surgeons, pathologists, and radiologists.

The epithelial-mesenchymal transition phenotype is associated with the frequency of tumor spread through air spaces (STAS) and a High risk of recurrence after resection of lung carcinoma.

OBJECTIVES: The prognostic value of spread through air spaces (STAS) in lung carcinoma has been validated in independent cohorts. Epithelial-mesenchymal transition (EMT) is a biological process that promotes the migration and invasiveness of tumor cells. To investigate the role of the EMT phenotype in the occurrence of STAS, we analyzed patients with therapy-naive lung adenocarcinoma and squamous cell carcinoma undergoing lobectomy (n = 635). MATERIALS AND METHODS: STAS was defined by the presence of tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The expression of E-cadherin, vimentin, and ®-catenin was evaluated by immunohistochemistry using tissue microarray. Tumors were classified into three EMT phenotypes (epithelial, intermediate, and mesenchymal). Recurrence-free probability and overall survival were analyzed using the log-rank test and the Cox proportional hazards model. RESULTS: STAS was less frequently observed in tumors with epithelial phenotype than in those with non-epithelial phenotype (p = 0.034), and more frequent in patients with nuclear ß-catenin-positive tumors (p < 0.001). The EMT phenotype was an independent prognostic factor of recurrence (mesenchymal vs. epithelial: hazard ratio [HR] = 2.27, p = 0.014; mesenchymal vs. intermediate: HR = 2.13, p = 0.019). CONCLUSION: We have demonstrated that in patients with resected lung carcinoma, STAS was less frequent in tumors with an epithelial phenotype than in those with non-epithelial phenotype, and that the nuclear translocation of ß-catenin was associated with a higher rate of STAS. The mesenchymal state was an independent predictor of high risk of recurrence in patients with STAS.

Reconstruction of the carina using bronchial autograft: an alternative approach.

We report successful engraftment by autologous transplantation of the bronchial wall of the resected specimen in extensive tracheobronchial resection with left pneumonectomy. Since the adenoid cystic carcinoma had spread beyond the carina to the right bronchus, we resected three rings of tracheal cartilage and three rings of left main bronchus cartilage. Reconstruction was performed using the bronchial wall of the resected specimen to relieve tension on the anastomosis. No stricture or recurrence was observed four years after the operation. Further research relating to maximization of blood flow to the reconstructed tissue based on engraftment area and shape is required.

Two cases of nodular smooth muscle proliferation suspected of primary lung cancer from preoperative images: a case report.

BACKGROUND: It is difficult to obtain a definitive diagnosis for nodular smooth muscle proliferation (NSMP) before surgery, and a pathological diagnosis is necessary to differentiate it from primary lung cancer. We report two cases of NSMP that were suspected to be primary lung cancer on preoperative images. CASE PRESENTATION: Case 1: An 81-year-old man who had undergone right upper lobectomy for lung cancer 2 years earlier was point out a nodular shadow with ground glass opacity (GGO) in the lower right lobe, suggesting a second primary lung cancer by chest computed tomography (CT). A thoracoscopic partial resection of the right lower lobe was performed, and pathological diagnosis was NSMP. The patient was discharged without any problems at 3 days postoperatively. Case 2: A 72-year-old woman was pointed out a nodular shadow suspected primary lung cancer in the left lower lobe by chest CT. Therefore, thoracoscopic partial resection of the left lower lobe was performed, and pathological diagnosis was NSMP. The patient was discharged without any problems at 5 days postoperatively. CONCLUSION: This report demonstrates that NSMP can be distinguished from leiomyoma and hamartoma by imaging features and pathological findings.

[Successful Treatment of Spontaneous Esophageal Rupture with Empyema by the Open Drainage and Application of Basic Fibroblast Growth Factor].

A 77-year-old man vomited after alcohol drinking and was sent to our hospital by an ambulance due to sustained chest pain. Chest computed tomography (CT) showed pneumothorax and pleural effusion, and thoracic drainage was performed. Since food residue was found from chest drainage and esophagoscopy and esophagography showed injured potion on the left wall of the lower thoracic esophagus perforating to the left thoracic cavity, a spontaneous esophageal rupture was diagnosed. Establishment of fenestration for open drainage and gastrostomy were performed. After 49 days, the fistula was successfully closed by cleaning of the left thoracic cavity, with application of basic fibroblast growth factor and enteral nutrition through gastrostomy. The fenestration was closed after 53 days and the patient was discharged after 78 days.

Systemic expression of Alu RNA in patients with geographic atrophy secondary to age-related macular degeneration.

