Language：Japanese   Publisher：日本分子腫瘍マーカー研究会  

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

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BACKGROUND: The da Vinci Si version robot lacks a vascular stapler that can be controlled by the operating surgeon at the surgical console when dividing pulmonary vessels. Therefore, to initiate and safely perform robotic anatomical lobectomy for lung cancer, it is important to develop a safe method for introducing a surgical stapler. METHODS: We performed a retrospective study of the first 42 consecutive patients who underwent robotic lobectomy for lung cancer at Nippon Medical School Hospital between January 2019 and December 2020. RESULTS: Up to case 18, we performed robot-assisted thoracoscopic surgery (RATS) lobectomy by using a four-arm approach with two assistant ports. For dividing pulmonary vessels, the surgical stapler was introduced through the assist ports. However, since this is not the port position usually used in video-assisted thoracoscopic surgery (VATS), there were many difficult situations. For RATS lobectomy case 19 and all subsequent cases, we utilized a total port approach that uses three robotic arms and two assistant ports. To resect the pulmonary vessels or bronchi with endoscopic staplers, the port for the robotic arm was removed and the endoscopic staplers were placed through a 12-mm Xcel bladeless port. This change reduced operation time, blood loss, and robotic arm interference. No patient developed intraoperative complications during RATS lobectomy. CONCLUSION: The present total port approach, with three robotic arms, appears to be feasible for introducing surgical staplers during RATS with the da Vinci Si robotic system.

DOI： 10.1272/jnms.JNMS.2022_89-211

PubMed

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Language：Japanese   Publisher：Japan Society for Laser Surgery and Medicine  

Photodynamic therapy (PDT) is a standard treatment for centrally located early lung cancer. Accurate diagnosis of the tumor extent and appropriate application of laser irradiation are important for improving treatment outcome. However, some endoscopic systems are unsuitable for evaluating tumor extent after injecting taraporfin sodium, a photosensitizer, and because of the loss of color information with the use of strong laser light, complicating appropriate irradiation of the tumor. In this study, we investigated the ingenuity of PDT to improve the therapeutic outcome with the simultaneous use of endoscopic system ELUXEO 7000^® (Fujifilm Corporation).

DOI： 10.2530/jslsm.jslsm-43_0004

CiNii Research

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Most cardiac diseases cause a non-physiological blood flow pattern known as turbulence around the heart and great vessels, which further worsen the disease itself. However, there is no consensus on how blood flow can be defined in disease conditions. Especially, in the left atrium, the fact that vortex flow already exists makes this debate more complicated. 3D time-resolved phase-contrast (4D flow) MRI is expected to be able to capture blood flow patterns from multiple aspects, such as blood flow velocity, stasis, and vortex quantification. Previous studies have confirmed that physiological vortex flow is predominantly induced by the higher-volume flow from the superior left pulmonary vein. In atrial fibrillation, 4D flow MRI reveals a non-physiological blood flow pattern, which information may add value to well-established clinical risk factors. Currently, the research target of LA analysis has also widened to lung surgeons, pulmonary vein stump thrombosis after left upper lobectomy. 4D flow MRI is expected to be utilized for many more variable diseases that are currently unimaginable.

DOI： 10.2463/mrms.rev.2021-0137

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Language：English   Publishing type：Research paper (scientific journal)  

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small-cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy (ADJ) according to real-world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were carried out. Formalin-fixed, paraffin-embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009-0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages: HR, 1.214; 95% CI, 0.848-1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side-effects of ADJ, and saving medical costs.

DOI： 10.1111/cas.15228

PubMed

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Introduction: To investigate the genomic profiles of patients with lung cancer with idiopathic pulmonary fibrosis (IPF-LC), mechanism of carcinogenesis, and potential therapeutic targets. Methods: We analyzed 29 matched, surgically resected, cancerous and noncancerous lung tissues (19 IPF-LC and 10 non–IPF-LC) by whole-exome sequencing and bioinformatics analysis and established a medical-engineering collaboration with the Department of Engineering of the Tokyo University of Science. Results: In IPF-LC, CADM1 and SPC25 were mutated at a frequency of 47% (9 of 19) and 53% (10 of 19), respectively. Approximately one-third of the IPF-LC cases (7 of 19; 36%) had both mutations. Pathway analysis revealed that these two genes are involved in transforming growth factor-β1 signaling. CADM1 and SPC25 gene mutations decreased the expression of CADM1 and increased that of SPC25 revealing transforming growth factor-β1–induced epithelial-to-mesenchymal transition and cell proliferation in lung cancer cells. Furthermore, treatment with paclitaxel and DNMT1 inhibitor suppressed SPC25 expression. Conclusions: CADM1 and SPC25 gene mutations may be novel diagnostic markers and therapeutic targets for IPF-LC.

DOI： 10.1016/j.jtocrr.2021.100232

Scopus

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Photodynamic therapy (PDT) is established as one of the standard treatment options for centrally located early lung cancer. In order to improve the effectiveness of PDT, it is very important to accurately diagnose the extent of the tumor and focus the laser irradiation accurately. With the use of the conventional video-endoscope system, which adopts the frame-sequential (RGB-based) display method, mainly used in Japan, for PDT laser irradiation, the system only recognizes the strong white light, and color information is lost. Therefore, it is difficult to irradiate the lesion while simultaneously observing the lesion. In this study, we investigated the usefulness of a new type of video-endoscope system during PDT. METHODS: We used ELUXEO 7000® (FUJIFILM, Japan), which is a simultaneous-type video-endoscope system that has been in use at Nippon Medical School Hospital since October 2018. We analyzed the clinical usefulness of the ELUXEO® system for PDT as compared to other endoscope systems, such as EVIS LUCERA ELITE® (Olympus, Japan), an autofluorescence imaging (AFI) system. RESULTS: After the administration of talaporfin sodium for PDT, the tumor lesion was not visualized in magenta color with AFI, yielding false-negative results. On the other hand, no false-negative results after the administration of talaporfin sodium were obtained with the use of ELUXEO®. Using the ELUXEO® system in the blue light imaging (BLI) mode, we were able to deliver a red laser light while observing the extent of the tumor. Missed laser exposure was avoided and the accuracy of PDT was improved with the use of this system. CONCLUSIONS: ELUXEO® is useful for accurate evaluation of the extent of centrally located lung cancer and therefore, for accurate laser irradiation of the tumor lesion.

DOI： 10.1016/j.pdpdt.2021.102345

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Language：English   Publishing type：Research paper (scientific journal)  

Epithelial-mesenchymal transition (EMT) is considered to serve an important role in the metastatic/invasive ability of cancer cells, in the acquisition of drug resistance, and in metabolic reprogramming. In the present study, it was hypothesized that the Klotho gene is involved in the metastatic/invasive ability of lung cancer. We previously reported an association between Klotho expression and overall survival in patients with small cell lung cancer and large cell neuroendocrine cancer. We also found that Klotho expression was associated with EMT-related molecules in lung squamous cell carcinoma. The present study aimed to analyze the function of the Klotho gene and to elucidate its relevance to the regulation of the EMT. For this purpose, GFP-Klotho plasmids were transfected into lung adenocarcinoma cells (A549) and cell lines with stable expression (A549/KL-1 and A549/KL-2) were established. A549/KL-1 cells expressed higher levels of Klotho protein by western blot analysis compared with A549/KL-2 cells. In western blotting of A549 and A549/KL-1 cells, the expression of the mesenchymal marker N-cadherin was found to be completely inhibited in A549/KL-1 cells suggesting that Klotho expression may regulate the EMT in cancer cells via the inhibition of N-cadherin. The results of the sensitivity tests demonstrated that A549/KL-1 cells were significantly more sensitive to pemetrexed compared with A549 cells (IC50 A549/KL-1 vs. A549 cells, 0.1 µM vs. 0.7 µM). The results of the microarray analysis demonstrated that a very high level of lipocalin-2 (LCN2) expression was induced in the A549/KL-1 cells. Klotho overexpression completely suppressed the expression of mesenchymal markers, such as N-cadherin and Snail1 (Snail). The results of the present study suggested that there may be a new mechanism of action for the antitumor effects of pemetrexed, namely, LCN2-mediated modulation of N-cadherin expression. Klotho expression during cancer treatment has great potential as a predictor for efficacy of pemetrexed and as a factor in the selection of personalized medicine for postoperative adjuvant chemotherapy.

DOI： 10.3892/ol.2021.12679

PubMed

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The purpose of the current study was to clarify the blood flow pattern in the left atrium (LA), potentially causing the formation of thrombosis after left upper lobectomy (LUL). The blood flow in the LA was evaluated and compared between LUL patients with and without thrombosis. For the evaluation, we applied highly accelerated 4D flow MRI with dual-velocity encoding (VENC) scheme, which was expected to be able to capture slow flow components in the LA accurately. METHODS: Eight volunteers and 18 patients subjected to LUL underwent dual-VENC 4D Flow MRI. Eight patients had a history of thrombosis. We measured the blood flow velocity and stasis ratio (proportion in the volume that did not exceed 10 cm/s in any cardiac phase) in the LA and left superior pulmonary vein (LSPV) stump. For visual assessment, the presence of each collision of the blood flow from pulmonary veins and vortex flow in the LA were evaluated. Each acquired value was compared between healthy participants and LUL patients, and in LUL patients with and without thrombosis. RESULTS: In LUL patients, blood flow velocity near the inflow part of the left superior pulmonary vein (Lt Upp) and mean velocity in the LA were lower, and stasis ratio in the LA was higher compared with healthy volunteers (Lt Upp 9.10 ± 3.09 vs.13.23 ± 14.19 cm/s, mean velocity in the LA 9.81 ± 2.49 vs. 11.40 ± 1.15 cm/s, and stasis ratio 25.28 ± 18.64 vs. 4.71 ± 3.03%, P = 0.008, 0.037, and < 0.001). There was no significant difference in any quantification values between LUL patients with and without thrombosis. For visual assessment, the thrombus formation was associated with no collision pattern (62.5% vs. 10%, P = 0.019) and not with vortex flow pattern (50% vs. 30%, P = 0.751). CONCLUSION: The net blood flow velocity was not associated with the thrombus formation. In contrast, a specific blood flow pattern, the absence of blood flow collision from pulmonary veins, correlates to the thrombus formation in the LA.

DOI： 10.2463/mrms.mp.2020-0170

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Language：English   Publishing type：Research paper (scientific journal)  

Pulmonary adenofibroma is a rare biphasic tumor that contains epithelial and stromal components. We report a case of pulmonary adenofibroma in which the tumor was resected by thoracoscopic surgery and the diagnosis was established by histopathology. A 59-year-old woman with a past medical history of pyelonephritis visited our hospital for evaluation of an abnormal opacity on a plain chest x-ray during a comprehensive medical examination. A follow-up chest x-ray showed enlargement of the lesion, and the patient was referred to our department for further management. Chest computed tomography revealed a well-circumscribed nodule measuring 1.4 cm in diameter in the upper lobe of the left lung. The chest imaging findings suggested a benign tumor, but because of evidence of lesion enlargement and elevated serum carcinoembryonic antigen levels, we performed wide wedge resection of the left upper lobe by video-assisted thoracoscopic surgery, for diagnosis and treatment. The resected specimen was submitted for rapid pathological diagnosis during the operation, and a benign tumor, possibly sclerosing pneumocytoma, was suspected. Therefore, we completed the operation with wide wedge resection. The final histopathological diagnosis was pulmonary adenofibroma. The patient had an uneventful postoperative course, and at this writing, 6 months postoperatively, there has been no evidence of tumor recurrence. We have reported this case of pulmonary adenofibroma because the tumor is rare, has not yet been well-characterized, and has an unclear prognosis. Collection of data from a larger number of patients is necessary.

DOI： 10.1272/jnms.JNMS.2021_88-516

PubMed

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In the original publication, the name of fourteenth author was published incorrectly as Nagayasu Takeshi, the correct name is Takeshi Nagayasu.

DOI： 10.1007/s00595-020-02132-1

Scopus

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English  

DOI： 10.21037/jtd-20-1386

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Language：English   Publishing type：Research paper (scientific journal)  

The use of uniportal video-assisted thoracoscopic surgery (VATS) has increased worldwide. The number of facilities introducing this simple and cost-effective surgical procedure in Japan has also increased. Partial lung resection is performed to diagnose or treat various cases and surgeons are required to flexibly deal with it. This report describes the technique and pitfalls of partial lung resection by uniportal VATS.

DOI： 10.1093/ejcts/ezaa085

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

背景.肺カルチノイドは原発性肺悪性腫瘍の1〜2%を占め,稀にadrenocorticotropic hormone(ACTH)産生を伴う.症例.42歳,女性.1年前より体重増加,満月様顔貌を自覚しており,2ヵ月前からの腰背部痛を主訴に当院を受診.特徴的な身体所見や,ACTH及びコルチゾールの上昇を認め,他の内分泌学的精査と合わせてCushing症候群と診断された.胸部CTで左肺上葉に腫瘍を認め,異所性ACTH産生腫瘍が疑われたため,左上葉切除術,リンパ節郭清術を施行した.病理診断は定型カルチノイドで,大動脈下リンパ節に転移を認めた.また,免疫染色でACTHが陽性であり,ACTH産生肺定型カルチノイド,pT1bN2M0,stage IIIAと診断された.術後,ACTH及びコルチゾールは一過性に低下したが,速やかに再上昇し,高値が遷延した.術後精査でその原因を説明する所見はなく,トリロスタン投与後,切除7ヵ月後にいずれも正常範囲まで低下した.現在,術後3年であるが,再発や症状増悪は認めていない.結論.特異的な術後ホルモン濃度の推移を辿ったACTH産生肺定型カルチノイドの1例を経験した.(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01244&link_issn=&doc_id=20200914250012&doc_link_id=130007896359&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007896359&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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PURPOSE: The anatomical site of resected lobes may influence postoperative cerebral infarction. The objective of the current study was to determine if left upper pulmonary lobectomy is a risk factor for postoperative cerebral infarction. METHODS: This was a retrospective case-control study in patients undergoing pulmonary lobectomy from 2004 to 2013 in Japan. We retrospectively identified 610 patients from 153 institutions who had developed postoperative cerebral infarction following pulmonary lobectomy. The control group consisted of 773 patients who underwent lobectomy without cerebral infarction during a randomly selected single month in 2009 at the same institutions. RESULTS: Factors associated with cerebral infarction were age [10-year intervals, odds ratio (OR): 1.46; 95% confidence interval (CI): 1.23-1.73; p < 0.001], male sex (OR 1.92; 95% CI 1.29-2.86; p = 0.001), presence of comorbidities (OR 1.82; 95% CI 1.35-2.44; p < 0.001), perioperative anti-platelet or anti-coagulant drug use (OR 1.71; 95% CI 1.20-2.45; p = 0.003), and lobectomy. Subgroup analyses revealed that cerebral infarction was strongly associated with left upper lobectomy. CONCLUSIONS: Our findings suggest that left upper lobectomy is associated with a higher risk of cerebral infarction than other types of lobectomy, particularly in the early postoperative period.

DOI： 10.1007/s00595-020-02032-4

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Uniportal video-assisted thoracic surgery (U-VATS) has become prevalent among thoracic surgeon in a part of countries including Japan. U-VATS and robotic-assisted thoracoscopic surgery( RATS) are 2 types of minimally invasive surgical techniques. Uniportal procedures are feasible although they can be technically challenging. RATS is superior to U-VATS in terms of the ability to perform procedures that require fine motor skills and to maintain wide visual fields during the procedure;however, it is not as feasible and more costly compared with U-VATS. U-VATS is also considered safer as it is easier than RATS to be converted to thoracotomy when needed. Thus, suitable procedures should be selected to meet the needs of specific cases. In the present study, we review the treatment outcomes of U-VATS for anatomical lung resection that were performed at our institution for patients with early-stage lung cancer.

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION/AIM: Photodynamic therapy (PDT) involves the use of a tumor-specific photosensitizer and laser irradiation, and one of the treatment options recommended for early centrally located lung cancers, but not yet for peripheral-type lung cancers. We developed a new laser probe, the composite-type optical fiberscope (COF), which allows accurate laser irradiation of a cancer lesion with simultaneous visualization of the lesion. In this study, we attempted a new endobronchial PDT technique using the new laser probe, and evaluated the effectiveness and feasibility of this novel PDT technique for peripheral lung cancers. METHODS: This phase I study was conducted in 7 patients with peripheral lung cancers (primary tumor ≤20 mm in diameter). We performed endobronchial PDT for these patients using the new laser probe and talaporfin sodium as the photosensitizer. RESULTS: We performed PDT for 3 patients with peripheral lung cancer using a laser dose of 50 J/cm2 at 120 mW, and confirmed the feasibility of using this dose. Then, we escalated the laser dose to 100 J/cm2 in 4 additional patients. A total of 7 patients met our inclusion criteria. Evaluation at 2 weeks and 3 months after the PDT revealed no complication such as pneumonia or pneumothorax. At the evaluation conducted 6 months later, we found CR in 3 cases and SD in the remaining 4 cases. CONCLUSION: PDT was found to be a feasible and non-invasive treatment modality for early peripheral-type lung cancer. In the future, PDT could become a standard treatment option for peripheral-type lung cancer.

DOI： 10.1016/j.pdpdt.2020.101698

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We present the case of a 76-year-old woman who underwent left upper lobectomy for lung adenocarcinoma. Three days after the surgery, a thrombus was observed in the pulmonary vein (PV) stump. Four months after the surgery, we performed 4D flow MRI, which revealed decreased blood flow, not only in the left superior PV stump, but also over a widespread region around the left atrium-left superior PV junction. 4D flow MRI can clarify the altered hemodynamics underlying thrombus formation.

DOI： 10.2463/mrms.ici.2019-0142

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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DOI： 10.21037/tlcr.2019.11.21

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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The aim of this study was to evaluate the feasibility of a combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent (gold studded stent [GSS]). Laser irradiation (664 nm, continuous wave) was performed through the GSS using a straight and cylindrical fiber 1.0 cm away from a power meter. There are two types of GSS: the TD type for the trachea and the BD type for the bronchus. Laser outputs were set to 150 mW, 180 mW, 210 mW, 240 mW, 270 mW, and 300 mW. The laser powers passing through the both types of GSS were measured three times for each outputs and the averages were calculated. Based on the results, animal experiment was performed using two female pigs. Under general anesthesia, a GSS (BD type) was inserted into trachea of pigs, and PDT using NPe6 as a photosensitizer was performed by 100 J/cm2 laser irradiation on parts of the trachea with and without a GSS. Immediately after and 1 week after PDT, pig tracheas were harvested and histological analysis was performed. Histological analysis of areas with or without the stent showed edematous changes between the cartilage and submucosal layer immediately after PDT, and necrotic changes 1 week later. The effectiveness of NPe6-PDT for pigs' trachea covered by the stent was same as trachea without the stent. The use of a GSS may enable PDT to be effective even in the area covered by the stent.

