Suspected Aspergillus nodule histologically consistent with pulmonary nodular lymphoid hyperplasia:a case report.

Aspergillus nodules (AN) are an unusual form of chronic pulmonary aspergillosis. On the other hand, pulmonary nodular lymphoid hyperplasia (PNLH) is classified as a reactive pulmonary lymphoproliferative disorder. A 65-year-old male was referred to our hospital due to a nodule in the left upper lobe. Histologically, a mixture of prominent lymphoid follicular formation, and hyaline necrosis were observed. Grocott staining revealed morphological forms of Aspergillus spp. in the necrosis. The final clinical diagnosis was suspected AN histologically consistent with PNLH. This case suggests that there may be PNLH cases in which local infection with Aspergillus contributes to its pathophysiology. J. Med. Invest. 70 : 499-502, August, 2023.

Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids.

Introduction: The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Methods: Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. Results: The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Conclusions: Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.

Solitary Ground-Glass Nodule Mimicking Lung Cancer due to Focal Progression of Usual Interstitial Pneumonia.

Idiopathic pulmonary fibrosis is often associated with lung cancer, but early malignant lesions mixed with fibrous lesions are not always easy to diagnose. A 78-year-old woman was referred to our hospital due to a ground-glass nodule in the left upper lobe detected on chest high resolution computed tomography during follow-up of chronic idiopathic interstitial pneumonia. Pathological examination of the resected specimen revealed that the ground-glass nodule was locally progressed usual interstitial pneumonia (UIP). It should be noted that focal progression of UIP may occur and present with ground-glass nodule mimicking lung cancer, even if lesions in other areas remain unchanged. Moreover, in such cases, recognition of nodular lesions by the gross findings on the pleural surface and palpation during surgical resection are difficult and require precise marking.

Type A thymoma: a rare cause of neoplastic cardiac tamponade with long-term survival.

BACKGROUND: The prognosis of thymoma with cardiac tamponade is generally poor. Most of the reported thymomas with cardiac tamponade were type B or type AB (mixed thymoma), and cardiac tamponade due to type A thymoma, which has a better prognosis compared to type B thymoma, is extremely rare. CASE PRESENTATION: We encountered a case of cardiac tamponade in a 71-year-old male. He visited our emergency department due to exacerbation of fatigue and dyspnea on exertion that lasted for two weeks. Chest imaging revealed a large amount of pericardial fluid and a contrast-enhanced tumor with calcification in the anterior mediastinum. The patient underwent thoracoscopic tumor biopsy and pathological examinations revealed type A thymoma. In this case, long-term disease-free survival (7.5 years) was achieved by multidisciplinary treatment (preoperative chemotherapy, surgical excision, and postoperative radiation therapy), in accordance with the histological type. CONCLUSIONS: This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes.

An 18 F-FDG-PET-Positive Mucoid Impaction With Ring Enhancement on CT Mimicking Lung Cancer.

ABSTRACT: We encountered a case of an 18 F-FDG PET-positive solitary nodule with ring enhancement on CT mimicking lung cancer in the left S6 region of an 80-year-old woman. Since transbronchial biopsy by endobronchial ultrasonography with a guide sheath could not obtain sufficient material, despite the guide sheath being placed within the lesion, the patient underwent thoracoscopic partial left S6 resection. The nodule was diagnosed as acquired cystic bronchiectasis and mucoid impaction associated with chronic inflammation. The ring-shaped enhancement and the 18 F-FDG uptake may reflect angiogenesis in the cystic wall and accumulation of viable inflammatory cells in the wall and inner space, respectively.

Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. CASE: A 65-year-old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD-L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3-positive T cells and CD138-positive plasma cells. Second-line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. CONCLUSION: Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

Dramatic response to immunochemotherapy followed by salvage surgery in an elderly lung cancer patient.

Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment of lung cancer. Here, we encountered a case of inoperable locally advanced squamous cell carcinoma of the lung that became operable with pembrolizumab-based immunochemotherapy and achieved a pathological complete response. An 82-year-old man suspected of having lung cancer was referred to our hospital. The patient was clinically diagnosed with left upper lobe squamous cell carcinoma cT2aN3M0 c-stage IIIC. Immunostaining revealed the expression of programmed death-ligand 1 in 60% of tumor cells. The cancer cells disappeared after two cycles of chemotherapy with carboplatin and nanoparticle albumin-bound paclitaxel plus pembrolizumab. As the abnormal accumulation of 18 F-fluorodeoxyglucose (FDG) on FDG-positron emission tomography/computed tomography before chemotherapy almost disappeared after pembrolizumab-based immunochemotherapy, left upper lobectomy and lymph node dissection were performed. No cancer cells were pathologically detected from the resected tissue. Therefore, ICIs combined with chemotherapy may enable inoperable advanced lung cancer patients to undergo surgery and achieve a complete response.

A rare anomaly of A4+5 on three-dimension multidetector computed tomography in lung cancer: A case report.

