imaizumi kazuyoshi

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.

末梢血を用いたiPS細胞作出において、これまでリンパ球が用いられ、単球と市販ベクターを用いて作出することはできなかった。我々は細胞生物学的見地から、末梢血単球の短期浮遊培養とiPS細胞へのリプログラミング法を新規開発した。作出された単球由来iPS細胞は、三胚葉への多分化能を有しており、単球、マクロファージおよび複数の抗原に反応性を有する樹状細胞に分化誘導できた。今後、さまざまな抗原に対する免疫寛容細胞への効率的な分化誘導法を検討し、自己免疫疾患に対する自己細胞療法の開発をめざしたい。(著者抄録)

病理診断において,肺癌の組織型を正確に把握することは,治療方針を決定するために重要である.病理医は画像のみでなく,患者の臨床的背景を理解して診断を行なっている.そこで本研究では,液状細胞診(LBC)画像と患者臨床情報を用いた肺癌組織型分類手法を開発し,基礎評価を行った.はじめに,深層畳み込みニューラルネットワークを用いて,LBC画像から肺癌組織型に関する画像特徴量を抽出した.次に,電子カルテより患者臨床情報(喫煙情報等)を収集し,主成分分析により次元圧縮を行った.得られた画像特徴量とその画像に対応する患者臨床情報の主成分を識別器に入力し,3種類の肺癌組織型の分類結果を得た.149症例の臨床データを用いて,3-fold交差検証にて評価を行ったところ,LBC画像単体での分類精度は、82.9%であった.画像特徴に喫煙情報・腫瘍マーカー値を加えて,SVMで識別を行ったところ,それぞれ総合識別率は向上した.これらの結果から,提案手法の有用性が示唆された.(著者抄録)

Background: Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. Subjects, Materials, and Methods: In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self-assessment questionnaire to determine whether the patients believed oral morphine was effective. Results: Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty-four patients (76.1%) reported that oral morphine was effective on the self-assessment questionnaire. Among the background factors, a high score for “sense of discomfort” on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack-years were associated with greater effectiveness. Conclusion: Oral morphine was effective and feasible for treating cancer-related dyspnea. A higher score for “sense of discomfort” on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. Implications for Practice: This study demonstrated that oral morphine was effective in alleviating cancer-related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for “sense of discomfort” on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in “morphine-ineffective” patients.

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC. (C) 2018 Elsevier Inc. All rights reserved.

BACKGROUND/AIM: The β2-adrenergic receptor (β2AR) is highly expressed in various human cancers and has been linked to tumor growth and metastases. Although β2AR is considered a novel therapeutic target of human neoplasms, the clinicopathological significance of β2AR expression in patients with pulmonary pleomorphic carcinoma (PPC) remains unclear. The aim of this study was to clarify the prognostic impact of β2AR in PPC. PATIENTS AND METHODS: One hundred and five Japanese patients with surgically resected PPC were included in the study. The expression levels of β2AR were assessed by immunohistochemistry in specimens from the resected tumors, and their association with patient survival, as well as with tumor characteristics was investigated. RESULTS: β2AR was highly expressed in 63% of all patients, irrespective of adenocarcinoma components present. The β2AR expression was significantly associated with lymph node metastasis, lymphatic permeation and tumor cell proliferation in PPC patients with early-stage disease (stage I or II). A high β2AR expression was identified as a significant predictor of worse prognosis for PPC patients during early stages of the disease. Multivariate analysis confirmed that β2AR expression was an independent factor for predicting the overall survival of PPC patients. CONCLUSION: β2AR can serve as a significant predictor of tumor aggressiveness and poor survival for PPC patients, especially those with early-stage disease.

Objectives: Positron emission tomography/computed tomography (PET/CT) examination is commonly used for the evaluation of pulmonary nodules since it provides both anatomical and functional information. However, given the dependence of this evaluation on physician's subjective judgment, the results could be variable. The purpose of this study was to develop an automated scheme for the classification of pulmonary nodules using early and delayed phase PET/CT and conventional CT images. Methods: We analysed 36 early and delayed phase PET/CT images in patients who underwent both PET/CT scan and lung biopsy, following bronchoscopy. In addition, conventional CT images at maximal inspiration were analysed. The images consisted of 18 malignant and 18 benign nodules. For the classification scheme, 25 types of shape and functional features were first calculated from the images. The random forest algorithm, which is a machine learning technique, was used for classification. Results: The evaluation of the characteristic features and classification accuracy was accomplished using collected images. There was a significant difference between the characteristic features of benign and malignant nodules with regard to standardised uptake value and texture. In terms of classification performance, 94.4% of the malignant nodules were identified correctly assuming that 72.2% of the benign nodules were diagnosed accurately. The accuracy rate of benign nodule detection by means of CT plus two-phase PET images was 44.4% and 11.1% higher than those obtained by CT images alone and CT plus early phase PET images, respectively. Conclusion: Based on the findings, the proposed method may be useful to improve the accuracy of malignancy analysis.