DOI： 10.1007/s10103-019-02876-4

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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BACKGROUND: Post-thoracotomy pain syndrome (PTPS) is difficult for thoracic surgeons to manage. PTPS should never arise after minimally invasive surgery (MIS). Uniportal video-assisted thoracoscopic surgery (U-VATS), a form of MIS for thoracic disease, has become more common around the world and might reduce the risk of PTPS after thoracic surgery. We compared the frequencies of PTPS after U-VATS-based and multi-port VATS (M-VATS)-based lobectomy for lung cancer. METHODS: We compared the data for 142 and 70 cases in which U-VATS- and M-VATS-based lobectomies were performed, respectively. General surgical outcomes, the numeric rating scale (NRS) score, analgesic usage, and neuropathic pain according to the pain DETECT questionnaire (PDQ) were assessed. The presence of >1 of the following items at two postoperative months (POM) was used to diagnose PTPS: (I) an NRS score of >3, (II) analgesic use, and (III) exhibiting >1 of a list of 7 symptoms according to the PDQ. RESULTS: There were no significant intergroup differences in the operation time, intraoperative blood loss, the number of dissected lymph nodes, or the duration of the drainage period or hospital stay. In the U-VATS and M-VATS groups, the mean NRS score during two postoperative months was 0.5±0.1 and 1.5±0.3, respectively (P<0.01), and analgesics were used for a mean of 7.3±1.5 and 13.3±1.8 days, respectively, during the postoperative 2 months (P<0.01). As for the frequency of PTPS-related symptoms on postoperative month (POM) 2, allodynia (U-VATS: 2.1% vs. M-VATS: 10%, P=0.028), hypoesthesia (2.1% vs. 10%, P=0.028), and numbness (1.4% vs. 8.6%, P=0.029) often arose in both groups. PTPS occurred in 2.8% and 11.4% of the patients in the U-VATS and M-VATS groups, respectively (P=0.025). CONCLUSIONS: Compared with M-VATS, U-VATS exhibited a significantly lower incidence of PTPS.

DOI： 10.21037/jtd.2019.09.07

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：(NPO)日本肺癌学会  

症例は68歳男性で、両下肢に有痛性の筋硬直が現れ、歩行障害を生じた。当初は脊髄炎を疑いステロイド療法を施行したが、症状は不変であった。胸部CTを施行したところ、前縦隔腫瘍を発見した。血液検査では抗グルタミン酸脱炭酸酵素(GAD)抗体の抗体価が高値であることが判明した。これらの所見から、両下肢の症状は縦隔腫瘍に合併した傍腫瘍性神経症候群に起因するものであると考えられ、さらに特徴的な症状と臨床検査所見からStiff-person症候群であることが示された。ベンゾジアゼピンとバクロフェンを投与し、免疫グロブリン大量静注療法を開始したところ、治療初日から症状は改善し始め、後に杖つき歩行が可能になった。さらに根治手術として経胸骨アプローチにて胸腺摘出術を施行した。切除した腫瘍は5.8×5.5cm大で、病理組織学的解析の結果からB2型胸腺腫と診断された。術後経過に問題はみられず、手術から約1ヵ月後に退院となった。術後3ヵ月時点での経過観察では、血清中の抗GAD抗体価は依然として高値であったものの胸腺腫の再発は認められず、下肢の有痛性筋硬直も消退していた。

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背景.月経随伴性気胸は月経前後に発症し、妊娠中など無月経の時期には発症しないことが特徴とされている。しかし、その発生機序に関しては、未だに明確な見解は確立されていない。今回我々は、妊娠中に発症した月経随伴性気胸の1例を経験したので報告する。症例.32歳、女性。29歳時より月経時に胸痛を自覚しており、月経随伴性気胸を疑われていたが、保存的加療で軽快していた。今回は妊娠34週4日目に胸痛を自覚し、右気胸の診断となった。帝王切開にて出産した後もair leakが持続したため、胸腔鏡下手術を施行した。胸腔内を観察すると、中葉に1cm大の嚢胞、横隔膜に複数個の小孔を認めたため、右中葉部分切除術と横隔膜病変の生検、縫縮術を施行した。病理組織学的に嚢胞壁及び横隔膜の小孔周囲にエストロゲンレセプター及びプロゲステロンレセプター陽性細胞を認め、月経随伴性気胸と診断した。結論.本症例は妊娠中に気胸を発症しており、月経随伴性気胸の発生機序を考察する上で貴重な症例と考えられた。(著者抄録)

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DOI： 10.1158/1538-7445.AM2019-1602

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Language：Japanese   Publisher：日本レーザー治療学会  

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Beta-blockers have been reported to improve prognosis for various cancers, but the usefulness of perioperative administration remains unclear. To assess the efficacy of perioperative administration of landiolol hydrochloride, an intravenous beta-blocker, for lung cancer, we conducted a single-center, retrospective study. This study included patients who participated in a research conducted by Nippon Medical School Hospital from August 2012 to November 2013. The main selection criteria were males and females younger than 85 years old who have undergone anatomic lung resection for lung malignancies. Fifty-seven patients, 28 in the landiolol group and 29 in the control group, were included. The postoperative relapse-free survival rate at 2 years was 0.89 (95% CI, 0.78-1.01) in the landiolol group and 0.76 (95% CI, 0.60-0.91) in the control group (Chi-squared test; P = 0.1828). The relapse-free survival rate tended to be higher in the landiolol group than in the control. Hazard ratio for relapse-free survival in the landiolol group compared to the control was 0.41 (95% CI, 0.13-1.34), demonstrating that relapse free survival was prolonged in the landiolol group (log-rank test; P = 0.1294). It was suggested that relapse-free survival was prolonged when landiolol hydrochloride was administered from the induction to completion of anesthesia. Further studies are needed to confirm our findings.

DOI： 10.1038/s41598-019-41520-7

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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DOI： 10.1016/j.ehpc.2018.06.003

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Other Link： http://orcid.org/0000-0003-4495-7982

Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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INTRODUCTION: Hydrothorax due to pleuroperitoneal communication (PPC) can occur in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We report our experiences of the safety and efficacy of the treatment of four patients with a novel video-assisted thoracoscopy method. METHODS: Single-port video-assisted thoracoscopic surgery (VATS) was performed with a mini-thoracotomy of 5 cm in length. The PPC site was identified on the diaphragm and ligated using an endoscopic loop. The diaphragm was then covered using a polyglycolic acid (PGA) sheet, over which adhesive chemicals (OK432 and tetracycline) were sprayed. RESULTS: We assessed the efficacy of our approach in four patients (one female and three males) aged 42-74 years (mean: 62.0 years). The hydrothoraxes were right sided in all the patients. The mean operation and postoperative drainage times were 92.5 min and 3.0 days, respectively. The hydrothoraxes did not recur in any patient during follow-up periods of 8-46 months. CONCLUSION: Our suture- and staple-free technique is not only easy to perform but also appears to be safe and effective for the management of hydrothorax in patients receiving CAPD. Larger scale studies are now indicated.

DOI： 10.5761/atcs.nm.18-00066

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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DOI： 10.1007/s00595-017-1620-9

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

OBJECTIVES: Division of incompletely lobulated fissures is often performed during surgical resection of non-small-cell lung cancer (NSCLC)
however, the effect of lobulation on tumour recurrence is unclear. This study aimed to assess the prognostic effect of lobulation in patients with NSCLC according to their preoperative and operative findings. METHODS: A retrospective study of patients with p-stage I NSCLC who underwent lobectomy was conducted between April 2008 and April 2016. A receiver operating characteristic curve of the number of stapling cartridges was constructed to determine the optimal cut-off value. Patients who underwent division of the interlobar fissure using 2 or more stapling cartridges (H group) were compared with those who did not undergo division of the interlobar fissure or who underwent division of the interlobar fissure using only 1 cartridge (L group). RESULTS: The study included 85 patients, and of these patients, 46 were included in the L group and 39 in the H group. Survival analysis showed better disease-specific survival (P = 0.0135) and disease-free survival (P = 0.0412) in the L group. Cox regression analysis showed better disease-specific survival in patients who underwent division of the interlobar fissure with few stapler cartridges than in those who underwent division with more stapler cartridges (P = 0.021). CONCLUSIONS: The extent and status of incompletely lobulated fissures are significant risk factors for disease-specific survival in patients with resected p-stage I NSCLC.

DOI： 10.1093/icvts/ivx305

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: The second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period.
Methods: The NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10 min after NPe6 administration as well as at the time of PDT (4-5 h after administration), at discharge (2 or 3 days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT.
Results: Nine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2-3 days after administration) in most cases and it decreased at 1 or 2 weeks after PDT.
Conclusions: The fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT.

DOI： 10.1016/j.pdpdt.2017.10.001

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Klotho is known as an anti-aging gene. We previously reported that the expression of Klotho is a postoperative prognostic factor for patients with lung large cell neuroendocrine carcinoma and lung small cell carcinoma. Recently, Klotho was shown to suppress the epithelial-mesenchymal transition (EMT). In the present study, we examined the association between the expression of Klotho and the regulation of EMT in lung squamous cell carcinoma. We immunohistochemically examined the expression of Klotho in patients with lung squamous cell carcinoma who had undergone surgical resection or photodynamic therapy. The immunohistochemical analysis showed that Klotho expression was observed not only in normal bronchial epithelial cells, but also in centrally located early lung cancers, which were all carcinomas in situ and were treated using PDT. However, in lung cancer patients with invasive and or advanced squamous cell carcinoma who had undergone a complete surgical resection, Klotho expression was observed in only 4 patients (13%). To elucidate the associations between the expression of Klotho and the expressions of EMT-related proteins, such as E-cadherin, N-cadherin, vimentin, and Snail, we transiently transfected GFP-Klotho plasmid DNA into the human squamous lung cancer cell line SQ5 and examined the expressions of these proteins of GFP-positive cells after sorting using flow cytometry. In SQ5 cells overexpressing GFP-Klotho, the expression of N-cadherin, which is a mesenchymal marker, was completely inhibited, compared with that in SQ5 cells transfected with the GFP vector. The overexpression of Klotho did not affect the regulation of either other mesenchymal markers (such as vimentin and Snail) or the regulation of an epithelial marker (E-cadherin). We concluded that the expression of Klotho was related to the degree of cancer invasiveness and that Klotho inhibits the expression of N-cadherin and regulates the EMT in lung cancer.

DOI： 10.3892/ol.2017.6862

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2017404468

Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME PUBL CO  

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is hyperplasia of noninvasive neuroendocrine cells originating from Kultchitsky cells. This is a rare pathological condition, suspected to be a precursor lesion of carcinoid, together with tumorlet. In the WHO histological classification (4th edition) revised in 2015, DIPNECH was added to the category that includes neuroendocrine tumors. Our patient was a 77-year-old woman who initially visited another doctor because of coughing. Chest CT revealed a mass occluding the right intermediate bronchial trunk, and bronchial carcinoid was suspected from biopsy findings, leading to referral of this patient to our department. The tumor was excised under a rigid bronchoscope for the purpose of making a definitive histological diagnosis and determining the extent of spread. The stalk portion of the tumor extended from the bifurcation of the middle and lower lobe bronchi in the membranous part of the intermediate trunk to the central side. The airway appeared to be almost completely occluded under bronchoscopy, but aeration from the periphery was maintained. Histopathologically, there was hyperplasia of oval atypical cells with relatively poor cytoplasm beneath the bronchial mucosa on HE staining, suggesting neuroendocrine tumor. Immunostaining revealed that these cells were positive for CD56, chromogranin A, and synaptophysin, and that there was moderate mitosis, leading to a diagnosis of atypical carcinoid. At a later date, radical surgery comprised of right pulmonary middle and lower lobectomy and lymph node dissection was performed. The final histopathological diagnosis was atypical carcinoid of the bronchus (pT1aN0M0, stage IA). There were multiple aggregations of atypical cells, measuring approximately 1-3 mm, along the airway around the bronchioles in the excised lung, indicating concomitant DIPNECH. The patient currently has no evidence of either recurrence or metastasis at 12 months after surgery, but we will continue meticulous follow-up.

DOI： 10.21037/jtd.2017.08.75

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. This study was designed to evaluate the feasibility of video-assisted thoracoscopic surgery (VATS) and to compare the oncologic outcomes of VATS with those of sternotomy in patients with thymoma.
Methods. The clinical outcomes of 2,835 patients with thymic epithelial tumors treated between 1991 and 2010 in 32 Japanese institutions were collected retrospectively. The study compared postoperative complications, positive surgical margins, location of recurrence, and survival in 140 of 142 VATS-treated patients (VATS group) matched with 140 of 1,294 sternotomy-treated patients (ST group) by using propensity scores.
Results. Postoperative complications were observed in 8 patients in the VATS group. The morbidity rate in the VATS group was not different from that of the ST group (p = 0.25). Positive surgical margins were noted in 4 patients (3 in the VATS group; 1 in the ST group). There was no statistically significant difference in the recurrence rate between groups (median follow-up period: 3.7 years in the VATS group; 5.2 years in the ST group). In total the most frequent site of recurrence was pleural dissemination. In the VATS group, the 5-year recurrence-free survival rate was 93.8%, and the 5-year overall survival rate was 97.9%. There was no difference in the recurrence-free survival and overall survival rates between the VATS group and the ST group (p = 0.91 and p = 0.74, respectively).
Conclusions. VATS thymectomy was feasible and comparable to sternotomy for the treatment of patients with thymoma with regard to morbidity, incomplete resection rate, and prognosis. However, additional follow-up is required to evaluate long-term outcomes. (C) 2017 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2017.03.054

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Objective: This study aimed to investigate whether perioperative inhalations of long-acting beta-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) might decrease the incidence of postoperative complications in lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods: We retrospectively analyzed 108 patients with COPD who underwent pulmonary resections for primary lung cancer at our hospital between January 2013 and January 2016 to determine the association between the incidence of postoperative complications (e.g., prolonged air leakage and pneumonia) and the use of LABAs or LAMAs. Results: Thirty patients with COPD experienced postoperative complications (27.8%): Fourteen patients had prolonged air leakages (more than 7 days), ten patients developed pneumonia. The frequency of these postoperative pulmonary complications was significantly higher among the patients with COPD (24/108 cases, 22.2%), compared with the frequency among non-COPD patients (15/224 cases, 6.7%). Inhaled bronchodilators, such as LAMA or LABA, were prescribed for 34 of the 108 patients with COPD
the remaining 74 patients were not treated with bronchodilators. Pulmonary complications were significant lower among the LAMA or LABA users (3/34 cases, 8.8%) than among the untreated COPD patients (21/74 cases, 28.4%). Conclusion: For lung cancer patients with COPD, preoperative management using LABA or LAMA bronchodilators and smoking cessation can reduce the frequency of postoperative pulmonary complications after surgical lung resection. LAMA or LABA inhalation might be useful for not only perioperative care, but also for the long-term survival of COPD patients after surgery.

DOI： 10.1007/s11748-017-0761-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

DOI： 10.1272/jnms.84.87

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Language：Japanese   Publisher：The Japan Society for Respiratory Endoscopy  

<p>Background. A malignant tumor metastasizing to the trachea/tracheal lumen is relatively rare, and liver cancer metastasizing to the tracheal lumen and blocking the central airway is even rarer. Case. A 75-year-old woman underwent right lower lobectomy for a metastatic lung tumor 3 years after undergoing surgery for liver cancer. Subsequently, she had been relapse-free for 2 years but was referred to our department because of the appearance of bloody phlegm during follow-up. A tumor was found immediately above the carina trachea on chest computed tomography, and liver cancer metastasizing to the tracheal lumen was suspected based on the clinical course. The tumor was resected to the maximum extent possible via rigid bronchoscopy to relieve the airway stenosis. The pathological diagnosis was liver cancer metastasizing to the tracheal lumen. The patient is currently under observation as an outpatient. Conclusion. We encountered a case of liver cancer metastasizing to the tracheal lumen in which the tumor was resectable via rigid bronchoscopy. As shown in our present case, rigid bronchoscopic treatment for tracheal neoplasms causing airway stenosis is a safe procedure that enables secure maintenance of the airway and also effectively treats bleeding.</p>

DOI： 10.18907/jjsre.39.2_146

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© 2017 SPIE. We studied a 3-compartment dynamic model of talaporfin sodium pharmacokinetics in silico. Drug distribution might change after intravenous injection from plasma to interstitial space and then into myocardial cells. We have developed a new cardiac ablation using photosensitization reaction with laser irradiation shortly after talaporfin sodium injection. We think that the major cell-killing factor in our cardiac ablation would be an oxidation by singlet oxygen produced in the interstitial space in myocardium with laser irradiation shortly after the photosensitizer administration. So that the talaporfin sodium concentration change in time in the interstitial space should be investigated. We constructed the pharmacokinetics dynamic model composed by 3-compartments, that is, plasma, interstitial space, and cell. We measured talaporfin sodium fluorescence time change in human skin by our developed fluorescence measurement system in vivo. Using the measured concentration data in plasma and skin in human, we verified the calculation accuracy of our in silico model. We compared the simulated transition tendency of talaporfin sodium concentration from interstitial space to cells in our in silico model with the reported uptake tendency using cultured myocardial cell. We identified the transition coefficients between plasma, interstitial space, and cell compartment, and metabolization coefficient from plasma by the fitting with measured data.

DOI： 10.1117/12.2250716

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DOI： 10.1117/12.2250716

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Association for Coronary Artery Surgery  

Birt-Hogg-Dubé syndrome is an autosomal dominant genetic disorder characterized by a triad of skin tumors, renal tumors, and multiple pulmonary cysts. Our patient was a 40-year-old man with a history of recurrent bilateral pneumothorax and a family history of pneumothorax. The patient visited our department with chest pain and was diagnosed with left pneumothorax based on a chest X-ray. Thoracic computed tomography (CT) showed multiple cysts in both lungs. We performed thoracoscopic bilateral bullectomy with curative intent. Intraoperative observation showed numerous cysts in the lung apex, interlobular region, and mediastinum. We resected the cysts that we suspected to be responsible for the symptoms and ligated the lesions, and then performed total pleural covering. After surgery, genetic testing was performed. The result enabled us to diagnose Birt-Hogg-Dubé syndrome in this patient. Although the patient has developed neither recurrent pneumothorax nor any renal tumors, to date, long-term monitoring is necessary.

DOI： 10.5761/atcs.cr.16-00295

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In this special issue, I review the types of thoracic surgery that uniportal video-assisted thoracic surgery (U-VATS) is most suited to.

