Noninvasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDGPET/CT and CT.

We established patient-like models of lung cancer metastasis by orthotopically implanting human non-small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small-animal computed tomography (CT) and positron-emission tomography-computed tomography (PET/CT) in these models to non-invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non-small cell lung cancer cell lines, A549, FT821 and PC-9, into SCID mice. These mice were then divided into three groups: Control, cis-diamminedichloroplatinum (II) (CDDP) (7-mg/kg CDDP, single administration intraperitoneally), and erlotinib (25 mg/kg erlotinib/day, oral administration 5 days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC-9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18FDG-PET/CT and CT imaging non-invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.


CT lymphography for superficial esophageal cancer. Lymph Node Metastasis in Gastrointestinal Cancer" Part IV. Sentinel node navigation surgery, Chapter 17, Methodology: CT lumphography

Lymph Node Metastasis in Gastrointestinal Cancer. Ed. By Natsugoe S, Springer-Verlag, Tokyo


「がんゲノム医療」によせて

「がんゲノム医療」によせて


Acase of advanced colon cancer arising from a colonic graft foran esophago-bronchial fistula : A case report.

Neoplasm of a colonic graft after esophageal reconstruction is rare. We treated a colon cancer patient who developed malignancy in a colonic graft after esophagectomy and reconstruction through a retrosternal route. A male had undergone esophagectomy in his 50s due to a benign esophago-bronchial fistula. His dysphagia became exacerbated 20 years later, and further examinations showed a circumferential tumor on the esophagocolonic anastomosis. He underwent resection of the colonic graft adenocarcinoma with median sternotomy after neoadjuvant chemotherapy. Gastric tube reconstruction was performed through a retrosternal route. This report should be informative in terms of making decisions from an initial reconstruction to follow-up and choosing a therapeutic strategy for colonic graft cancer in the future. J. Med. Invest. 66 : 190-193, February, 2019.

The Journal of Medical Investigation : JMI


Surgical training in video-assisted neck surgery-based thyroidectomy using fresh frozen human cadavers.

Endoscopic surgery has been introduced in various surgical fields. Endoscopic surgery requires different skills from open surgery due to the restricted surgical field and difficulty in identifying anatomical structures from certain viewpoints. Therefore, surgeons need to undergo sufficient surgical training before performing such surgery in the clinical setting. We examined the utility of fresh frozen human cadavers for surgical training aimed at introducing video-assisted neck surgery (VANS) at our department. First, we performed surgical training using fresh human cadavers four times. Next, we performed hemi-thyroidectomy with VANS in 5 clinical patients. After the cadaver training and the actual surgery, the surgeons evaluated each step of the surgical procedure using a 3-point scale. In the cadaver training, the scores for steps : creation of a subcutaneous tunnel and lifting up the skin flap and pre-thyroid muscles were higher than other steps. And a tracheal injury occurred as a complication. However, we were able to recognize anatomical structures under the endoscopic view. And it was also useful for confirming the role of surgical staff and simulating the placement of surgical equipment. Surgical training using fresh frozen human cadavers was effective at introducing a new surgical method. J. Med. Invest. 66 : 293-296, August, 2019.


Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum

Video-assisted thoracoscopic surgery (VATS) and robotic surgery are minimally invasive surgeries for mediastinal parathyroid adenomas. However, a transthoracic approach is often difficult in the cervicothoracic transition area because of the limited visual field. We report a novel minimally invasive surgery for an ectopic parathyroid adenoma in the middle mediastinum using a cervical approach under a pneumomediastinum.

Seminars in Thoracic and Cardiovascular Surgery


Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum.


Selective lobar blockade for lung resection : A report of two cases

選択的肺葉ブロックを用いた肺切除の2例

There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8．5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.


The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.


A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.

Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.