Lung cancer is a leading cause of death worldwide. Although computed tomography (CT) examinations are frequently used for lung cancer diagnosis, it can be difficult to distinguish between benign and malignant pulmonary nodules on the basis of CT images alone. Therefore, a bronchoscopic biopsy may be conducted if malignancy is suspected following CT examinations. However, biopsies are highly invasive, and patients with benign nodules may undergo many unnecessary biopsies. To prevent this, an imaging diagnosis with high classification accuracy is essential. In this study, we investigate the automated classification of pulmonary nodules in CT images using a deep convolutional neural network (DCNN). We use generative adversarial networks (GANs) to generate additional images when only small amounts of data are available, which is a common problem in medical research, and evaluate whether the classification accuracy is improved by generating a large amount of new pulmonary nodule images using the GAN. Using the proposed method, CT images of 60 cases with confirmed pathological diagnosis by biopsy are analyzed. The benign nodules assessed in this study are difficult for radiologists to differentiate because they cannot be rejected as being malignant. A volume of interest centered on the pulmonary nodule is extracted from the CT images, and further images are created using axial sections and augmented data. The DCNN is trained using nodule images generated by the GAN and then fine-tuned using the actual nodule images to allow the DCNN to distinguish between benign and malignant nodules. This pretraining and fine-tuning process makes it possible to distinguish 66.7% of benign nodules and 93.9% of malignant nodules. These results indicate that the proposed method improves the classification accuracy by approximately 20% in comparison with training using only the original images.

Since induced pluripotent stem (iPS) cells have been established, in recent years, clinical transplantation of cells differentiated from iPS cells derived from human skin fibroblasts is been in progress. On the contrary, monocytes have complete genome information without damage and gene recombination, they are contained in the peripheral blood by ∼3%-8% and differentiate into dendritic cells that are the type of control tower for immune cells. However, generation of monocyte-derived iPS cells has only been successful when special persistent Sendai virus vectors have been used. Therefore, in this study, as a preculture method for monocytes, a culture method for maintaining activity without using any cytokine was established, and using a commercially available vector without genetic toxicity without damaging the chromosome of the cell, iPS cells derived from monocytes were successfully produced. This cell has the ability to differentiate into three germ layers, and when compared with commercially available iPS cells, there was no significant difference between self-renewal and gene expression in the three germ layers. In future, we will compare the differentiation induction of monocyte-derived iPS cells with dendritic cells and investigate the production of dendritic cells that can cope with various antigens.

In recent research on regenerative medicine, three-dimensional (3D) tissue reconstruction using the induced pluripotent stem cell (iPS cell) differentiated cells has attracted attention. In this study, mouse lungs at 1.5, 10, and 20 d old were subjected to enzyme treatment, and aggregates formed in serum-free suspension culture (3D-culture) were observed. The number of aggregates formed was the highest in 1.5 d. The cell aggregates in which the interior of the aggregate is filled and form small vacuoles and the organoid-like aggregates having a relatively large vacuole inside and forming the alveolar-like structure were observed. At 1.5 d, the formation ratio of the organoid-like aggregates was the highest and aggregate size was small at 20 d. For the cell aggregates derived from 1.5 d, positive cells of SSEA-1, CD29, CD90, CD105, alveolar epithelial stem cell marker of SP-C, and Sca-1 were observed in the center. In the cell aggregates derived from 10 d, the expression level of 1.5 d each protein markers and OCT4 gene of transcription factor was decreased, and furthermore, markers were hardly observed in the organoid-like aggregates derived from 10 d. In addition, cells surrounding the vacuole of organoid-like aggregate obtained over 10 d differentiated into periodic acid-Schiff (PAS), podoplanin-positive cells. When the formed cell aggregates were dispersed, cell aggregates and organoid-like aggregates were reformed. Comparing 3D-culture and adhesion culture (2D-culture), SP-C expression of 10 d of cells was maintained. Expression of markers of undifferentiated markers and alveolar tissue stem cells decreased when cell aggregates were cultured with the addition of fetal bovine serum.

A previous randomized phase II study in patients with non-small cell lung cancer (NSCLC) identified that combination treatment with erlotinib plus bevacizumab prolonged progression-free survival compared with erlotinib alone. However, combination bevacizumab and erlotinib treatment generally increased the risk of severe adverse events, including hemorrhage, thrombosis, fistula formation and gastrointestinal perforation. The present report describes two patients with NSCLC harboring epidermal growth factor receptor (EGFR) mutations, who experienced gastrointestinal perforation associated with erlotinib plus bevacizumab combination therapy. The first patient, a 67-year-old male with stage IIIB lung adenocarcinoma harboring a L858R point mutation in EGFR exon 21, received concurrent chemoradiotherapy. However, seven months later, the patient experienced a relapse and was administered erlotinib plus bevacizumab treatment. A total of two months subsequent to commencing treatment, the patient developed a perforated duodenal ulcer. The second patient, a 66-year-old male with lung adenocarcinoma harboring a deletion in EGFR exon 19 and multiple pulmonary metastases, demonstrated a partial response to erlotinib plus bevacizumab treatment. A total of seven months subsequent to starting treatment, the patient experienced lower abdominal pain, and abdominal computed tomography confirmed a diagnosis of colocutaneous fistula complicating sigmoid diverticulitis. Following repair of the perforation, both patients were restarted on erlotinib treatment alone. Gastrointestinal perforation may be a potentially severe adverse event of erlotinib plus bevacizumab combination therapy, even in the absence of tumor metastasis in the abdomen.