DOI： 10.21037/jovs.2017.07.06

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Differentiating low-grade lymphoma from preexisting sarcoidosis is difficult because of their pathological similarity. This article describes a case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis. The patient, a 45-year-old Japanese man, presented with a 10-year history of pulmonary sarcoidosis and 5-year history of ocular sarcoidosis with histologic findings. Because only the right S3 lung nodule had gradually enlarged, partial resection was performed. Pathological study revealed noncaseous epithelioid granulomas with lymphoplasmacytic proliferation but also marked lymphoid cell proliferation with lymphoepithelial lesion findings that differed from findings of typical sarcoid lesions. Our lymphoepithelial lesion evaluation via immunohistochemistry and analysis of Ig heavy-chain gene rearrangements with assessment of Propionibacterium acnes specific antibody reactions allow us to report, for the first time, this case of pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis in exactly the same location, which may be significant for differentiating these diseases and understanding their pathogenic association. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2015.12.019

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PIONEER BIOSCIENCE PUBL CO  

Background: Single-port video-assisted thoracic surgery (SPVATS) emerged several years ago as a new, minimally invasive surgery for diseases in the field of respiratory surgery, and is increasingly becoming a subject of interest for some thoracic surgeons in Europe and Asia. However, the adoption rate of this procedure in the United States and Japan remains low. We herein reviewed our experience of SPVATS for early lung cancer in our center, and evaluated the safety and minimal invasiveness of this technique.
Methods: We retrospectively analyzed patients who had undergone SPVATS for pathological stage I lung cancer in Nippon Medical School Chiba Hokusoh Hospital between September 2012 and October 2015. In SPVATS, an approximately 4-cm incision was made at the 4th or 5th intercostal space between the anterior and posterior axillary lines. A rib spreader was not used at the incision site, and surgical manipulation was performed very carefully in order to avoid contact between surgical instruments and the intercostal nerves. The same surgeon performed surgery on all patients, and analyzed laboratory data before and after surgery.
Results: Eighty-four patients underwent anatomical lung resection for postoperative pathological stage I lung cancer. The mean wound length was 4.2 cm. Eighty-four patients underwent lobectomy and segmentectomy, respectively. The mean preoperative forced expiratory volume in 1 second (FEV1%) was 1.85% +/- 0.36%. Our patients consisted of 49 men (58.3%) and 35 women (41.7%), with 64, 18, 1, and 1 having adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and small-cell lung cancer, respectively. The mean operative time was 175 +/- 21 min, operative blood loss 92 +/- 18 mL, and duration of drain placement 1.9 +/- 0.6 days. The duration of the postoperative hospital stay was 7.1 +/- 1.7 days, numeric rating scale (NRS) 1 week after surgery 2.8 +/- 0.6, and occurrence rate of allodynia 1 month after surgery 10.7%. No patient developed serious complications, and no deaths occurred within 30 days of surgery. Two patients (2.4%) were converted to open thoracotomy.
Conclusions: SPVATS is a safe and feasible technique, and is promising for next-generation thoracoscopic surgery. It may also reduce postoperative wound pain and contribute to improvements in the activities of daily living of patients.

DOI： 10.3978/j.issn.2072-1439.2016.02.26

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL TRIBUNE INC  

Background: In the elderly patients, optimal surgical treatment can be difficult to achieve, because of comorbidity. Therefore, we aimed to clarify the preferred surgical management in this patient group.
Methods: A retrospective study was conducted between April 2008 and March 2015 that included patients with non-small cell lung cancer (NSCLC) aged &gt;= 75 years.
Results: We included 44 patients who underwent partial resection (n = 20) or lobectomy (n = 24). There were no significant differences between the two groups on most variables, except for some character. Survival analysis revealed a significant difference in overall survival (OS) between the two groups; however, no significant differences existed in the disease-free survival or in the OS for stage I disease. Postoperative complications led to poor prognoses. Cox regression analysis revealed statistical significance for the Brinkman Index, the ratio of the pulmonary artery diameter to the ascending aorta diameter (PA:A), and the alveolar-arterial oxygen gradient. Only the PA:A ratio remained significant after multivariate analysis, with a higher ratio associated with better survival.
Conclusion: In elderly patients with NSCLC, surgical resection should not be denied because of age alone. However, partial resection should be favored to lobectomy when possible.

DOI： 10.5761/atcs.oa.15-00365

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PIONEER BIOSCIENCE PUBL CO  

Background: Postoperative recurrent pneumothorax (PORP) can arise after surgery for primary spontaneous pneumothorax (PSP) that is recurrent or involves prolonged air leakage. In this study, which included 265 patients (279 cases) with PSP who underwent surgery at our department, the percentage of patients that did not experience PORP was compared between a group that underwent bullectomy alone (group A) and a group in which the staple line and the surrounding visceral pleura were covered with a PGA sheet after bullectomy (group B) in order to study the utility of PGA sheets for preventing PORP.
Methods: Among the patients with PSP who underwent surgery, the cases of 92 patients (98 cases) from Group A and 173 patients (181 cases) from Group B were reviewed retrospectively. The incidence rates of PORP in these two groups were statistically analyzed in addition to the associations between PORP and age, gender, the affected side, height, body weight, height/weight ratio, smoking habits, or the surgical procedure.
Results: In total, 96.7% of the patients in group B did not suffer PORP, which was significantly higher than the equivalent figure for group A (83.7%, log-rank test: P=0.0003). Moreover, among the examined parameters, only covering the staple line with a PGA sheet was found to be an independent prognostic factor (Cox regression: P=0.0003; HR =0.212; 95% CI, 0.082-0.547).
Conclusions: It was revealed that when bullectomy is performed in patients with PSP, wide coverage of the staple line and the surrounding visceral pleura with a PGA sheet significantly reduces the risk of PORP.

DOI： 10.3978/j.issn.2072-1439.2015.11.23

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Association for Cardio-Thoracic Surgery  

OBJECTIVES: To assess the feasibility, safety and postoperative wound pain of single-incision thoracoscopic surgery (SITS) for Stage I lung cancer in patients who had previously undergone surgery compared with conventional video-assisted thoracoscopic surgery (c-VATS). METHODS: Lobectomy by SITS (60) and c-VATS (20) was performed for Stage I lung cancer between 2011 and 2014. In SITS, an ~5-cm small incision was placed at the fourth or fifth intercostal space from the anterior to posterior axillary line. C-VATS was performed via three or four ports using trocars only. The evaluation items were general operative outcomes, pain stress using the Numeric Rating scale (NRS) on postoperative days 3, 7 and 30, and some pathological symptoms related to the neuropathic wound pain through the operative course. The number of days of use of analgesic agents was also evaluated for 1 month after surgery. RESULTS: SITS showed similar perioperative outcomes (postoperative hospital stay, blood loss, surgical time, drainage duration, creatine phosphokinase (CPKmax), creactive protein (CRPmax) and frequency of postoperative complications) to those of c-VATS. Additionally, the average NRS in SITS decreased on postoperative days 7 and 30 (Day 7: 2.4 ± 0.4 vs 4.2 ± 0.3, P = 0.041, Day 30: 1.7 ± 0.4 vs 3.3 ± 0.3, P = 0.038) and the number of days analgesic agents were administered was also reduced (SITS: 8.1 ± 0.9 vs c-VATS 13.1 ± 1.2 days, P = 0.045). The frequency of allodynia, hyperalgesia, hypaesthesia and numbness was significantly reduced in the SITS group. CONCLUSIONS: Although conclusive evidence has not yet been obtained, SITS is more minimally invasive in regard to postoperative wound pain compared with c-VATS. This procedure should be considered as a treatment option for early-stage lung cancer.

DOI： 10.1093/ejcts/ezv320

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publisher：(NPO)日本レーザー医学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier USA  

Thoracoscopic surgery for the treatment of Wolff-Parkinson-White syndrome is rare. We report a case of thoracoscopic surgical ablation of the epicardial pathway in a 13-year-old female patient. Intraoperative electroanatomic mapping was performed to identify the exact location of accessory electrical conduction in the right atrioventricular groove. Stamping ablation using a bipolar radiofrequency pen device achieved irreversible disappearance of the delta wave. Eight months after the surgical procedure, there has been no recurrence of arrhythmia in this patient.

DOI： 10.1016/j.athoracsur.2015.04.081

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Language：Japanese   Publisher：The Japanese Association for Chest Surgery  

Postoperative pain after thoracotomy and thoracoscopic surgery is often prolonged because of the occurrence of neuropathic pain due to intercostal nerve injury. The aim of this study was to examine whether the combination therapy of pregabalin with NSAID for postoperative pain with a neuropathic component is effective. The present study demonstrated that, in patients with neuropathic pain treated by combination therapy of pregabalin in conjunction with NSAID, the mean visual analogue scale (VAS) and numeric rate scale (NRS) reduction rate were significantly reduced compared to NSAID-only therapy in both the thoracotomy group and thoracosopic surgery group. This pain is thought to be composed of both nociceptive and neuropathic components and linked with late convalescence after an operation. The novel analgestic drug, pregabalin, may attenuate a patients symptoms including neuropathic pain after thoracotomy combined with NSAID.

DOI： 10.2995/jacsurg.29.428

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Other Link： http://search.jamas.or.jp/link/ui/2015257814

Language：Japanese   Publisher：The Japanese Association for Chest Surgery  

Postoperative pain after thoracotomy and thoracoscopic surgery is often prolonged because of the occurrence of neuropathic pain due to intercostal nerve injury. The aim of this study was to examine whether the combination therapy of pregabalin with NSAID for postoperative pain with a neuropathic component is effective. The present study demonstrated that, in patients with neuropathic pain treated by combination therapy of pregabalin in conjunction with NSAID, the mean visual analogue scale (VAS) and numeric rate scale (NRS) reduction rate were significantly reduced compared to NSAID-only therapy in both the thoracotomy group and thoracosopic surgery group. This pain is thought to be composed of both nociceptive and neuropathic components and linked with late convalescence after an operation. The novel analgestic drug, pregabalin, may attenuate a patients symptoms including neuropathic pain after thoracotomy combined with NSAID.

DOI： 10.2995/jacsurg.29.428

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Other Link： http://search.jamas.or.jp/link/ui/2015257814

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Video-assisted thoracoscopic surgery (VATS) lobectomy is increasingly used for pulmonary sequestration; however, there are few descriptions of safe handling of the aberrant artery. Here we clarify the safe handling of an aberrant artery using a clinical review and an experimental model.
Methods: We retrospectively reviewed the records of patients who underwent lobectomy for pulmonary sequestration with aberrant arteries at the Nippon Medical School between January 2008 and December 2010. This was supplemented by an experimental pressure test using vessels obtained from pigs.
Results: We identified four patients with aberrant arteries that were successfully occluded via either stapling. In the experimental model, we divided pig vessels into small-diameter (S) and large-diameter (L) groups. The 1.0-mm-high staples were stronger in the S group than in the L group (p = 0.028). In the L group, the 2.0-mm-high staples were stronger than the 1.0-mm staples (p = 0.015). Leakage from the staple line was associated with a poorer B-shape of inserted staples.
Conclusions: The techniques described in this report are useful in successful minimally invasive transection of an aberrant artery (other than very thin vessels) when resecting a pulmonary sequestration by stapler only. A detailed investigation should be performed to determine the most appropriate stapler or cartridge.

DOI： 10.1186/s12893-015-0009-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-Ill that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (P=0.04). The robustness of PIK3CAT/SOX2(+) classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (P=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (P=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

DOI： 10.3892/ijo.2014.2742

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

To identify a possible new treatment modality for malignant pleural mesothelioma (MPM), we examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer NPe6, enhanced the antitumor effect in both in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell lines (MSTO-211H, H2052, H2452 and H28) were assayed using the WST assay after treatment with pemetrexed and NPe6-PDT. The treatment schedule for the combination treatment was examined using nude mice. Pemetrexed pre-treatment enhanced the lethal effect of NPe6-PDT in the four malignant mesothelioma cell lines, but NPe6-PDT followed by pemetrexed treatment did not enhance cell lethality in the in vitro assay. Pemetrexed pre-treatment did not enhance the intracellular accumulation of NPe6, which is one of the determinants of the antitumor effect of PDT. In nude mice injected with MSTO-211H cells and then treated using a combination of pemetrexed and NPe6-PDT (10 mg/kg NPe6, 10 J/cm(2) laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pre-treatment value after 14 days. Pemetrexed treatment followed by NPe6-PDT resulted in an 80% reduction in the tumor size and inhibited re-growth. NPe6:PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth. NPe6-PDT induced the expression of thymidylate synthase (TS), which confers resistance to pemetrexed, and NPe6-PDT followed by pemetrexed treatment did not enhance the treatment outcome in vivo. In conclusion, combination treatment, consisting of pemetrexed followed by NPe6-PDT, should be further investigated as a new treatment modality for MPM. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with MPM.

DOI： 10.3892/ijo.2014.2746

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S154_3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL TRIBUNE INC  

A 76-year-old man took a chest X-ray for his medical checkup and an abnormal shadow was detected in the right lower lung field. For more detailed examination, he was referred to our hospital. Chest computed tomography showed a 20-mm nodule with relatively regular margins in the right lower lobe. A compact proliferation of circular to polygonal cells with a high nucleus-cytoplasm ratio was evident in a transbronchial lung biopsy. Based on pathological findings, a mature large B-cell lymphoma was diagnosed. Thoracoscopic right lower lobectomy and mediastinal lymphadenectomy were performed. The post-surgical pathological examination showed that the tumor consisted of diffuse to compact proliferation of medium to large atypical lymphocyte-like cells. Immunohistochemical staining yielded positive results for B-cell lineage markers. Five months after surgical resection, neither local recurrence nor accumulation in remote organs was observed on gallium scintigraphy. The diagnosis of primary pulmonary diffuse large B-cell lymphoma was established.

DOI： 10.5761/atcs.cr.14-00298

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S154_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S270_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S138_2

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S306_3

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S239_3

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Language：Japanese   Publisher：The Japanese Association for Chest Surgery  

A 27-year-old woman has been followed up for the previous 12 years because of an abnormal shadow in the left middle lung field on a chest radiograph. Although there was no enlargement of the tumor, she was referred to our hospital for diagnostic and therapeutic purposes. Chest CT showed a 30-mm oval solitary tumor in the left S¹⁰ that had no contrast effect. Left lower lobectomy was performed thoracoscopically, because the tumor was large and proximal to the left inferior pulmonary vein. The tumor was diagnosed as a granular cell tumor. As a granular cell tumor is associated with a favorable prognosis and juvenile-onset, thoracoscopic surgery is a suitable operation for this tumor.

DOI： 10.2995/jacsurg.29.781

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Other Link： http://search.jamas.or.jp/link/ui/2015404773

Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S209_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.6_697_5

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Language：Japanese   Publishing type：Research paper (international conference proceedings)   Publisher：Japan Lung Cancer Society  

Photodynamic therapy (PDT) consists of using a tumor specific photosensitizer and low power laser irradiation to induce production of reactive oxygen species in cancer cells. PDT is not like burning the cancer cells and a minimally invasive treatment. PDT is not only recommended in Japan but also in the US, Canada and several European countries to treat early stage non-small cell lung cancer that is located around pulmonary hilar lesion. PDT was first approved for centrally located early lung cancers in 1994, and in 2010 PDT was approved for the improvement of the respiratory tract obstruction caused by advanced lung cancers, for the improvement of the quality of life (QOL), and for progressive lung cancer. Because smoking is the greatest cause of centrally located early lung cancers, most patients with this disease suffer from poor cardio-pulmonary function. Also, 20-30% of these patients are multicentric and treatment preserving pulmonary function should be considered. As PDT exercises minimal invasiveness, it can be performed with safety. Also its high effectiveness has been proven by its clinical tests. Recently, the effectiveness of PDT using against early lung cancer that was found in the central types of the lung that is less than 1 cm in size, can terminate the cancer completely, the CR (complete remission) rate was 90.4%. In this way, when it comes to early lung cancer that is located in the central part of the lung which is the pulmonary hilar lesion, PDT is becoming to be the standard treatment.

DOI： 10.2482/haigan.54.983

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J03156&link_issn=&doc_id=20141007210019&doc_link_id=10.3919%2Fjjsa.75.2462&url=https%3A%2F%2Fdoi.org%2F10.3919%2Fjjsa.75.2462&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J03156&link_issn=&doc_id=20141007210019&doc_link_id=10.3919%2Fjjsa.75.2462&url=https%3A%2F%2Fdoi.org%2F10.3919%2Fjjsa.75.2462&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J02256&link_issn=&doc_id=20140929290003&doc_link_id=10.2995%2Fjacsurg.28.707&url=https%3A%2F%2Fdoi.org%2F10.2995%2Fjacsurg.28.707&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

The form and timing of the local recurrence of lung cancer can be unpredictable and unexpected. Pseudomesotheliomatous adenocarcinoma is a rare tumor that mimics malignant pleural mesothelioma both clinically and pathologically. Distinguishing pseudomesotheliomatous adenocarcinoma from malignant pleural mesothelioma on the basis of clinical findings can be difficult; therefore, a biopsy is usually required for diagnosis. Here we report on a 73-year-old Japanese man who presented with extensive dissemination along the pleural surfaces and clinical findings similar to those of pseudomesotheliomatous lung cancer 10 years after undergoing left upper lobectomy for lung adenocarcinoma. This report provides information that will help physicians establish an accurate diagnosis in similar cases.

DOI： 10.1272/jnms.81.173

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. Thymoma is a rare mediastinal tumor with relatively slow growth. However, advanced-stage cases with pleural dissemination are occasionally encountered. The outcome of surgical resection for thymomas with pleural dissemination has not been clearly determined.
Methods. We retrospectively investigated the clinical records of 2,835 patients with thymic epithelial tumors that were treated from 1991 to 2010 in 32 institutions that participated in the Japanese Association for Research on the Thymus. In this study, we analyzed the clinicopathologic factors and prognosis of thymoma patients with pleural dissemination who underwent surgical resection.
Results. The thymomas with pleural disseminations numbered 148 cases (5.2% in the 2,835 thymic epithelial tumors). Surgical resection was performed in 136 cases. Pathologic Masaoka stages were classified as IVA (n = 118) and IVB (n = 18). In Masaoka stage IVA disease, the small number of disseminated pleural nodules (10 or fewer) was related to the curative resection. The prognosis was also better in these cases than in those with greater than 10 disseminated pleural nodules (certified during the operation; p = 0.0057). Patients who underwent macroscopic total resection of disseminated nodules had a better prognosis than those with residual tumors (p = 0.037). In stage IVA cases with complete resection (n = 42), the efficacy of adjuvant chemotherapy, radiotherapy, or both was not demonstrated.
Conclusions. Macroscopic total resection of tumors appears to be a promising prognostic factor in Masaoka stage IVA thymomas. The number of disseminated pleural nodules correlated with resectability. (C) 2014 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2014.01.042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL TRIBUNE INC  

Exostosis occurs in the ribs either sporadically or as a manifestation of a genetic disorder known as hereditary multiple exostoses. Costal exostosis may cause chest pain and, on rare occasions, result in hemothorax, pneumothorax, hemopneumothorax, and diaphragmatic or pericardial laceration. We report a case of pneumothorax in a 16-year-old boy with exostosis in the right seventh and eighth ribs. He previously received a diagnosis of multiple exostoses and underwent costal resection. The lung and pleura were injured because of long-term friction between the exostoses and the visceral pleura. To the best of our knowledge, this is only the fourth report of pneumothorax caused by costal exostosis. Moreover, all previously reported cases of pneumothorax or hemopneumothorax caused by costal exostosis, including the present case, involved lower lobe injury.

DOI： 10.5761/atcs.cr.12.01955

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.36.Special_S285_3

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.36.6_678_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.36.Special_S202

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DOI： 10.18907/jjsre.36.1_5

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Intrathoracic neurofibromas originating from the vagus nerve in patients without von Recklinghausen disease is rare and poses a problem in etiological diagnosis. Surgical resection is usually necessary for precise diagnosis of such tumors. We report the first case of a neurofibroma originating from the right pulmonary branch of the vagus nerve in a 34-year-old male without von Recklinghausen disease. The diagnosis was suggested by the radiological features and was confirmed histologically after resection.

