今泉 和良

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)

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.