INTRODUCTION: There are several anomalies of the pulmonary vessels. Clinicians need to be well informed about anatomy, particularly before video-assisted thoracic surgery, to prevent fatal complications. PRESENTATION OF CASE: We report the case of an 80-year-old woman who was suspected of having lung cancer in the right lower lobe. The patient was accordingly scheduled for surgery. Three-dimension multidetector computed tomography (3D-MDCT) showed an extremely rare anomaly in which A4 + 5 ran between V2 and V1 + 3. We scheduled a non-anatomical wedge resection of the lesion and performed rapid pathological diagnosis during surgery. Because adenocarcinoma was diagnosed, we performed right lower lobectomy using video-assisted thoracic surgery. Station 11i lymph node rigidly adhered to the main pulmonary artery, V2, and intermedius bronchus. Thus, the surgery was shifted to middle and lower lobectomy. DISCUSSION: To the best of our knowledge, this type of anomaly has not been reported yet. Pulmonary vessels can be accurately identified using 3D-MDCT; thus, a rare anatomy can be identified, and information can be shared across the surgical team simulating familiarity with this rare anatomy. CONCLUSION: Using 3D-MDCT, we could accurately divide A4 + 5 and safely perform the surgery.

A case of thoracoscopic medial basal segmentectomy.

INTRODUCTION: Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. PRESENTATION OF CASE: A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. DISCUSSION: B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. CONCLUSION: In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.

Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer.

OBJECTIVES: This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. METHODS: Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. RESULTS: The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. CONCLUSIONS: The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma.

Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.

Safe and successful treatment with afatinib in three postoperative non-small cell lung cancer patients with recurrences following gefitinib/erlotinib-induced hepatotoxicity.

BACKGROUND: Gefitinib and/or erlotinib-induced hepatotoxicity sometimes lead to treatment failure in EGFR mutation-positive patients with non-small cell lung cancer (NSCLC), even though the therapeutic effect is evident. CASES: Here, we report three postoperative NSCLC patients with recurrences who experienced severe hepatotoxicity while receiving gefitinib and/or erlotinib treatment but could be safely switched to afatinib treatment. CONCLUSION: Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs.

[Current Status and Effectiveness of Perioperative Oral Health Care Management for Lung Cancer and Esophageal Cancer Patients].

The effectiveness of perioperative oral health care management to decrease the risk of postoperative pneumonia have been reported lately. Since 2014, we introduced perioperative oral health care management for lung cancer and esophageal cancer patients. We report current status and effectiveness of perioperative oral health care management for lung cancer and esophageal cancer patients. Every 100 cases of lung cancer and esophageal cancer patients treated by surgery were classified 2 group with or without perioperative oral health care management and compared about postoperative complications retrospectively. In the lung cancer patients, the group with oral health care management could prevent postoperative pneumonia significantly and had shorter length of hospital stay than the group without oral health care management. In the esophageal cancer patients, there was little occurrence of postoperative pneumonia without significant difference between both group with or without oral health care management. A large number of esophageal cancer patients received neo-adjuvant chemotherapy and some patients developed oral mucositis and received oral care treatment before surgery. Treatment for oral mucositis probably improved oral environment and affected prevention of postoperative pneumonia. Perioperative oral health care management can prevent postoperative pneumonia of lung cancer and esophageal cancer patients by improvement of oral hygiene.

Primary Pulmonary Synovial Sarcoma Showing a Prolonged Survival with Multimodality Therapy.

A 54-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Thoracoscopic lobectomy yielded a diagnosis of primary pulmonary synovial sarcoma according to the histology and SYT-SSX1 gene analyses. Five months after the thoracic surgery, he developed brain metastasis; therefore, we performed resection of the brain metastatic focus followed by radiotherapy. As a local recurrence in the thoracic cavity concurrently emerged, systemic chemotherapy was also administered. These observations indicated that a multidisciplinary approach may be useful against primary pulmonary synovial sarcoma, although there is presently no established therapeutic strategy due to its rarity and highly aggressive nature.

Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.

BACKGROUND AND AIMS: The changes of autonomic nervous activity during bronchoscopic procedures are closely related to the development of cardiovascular complications. We aimed to evaluate the changes of autonomic nervous activity during bronchoscopic procedures using R-R interval variability from electrocardiograms (ECGs) obtained during diagnostic bronchoscopy. METHODS: Twenty-four patients who underwent bronchoscopy were included. Continuous ECG was recorded prior to, during and after the bronchoscopic procedure. Time and frequency domain analyses of heart rate variability were performed. RESULTS: Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion. CONCLUSIONS: This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.

Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab.

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.

Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones.

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC), an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3'5'-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF), surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.

S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.

Thoracoscopic pericardial fenestration for effective long-term management of non-tuberculous mycobacterium pericarditis.

The long-term consequences of non-tuberculous mycobacterium pericarditis with pericardial effusion after fenestration have not been described. We encountered a case of non-tuberculous mycobacterium pericarditis in a 59-year-old woman with an underlying collagenosis. Repeated drainage was required because of rapid reaccumulation of the effusion. To definitively control the effusion, pericardial fenestration was performed by video-assisted thoracoscopic surgery. Chest radiography performed 6 years postoperatively showed no accumulation of pericardial or pleural fluid. The patient required careful follow-up and, to date, the pulmonary non-tuberculous mycobacterium (NTM) infection has been successfully suppressed by continuous antibiotic therapy. Pericardial fenestration with antibiotic therapy was an appropriate treatment for recurrent effusion in this case of NTM pericarditis.