DOI： 10.1055/s-0033-1348477

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Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

To define the clinicopathological features and discuss the optimal management of carcinoma showing thymus-like differentiation (CASTLE).
We retrospectively analyzed six patients with CASTLE.
The subjects comprised two men and four women (average age at initial diagnosis, 61 years, range 47-75 years). Preoperative biopsy yielded a correct diagnosis in two patients. Five patients underwent surgery and one was treated with radiation therapy alone. Four had extrathyroidal invasion and three had lymph node metastasis. During the clinical course, tracheal invasion was detected in five patients, the upper extent of the tumor being the lower half of the first tracheal ring. Two of these patients underwent tracheal sleeve resection. Two patients received postoperative radiotherapy for nodal metastasis, and one, after palliative surgery. The median follow-up period was 67 months (range 38-129). Recurrence was found 10 years post-therapy in the patient treated with radiation therapy only, resulting in death soon after. Although local recurrence was not found in the remaining five patients, new pulmonary metastases were diagnosed in the patient who underwent non-curative surgery.
CASTLE can be diagnosed preoperatively by core needle biopsy and CD5 staining. Curative resection with neck dissection followed by radiotherapy can yield a good outcome. Larynx-sparing complete resection may be more feasible for CASTLE, even though it has a higher incidence of tracheal invasion than differentiated thyroid carcinoma.

DOI： 10.1007/s00595-013-0560-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Background: We investigated blood vessel invasion (BVI) as a possible negative prognostic factor in patients with stage I non-small cell lung cancer (NSCLC) according to the 7th edition of the TNM classification. Methods: Between 1999 and 2007, a total of 694 consecutive patients with pathological stage I NSCLC underwent complete resection with systematic lymph node dissection at Tokyo Medical University Hospital. All sections of the specimens were stained by Elastica van Gieson to visualize elastic fibers and were examined to determine the prognostic symptoms of BVI. We statistically analyzed the association between BVI and clinicopathologic factors, as well as clinical outcomes. Results: BVI was detected in 201 patients with stage I NSCLC (29.0%). The 5-year overall survival (OS) rates of the non-BVI and BVI patients were 90.5% and 66.0%, respectively (p&lt
0.0001). BVI was found to be a significant independent prognostic factor by multivariate survival analysis in stage IA and stage IB NSCLC (HR 2.591, p&lt
0.001
HR 2.347, p=0.009, respectively). The 5-year OS rate of patients with BVI was significantly worse than that of patients without BVI in the T1a (94.5% vs 87.5%, p&lt
0.0001), T1b (82.7% vs 65.9%, p&lt
0.0001), and T2a (90.9% vs 61.8%, p&lt
0.0001) subgroups. Conclusion: We identified the presence of BVI as an independent poor prognostic factor in patients with stage I NSCLC. In the future revision of the TNM staging system, the routine use of elastic fiber stains in pathological evaluations of lung cancer for BVI determination might be recommended, and tumors with BVI should be upstaged to the higher current T staging. © 2013 Elsevier Ireland Ltd.

DOI： 10.1016/j.lungcan.2013.04.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER COLL CHEST PHYSICIANS  

Objective: The objective of this study was to identify the clinicopathologic factors influencing postrecurrence survival (PRS) in and the effect of postrecurrence therapy (PRT) on patients with completely resected stage I non-small cell lung cancer (NSCLC).
Methods: We reviewed the data of 919 patients in whom complete resection of stage I NSCLC had been performed.
Results: Of the 919 patients, 170 (18.5%) had recurrent disease. Initial PRT was performed in 118 patients (69.1%) (surgery in eight, chemotherapy in 79, radiotherapy in 10, and chemoradiotherapy in 21). On multivariate analyses, PRT (hazard ratio [HR], 0.542; 95% CI, 0.344-0.853; P =.008), female sex (HR, 0.487; 95% CI, 0.297-0.801; P =.005), and differentiation (HR, 1.810; 95% CI, 1.194-2.743; P =.005) demonstrated a statistically significant association with favorable PRS. Bone metastasis (HR, 3.288; 95% CI, 1.783-6.062; P &lt;.001), liver metastasis (HR, 4.518; 95% CI, 1.793-11.379; P =.001), chemotherapy (HR, 0.478; 95% CI, 0.236-0.975; P =.040), epidermal growth factor receptor-tyrosine kinase inhibitors treatment (EGFR-TKIs) (HR, 0.460; 95% CI, 0.245-0.862; P =.015), and nonadenocarcinoma (HE, 2.136; 95% CI, 1.273-3.585; P =.004) were independently and significantly associated with PBS in the 118 patients who underwent any PRT. Subgroup analysis with a combination of these five PRS factors in the patients who underwent any PRT revealed median PRS times of 42.4 months for 20 patients lacking all five risk factors and 18.8 months for 98 patients with at least one of these risk factors (P =.001).
Conclusions: PRT, sex, and differentiation were independently associated with PRS. In the patients who underwent any PRT, PBS was related to EGFR-TKIs, chemotherapy, histology, and initial recurrence sites. One challenge for the future will be to create systematic treatment strategies for recurrent NSCLC according to the risk factor status of individual patients.

DOI： 10.1378/chest.12-1717

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER COLL CHEST PHYSICIANS  

Background: We previously reported the prognostic impact of the number of involved lymph nodes (LNs) on survival in non-small cell lung cancer (NSCLC). However, it remains unknown whether the total number or anatomic location of involved LNs is a superior prognostic factor.
Methods: A total of 689 patients with NSCLC who underwent complete resection involving dissection of the hilar and mediastinal LNs with curative intent of 10 LNs were enrolled. The association between the total number of LNs (nN) involved and survival was assessed by comparison with the anatomic location of LN involvement (pathologic lymph node [pN]), the present nodal category.
Results: We classified the patients into five categories according to the combined pN and nN status as follows: pN0-nN0, pN1-nN1-3, pN1-nN4-, pN2-nN1-3, and pN2-nN4. Although there was no statistically significant difference between the pNl-nN4- and pN2-nN1-3 categories, pN2-nN1-3 had better prognoses than pNl-nN4. On multivariate analysis, the nN category was an independent prognostic factor for overall survival and disease-free survival (vs nN4; the hazard ratios of nNO and nN1-3 for overall survival were 0.223 and 0.369, respectively, P &lt;.0001 for all), similar to the pN category. We propose a new classification based on a combination of the pN and nN categories: namely, NO becomes pN0-nN0, the Ni category becomes pN1-nN1-3, the N2a category becomes pN2-nN1-3 + pNl-nN4, and the N2b category becomes pN2-nN4. Each survival curve was proportional and was well distributed among the curves.
Conclusions: A combined anatomically based pN stage classification and numerically based nN stage classification is a more accurate prognostic determinant in patients with NSCLC, especially in the prognostically heterogeneous pN1 and pN2 cases. Further large-scale international cohort validation analyses are warranted.

DOI： 10.1378/chest.12-0750

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Language：Japanese  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J04260&link_issn=&doc_id=20130624400003&doc_link_id=%2Fcw1nimed%2F2013%2F000903%2F004%2F0156-0159%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw1nimed%2F2013%2F000903%2F004%2F0156-0159%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本サイトメトリー学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Clinicohistopathological staging is insufficient to predict disease progression and clinical outcome in lung carcinoma. Based on the results of the principal component analysis of 24 samples of early-stage lung adenocarcinoma, two subgroups were identified within the early-relapse group. The histological classification of all samples of group A was poorly differentiated, whereas one out of three in group B was poorly differentiated. DAVID functional annotation analysis revealed that the molecular pathways enriched in group A included those associated with cell adhesion molecules (CAMs), cell cycle and antigen processing and presentation, whereas those in group B included CAMs, T cell receptor signaling, cytokine-cytokine receptor interaction, toll-like receptor signaling, chemokine signaling, primary immunodeficiency and natural killer cell-mediated cytotoxicity. The CAM pathway was enriched in both groups. This comprehensive gene expression and functional pathway analysis identified a distinct molecular pathway, CAMs, that correlated with the early relapse of patients with early-stage lung adenocarcinoma.

DOI： 10.3892/or.2013.2332

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As a result of increased use of CT in both screening and daily practice, the number of early lung cancers has increased enormously. Surgeons pursue both curativity and reduced invasiveness in treating patients with early stage lung cancer; therefore, minimally invasive operations, such as video-assisted thoracoscopic surgery (VATS) lobectomy are now being routinely performed. Most previous reports have shown that there is no difference in mortality and local recurrence between open surgery and VATS in stage I patients. However, surgeons' improved technical experience and patients' demands could soon make VATS lobectomy the operative method of choice for early stage lung cancer. Moreover, the indications for VATS are expanding to encompass complex procedures such as segmentectomy or sleeve resection. Training and dissemination of the technique and the monitoring of outcomes are necessary.

DOI： 10.1111/ases.12013

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.35.Special_S262_2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The purpose of the present study was to determine the nodal spread patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location, and to attempt to evaluate the possible indications of selective lymph node dissection (SLND).
We retrospectively analyzed nodal spread patterns in 207 patients with NSCLC of less than 5 cm with N2 involvement.
The tumor location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of upper mediastinal (UM) involvement (96 and 100 %, respectively) and a lower incidence of subcarinal involvement (15 and 10 %, respectively) than lower lobe tumors (UM; RLL 60 %, LLL 42 %; subcarinal: RLL 60 %, LLL 46 %, respectively). Among the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2 showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1, suggesting that UM dissection may be unnecessary in lower lobe tumors with no metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections according to the preoperative T status. Among the patients with 12 subcarinal-positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL or LUD tumors with no metastasis to hilar and UM nodes on frozen sections.
The present study appears to provide one of the supportive results regarding the treatment strategies for tumor location-specific SLND.

DOI： 10.1007/s00268-012-1743-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: In this study, we investigated visceral pleural invasion (VPI) as a poor prognostic factor in patients with non-small cell lung cancer (NSCLC) according to the 7th edition of the TNM classification.
Methods: Between January 2000 and December 2007, 886 consecutive patients with pathological T1a-T2b NSCLC underwent complete resection with systematic lymph node dissection in Tokyo Medical University. We statistically analyzed the association between VPI and clinicopathologic factors, or clinical outcomes.
Results: The 5-year overall survival (OS) rates of the pl0, pl1, and pl2 patients were 80.8%, 63.7%, and 49.6%, respectively, with significant differences between pl0 and pl1 (p = 0.002), pH and pl2 (p = 0.03). Thus, the pl1 and pl2 patient groups were defined as patients with VPI. VPI was found to be a significant independent prognostic factor by multivariate survival analysis (p = 0.0002). In patients with tumors &lt;= 3 cm, especially with tumors &lt;= 2 cm, VPI was significantly associated with an increased rate of lymph node metastasis, compared with non-VPI (p = 0.0003 and p = 0.015, respectively). Analysis of the OS of patients stratified by tumor size (&lt;= 3 cm, 3.1-5 cm, 5.1-7 cm) and VPI status showed that in any nodal status, patients with 3.1-5 cm/VPI tumors had significantly worse survival than patients with &lt;= 3 cm/VPI tumors (p = 0.019) and patients with 3.1-5 cm/non-VPI tumors (p = 0.001). On the other hand, there was no significant difference in the OS between patients with 3.1-5 cm/VPI tumors and patients with 5.1-7 cm tumors regardless of lymph node metastasis (T2b tumors). Similar relationships were observed among these groups with N0 disease.
Conclusion: We identified the presence of VPI as an independent poor prognostic factor in patients with NSCLC of &lt;= 7 cm. Tumors 3.1-5 cm with VPI should be upstaged to T2b tumors in the future in the TNM classification of the Union of International Cancer Control staging system. In addition, the surgical strategy involving more extensive lymph node dissection for patients with &lt;= 3 cm/VPI tumors, especially &lt;= 2 cm/VPI, is warranted owing to more frequent lymph node metastasis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2012.08.004

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Intrapericardial foregut cysts are rare, and are usually found serendipitously. An abnormal shadow was incidentally found on a chest X-ray film of a 45-year-old asymptomatic female undergoing a regular check-up. Computed tomography revealed a smooth-walled, left mediastinal cyst (70 × 46 mm) immediately adjacent to the pericardium and left ventricle. We performed video-assisted thoracic surgery, which suggested that the lesion had macroscopically originated from the epicardium. However, the resected cyst was histologically determined to be an intrapericardial foregut cyst. This experience taught us that, while intrapericardial cysts possess the latent possibility of causing sudden death, cardiac failure, or eventual malignant changes, carefully planned and meticulously executed resection, avoiding damage to adjacent organs or vessels, is recommended.

DOI： 10.1007/s00595-012-0166-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

Although an association between prognosis and lobar location of lung cancer, particularly the left lower lobe (LLL), has been suggested, the certainty of such association remains controversial. The purpose of this study was to evaluate the impact of tumour lobar location on surgical outcomes as an independent prognostic factor for survival in our non-small cell lung cancer (NSCLC) patient series.
We retrospectively reviewed 978 NSCLC patients who underwent complete resection in our hospital between 2000 and 2007. We statistically analysed the association between clinicopathological factors and clinical outcomes.
Among the 978 patients reviewed, the NSCLC was located in the LLL in 143 (14.6%) patients, and lymph node involvement was identified in 210 patients (21.5%). The 5-year overall survival rates of patients whose NSCLC was located in the LLL and in other lobes (non-LLL) were 73.1 and 74.3%, respectively, and showed no significant association (P = 0.86). On the other hand, the 5-year survival rates of patients whose NSCLC occurred in the LLL (n = 33) and non-LLL (n = 177) and with lymph node metastasis were 32.7 and 57.7%, respectively, and showed a significant association (P = 0.01). Therefore, we performed a more detailed analysis on the 210 NSCLC patients with lymph node metastasis. On multivariate analysis, we found that LLL tumour (P = 0.02), tumour size &gt; 3 cm (P = 0.02) and N status (P &lt; 0.001) were significant independent predictors for survival.
LLL tumours with lymph node metastasis are strongly associated with mortality in NSCLC patients. The location of the primary tumour may contribute in determining the optimal management strategy and accurate prediction of prognosis.

DOI： 10.1093/ejcts/ezs065

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Introduction: The appropriate therapeutic strategy and postoperative management for patients with stage IA non-small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC.
Methods: We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan-Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors.
Results: On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p &lt; 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068).
Conclusion: These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy.

DOI： 10.1097/JTO.0b013e31825cca6e

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Previously, we evaluated use of the da Vinci Surgical System for anterior and middle mediastinal tumors in clinical cases, focusing on feasibility, safety, and appropriate settings. In this study, we evaluated extending the indications for robotic surgical treatment of posterior mediastinal tumors to include those located adjacent to the upper vertebrae or aorta. Three patients with mediastinal tumors located immediately adjacent to the vertebrae or aorta, underwent resection with the da Vinci Surgical System. All resected tumors were benign histologically. Robotic surgery enabled treatment of tumors located in the posterior mediastinum, which are very difficult to reach, making resection with the conventional video-assisted thoracoscopic surgery technique extremely difficult. All procedures were performed safely, smoothly, and extremely precisely. Crucial to the success of these operations were the appropriate placement and angle of the special da Vinci surgical ports in relation to the target and the patient's position, which varied according to the tumor location. © The Author(s) 2012.

DOI： 10.1177/0218492311434332

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Language：English   Publishing type：Part of collection (book)   Publisher：Wiley-Blackwell  

DOI： 10.1002/9781444346428.ch20

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Language：Japanese  

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.34.2_197_4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: The important role of surgery in early-stage small cell lung cancer (SCLC) has been recognized, and curative surgical resection is recommended. However, the role of adjuvant chemotherapy for stage I SCLC has not yet been evaluated, and novel approaches focusing on the specific genomic characteristics of SCLC may be invaluable for customized therapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the expression of Klotho, assessed by immunohistochemistry, can predict survival in patients with resected SCLC.
Methods: The medical records of patients diagnosed as having limited-disease (LD) SCLC and treated by surgical resection (n = 30) at Tokyo Medical University Hospital were retrospectively reviewed. The expression status of Klotho, and of the ATP-binding cassette (ABC) transporters MRP1, MDR and breast cancer resistant protein (BCRP), which can cause resistance to anticancer drugs, including irinotecan, was assessed by immunohistochemical analysis in resected surgical specimens of patients with early-stage SCLC.
Results: Of the 30 patients, Klotho expression was seen in the specimens from 18 patients (60.0%), but not in those of the remaining 12 patients (40.0%). The immunostaining for Klotho was mostly localized in the cytoplasm. The expression of Klotho was significantly associated with the overall survival (OS) (ratio 0.088; 95% confidence interval 0.019-0.409; P = 0.002). The administration of perioperative chemotherapy had no significant effect in improving the survival, as assessed by the Kaplan-Meier method. However, the patients showing Klotho expression in the resected specimens in p-stage I and II, may have benefited from perioperative chemotherapy. A multivariate analysis revealed no significant association between the expression status of MRP1, MDR or BCRP and the OS.
Conclusion: Expression of Klotho was predictive of a favorable outcome following resection in limited-disease SCLC patients, and the Klotho expression status may serve as a new biomarker for the need of additional therapies to be developed in the future. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2011.03.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background: Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis.
Methods: We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007.
Results: The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and &gt;= 10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and &gt;= 4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p &lt; 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p &lt; 0.0001).
Conclusion: Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.

DOI： 10.1097/JTO.0b013e31822a35c3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL TRIBUNE INC  

Objectives: In Japan, as of March 2010, only 13 hospitals were using the da Vinci system and only for selected cases. Few clinical robotic lung surgery has been done in Japan, and there are no standardized training programs, although some exist in the U.S. and are under consideration by the Japanese society for thoracic surgery. We have used the da Vinci S (R) Surgical System for pneumonectomy and lymph node dissection in pigs. We report and review future possibilities and problems of robotic surgery, especially concerning education, training, safety management and ethical considerations for pneumonectomy and lymph node dissection in clinical practice.
Methods: The da Vinci (R) system consists of a surgeon&apos;s console connected to a patient-side cart, a manipulator unit with three instrument arms and a central arm to guide the endoscope. The surgeon, sitting at the console, triggers highly sensitive motion sensors that transmit the surgeon&apos;s movements to the instrument arm.
Results: We experienced exactly the same sensation as when performing standard open thoracotomy. Visual recognition is 3-D, and the high manipulation potential allows free movement of the various accessory instruments, exceeding the capacity of a surgeon&apos;s hands in video-assisted thoracic surgery (VATS) or even standard thoracotomy.
Conclusions: Robotic surgery achieves at least the same level of operation technique for pneumonectomy and lymph node dissection under standard open thoracotomy, and it seemed as safe and easily performed as conventional VATS. The training program using pigs was effective and holds promise as a system to train thoracic surgeons in robotic lung surgery.

DOI： 10.5761/atcs.oa.10.01613

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Purpose: The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. Methods: Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. Results: Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. Conclusion: Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy. © 2011 The Japanese Association for Thoracic Surgery.