A case of painful Hashimoto s thyroiditis with difficulty of different from subacute thyroiditis

亜急性甲状腺炎との鑑別が困難であった橋本病急性増悪の1例

橋本病急性増悪は，橋本病に急性炎症症状を伴う稀な疾患である．今回，亜急性甲状腺炎と鑑別が困難であった橋本病急性増悪の1例を経験したので報告する．症例は14歳，女性．2年前に学校検診で橋本病と診断された．1年10カ月前に甲状腺腫大増悪，頸部右側の圧痛を認めた．血液検査所見では，甲状腺機能正常であり，抗Tg抗体277IU/mL，抗TPO抗体246IU/mLと高値であった．白血球，CRPは正常値であり，赤沈の軽度亢進を認めた．亜急性甲状腺炎もしくは橋本病急性増悪が疑われ，NSAIDsが投与された．しかし，頸部疼痛が改善せずprednisolone(PSL)投与が開始された．治療中，疼痛部位は移動した．また，血液検査所見で自己抗体値が低下したため，亜急性甲状腺炎の可能性も否定できなかった．PSL投与後，症状は軽減したが，PSL漸減で疼痛が再燃し，PSL中止が困難であった．再燃を繰り返すことから橋本病急性増悪と診断した．PSLの離脱困難なため手術の方針となり，甲状腺全摘を行った．

Official Journal of the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery

日本内分泌・甲状腺外科学会雑誌


Ipsilateral shoulder pain in patients following lung resection in the decubitus position

Aims and objectives: To examine the frequency, influencing factors and clinical course of shoulder pain in patients following lung resection. Background: Thoracoscopes have been introduced in the surgical treatment of lung cancer and allow for less invasive surgery with a minimal incision. However, decubitus position-related shoulder pain on the operated side has not yet been investigated. Design: A longitudinal descriptive study. Methods: Patients who underwent lung resection in the decubitus position. Patients were interviewed 2 days before surgery and once daily for 5 days after surgery. Interview items included background data, the concomitant use of epidural anaesthesia, operative duration, the presence of preoperative shoulder stiffness (excluding shoulder pain), type of surgery and site of operation. The intensity of pain was approximately 5 on an 11-point numerical rating scale. Descriptive statistics on patient backgrounds were obtained using SPSS Statistics 22 for Windows. Results: Of the 74 patients who underwent lung resection in a decubitus position, 30 (40.5%) developed shoulder pain on the operated side. The highest rating occurred 1 day after surgery and decreased over time. The following two factors were found to influence shoulder pain on the operated side: operative duration (Z = 2.63; p = .01) and the presence of preoperative shoulder stiffness (excluding shoulder pain) (X2= 4.16; p = .04). Conclusions: This study demonstrated that approximately 40% of patients who underwent lung resection in the decubitus position developed shoulder pain. Relevance to clinical practice: The presence of postoperative shoulder pain was related to both the duration of the operation and to the presence of preoperative shoulder stiffness. Although the shoulder pain resolves within 4 days, it causes the patient additional discomfort and distress. Therefore, further research is needed on positioning for thoracotomy in order to investigate ways to reduce or eliminate this complication of lung surgery.


Surgical treatment of locally advanced papillary thyroid carcinoma after response to lenvatinib

Differentiated thyroid carcinomas (DTC) have good prognoses after complete resection. Nevertheless, when DTC is associated with an aerodigestive invasion, curative surgery is difficult to perform. However, there is no established neoadjuvant therapy for advanced DTC. A 73-year-old man with thyroid papillary carcinoma was referred to our hospital. A computed tomography examination revealed a tumor in the upper right lobe of the thyroid, and multiple bilateral enlarged lymph nodes in the neck, involving the surrounding structures. The enlarged lymph node at the right upper neck was suspected to have invaded the right internal jugular vein, and the left paratracheal lymph node was suspected to have invaded the cervical esophagus and trachea. The tumor was considered resectable; however, surgery would have been highly invasive. Therefore, we initiated neoadjuvant therapy with lenvatinib. After administration of lenvatinib, the tumor decreased in size by 84.3% and the cervical lymph nodes by 56.0%. The patient underwent a total thyroidectomy, modified neck dissection, a resection of the muscular layer of the esophagus, and a tracheal sleeve resection and reconstruction. The SELECT trial demonstrated that lenvatinib had high response rate with short response time, in patients with radioiodine-refractory DTC. The results suggested that lenvatinib could be effective as neoadjuvant therapy. For an advanced DTC that requires removal through invasive surgery, preoperative lenvatinib treatment might be one of the options for a less invasive surgery.