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is characterized by irreversible loss of macular retinal tissue and retinal pigment epithelium (RPE) cells. Several studies have revealed that accumulation of Alu RNA in RPE cell causes RPE cell degeneration in AMD. In the present study, systemic Alu RNA expression levels were determined in 33 subjects with GA and 40 control subjects using a proprietary Alu RNA quantification method. It was observed that the expression level of Alu RNA was not significantly different between GA and Control groups (median = 21.3 in both GA and Control groups, P = 0.251). In addition, the systemic level of Alu RNA was not associated with subject characteristics, such as GA lesion size and SNP profiles of complement factors associated with increased risk of AMD. In conclusion, the usability of systemic Alu RNA expression level as a biomarker of GA secondary to AMD could not be established in this study.

[Intraphrenic Bronchogenic Cyst;Report of a Case].

Bronchogenic cyst is not a rare disease, but cases of bronchogenic cyst in the diaphragm are rare. We report a case of intraphrenic bronchogenic cyst. A 68-year-old woman was pointed out a 30 mm tumor on the left diaphragm by chest computed tomography (CT) 12 years ago. Because the size of the tumor had been increasing for 12 years, she was hospitalized for surgery. The tumor in the left diaphragm was removed by thoracotomy. Histologically, the tumor was diagnosed as a intraphrenic bronchogenic cyst.

[Multiple Pulmonary Inflammatory Myofibroblastic Tumor].

A 67-year-old man visited hospital because of prolonged cough. Chest computed tomography (CT) revealed multiple tumors in bilateral lungs. Transbronchial lung biopsy did not reveal malignancy. Because antibiotic treatment was ineffective, partial resection of the right lung was performed for establishing the diagnosis. The pathological diagnosis was inflammatory myofibroblastic tumor. The postoperative course was uneventful. After 6 months postsurgery, he complained of breathing difficulty and exacerbation of the lesions was found by chest CT. By methylprednisolone pulse therapy, the symptom was improved, and the size of lesions reduced. Since this event, he has been administered oral prednisolone (PSL) 10 mg/day, and the exacerbation of the disease has not been noted.

[Right Upper Lobectomy for Lung Cancer with Partial Anomalous Pulmonary Venous Connection;Report of a Case].

A 75-year-old woman was pointed out a mass shadow in the right upper lobe by chest computed tomography (CT) 3 month ago. Bronchoscopic examination revealed adenocarcinoma, and right upper lobectomy was performed. Preoperatively, it was revealed that V1+2 returned to the superior vena cava while V3 returned to the normal position. Postoperative course was uneventful and there has been no recurrence 6 months post-surgery.

[Pulmonary Fetal Adenocarcinoma Requiring Differential Diagnosis of Metastatic Lung Tumor;Report of a Case].

Fetal adenocarcinoma is a rare disease. We report a case of fetal adenocarcinoma requiring differential diagnosis of metastatic lung tumor. A 75- year-old woman was pointed out a 8 mm tumor in the right lower lobe by chest computed tomography(CT) 6 month ago. Because the size of the tumor had been increasing for 6 months, she was hospitalized for surgery. Because of the tumor shape, we suspected that the tumor was metastatic lung tumor of hepatocellular carcinoma for which she had undergone hepatic arterial infusion chemotherapy and radiofrequency ablation. A right lower lobectomy with lymph node dissection was performed and pathological diagnosis was high-grade fetal adenocarcinoma, stage IV.

[Pulmonary Nontuberculous Mycobacteriosis Appeared at the Surgical Margin of the Lung Cancer Surgery;Report of a Case].

A 70-year-old woman had undergone right S8+9 segmentectomy for stage I A lung cancer. Surgical staplers were used for an intersegmental line. Two years after surgery, routine chest computed tomography(CT) showed a 40-mm mass around the staple line in the right lower lobe, and positron emission tomography (PET) was positive. The mass was suspected to be local recurrence of lung cancer, and she was done additional surgery for resection of the remaining right lower lobe. The pathologic diagnosis was lung nontuberculous mycobacteriosis. It was suggested that nontuberculous mycobacteriosis developed at the atelectasis around the staple line. In addition to local recurrence, the possibility of nontuberculous mycobacteriosis should be considered in cases of pulmonary nodules appearing at the staple line after pulmonary resection.

[Pulmonary Chondroma; Report of a Case].

A 66-year-old man was pointed out a nodular shadow in the right lower lobe by chest computed tomography (CT) 4 years ago. Since the size of the shadow has been increasing for 4 years, he hospitalized for surgery. Partial resection of the right lower lobe was performed. Histopathologically, the tumor was composed of cartilage tissue without epithelial components, and was diagnosed as a chondroma. Postoperative course was uneventful and there has been no recurrence at 1 years and 8 months after surgery.