DOI： 10.1007/s11748-010-0790-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Background and Objectives: PDT induces apoptosis, inflammatory reactions, immune reactions, and damage to the microvasculature around the tumors. The mechanisms responsible for the anticancer effects of Photofrin-PDT and NPe6-PDT differ somewhat. To select a photosensitizer for lung cancer treatment and to improve the efficacy of PDT, the mechanisms of action for PDT using Photofrin or NPe6 must be elucidated and the phenomena validated by analyzing molecular determinants from clinical samples. Study Design/Materials and Methods: We examined the role of immunological reactions in the anti-tumor effects of PDT using cytokine-overexpressing cells and investigated whether the anti-apoptotic protein Bcl-2 may be a molecular target. Moreover, we investigated the association between ATP-binding cassette transporter proteins such as breast cancer-resistant protein (BCRP), which can pump out some types of photosensitizer, and the efficacy of PDT using clinical samples from 81 early lung cancer lesions treated with PDT between 1998 and 2006 at the Tokyo Medical University Hospital.
Results: Photofrin-PDT damaged Bcl-2 and rapidly induced apoptosis, but NPe6-PDT did not damage Bc-2 nor did it induce morphologically typical apoptosis. However, NPe6-PDT exerted a strong anti-tumor effect, regardless of the overexpression of Bcl-2. By analyzing the BCRP-overexpressing cells, Photofrin, but not NPe6, was found to be a substrate of BCRP. All 81 lung cancer lesions were BCRP-positive; as Photofrin was found to be a substrate of BCRP, the expression of BCRP significantly affected the efficacy of Photofrin-PDT. However, NPe6-PDT exerted a strong antitumor effect regardless of BCRP expression, and the complete response rate after NPe6-PDT was much higher than that after Photofrin-PDT.
Conclusions: Our translational research suggests that NPe6-PDT may be superior to Photofrin-PDT for the treatment of lung caner, and individualized approaches to PDT based on the expression status of Bcl-2 and/or BCRP may improve the efficacy of PDT in patients with lung cancers. Lasers Surg. Med. 43: 591-599, 2011. (C) 2011 Wiley-Liss, Inc.

DOI： 10.1002/lsm.21097

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background: and Objective Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for central type early stage lung cancer (CELC). Recent advances in the ability to diagnose CELC, and in photosensitizers, as well as sophisticated clinical management, may improve the therapeutic outcome and expand the indications of PDT.
Materials and Methods: We made the search for papers on PDT for lung cancer to select the most relevant articles. Based on this review and our recent data, we discussed the best available evidence for the diagnosis, the definition of indications, photosensitizers, and clinical management with regard to PDT.
Results: To obtain complete response (CR) by PDT, the selection of the indications is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) have had a large impact on diagnostic bronchoscopy for CELC. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this is a good indication for PDT. The relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin, showed similar treatment outcome even for large tumors &gt;1.0 cm in diameter. Furthermore, comprehensive management including photodynamic diagnosis before and after PDT should be effective to minimize the possibility of local recurrence after PDT.
Conclusion: The present guidelines of PDT for CELC were established based on the data obtained from studies in the 1980&apos;s. We postulate that comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors. Lasers Surg. Med. 43: 749-754, 2011. (C) 2011 Wiley-Liss, Inc.

DOI： 10.1002/lsm.21091

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: In terms of prognosis, large cell neuroendocrine carcinoma (LCNEC) differs distinctively from other non-small cell lung cancers, with the prognosis of LCNEC being poor, even for early-stage disease. Improvements in survival require a biomarker capable of defining a subset of patients destined to do poorly so that these patients can be targeted for additional therapies, including chemotherapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the immunohistochemical expression of Klotho can predict survival patients with resected LCNEC.
Methods: The histological characteristics of patients receiving an initial diagnosis of LCNEC (n = 30) at Tokyo Medical University Hospital were retrospectively reviewed, and multiple variables including stage, lymphangioinvasion, lymph node status and the expression of Klotho as identified using an immunohistochemical analysis, were assessed.
Results: Immunostaining for Klotho was mostly cytoplasmic, and Klotho expression was seen in 10 patients (33.3%) but not in 20 patients (66.7%). The expression of Klotho was significantly associated with a good outcome of resected patients with LCNEC and Klotho(-) was associated with increased LCNEC risk by multivariate analysis (hazard ratio 4.92, 95% confidence interval 1.04-23.24, p = 0.044). Neither lymph node status nor lymphangioinvasion were significantly associated with a poor survival. However, among patients without lymph node metastasis or angioinvasion, the survival benefit of Klotho expression in the primary tumor was significantly higher, compared with that of patients without Klotho expression.
Conclusion: Klotho staining provides a new biomarker for a good outcome in patients with LCNEC, especially among patients without lymph node metastasis or lymphangioinvasion. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2010.10.008

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Language：Japanese   Publisher：The Laser Society of Japan  

Photodynamic therapy (PDT) uses a photosensitizer and laser irradiation to induce reactive oxygen

DOI： 10.2184/lsj.39.101

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Other Link： https://jlc.jst.go.jp/DN/JALC/00364190515?from=CiNii

Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.33.Special_S292_1

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Language：English   Publishing type：Research paper (scientific journal)  

Objective: To select minimally stressful methods for patients with benign bronchial tumors, and evaluate interventional strategies in relation to location, size, character and morphology. Methods: We reviewed the indications and efficacy of various interventional bronchology techniques at our institution, including individual or combined laser resection, electrocautery, argon plasma coagulation and high radiofrequency snaring for the treatment of various types of benign bronchial tumors. Results: It is essential to treat endoscopically that the tumor is visible and has a stalk and not invade beyond bronchial wall. By using combined techniques, no complications or recurrences were encountered. Conclusions: Interventional bronchology techniques for benign bronchial tumors can be simple and safe, and therapeutic strategies should be designed in relation to location, size, character and morphology of tumors. © 2011 Pioneer Bioscience Publishing Company.

DOI： 10.3978/j.issn.2072-1439.2011.04.06

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.33.2_135_2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Approximately 30% of lung cancer patients will develop central airway obstruction (CAO). Interventional therapeutic bronchoscopy including airway stenting (AS) providing immediate and effective palliation is therefore essential to improve quality of life (QoL). However, no report has demonstrated the survival benefit of AS. We retrospectively reviewed 65 patients with CAO due to lung cancer who underwent AS from June 1994 to May 2008. Seventy-nine stents were required. Silicon, metallic, or both stents were placed in 42 (60%), 19 (29%), or eight (11%) patients, respectively. Single stent was required in 53 (83%) patients, double in 10 (14%), and triple in two (3%). AS could provide acute relief of central airway and significant improvement was seen in 98% of patients. Fifty-nine patients with detailed observations were assessed further. Morbidity and mortality rates were 22% and 8%, respectively. AS resulted in 25.2% of one-year survival rate and 6.2 months of median survival time (MST). AS followed by adjuvant therapy provided a four-month increase in MST, although overall survival was not significantly changed. This study represents a single-institution experience. Although an aggressive strategy of AS is justified in order to improve symptoms and QoL, AS itself did not contribute to survival benefit. (C) 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

DOI： 10.1510/icvts.2010.238196

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The objective: To evaluate the hypothesis that lung cancer treatment planning (whether or not to use induction therapy) can be improved if respiratory dynamic cine magnetic resonance imaging (RD MR) is used.
Method: We studied 100 lung cancer patients, 76 men and 21 women, scheduled for thoracotomies between May 1997 and December 2006 wherein it was unclear preoperatively whether chest wall invasion would be found. We evaluated the accuracy of RD MR as compared with the findings at operation and postoperative pathology. The accuracy of RD MRI for evaluating chest wall invasion was compared with the efficacy of CT and MRI within our own group of patients and with data from the studies of other investigators.
Results: Concerning the evaluation of chest wall invasion, conventional computed tomography (CT) had 43.9% specificity, 60.0% sensitivity and 47.1% accuracy, while RD MR had 68.5% specificity, 100.0% sensitivity and 77.0% accuracy. RD MRI was particularly useful in the evaluation of cancers around 5 cm in diameter that were located adjacent to the diaphragm. Postoperative evaluation of superior sulcus tumor cases that had received induction therapy also showed that the RD MR procedure enabled an accurate decision in 87.5% of cases, and there were no false negative cases.
Conclusions: RD MR is more useful than CT or standard MRI for evaluating thoracic wall invasion. This noninvasive method enhances the reliability of deciding whether induction therapy should be employed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2009.10.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

Recently, a second-generation photosensory agent for photodynamic therapy (PDT), mono-l-aspartyl chlorine e6 (NPe6), which degrades rapidly in vivo, has been developed. We evaluated its feasibility and efficacy for treatment in biliary tract carcinoma.
A transmittance of semiconductor laser light (664 nm), sensitivity of a human biliary tract carcinoma cell line, and disorder to normal tissue including Glissonian constructs and adjacent hepatocytes were investigated.
The transmittance of the laser was 85-91% through yellow clear bile and that of the bile including 50 mu g/ml NPe6 was 17-48%. The effective concentration of NPe6 which showed LD50 for a cell line was 12.5 mu g/ml, and that of LD95 was 25 mu g/ml. NPe6 in the supernatant reduced laser transmissiveness, but it had little influence on the antitumor effect in supernatant with or without NPe6. The NOZ cell-tumor volume was reduced significantly 14 days after irradiation in the PDT group (PDT 69.9 +/- A 44.6 mm(3) vs control 296.3 +/- A 239.9 mm(3) P &lt; 0.05). No severe hepatic disorder including Glisson components was observed by the histological findings.
NPe6 PDT was effective in carcinomas even in the presence of bile, and causes no serious complication for the liver and Glisson structure. Therefore, NPe6 PDT will be a useful candidate as a new therapy for biliary tract carcinomas.

DOI： 10.1007/s00534-009-0246-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC CLINICAL ONCOLOGY  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: Most centrally located early lung cancers (CLELC) &lt;1.0 cm in diameter do not invade beyond the bronchial cartilage, and photodynamic therapy (PDT) with Photofrin is currently recommended as a treatment option for such lesions. NPe6 is a second-generation photosensitizer, and because it has a longer absorption band (664 nm) than Photofrin (630 nm), we hypothesized that NPe6-PDT would exert a strong antitumor effect against cancer lesions &gt;1.0 cm in diameter, which are assumed to involve extracartilaginous invasion and to be unsuitable for treatment with Photofrin-PDT.
Experimental Design: Between June 2004 and December 2008, 75 patients (91 lesions) with CLELC underwent NPe6-PDT after the extent of their tumors had been assessed by fluorescence bronchoscopy for photodynamic diagnosis and tumor depth had been assessed by optical coherence tomography.
Results: Seventy cancer lesions &lt;= 1.0 cm in diameter and 21 lesions &gt;1.0 cm in diameter were identified, and the complete response rate was 94.0% (66 of 70) and 90.4% (19 of 21), respectively. After the mass of large tumors and deeply invasive tumors had been reduced by electrocautery, NPe6-PDT was capable of destroying the residual cancer lesions.
Conclusion: NPe6-PDT has a strong antitumor effect against CLELCs &gt;1.0 cm in diameter that have invaded beyond the bronchial cartilage, thereby enabling the destruction of residual cancer lesions after mass reduction of large nodular-or polypoid-type lung cancers by electrocautery. The PDT guidelines for lung cancers should therefore be revised because use of NPe6-PDT will enable expansion of the clinical indications for PDT. Clin Cancer Res; 16(7); 2198-204. (C)2010 AACR.

DOI： 10.1158/1078-0432.CCR-09-2520

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

To our knowledge there is no in-depth report on the benefits of airway stenting, which focuses specifically on patients with inoperable advanced lung cancer causing severe central airway obstruction. We evaluated the role of airway stenting as one aspect of the multidisciplinary management of advanced lung cancer.
We performed airway stenting in 40 lung cancer patients, placing a total of 58 stents. Stenting was done as a final modality in 22 patients with terminal-stage lung cancer (group A). The other 18 patients received additional therapy after stenting (group B), 12 (66.7%) of whom were treatment-na &lt; ve on admission.
The performance status (PS) and Hugh-Jones classification (H-J) scores improved in both groups after stenting: from 3.56 to 2.48 (P = 0.001) and 4.29 to 3.20 (P = 0.004) in group A, and from 3.15 to 1.25 (P &lt; 0.001) and 4.10 to 2.10 (P &lt; 0.001) in group B, respectively. The median survival time and 1-year survival rate after stenting were 1.6 months and 5.1%, respectively, in group A, and 5.6 months and 25.0%, respectively, in group B.
Airway stenting followed by adjuvant therapy may improve the survival of treatment-na &lt; ve patients with severe symptomatic airway obstruction caused by advanced lung cancer.

DOI： 10.1007/s00595-008-4058-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The ATP-binding cassette (ABC) transporter protein, BCRP (breast cancer resistance protein)/ABCG2 pumps out some types of photosensitizers used in photodynamic therapy (PDT) and causes resistance to the antitumor effect of PDT. The purpose of this study was to investigate the association between the expression of BCRP and the efficacy of PDT using Photofrin, or the second-generation photosensitizer, NPe6, for centrally located early lung cancers.
Using human epidermoid carcinoma cells, A431 cells and the BCRP-overexpressing A431/BCRP cells, we examined the effects of BCRP expression on the effect of PDT by cell viability assay in vitro, and investigated the expression of BCRP by immunohistochemical analysis in 81 tumor samples obtained from patients with centrally located early lung cancers.
The A431/BCRP cells were more resistant to Photofrin-PDT than A431 cells in vitro, and Fumitremorgin C, a specific inhibitor of BCRP, reversed the resistance.
However, there was no significant difference in the antitumor effect of NPe6-PDT between these cells. All of the 81 centrally located early lung cancer lesions were BCRP-positive (2+,45 lesions; 1+, 30 lesions) and all the patients were male and heavy smokers (&gt;30 pack-years). The expression of BCRP significantly affected the efficacy of Photofrin-PDT in cancer lesions &gt;= 10 mm in diameter (P = 0.04). On the other hand, NPe6-PDT exhibited a strong antitumor effect, regardless of the expression status of BCRP.
Photofrin may be a substrate of BCRP and be pumped out from the cells, therefore, BCRP may be a molecular determinant of the outcome of Photofrin-PDT. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2009.04.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background: Patients with centrally located early lung cancer (CLELC) are often heavy smokers with a considerably high risk of multiple primary lung cancer (MPLC) lesions; treatment strategies for such patients must preserve the cardiopulmonary function.
Methods: Between July 2004 and July 2008, patients with CLELC underwent photodynamic therapy (PDT) using NPe6, second-generation photosensitizer at Tokyo Medical University Hospital. Among these patients, we retrospectively analyzed MPLC, which was treated by surgery plus PDT or PDT alone and examined the effectiveness of PDT, and we propose a treatment strategy for patients with MPLC.
Results: A total of 64 patients with CLECL received NPe6-PDT, and MPLCs were found in 22 patients (34.4%) using sputum cytology and a bronchoscopical examination using autofluorescence bronchoscopy. Among these 22 patients, 10 patients underwent surgery for primary lung cancer and underwent NPe6-PDT for the treatment of secondary primary CLELC, one patient underwent PDT for CLELC as a primary lesion followed by an operation for peripheral-type lung cancer as a secondary primary lesion, and 11 patients underwent PDT alone for MPLC lesions (28 lesions) that were roentgenographically occult lung cancers. Among these 22 patients with MPLC including peripheral-type lung cancers, which were resected by surgery, all 39 CLELC lesions exhibited a complete response after PDT, and all patients were alive.
Conclusions: For patients with lung cancer with a long-term history of smoking, careful follow-up examinations after surgical resection are needed considering the incidence of metachronous primary lung cancers. PDT can play an important role for the treatment strategy for MPLC.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox&apos;s proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P=0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 875%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P=0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials. Anti-Cancer Drugs 21:89-93 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

DOI： 10.1097/CAD.0b013e328330fd79

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. The therapeutic strategies for non-small cell lung carcinoma (NSCLC) with N1 and N2 disease differ remarkably. Debate exists about the definition of the borderline between N1 and N2 stations. This study evaluated the prognostic effect of N1 disease, especially focused on the significance of the main bronchial node (No. 10) vs N2 disease.
Methods. The records of 1601 patients who underwent complete pulmonary resection for NSCLC were reviewed to examine the clinical features of lymph nodal involvement.
Results. There were 1086 patients (67.8%) with pN0 disease, 202 (12.6%) with pN1, and 274 (17.1%) with pN2 disease; overall 5-year survival rates were 74.7%, 56.1% and 28.9%, respectively (p &lt; 0.001). Overall 5-year survival rates were 60.2% in hilar N1 and 49.6% in intralobar N1. Overall 5-year survival rates were 58.6% in N1 without node 10 and 35.1% in N1 with node 10. A significant difference was observed between N0 and N1 without node 10 (p &lt; 0.001), and N1 without node 10 and N1 with node 10 (p = 0.033); however, the difference between N1 with node 10 and N2 was not significant. The status of node 10 involvement was an independent prognostic factor of pN1 patients, as well as age and gender.
Conclusions. Patients with node 10-positive N1 disease have an unfavorable prognosis, and the disease behaves like N2 disease. The definition of clear borderline between N1 and N2 is mandatory to achieve a uniform classification map. This study offers further information for clinical and therapeutic purposes. (Ann Thorac Surg 2009;88:1583-8) (C) 2009 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2009.04.065

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.31.Special_S91_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.31.Special_S77_3

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Language：Japanese   Publisher：日本臨床プロテオーム研究会  

DOI： 10.14905/jscp.2009.0_21

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.31.Special_S75_3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

Inactivation of the p16 and ESR1 tumor suppressor genes by promoter lesion methylation has been reported in many tumor types, including lung cancer. We examined the blood of 95 non-small cell lung cancer patients (66 cases of adenocarcinoma, 23 of squamous cell carcinoma and 6 of large cell carcinoma) and 30 controls consisting of normal subjects and benign disease patients to determine the methylation ratios of p16 and ESR1 using real-time PCR. For both genes, there was a statistically significant difference in the methylation ratio between non-small cell lung cancer patients and controls (p16; p &lt; 0.01, ESR1; p &lt; 0.001). In addition, there was a strong correlation between the methylation ratio of each gene and old age (p16; p &lt; 0.01, ESR1; p &lt; 0.001 and p16 or ESR1; p &lt; 0.001), and between p16 or ESR1 methylation rate and smoking history (p &lt; 0.01). Moreover in Stage I cases, the methylation positive rate of each gene (p16, ESR1 and p16 or ESR1) was higher than the CEA positive rate (p &lt; 0.05, p &lt; 0.001, p &lt; 0.001). Evaluation of p16 and ESR1 promoter methylation in blood using real-time PCR appears to be very useful for lung cancer diagnosis and there is some possibility that these methylated genes might come to represent useful biomarkers for the early detection of lung cancer. Our study results also suggested that comparative evaluation of the methylation ratio before and after surgery might be a powerful tool to predict the prognosis of lung cancer patients.

DOI： 10.3892/or_00000121

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

It is very important to elucidate the mechanism of action and identify the molecular determinant of photodynamic medicine, in order to increase the number of clinical applications of photodynamic therapy (PDT) and perform personalized medicine. We have previously reported that PDT using some photosensitizers, such as phthalocyanine 4 (Pc 4) damages the anti-apoptotic protein Bcl-2, and that Bcl-2 is a molecular PDT target using a mitochondrion-targeting photosensitizer. In this study., we examined the molecular targets of Photofrin-PDT and NPe6-PDT, which are approved for early stage lung cancers by the Japanese Ministry of Health Labor and Welfare, by evaluating the photodamage to Bcl-2 using Western blot analysis. Our results showed that Photofrin-PDT damaged Bcl-2, induced morphologically typical apoptosis, and demonstrated equal sensitivity between MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) and Bcl-2 overexpressing cells, MCF-7c3-GFP-Bcl-2 cells, with a clonogenic assay. However, NPe6-PDT did not damage Bcl-2 and took longer to induce typical apoptosis compared with Photofrin-PDT. MCF-7c3-GFP-Bcl-2 cells were considerably more resistant to the lethal effects of NPe6-PDT than parental MCF-7c3 cells. In conclusion, Photofrin-PDT damages different molecular targets, and our data indicate that the extent of Bcl-2 photodamage can determine the sensitivity of cancer cells to apoptosis and to overall cell killing caused by PDT using Photofrin, but not the lysosomal targeting NPe6. The application of these findings to clinical PDT may depend on the levels of the Bcl-2 proteins in the tumor being treated, and the tailor-made medicine based on the Bcl-2 photodamage may overcome any resistance afforded by elevated amounts of Bcl-2.