International Journal of Surgery Case Reports


A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.


A case of atypical type A thymoma with vascular invasion and lung metastasis

We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.

General Thoracic and Cardiovascular Surgery


Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.


Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue : Report of a Case

悪性胸膜中皮腫に合併した難治性気胸に対し胸腔内フィブリン糊注入療法が有効であった1例

The Japanese Journal of Thoracic Surgery


Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.


Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.


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

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

European Journal of Cardio-Thoracic Surgery


Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus


肺癌手術における周術期口腔機能管理の術後肺炎予防効果

肺癌手術における周術期口腔機能管理の術後肺炎予防効果

The Journal of the Japanese Association for Chest Surgery


外科診療におけるチーム医療の現況と展望 4．周術期の口腔ケア-食道癌，肺癌手術における周術期口腔機能管理-


Surgical resection after BEP therapy induced interstitial pneumonia during treatment for primary mediastinal malignant germ cell tumor

縦隔原発悪性胚細胞性腫瘍に対するBEP療法中に発症した間質性肺炎治療後に手術を施行した2例

The incidence of interstitial pneumonia caused by bleomycin is increasing, dependent on the total dose. Care should be taken in the treatment of a germ cell tumor requiring high-dose administration. If interstitial pneumonia occurs during treatment for a primary mediastinal malignant germ cell tumor, it may influence the subsequent surgical treatment. We report two surgical cases of interstitial pneumonia that occurred during BEP (bleomycin+etoposide+cisplatin) therapy for a primary mediastinal malignant germ cell tumor. Case 1 was a 19-year-old man and case 2 was a 24-year-old man. They both had an anterior mediastinal tumor of around 10 cm in diameter that was diagnosed as a yolk sac tumor by needle biopsy, and received BEP therapy. Interstitial pneumonia occurred at total bleomycin doses of 360 and 330 mg, respectively. They received steroid pulse treatment 103 and 109 days after starting therapy, respectively. Thereafter, they received steroid maintenance treatment by oral administration. Because they showed the improvement of interstitial pneumonia on imaging examinations, they received residual tumor resection and partial resection of the lung 17 and 26 days after starting steroid pulse treatment, respectively. Both post-operative courses were good, without the onset of respiratory failure.

ブレオマイシンによる間質性肺炎は総投与量依存性に頻度が増加する．高容量投与が必要となる縦隔胚細胞性腫瘍において，治療中に間質性肺炎を生じた場合は，その後の手術にも影響がおよぶ可能性がある．今回BEP(bleomycin+etoposide+cisplatin)療法中に生じた間質性肺炎を治療し，早期に手術を施行した2例を報告する．症例1は19歳の男性，症例2は24歳男性で，ともに前縦隔に約10 cmの腫瘍を認め，針生検で卵黄囊腫瘍と診断された．BEP療法を開始し，それぞれ，ブレオマイシン総投与量360，330 mgで間質性肺炎を発症した．化学療法開始103日目，109日目から3日間のステロイドパルスを行い，その後内服で維持療法を行った．画像上，間質性肺炎の改善を認めたため，手術はパルス療法開始後17日目と26日目に残存腫瘍切除と肺部分切除を行った．ともに術後呼吸不全の発症なく経過良好であった．


A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy

A 62-year-old man was admitted to our hospital for squamous cell lung carcinoma. We performed video-assisted right pneumonectomy after the induction chemoradiation therapy. We used portable thoracic drainage systems: Thopaz® and 19-Fr blake drain®. The patient had a severe cough and showed progressive subcutaneous emphysema. Thopaz® showed little air leakage. We confirmed the absence of a fistula at the bronchial stump via bronchoscopy and the absence of air suction from outside the drainage tube. We removed the thoracic drain because we believed Thopaz® caused the subcutaneous emphysema, and the subcutaneous emphysema subsequently fully resolved.