DOI： 10.3892/ijo_00000054

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Language：Japanese   Publisher：東京医科大学医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J00877&link_issn=&doc_id=20081202420013&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1111%2F00002801%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1111%2F00002801%2F&type=%93%8C%8B%9E%88%E3%89%C8%91%E5%8Aw%81F%93%8C%8B%9E%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%8F%EE%95%F1%83%8A%83%7C%83W%83g%83%8A&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80090_3.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background and objective: Airway stenting can be a valuable therapeutic option for symptomatic airway stenosis, but its role in the palliation of advanced thyroid cancers invading the upper airway is unclear. This study examined the hypothesis that durable and replaceable silicone stents would give better results than self-expanding metallic stents.
Methods: A retrospective analysis was conducted of consecutive patients stented for laryngotracheal obstruction due to thyroid cancer. Stenting was performed via a rigid bronchoscope when airway patency after dilatation was &lt;= 50% of normal. Symptomatic improvement, Hugh-Jones (H-J) classification, Eastern Cooperative Oncology Group performance status (PS), and complications were analysed.
Results: There were 37 stenotic lesions treated in 35 patients. The most common sites for these lesions were in the inclusive area extending from the cricoid cartilage to the first tracheal ring (26/37 lesions, 70%). Forty-five stents (12 silicone, 20 metallic, 13 T-tubes) were used in 43 interventions. All patients showed immediate symptomatic relief and significant improvement in both PS and H-J classifications. Critical complications were supraglottic stenosis (5/43 interventions, 12%) and, of those same five cases, stent migration was seen in all but one (4/45 implantations, 9%). As these complications occurred only in patients in whom the silicone stents had been placed in close proximity to the cricoid cartilage (5/10 patients, 50%), this emphasizes the unsuitability of silicone stents in such cases. The median survival time from stenting was 8 months. The 1-year survival rate was 40%.
Conclusions: Airway stenting can achieve significant palliation in patients with thyroid cancer and airway obstruction. The study showed that for the most common lesions, the uncovered Ultraflex stent is associated with fewer critical complications than the silicone stents.

DOI： 10.1111/j.1440-1843.2008.01309.x

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Language：Japanese   Publisher：Japan Society for Laser Surgery and Medicine  

To discuss the feasibility of performing percutaneous interstitial laser treatment as a minimally invasive therapy for thyroid micro cancer, we investigated the correlation between the power/energy and treatment effect, and measured fluctuations in the internal and superficial temperature of thyroid tissues using experimental animals.<BR>A laser fiber was inserted through an introducer needle into a pig's thyroid, and photoablation was performed with a diode laser emitting light at a wavelength of 830nm. After formalin fixation, the mean diameter of the necrosis was measured. Using 2W at fiber tip, there is no correlation between irradiational condition and necrosis. At 3W and 5W, the necrotic area enlarged in proportion to increased energy (J) producing a spindle-shaped lesion over the fiber tip. Using the same energy, a larger necrosis was consistently produced at 3W. However, there was no significant difference in the size of necrosis when treated for the same length of time. The largest necrosis of 12.3 mm was produced at 3W, 1500J. At 5 mm (necrotic site), 10 mm (peripheral of necrotic site), and 15 mm (non-necrotic site) from treatment point, the temperature within the tissue reached maximum, 300 seconds after laser delivery. At 3W, the temperature increased moderately, measuring 160°C, 81°C and 54°C respectively. At 5W, the temperature increased rapidly to 154°C, 64°C, 46°C respectively. Carbonization was seen around the fiber tip at 5W. The surface temperature of thyroid was 38°C at 3W, and 55°C at 5W.<BR>Interstitial laser treatment enables ablation of thyroid tissue up to 1 cm in diameter using 3W for 5 minutes without increased surface temperature or carbonation-induced attenuation in laser transmission, suggesting that this can be a minimally invasive therapy enforceable for outpatients by using the portable diode laser under ultrasound guidance.

DOI： 10.2530/jslsm.29.5

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2008233713

Language：Japanese   Publisher：Japan Society for Laser Surgery and Medicine  

Malignant pleural mesothelioma is an aggressive malignancy which can be associated with asbesto's exposure. There is no proven curative modality and the median survival ranges from 6-18 months. Recently, the multitargeted antifolate pemetrexed (ALIMTA^®) has been approved as the front-line agent in combination with cisplatin for the treatment of malignant mesothelioma. However, the overall outcome remains very poor despite current available therapies. In this study, we developed a new treatment strategy for malignant mesothelioma by photodynamic therapy (PDT) using Laserphyrin^® and an LED (light emitting diode). We performed sensitivity tests on human malignant mesothelima cell lines, MSTO-211H, NCI-H2052, NCI-H2452, NCI-H28 cells against PDT using LED in vitro. PDT using LED and Laserphyrin^® had strong anti-tumor effect. Furthermore, we transplanted MSTO-211H cells into Balb/c nude mice, and we performed PDT in vivo. PDT using an LED cured the tumor as completely as PDT using laser in vivo. <BR>We conclude that PDT using LEDs can be useful for malignant mesothelioma in the experiment clinically and we hope to develop LEDs system for the thoracic wall. we will conduct clinical study combining PDT using LEDs and anti-cancer agents for malignant mesothelioma.

DOI： 10.2530/jslsm.29.12

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2008233714

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

We report a case of left main bronchial glomus tumor in a 39-year-old man who presented with a cough he had had for 1 month. A computed tomography (CT) scan revealed a polypoid tumor in the membranous portion of the left main bronchus. The tumor showed marked enhancement on the early phase of dynamic contrast-enhanced CT, and it was thought to be a hypervascular tumor. The tumor was carefully resected by a rigid bronchoscope, and the pathological and immunohistochemical findings yielded a diagnosis of glomus tumor. Marked enhancement of early phase dynamic contrast-enhanced CT may be useful for a diagnosis of bronchial, glomus tumor. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2007.08.015

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

NPe6 is a novel second-generation photosensitizer used for photodynamic therapy (PDT). PDT using NPe6 and diode laser (664 nm) induces cell death, inflammatory reactions, immunological responses and damage to the microvasculature. In this study, we evaluated the influence of the immunological responses and of enhanced angiogenesis on the anti-tumor effect of NPe6-PDT using cytokine-overexpressing Lewis lung carcinoma (LLC), LLC-IL-2 cells both in vitro and in vivo. We showed by DNA microarray analysis in vitro that IL-2 and GADD-45 alpha (growth arrest and DNA damage 45 alpha) mRNA expressions were induced by 3 h after NPe6-PDT applied at a dose killing 90% of the cells (LD90). IL-2-overexpres sing cells (LLC/IL-2 cells) were resistant to the loss of clonogenicity as compared to the parental LLC cells in vitro. Furthermore, in female C57BL/6 mice, NPe6-PDT produced a cure rate of 66.7% in LLC tumors, whereas the cure rate was only 16.6% in LLC/IL-2 tumors, and overexpression of IL-2 caused failure of NPe6-PDT, with tumor recurrence, in vivo. These results suggest that IL-2 expression may play an unfavorable role in attenuation of the antitumor effect of NPe6-PDT. It has been reported that the expression of vascular endothelial growth factor (VEGF), in particular, may cause tumor recurrence after PDT and exert unfavorable effect in relation to attenuate the anti-tumor activity of PDT. Results of immunohistochemical analysis of LLC/IL-2 tumors have revealed that the expressions of GADD-45 alpha and VEGF are induced in these tumors after PDT, and in particular, 12 h after PDT, the expression levels were much higher as compared with those in the LLC tumors. The results of our studies using in vitro and in vivo models suggest that the cell death caused by PDT was inhibited by induction of GADD-45 alpha expression and that tumor recurrence was promoted by the enhancement of VEGF expression mediated by IL-2 upregulation. Therefore, it is speculated that the use of an IL-2 inhibitor may improve the efficacy of NPe6-PDT.

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.30.Special_S143_3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusions. Endoscopic tumor ablation is a valuable option for inoperable postoperative laryngotracheal intraluminal invasion of well-differentiated thyroid carcinoma (DTC). Objectives. To investigate whether DTC invasion to the laryngotracheal mucosa can be controlled by &apos;simple&apos; tumor ablation considering its relatively slow-growing nature. Patients and methods. Twenty-two consecutive patients underwent endoscopic tumor ablation caused by DTC for local control of intraluminal lesions with no significant extrinsic laryngotracheal compression in symptomatic or asymptomatic patients in whom radical operations were contraindicated. Debulking by Nd:YAG laser was followed by electrocoagulation and microwave coagulation for the residual tumor base. Results. The critical complication, post-treatment supraglottic stenosis, was managed by prophylactic minitracheotomy. During the follow-up period of up to 125 months, 6 of 22 patients died (median survival 50 months), mainly of lung metastases, but all had a patent airway at death. Post-surgical extraluminal lesion growth is indolent and since relapse of the intraluminal lesion is the main cause of symptoms, satisfactory local control could be obtained by re-ablation of the mucosal lesion every few years. Lesions requiring retreatment within I year after initial treatment usually have high-grade malignancy, causing extrinsic compression, and prognosis is unfavorable.

DOI： 10.1080/00016480701714285

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5978/islsm.17.219

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.30.Special_S122_2

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.30.4_228_5

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.30.5_326_4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: We had Previously developed the possibility of use of a photodynamic diagnosis (PDD) system using a tumor-selective photosensitizer and laser irradiation for the early detection and photodynamic therapy (PDT) for centrally located early lung cancers. Recently, we established the autofluorescence diagnosis system integrated into a videoendoscope (SAFE-3000) as a very useful technique for the early diagnosis of lung cancer. Patients and methods: Twenty-nine patients (38 lesions) with centrally located early lung cancer received PDD and PDT using the second-generation photosensitizer, talaporfin sodium (NPe6). Just before the PDT, we defined the tumor margin accurately using the novel PDD system SAFE-3000 with NPe6 and a diode laser (408 nm). Results: Red fluorescence emitted from the tumor by excitation of the photosensitizer by the diode laser (408 nm) from SAFE-3000 allowed accurate determination of the tumor margin just before the PDT. The complete remission (CR) rate following NPe6-PDT in the cases with early lung cancer was 92.1% (35/38 lesions). We also confirmed the loss of red fluorescence from the tumors immediately after the PDT using SAFE-3000. We confirmed that all. the NPe6 in the tumor had been excited and photobleached by the laser irradiation (664 nm) and that no additional laser irradiation was needed for curative treatment. Conclusions: This novel PDD system using SAFE-3000 and NPe6 improved the quality and efficacy of PDT and avoided misjudgement of the dose of the photosensitizer or laser irradiation in PDT. PDT using NPe6 will become a standard option of treatments for centrally located early lung cancer. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2007.06.026

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Development of acquired resistance to gefitinib after an initial good response is common. Recently, it was reported that this acquired resistance is related to a secondary mutation associated with a substitution of threonine by methionine at codon 790 (T790M) of the epidermal growth factor receptor (EGFR) gene. In this report, we present a "never smoking" woman with advanced lung cancer who showed acquired resistance to gefitinib, and analysis of autopsy samples revealed no evidence of EGFR mutations in either exons 18-21 or codon 790, and positive immunostaining for breast cancer resistance protein (BCRP). We describe, for the first time, a case in which expression of BCRP was associated with acquired resistance to gefitinib, independent of EGFR mutations. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2007.05.019

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

ATX-s10-Na(II) is a novel second-generation photo-sensitizer for photodynamic therapy (PDT). PDT using ATX-s10 and diode laser (670 nm) induces an apoptotic response, inflammatory reaction, immune reaction and damage to the microvasculature. In particular, the vascular shut-down effect plays an important role in the anti-tumor activity of ATX-s10-PDT. It has been reported that PDT induces hypoxia and expression of the vascular endothelial growth factor (VEGF) via the hypoxia-inducible factor 1 (HIF1)-alpha pathway. We hypothesized that the expression of VEGF may cause tumor recurrence after PDT and exert unfavorable effect against the anti-tumor activity of ATX-s10-PDT. In this study, we showed by DNA microarray analysis in vitro that VEGF mRNA expression was induced 3 h after laser irradiation in ATX-s10-PDT. We compared the antitumor activity of ATX-s10-PDT against lung cancer cell lines SBC-3 and SBC-3/VEGF, the latter overexpressing VEGF; there was no significant difference in the sensitivity to the PDT between the two cell lines as assessed by clonogenic assay. Furthermore, no statistically significant difference in the anti-tumor effect of PDT, as measured by tumor cures, was found between SBC-3 and SBC-3/VEGF tumors in female Balb/c-nu/nu nude mice in vivo. In conclusion, ATX-s10-PDT may prevent tumor recurrence despite induction of VEGF and promotion of tumor angiogenesis, which are known to enhance tumor proliferation and survival.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Due to advances in interventional. bronchoscopy, curative treatment has become possible for central type lung cancer if it is detected in the early stage. However, expertise is required to diagnose the extent of tumor invasion and the depth of tumor involvement by conventional white light bronchoscopy alone, but judgement is still subjective. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) has had a large impact on diagnostic bronchoscopy in the past decade and have been employed especialty for the diagnosis of central type tumors. Objective evaluation by a comprehensive approach using AFB, EBUS and optical coherence tomography (OCT) enables selection of the optimal therapeutic strategy for central type early lung cancer (CELC). (c) 2007 Etsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2007.01.009

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Language：English   Publishing type：Research paper (scientific journal)  

Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers, with patients having a poor prognosis. Approximately one third of NSCLC patients present with early-stage disease in which potentially curative resection and multi-modality therapy. Although adjuvant chemotherapy is the standard practice for patients with stages I-III breast and colorectal cancer, the therapeutic efficacy of adjuvant chemotherapy, following complete surgical resection of early stage NSCLC, has not been fully established. Several prospective randomized trials for patients with early stage NSCLC (stages I-IIIA) have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of patients with T2N0 (stage IB) disease. Two published meta-analyses based on abstracts have estimated a relative risk reduction in mortality of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was based on a pooled analysis of five randomized trials, has demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with completely resected NSCLC. This benefit depended on stage, being greatest in patients with stage II or IIIA disease. This analysis has suggested that platinum-based adjuvant chemotherapy may have no benefit for patients with stage IA and only a marginal benefit for patients with stage IB. Thus, the information available at the current time supports the administration of adjuvant chemotherapy for patients who have undergone complete resection of stages IB-IIIA NSCLC. Further research is needed to define the role of adjuvant platinum-based chemotherapy and its use, in conjunction with chest radiotherapy as the treatment for patients with resected stages IB and IIIA NSCLC.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器外科学会  

DOI： 10.2995/jacsurg.21.467_1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

ATX-s10 is a novel and second-generation photosensitizer for photodynamic therapy (PDT). In order to conduct clinical trials of ATX-s10-PDT and/or extend its clinical applications, it is very important to elucidate the mechanisms of the action of ATX-s10-PDT. We examined the apoptic response against ATX-s10-PDT using a Bcl-2 or Bcl-2 mutant overexpressing cells. Using fluorescent microscopy, ATX-s 10 localized not only to mitochondria but also to lysosomes and possibly other intracellular organelles, but not to the plasma membrane or the nucleus. These results suggest that ATX-s10-PDT can damage mitochondria and lysosomes. By Western blot analysis, ATX-s10-PDT damaged Bcl-2, which localized preferentially at mitochondrial membranes. and caused Bcl-2 to cross-link immediately after laser irradiation. However, ATX-s10-PDT was not able to rapidly induce morphologically typical apoptosis (i.e. chromatin condensation and fragmentation) as PDT using mitochondria targeted photosensitizers, such as phthalocyanine 4 (Pc 4). Pharmacological inhibitions of lysosomal cytokine protease cathepsins, such as cathepsin B and D, protected MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) from apoptosis caused by ATX-s10-PDT. Overexpression of wildtype Bcl-2 or Bcl-2A33-54 resulted in relative resistance of cells to ATX-s10-PDT, as assessed by the degree of morphological apoptosis or loss of clonogenicity. We conclude that lysosomal damage by ATX-s10-PDT can initiate apoptotic response and this apoptotic pathway can be regulated by photodamage to BcI-2 via mitochondrial damage.

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Background and Objectives: We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years. Study Design/Materials and Methods: PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition. Results: Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter. Conclusions: In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT. © 2006 Wiley-Liss, Inc.

DOI： 10.1002/lsm.20346

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Photodynamic therapy (PDT), a treatment for cancer, uses a photosensitizer and laser irradiation to produce reactive oxygen in cells. In Japan, the United States, and many other countries, PDT is a treatment option for stage 0 (TisN0M0) and stage 1 (T1N0M0) centrally located early stage lung cancer. PDT can preserve lung function, can be repeated, and can be combined with other therapeutic modalities such as chemotherapy. Recently, mono-L-aspartyl chlorine e6 (NPe6, Laserphyrin), a second-generation photosensitizer with lower photosensitivity than Photofrin (porfimer sodium), was approved by the Japanese government and a phase 11 clinical study using NPe6 with a new diode laser demonstrated an excellent antitumor effect and low skin photosensitivity. We expect PDT to be widely employed in many fields and the applications of PDT to be extended because of the decreasing cost of laser equipment and lower systemic photosensitivity induced by the photosensitizer. The purpose of this review is to introduce not only recent clinical trials of PDT for centrally located early lung cancer, but also new applications of PDT for cases of peripheral-type, early-stage lung cancers. We also discuss the applications of PDT for advanced lung cancer and combined therapy using PDT and other treatments for lung cancer.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The combination of white light and autofluorescence bronchoscopy has been reported to show better sensitivity in detecting dysplasia and cancer of the bronchus than white light alone. However, fiberoptic bronchoscopy has been replaced by videoendoscopy at most leading facilities for over a decade. To avoid interruption of the videoendoscopy examination to perform fiberscopy-based autofluorescence examination as well as enhancing the sensitivity of intraepithetial lesions, autofluorescence diagnosis system integrated into a videoendoscope (SAFE 3000, Pentax, Tokyo) was created. A total of 154 consecutive patients were studied using this system, containing 83 known or suspected tung cancer cases, 46 of the cases with abnormal sputum cytology findings, 10 follow up cases following lung cancer operations, and 15 heavy smokers with respiratory symptoms. Abnormal. findings were recognized by white light and/or SAFE 3000 at 166 sites and biopsies were taken to evaluate the relationship between endoscopic findings and pathology results. The sensitivity of the system for CIS + dysplasia was 65% in white light and 90% in SAFE. This videoendoscopy-based autofluorescence system had significantly higher sensitivity for intraepithelial lesions than white light videoendoscopy alone. (c) 2006 Elsevier Iretand Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2005.11.009

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DOI： 10.1007/s10147-005-0553-2

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.28.3_166_2

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.28.3_164_2

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：The Japan Society for Respiratory Endoscopy  

It is well known that central type early-stage lung cancer less than 1.0 cm in diameter shows almost 100% CR to photodynamic therapy (PDT). However, we have encountered cases of local recurrence after CR of tumors with a surface diameter less than 1.0 cm. Ninety three patients with 114 lesions were followed up, and cases of recurrence after CR has been obtained with initial tumors that had a diameter less than 1.0 cm were examined. We compared the cytological findings of local recurrence after CR to the cytological findings before PDT. The relationship between the cell features and the depth of bronchial tumor invasion before PDT and on recurrence was evaluated. Recurrences after CR were recognized in 9 out of 77 lesions (11.7%) less than 1.0 cm. When the recurrent tumor cells showed Type I-II at the same site initially treated, CR could be obtained by a second PDT. Type III cells showed the characteristics of tumor cells from deeper layers of the bronchial wall. Local recurrence at the same site may be caused by residual tumor cells from deep layers because of inadequate laser irradiation and penetration. To reduce the recurrence rate, it is essential to accurately grasp the tumor extent and the depth of the bronchogenic carcinoma before performing PDT. Analysis of cell features of recurrent lesions after CR appears to be a useful source of information as to the depth of cancer invasion in the bronchial wall. The description of this manuscript was presented in Chest 2005;128:3269-3275. (JJSRE. 2006;28:620-627)

DOI： 10.18907/jjsre.28.8_620

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER COLL CHEST PHYSICIANS  

Background: It is well known that central-type early stage lung cancer &lt; 1.0 cm in diameter shows almost 100% complete response (CR) to photodynamic therapy (PDT). However, we have encountered cases of local recurrence after CR of tumors with a surface diameter &lt; 1.0 cm.
Patients and methods: Ninety-three patients with 114 lesions were followed up, and cases of recurrence after CR has been obtained with initial tumors that had a diameter &lt; 1.0 cm were examined. We compared the cytologic findings of local recurrence after CR to the cytologic findings before PDT. The relationship between the cell features and the depth of bronchial tumor invasion before PDT and on recurrence was evaluated.
Results: The CR and 5-year survival rates of patients with lesions &lt; 1.0 cm were 92.8% (77 of 83 patients) and 57.9%, respectively; meanwhile, in the group of patients with lesions : 1.0 cm, CR and 5-year survival rates were 58.1% (18 of 31 patients) and 59.3%. There was a significant difference in efficacy between the two groups (p &lt; 0.001). Recurrences after CR were recognized in 9 of 77 lesions (11.7%) &lt; 1.0 cm. When the recurrent tumor cells showed type I-II (low-to-moderate atypia) at the same site initially treated, CR could be obtained by a second PDT. Type III cells (high-grade atypia) showed the characteristics of tumor cells from deeper layers of the bronchial wall. Local recurrence at the same site may be caused by residual tumor cells from deep layers because of inadequate laser irradiation and penetration.
Conclusions: To reduce the recurrence rate, it is essential to accurately grasp the tumor extent and the depth of the bronchogenic carcinoma before performing PDT. Analysis of cell features of recurrent lesions after CR appears to be a useful source of information as to the depth of cancer invasion in the bronchial wall.

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.27.3_189_2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

DOI： 10.1016/S1572-1000(04)00044-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Endoscopic low (Photodynamic therapy (PDT)) or high (vaporization) power laser treatment has been recognized as a lung-sparing local therapeutic modality that can achieve remarkable responses. This paper reviews the experience of our institution since 1978 in the treatment of lung cancer using laser. Endoscopic ablation of tracheobronchial malignancies is mainly intended to reduce respiratory distress and improve quality of life. Effective results were obtained in 143 (81%) of the 177 lesions. PDT is extremely attractive and has been used for the various purposes. In the curative PDT for centrally located early stage lung cancer, complete response (CR) rate was achieved in 86.4% (165 out of 191 lesions). Overall 5-year survival rate was 57.6% and the lung cancer specific 5-year survival rate was 92.5%. With regard to palliative PDT to opening obstructed bronchi in advanced cases, more than 50% opening of the obstruction was accomplished in 75%. Preoperative PDT was performed in 32 patients with lung cancer for the purpose of either reducing the extent of resection or increasing operability. The initial purpose of PDT was achieved in 27 of 32 patients treated. Conversion to an operable condition was achieved in 4 of 5 originally inoperable cases. In 23 of 27 patients who were originally candidates for pneumonectomy, it became possible to reduce the extent of resection to lobectomy or sleeve lobectomy. PDT could be used to treat peripheral tiny lung cancers safely and without unacceptable effects on surrounding tissue. The authors believe that PDT has a great potential and will achieve further development in the future. (C) 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/S1572-1000(04)00008-0

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器外科学会  

DOI： 10.2995/jacsurg.18.374_1

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器外科学会  

DOI： 10.2995/jacsurg.18.392_3

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.26.3_225_1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The role of Bax in the release of cytochrome c from mitochondria and the induction of apoptosis has been demonstrated in many systems. Using immunocytochemical staining, we observed that photodynamic therapy (PDT) with the photosensitiser Pc 4 induced Bax translocation from the cytosol to mitochondria, and the release of cytochrome c from mitochondria as early signalling for the intrinsic pathway of apoptosis in human breast cancer MCF-7c3 cells. To test the role of Bax in apoptosis, MCF-7c3 cells were treated with Bax antisense oligonucleotides, which resulted in as much as a 50% inhibition of PDT-induced apoptosis. In the second approach, Bax-negative human prostate cancer DU-145 cells were studied. Following PDT, the hallmarks of apoptosis, including the release of cytochrome c from mitochondria, loss of mitochondrial membrane potential, caspase activation, and chromatin condensation and fragmentation, were completely blocked in these cells. Restoration of Bax expression in DU-145 cells restored apoptosis, indicating that the resistance of DU-145 cells to PDT-induced apoptosis is due to the lack of Bax rather than to another defect in the apoptotic machinery. However, despite the inhibition of apoptosis, the Bax-negative DU-145 cells were as photosensitive as Bax-replete MCF-7c3 cells, as determined by clonogenic assay. Thus, for Pc 4-PDT, the commitment to cell death occurs prior to Bax activation.

DOI： 10.1038/sj.bjc.6601298

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC PHOTOBIOLOGY  

We have reported that photodynamic therapy (PDT) using the photosensitizer phthalocyanine (Pc) 4 and red light damages the antiapoptotic protein Bcl-2. Recently, using transient transfection of Bcl-2 deletion mutants, we identified the membrane anchorage domains of Bcl-2 as necessary to form the photosensitive target. However, it is not clear how Bcl-2 photodamage sensitizes cells to Pc 4-PDT-induced apoptosis, whether overall cell killing is also sensitized or how upregulation of Bcl-2 in tumors might make them more or less responsive to Pc 4-PDT. In this study we report on MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) overexpressing wild-type Bcl-2 or certain deletion mutants in either a transient or a stable mode. By flow cytometric analysis of transiently transfected cells, we found that wild-type Bcl-2, Bcl-2Delta33-54 and Bcl-2Delta37-63 (each of which can be photodamaged) protected cells from apoptosis caused by Pc 4-PDT. In contrast, Bcl-2Delta210-239, which lacks the C-terminal transmembrane domain and cannot be photodamaged, afforded no protection. We then evaluated the PDT sensitivity of transfected cell lines stably overexpressing high levels of wild-type Bcl-2 or one of the Bcl-2 mutants. Overexpression of wild-type Bcl-2, Bel-2Delta33-54 or Bcl-2Delta37-63 resulted in relative resistance of cells to Pc 4-PDT, as assessed by morphological apoptosis or loss of clonogenicity. Furthermore, overexpression of Bcl-2 also inhibited the activation-associated conformational change of the proapoptotic protein Bax, and higher doses of Pc 4 and light were required to activate Bax in cells expressing high levels of Bcl-2. Many advanced cancer cells have elevated amounts of Bcl-2. Our results show that increasing the dose of Pc 4-PDT can overcome the resistance afforded by either Bcl-2 or the two mutants. PDT regimens that photodamage Bcl-2 lead to activation of Bax, induction of apoptosis and elimination of the otherwise resistant tumor cells.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Photodynamic therapy using the photosensitizer Pc 4 and red light photochemically destroys the antiapoptotic protein Bcl-2 and induces apoptosis. To characterize the requirements for photodamage, we transiently transfected epitope-tagged Bcl-2 deletion mutants into DU-145 cells. Using confocal microscopy and Western blots, wild-type Bcl-2 and mutants with deletions near the N terminus were found in mitochondria, endoplasmic reticulum., and nuclear membranes and were photodamaged. A mutant missing the C terminus, including the transmembrane domain, spread diffusely in cells and was not photodamaged. Bcl-2 missing a-helices 5/6 was also not photodamaged. Bcl-2 missing only one of those a-helices, with or without substitutions of the singlet oxygen-targeted amino acids, behaved like wild-type Bcl-2 with respect to localization and photodamage. Using green fluorescent protein (GFP)-tagged Bcl-2 or mutants in live cells, no change in either the localization or the intensity of GFP fluorescence was observed in response to Pc 4 photodynamic therapy. Western blot analysis of either GFP- or Xpress-tagged Bcl-2 revealed that the photodynamic therapy-induced disappearance of the Bcl-2 band was accompanied by the appearance of bands indicative of heavily cross-linked Bcl-2 protein. Therefore, the alpha(5)/alpha(6) region of Bcl-2 is required for photodamage and cross-linking, and domain-dependent photodamage to Bcl-2 offers a unique mechanism for activation of apoptosis.

DOI： 10.1074/jbc.M205219200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

The human leukemia K562 cell line does not express wild-type p53 protein. Due to the loss of one p53 allele and an insertion mutation in exon 5 of the other allele resulting in a frameshift mutation, K562 cells express a truncated p53 protein of 148 amino acids. A human leukemia phorbol ester-resistant subline, K562/TPA, is cross-resistant to some anticancer agents. A remarkable difference in cell cycle progression at G1/S phase was observed in the synchronised K562/TPA cells as compared with K562 cells. Southern blot and DNA sequence analysis revealed no mutation in exon 5 of the p53 gene in K562/TPA cells. p21(Cip1) expression was also restored in K562/TPA cells confirming that the reversal of this p53 gene mutation restored wild-type p53 function in these cells. This is a unique report describing reversal of p53 gene mutation by drugs. This was associated with the expression of wild-type p53 mRNA and protein in K562/TPA cells. The K562/TPA cell line may provide a very useful tool for the investigation of the relationship between p53 status and chemosensitization.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC PHOTOBIOLOGY  

Photodynamic therapy (PDT) using the second-generation photosensitizer phthalocyanine (Pc) 4 causes mitochohdrial damage and induces apoptosis through the release of cytochrome c to the cytosol. Another protein of the mitochondrial intermembrane space, Smac/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-bindling protein with low pI), is also released to the cytosol in response to apoptotic stimuli and promotes caspase activation by binding IAP. To investigate the possible role of Smac/DIABLO in apoptosis induced by Pc 4-PDT, we transfected Smac/DIABLO (tagged at its C-terminus with green fluorescent protein [GFP]) into MCF-7c3 cells (human breast cancer MCF-7 cells stably transfected with procaspase-3) and DU-145 cells (human prostate cancer cells that express no Bax because of a frameshift insertion mutation). Confocal microscopy showed that recombinant Smac/DIABLO, like cytochrome c, localized to mitochondria and colocalized with MitoTracker Red. Three hours after exposure of MCF-7c3 cells to PDT (200 nM Pc 4 and 150 mJ/cm(2) red light), Smac/DIABLO-GFP, as well as cytochrome c, was found largely in the cytosol. In contrast, for DU-145 cells, both Smac/DIABLO-GFP and cytochrome c remained in the mitochondria after PDT. By staining with Hoechst 33342, typical apoptotic nuclei were observed in MCF-7c3 cells, but not in DU-145 cells, after Pc 4-PDT. These results suggest that the release of Smac/DIABLO from mitochondria may be regulated by a Bax-mediated mechanism and that Smac/DIABLO may cooperate with the cytochrome c-dependent apoptosis pathway. In addition, in MCF-7c3 cells transfected by Smac/DIABLO-GFP, apoptosis induced by Pc 4-PDT was greater than in cells transfected with the GFP vector alone or in untransfected c ells, as determined by flow cytometry. Thus, Smac/ DIABLO promotes apoptosis after Pc 4-PDT in a Bax-dependent manner and may facilitate the passage of PDT-treated cells through the late steps of apoptosis.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

The differential expressions of hundreds of tightly transcriptionally controlled genes in freshly isolated human lung cancers and respective normal lung tissues were analyzed by the cDNA macroarray technique. Three lung cancer patients received pre-operative chemotherapy with cisplatin containing regimens. After chemotherapy, these patients underwent surgery, and poly (A)-RNA expressions of 588 genes in the samples prepared from the lung cancer and normal lung tissues were compared. These expressions of the 588 genes were demonstrated by spotting onto a filter. Histogram analysis of gene expression revealed the tumors to show commonly up-regulated expression of angiogenesis and invasion related genes and adhesion molecules such as fibroblast growth factor 3 (FGFR3), matrix metalloproteinase (MMP)15, 16 and 10, integrin beta4, integrin alpha9, endonexin, and several types of collagens. Thus, post-chemotherapeutic tissues from lung cancer parents are characterized by remarkable up-regulation of molecules related to angiogenesis, invasion and adhesion. Tree view showed close clustering of angiogenesis related genes. Furthermore, when the angiogenesis related genes were selected and clustered, they were categorized into three groups depending upon gene expression profiles. These results suggest that angiogenesis related molecules are suitable candidates for target-based therapeutics and angiogenesis inhibitors are expected to be effective in lung cancer patients pretreated with chemotherapy.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG  

Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate vinorelbine-induced radio sensitization of human small cell lung cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization. A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by vinorelbine using different schedules combining exposure to both. The sensitizer enhancement ratios (SERs) at a cell survival level of 10% were 1.42 +/- 0.21 to 1.33 +/- 0.06, and 1.22 +/- 0.07 depending on schedule. Vinorelbine-induced radiosensitization did not depend on the schedule of the combined exposure. Flow cytometric analyses showed that the cells did not accumulate in the radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with vinorelbine and radiation. The results of an alkaline filter elution assay demonstrated that in the presence of vinorelbine at 1 nM radiation-induced DNA strand breaks were not completely repaired at 24 h postradiation. We conclude that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a possible mechanisms of vinorelbine-induced radiosensitization may at least in part be associated with impairment of DNA repair following radiation-induced DNA damage.

DOI： 10.1007/s00280-002-0430-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate radiosensitization produced by vinorelbine in human non-small cell lung cancer (NSCLC) PC-9 cells and to elucidate the cellular mechanism of radiosensitization. A clonogenic assay demonstrated that PC-9 cells were sensitized to radiation by vinorelbine with a maximal sensitizer enhancement ratio at a 10% cell survival level of 1.35 after 24-h exposure to vinorelbine at 20 nM. After 24-h exposure to vinorelbine at 20 nM, the approximately 67% of the cells that had accumulated in the G2/M-phase were cultured in the absence of vinorelbine and then irradiated at a dose of 8 Gy. Flow cytometric analyses showed prolonged G2/M accumulation concomitant with continuous polyploidization, and induction of apoptosis was observed in the cells subjected to the combination of vinorelbine-pretreatment and radiation. Polyploidization and induction of apoptosis were confirmed by morphological examination and a DNA fragmentation assay, respectively. We concluded that vinorelbine at a minimally toxic concentration moderately sensitizes human NSCLC cells to radiation by causing accumulation of cells in the G2/M-phase of the cell cycle. Prolonged G2/M accumulation concomitant with continuous polyploidization and increased susceptibility to induction of apoptosis may be associated with the cellular mechanism of radiosensitization produced by vinorelbine. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

PDT has been reported to induce cancer cell expression of cytokines, such as IL-6 and TNF-alpha, but it has been unclear whether cytokine expression by cancer cells is directly related to the antitumor effect of PDT. We treated Lewis lung carcinoma (LLC) cells with a new photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) and light from a diode laser and found that expression of the mRNA of IL-2, IL-6, and TNF-alpha was increased by NPe6-mediated-PDT 6 hr later. To elucidate the mechanism of the direct anti-tumor effect of cytokine expression, we examined the photosensitivity of cytokine-gene-transfected cells, namely LLC-IL-2, LLC-IL-6, and LLC-TNF-alpha cells, by MTT assay. The IL-6 gene transfected, LLC-IL-6 cells were significantly more sensitive to cytotoxic effects than the parent LLC cells and other cytokine gene-transfected cells. This Finding indicates that IL-6 expression modulates cellular sensitivity to PDT and that IL-2 and TNF-alpha expressions does not, In addition, the apoptosis of LLC-IL-6 cells induced by NPe6-PDT was greater than in the other cells as determined by DNA fragmentation and staining of apoptotic nuclei. Because IL-6 has been reported to induce apoptosis by downregulating expression of Bcl-2, we analyzed the expression of apoptosis-related Bcl-2, Bax, and cytochrome C by Western blot analysis. Decreased expression of Bcl-2 and cytochrome C was observed in both LLC calls and LLC-IL-6 cells. Bax protein increased in a time-dependent manner, and the ratio of Bax to Bcl-2 rose markedly after PDT in LLC-IL-6 cells, These results suggest that the increased sensitivity of LLC-IL-6 cells to PDT-induced cytotoxicity results from the high ratio of Bax to Bcl-2 in the IL-6-dependent apoptotic pathway, In conclusion, IL-6 expression plays a role in cellular sensitivity to PDT, and combination of IL-6 and PDT may provide a new strategy for cancer treatment. (C) 2001 Wiley-Liss, Inc.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Study Group of Microwave Surgery  

We have examined the possibility of the percutaneous microwave coagulation therapy (PMCT) guided by CT for the lung tumors. Microwave coagulation therapy was performed for the normal lung tissues of beagles and human lung after resection of central type lung cancer in the conditions of power : 20, 40, 60W and treatment time : 1, 2, 3, 4 min at the each power. We investigated the diameter of maximum coagulation area and histopathological changes of normal lung tissue by H-E and Elastica von Gieson stain. Maximum coagulation of 22 mm was obtained in the condition of 60W, 4 min. for the normal lung of beagles and 25 mm was obtained in the condition of 40W, 3 min and 60W, 3 min for the resected normal human lung. Histopathological examination showed the coagulating changes, e. g., small picnotic nuclear, pooling of exudate in alveolar cavity, coiling of elastic fiber, abruption of vessel. In clinical case, we performed PMCT for the patient with lung metastatic tumor 2.0 cm in diameter from colon. More than 90% of tumor necrosis was observed by H. E. stain. Our results showed the utility of PMCT for the inoperable lung tumor or small peripheral lung tumor.

DOI： 10.3380/jmicrowavesurg.19.55

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Other Link： http://search.jamas.or.jp/link/ui/2003054475

Language：English   Publishing type：Research paper (scientific journal)   Publisher：KLUWER ACADEMIC PUBL  

E7070 is a novel sulfonamide antitumor agent that exhibits potent antitumor activity in vitro and in vivo. This compound affects cell cycle progression in human tumor cells. To elucidate the mechanisms by which E7070 inhibits tumor cell growth, we established and characterized an E7070-resistant subline, A549/ER, from a human non-small cell lung cancer cell line A549. Flow cytometric analyses demonstrated an increase in G0/G1 and a decrease in S phase populations in cells treated with E7070 at 20 or 100 mug/ml for 24 h. Longer exposure to E7070, i.e. 48 and 72 h, increased the G2/M phase fraction in A549 cells. These inhibitory actions of E7070 on cell cycle progression were not observed in A549/ER cells. E7070 inhibited the phosphorylation of pRb, decreased expressions of cyclin A, B1, CDK2, and CDC2 proteins, and suppressed CDK2 catalytic activity with the induction of p53 and p21 proteins in A549 cells but not in A549/ER cells. Taken together, these results suggest that E7070 exerts its antitumor effects by disturbing the cell cycle at multiple points, including both the G1/S and the G2/M transition, in human lung cancer cells.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BUSINESS CENTER ACADEMIC SOCIETIES JAPAN  

Most anticancer agents induce cell cycle arrest (cytostatic effect) and cell death (cytotoxic effect), resulting in the inhibition of population growth of cancer cells. When asynchronous cells are to be examined, the currently used flow cytometric method can not provide checkpoint-specific and quantitative information on the drug-induced cell cycle arrest. Hence, despite its significance, no good method to analyze in detail the mechanism of cell cycle arrest and its contribution to overall growth inhibition induced by an anticancer agent has yet been established. We describe in this study the development of a discrete time (Markov model)-based computational model for cell cycle progression/arrest with transition probability (TPi) as a model parameter. TPi was calculated using model equations that include easily measurable parameters such as the fraction of cells in each cell cycle phase and population doubling time. The TPi was then used to analyze checkpoint-specific and quantitative changes in cell cycle progression. We also used TPi in a Monte-Carlo simulation to predict growth inhibition caused by cell cycle arrest only. Human SCLC cells (SBC-3) exposed to UCN-01 were used to validate the model. The model-predicted growth curves agreed with the observed data for SBC-3 cells not treated or treated at a cytostatic concentration (0.2 muM) of UCN-01, indicating validity of the present model. The changes in TPi indicated that UCN-01 reduced the G(i)-to-S transition rate and increased the S-to-G(2)/M and G(2)/M-to-G(1) transition rates of SBC-3 cells in a concentration- and time-dependent manner. When the model-predicted growth curves were compared with the observed data for cells treated at a cytotoxic concentration (2 muM), they suggested that 22% out of 65% and 32% out of 73% of the growth inhibition could be attributed to the cell cycle arrest effect after 48 h and 72 h exposure, respectively. In conclusion, we report here the establishment of a novel method of analysis that can provide checkpoint-specific and quantitative information about cell cycle arrest induced by an anticancer agent and that can be used to assess the contribution of cell cycle arrest effect to the overall growth inhibition.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

A tumor-suppressor gene, p16(INK4) which is deleted or mutated in tumors, regulates cell cycle progression through a G(1)-S restriction point by inhibiting CDK4(CDK6)/cyclin-D-mediated phosphorylation of pRb. We have found that ectopic p16(INK4) expression increased cellular sensitivity of human non-small-cell-lung-cancer (NSCLC) A549 cells to a selective growth-inhibitory effect induced by the topoisomerase-1 inhibitor 11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11) in vitro. In this study, we observed enhanced apoptosis characterized by DNA fragmentation in A549 cells transfected with p16(INK4) cDNA (A549/p16-1) and treated with CPT-11. This apoptosis was suppressed by the inhibitor of interleukin-1 beta-converting enzyme (ICE/caspase-1) or ICE-like proteases, Z-Asp-CH2-DCB, as determined by DNA fragmentation and proteolytic cleavage of poly(ADP-ribose) polymerase, a natural substrate for CPP32/caspase-3, In A549/p16-1 cells, cytosolic peptidase activities that cleaved Z-DEVD-7-amino-4-trifluoromethylcoumarin increased during CPT-11-induced apoptosis and were suppressed by a highly specific caspase-3 and caspase-3-like inhibitor, Z-DEVD-fluoromethylketone. These findings indicate that p16(INK) is positively involved in the activation pathway of the caspase-3 induced by CPT-11. The increased delay in S-phase progression and subsequent induction of apoptosis were observed in CPT-11-treated A549/ p16-1 cells on the basis of DNA histograms. Specific downregulation of the cyclin-A protein level in A549/p16-1 cells was observed after CPT-11-treatment, whereas cyclin B, cdk2, and cdc2 protein levels were unaffected. These results suggest that ectopic p16(INK4) expression inappropriately decreases cyclin A and thereby terminates CPT-11-induced G(2)/M accumulation, which is followed by increased apoptosis in p16(INK4)-expressing A549 cells. Int. J. Cancer 86:197-203, 2000, (C) 2000 Wiley-Liss, Inc.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

UCN-01 (7-hydroxystaurosporine) inhibits the growth of various malignant cell lines in vitro and in vivo. In this study, a human small cell lung carcinoma subline resistant to UCN-01, SBC-3/UCN, was established and characterized. SBC-3/ UCN cells showed 8-fold greater resistance to the UCN-01-induced growth-inhibitory effect than the parent cells, SBC-3. No UCN-01-induced GI accumulation in SBC-3 cells was observed in SBC-3/UCN cells and decreased expression of phosphorylated RE protein was found in SBC-3 cells. Neither basal expression nor induction of p21(Cip1) by UCN-01 treatment was detected in the SBC-3/UCN cell line. An inhibitory effect of UCN-01 on CDK2 activity, which is mediated by p21(Cip1)/CDK2 complex formation upon UCN-01 treatment, was observed in SBC-3 but not in SBC-3/UCN cells. SBC-3/ UCN showed higher CDK6 activity than SBC-3 cells. UCN-01 did not inhibit the CDK4 and CDK6 activities in both cells. We screened the cell cycle regulatory molecules associated with G(1)/S progression and found a remarked decrease in interferon regulatory factor I (IRF-I), which is known to cooperate with p53 in p21(Cip1) induction. Our results suggest that p21(Cip1) regulation via the IRF-I-associated pathway may represent a major determinant of UCN-01-induced growth inhibition in human lung cancer cells. Int. J. Cancer 85:275-280, 2000. (C) 2000 Wiley-Liss, Inc.

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.22.7_578_5

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Language：English   Publisher：The Japan Society for Respiratory Endoscopy  

Photodynamic therapy utilizing Photofrin has proven to be an effective modality that can be used in the treatment of a wide variety of solid tumors and luminal cancers. Over the past decade, 285 patients(338 lesions)with central type lung cancers have been treated in our hospital. Overall complete remission was obtained in 50.3% of the 170 lesions, significant remission in 48.9% and no remission was obtained in 0.8%. However, among 161 early stage lesions CR was obtained in 139(86.3%)and 48 cases were disease free in 2 to 228 months. We have been also studying the new clinical trial to expand the indication of PDT for the treatment of bronchogenic carcinoma. Twenty eight lung cancer patients were received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. The initial purpose of PDT, i.e.either to reduce the extent of resection or convertinoperable disease to operablestatus, was achieved in 24 out of 28 patients treated. We conclude that PDT is efficacious for the advanced bronchogenic carcinoma combined with surgery as well as in the treatment of superficial lung cancer where complete remission may be achieved.

DOI： 10.18907/jjsre.22.8_636

CiNii Books

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Language：English   Publisher：The Japan Society for Respiratory Endoscopy  

DOI： 10.18907/jjsre.22.3_179_2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

Mitogen-activated protein kinase (MAPK) pathway is proposed to be a therapeutic target for cancer cells. In order to find the potential therapeutic usefulness of MAPK for cancer cells, the effect of EAS1, an antisense oligonucleotide for an MAPK, on cancer-cell-growth were investigated in vitro. EAS1 effectively inhibited the growth of several human lung cancer cell lines such as PC-14 cells upon exposure to 10(-0)-10(-1) mu M of EAS1 determined dye-formation (MTT) assay. The ED50 values were comparable to those obtained for the inhibition of MAPK activity, DNA synthesis. EAS1 arrested the PC-14 cells at the G2/M phase of cell cycle followed by apoptosis in a dose-dependent manner. In order to determine the factors which influence the cellular sensitivity against MAPK inhibition, the effect of EAS1 on H-ms-transformed murine fibroblast cells were compared with that on parental cells. The NIH3T3 cells transformed by the H-ms gene (PT22-3) showed higher sensitivity against the effects of EAS1. Because MAPK activity was activated by H-ms gene transfection in PT22-3, the status of the MAPK cascade in cells was the determining factor for the efficacy of EAS1. In addition, cell permeabilization by digitonin enhanced the growth inhibitory effect of EAS1. Penetration of the cell membrane by EAS1 is also crucial for the growth inhibitory effect of EAS1. In conclusion, MAPK is an important target for cancer treatment and MAPK antisense oligonucleotide is a potentially significant antitumor oligonucleotide.

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

胸部CT検査の普及により末梢小型肺癌の増加が著しいが, それらの術前確定診断は困難である。腫瘍径20mm以下の肺末梢小型肺癌の確定診断を細径気管支ファイバースコープを用いた直視下擦過細胞診あるいは, CTガイド下針細胞診を施行し, 確定診断の方法と成績を検討した。対象は1996年から1998年に最終的に肺癌と診断された20mm以下の小型末梢陰影である。腫瘍と気管支の交通の認めた32例に細径気管支鏡下擦過細胞診を行い, また, 交通のない36例にCTガイド下針細胞診を行った。細径ファイバースコープは, 全長140cm, 有効長110cm, 外径2.3mmで, 内径0.8mmの多目的チャンネルを有している。レントゲン透視下に誘導し, 直視下に擦過細胞診を行った。細径気管支ファイバースコープ下径気管支擦過細胞診の診断率は, 84.4%(32例中27例)で, 陰影の大きさは最小1.2×1.2, 最大2.0×2.0(平均1.8×1.8cm)であった。CTガイド下針細胞診の診断率は, 72.2%(36例中26例)で, 大きさは最小0.7×0.7, 最大2.0×2.0(平均1.4×1.4cm)であった。

DOI： 10.18907/jjsre.21.8_558

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KLUWER ACADEMIC PUBL  

7-hydroxystaurosporine (UCN-01) is a new anticancer agent which exerts an inhibitory effect on cell cycle check points and is currently under phase I clinical trials in US and Japan. Preliminary clinical data indicated that UCN-01 remained in plasma at high concentrations for long periods of time. This unavoidable high plasma drug exposure is likely to lead to hematological toxicities in patients. In the present study, cultured human peripheral blood lymphocytes (PBLs) were used to evaluate the possible hematological toxicities of UCN-01 treatment. UCN-01 induces apoptosis, and the induction of apoptosis-related surface markers were also examined to investigate the involvement of these molecules in UCN-01-induced apoptosis in PBLs. in vitro viability of PBLs was decreased by high dose of UCN-01 (25 mu M, 3-day exposure). This effect of UCN-01 was significantly suppressed by the presence of human serum, suggesting that some specific inhibitory factor(s) in human serum may antagonize the lympholytic effect of UCN-01. The percentage of annexin V-positive PI-negative cells increased with exposure to UCN-01 in a time- and dose-dependent manner; by up to 30.3% after exposure to 25 mu M UCN-01 for 3 days. At the same time, the expression of both interleukin-2 receptor (IL-2R, CD25) and Fas (CD95), analyzed by flow cytometry, was induced. Con A-stimulated PBLs were more sensitive to UCN-01-induced apoptosis than non-stimulated lymphocytes and UCN-01 increased the sFas-L released into culture medium from con A-stimulated PBLs. Therefore, lymphocyte depletion mediated by activation-induced apoptosis is likely to occur in patients treated with UCN-01 at high doses.

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Harwood Academic Publishers GmbH  

Laser endoscopic surgery, especially the effectiveness of photodynamic therapy (PDT) using Photofrin as a photosensitizer, has now achieved a status as effective treatment modality for lung cancer. Twenty-six lung cancer patients received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. Bronchoscopical PDT is performed with topical anesthesia approximately 48 h after the intravenous injection of 2.0 mg/kg body weight of Photofrin. Operation was performed 2-9 weeks after initial PDT. The initial purpose of PDT, i.e. either to reduce the extent of resection or convert inoperable disease to operable status, was achieved in 22 out of 26 patients treated. The survival rate of T3 (main bronchus invasion) cases treated by surgery alone increased significantly from 50.9% to 60.0% with the application of preoperative PDT. This remarkable result may imply that this new option of PDT as preoperative laser irradiation may contribute to the management of advanced lung malignancy.

DOI： 10.1155/DTE.5.155

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Harwood Academic Publishers GmbH  

Since 1980, advanced lung carcinomas were treated with palliative laser therapy for the purpose of opening the endobronchial stenosis and obstruction by either photodynamic therapy (PDT) or Nd-YAG laser treatment at Tokyo Medical University. A total of 258 lesions were treated, 81 by PDT and 177 by Nd-YAG laser treatment. PDT achieved effective results in 61 (75%) of 81 lesions. In the Nd-YAG laser group, 143 (81%) of 177 lesions showed effective results. When the tumor was located in the trachea or main bronchi, effective results were obtained in 73% (19 of 26) of cases treated by PDT and in 93% of cases (64 of 69) treated by Nd-YAG laser. However, in cases in which the tumor was located in lobar or segmental bronchi, the tumor response was effective in 76% (42 of 55) of PDT-treated patients and 73% (79 of 108) of Nd-YAG laser-treated patients. With a mortality rate of 0%, the greatest advantage of PDT over Nd-YAG treatment was safety. Considering complications, PDT seems to be useful for obstruction of lobar and segmental bronchus. Nevertheless, when deciding among alternative therapies, physicians treating patients with advanced lung carcinoma should give careful consideration to the benefit and complications of both laser therapies and decide the most suitable modality.

DOI： 10.1155/DTE.5.161

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Language：English   Publisher：The Japan Society for Respiratory Endoscopy  

There has been a dramatic expansion in the role of the bronchoscope as a therapeutic instrument, "Interventional Bronchology", not only for advance bronchogenic carcinoma but also for early cancer. There is now considerable interest in the potential of PDT for treating early bronchial carcinoma. Similarly laser light can be used to detect tumors by fluorescence at an early, and therefore more treatable stage, when they may elude routine bronchoscopy. The total number of early stage lung cancer cases was 107 consisting of 126 lesions, and complete remission was obtained in 85 cases (107 lesions) out of 103 cases (126 lesions, 84.9%) and partial remission in 19 lesions. Eighty patients (98 lesions) were disease free from 2 to 200 months, however, 5 patients died with lung cancer. The survival curve was calculated by the Kaplan and Meier method. The overall survival rate is 68.3%. PDD is another aspect of photodynamic reaction. The effectiveness of a new excimer laser endoscopic imaging fluorescence analyzer system using the photosensitizer for the detection of tumors was evaluated. Autofluorescence (550±10nm, green fluorescence) from normal sites, red fluorescence (670 nm) of chlorine e6 in areas of cancer and the red fluorescence/green fluorescence ratio (R/G ratio) as the color image can be detected respectively. The greatest chlorine e6 fluorescence from the lesion was obtained at 3 hour after injection and the fluorescence disappeared at 24 hours. The greatest difference in the fluorescence of chlorine e6 and the R/G ratio in areas of tumor and in normal areas were observed at 5 hours after administration. At this period, chlorine e6 fluorescence from normal sites was negligible. These data suggest that fluorescence photodiagnosis may effective in the detection of cancers.

DOI： 10.18907/jjsre.20.8_659

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

The contribution of the 5'-flanking sequence of the human gamma-glutamylcysteine synthetase heavy subunit (gamma-GCS(h)) gene to cisplatin-induced transcriptional up-regulation was studied using various human growth hormone reporter constructs which were transfected to a human lung cancer cell line SBC-3. Cisplatin at the concentration of 3 mu M increased the transcriptional activity of the longest sequence from -1,413 to +91 bp of the gamma-GCS(h) gene to 246% of that in non-exposed cells. The distal sequence from -1,413 to -193 bp was shown to negatively regulate transcriptional activity in both cisplatin-exposed and non-exposed cells using deletion and thymidine kinase (TK) promoter-linked constructs. Cisplatin increased the transcriptional activity of the proximal GC-rich sequence from -192 to +91 hp to 340%, of which magnitude was the maximum among deletion constructs. A deletion from -108 to -28 bp, or +34 to +91 bp significantly decreased cisplatin-induced increases in transcriptional activity from 258 to 105%, or 340 to 160%, respectively. When the sequence from -108 to -22 bp, or +26 to +91 bp was linked to the heterologous TK promoter, cisplatin increased the transcriptional activity to 171 or 181%, respectively, from that of 128 or 137%, respectively, in non-exposed cells. These findings indicate that the proximal, sequence from -192 to +91 bp of the gamma-GCS(h) gene, especially from -108 to -28 bp, and +34 to +91 bp, is involved in cisplatin-induced transcriptional up-regulation in SBC-3 cells. (C) 1997 Academic Press.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH MED JOURNAL PUBL GROUP  

The case history is presented of a 61 year old man with von Recklinghausen's disease who developed a spontaneous haemothorax. In spite of being asymptomatic for five days after drainage, he died as a result of fatal sudden re-bleeding. The post mortem examination showed dissection and rupture of the left subclavian artery. Microscopically, disarrangement of smooth muscle and decrease of elastic fibre was observed in the ruptured artery. Haemothorax in patients with von Recklinghausen's disease may require thoracotomy, even if the condition of the patient appears to be stable.

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.18.3_279_3

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Language：Japanese   Publisher：Japan Society for Laser Surgery and Medicine  

Recently, fluorescence detection has been used in diagnosis of lung cancer. In highrisk patients, this method has been especially beneficial for localization of roentgenographically occult lung cancers. The excimer dye laser fluorescence image amalyzer system using Photofrin® as a photosensitizer has been tried for the early detection of lung cancer. With this system both a Photofrin®-specific fluorescence wavelength pat tern and endoscopic image can be seen simultaneously on the same monitor.<BR>Photodynamic diagnosis (PDD) employing this system has performed in 23 cases of lung cancer including 8 cases of caicinoma in situ and 2 cases of vocal coad cancer. Fluorescence was recognized in all cases except one case, however, false positive results were also observed in 10 out of 23 cases with 2 mg/kg of Photofrin®. There are still some problems in this system including improvements widening the angle of divergence of the laser beam and standardization of fluorescence measurement, however, the possibility of photodiagnosis for lung cancer using this system is suggested.

DOI： 10.2530/jslsm1980.17.1_69

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

The right middle lobe is unique because it is surrounded by two other lobes and the pericardium, and it is the smallest lobe. The proper surgical treatment and prognosis for cancer of the right middle lobe has not been definitively established. In order to clarify its prognosis and the best operative technique, 31 surgically treated patients with lung cancer of the right middle lobe were studied clinically and pathologically. The outcome of surgical treatment of the right middle lobe cancer was compared with other locations in the lung. The 5-year survival rate of this group was 51.5%, with a median survival time of 82.3 months. For resectable cases, the outcome for carcinomas of the middle lobe was no worse than for other locations. However the rate of exploratory thoracotomy was highest for the right middle lobe. All five patients with lobectomies are alive and disease free at 26.4-151.4 months. The 5-year survival rate of 23 bilobectomies was 40.0%, with a median survival time of 48.4 months. The difference between lobectomy and bilobectomy cases was statistically significant (P &lt
0.025). When the tumor was limited to the completely separated middle lobe without dissemination, pulmonary or mediastinal lymph node metastasis, lobectomy was sufficient for curative treatment.

DOI： 10.1016/0169-5002(96)00553-3

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PubMed

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器外科学会  

DOI： 10.2995/jacsurg.10.337_4

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.18.3_294_4

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.18.3_233

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