Thopaz® regulates the mean intrathoracic pressure by supplying air to the thoracic cavity when there is an excessive negative intrathoracic pressure. The mechanism of the increased subcutaneous emphysema by Thopaz® was considered as follows: sudden elevation of the intrathoracic pressure caused by the cough moved intrathoracic air into the subcutaneous space, instead of the blake drain®. Thopaz® supplied air into the thoracic cavity to restore the excessive negative intrathoracic pressure. This cycle was repeated and the subcutaneous emphysema worsened.

症例は62歳男性．右肺扁平上皮癌にて術前放射線化学療法後に胸腔鏡補助下右肺全摘術(ND2a-2)を施行した．ポータブル型胸腔ドレナージ装置であるThopazⓇ(トパーズ)にblakeドレーンⓇをつなげて術後胸腔内ドレナージした．術後，咳嗽が多く認められ，皮下気腫が増加した．トパーズのエアリーク表示量はほぼ0 ml/分であった．気管支鏡で気管支断端瘻がないことを確認した．トパーズのドレナージトラブルと判断し，ドレーン抜去すると皮下気腫は軽快した．トパーズには胸腔内圧調節機能があり，胸腔内が過陰圧になるとバルブが開き空気を吸い込ませる機能がある．本症例では咳嗽による急激な胸腔内圧上昇時に胸腔内の空気が皮下に漏れ，その結果起こった胸腔内圧の低下を感知したトパーズ経由で胸腔内へ空気が流入するという機序を繰り返したと考えられた．

The Journal of the Japanese Association for Chest Surgery


A case report of perivascular epithelioid cell tumor of the lung: A benign tumor with intense FDG uptake

FDG-PET/CT陽性を示した肺原発良性血管周囲類上皮細胞腫瘍の1例

The patient was a 36-year-old who was undergoing follow-up observation after a mediastinal mass was identified during a physical examination at a local clinic 3 years earlier. Over time, the mass showed a tendency to grow, and so the subject consulted our hospital for close examination and treatment. Chest CT revealed a mass shadow of 36 mm in the left middle mediastinum, and FDG-PET/CT revealed FDG uptake with an SUVmax of 4.93 at the same site. On suspicion of a mediastinal tumor such as a thymoma, video-assisted thoracoscopic surgery was performed; however, the lesion was a sessile intrapulmonary tumor. Rapid pathological diagnosis revealed low-grade malignancy, and left upper segmentectomy was performed. The postoperative pathology results led to the diagnosis of a benign perivascular epithelioid cell tumor (PEComa). PEComa is a rare condition, for which there are very few reports using PET/CT. We report a case of benign PEComa that showed elevated FDG uptake.

症例は36歳女性．3年前より近医の検診で縦隔腫瘤が疑われ，経過観察を行っていた．継時的に増大傾向を示し，精査加療目的に当院受診となった．胸部CTで左中縦隔に36 mmの腫瘤影を認め，FDG-PET/CTにて同部位にSUVmax 4.93の集積を認めた．胸腺腫などの縦隔腫瘍を疑い胸腔鏡下手術を施行したが，病変は広基性な肺内腫瘍であった．迅速病理にて低悪性度腫瘍の結果であり左肺上大区切除を行った．術後の病理結果より良性血管周囲類上皮細胞腫瘍(benign perivascular epithelioid cell tumor:PEComa)と診断した．PEComaはまれな疾患であり，PET/CTを使用した報告は極めて少ない．FDGの集積亢進を認めた良性PEComaの1例を報告する．


A case of aplastic anemia after thymothymectomy

胸腺腫摘出術後発症した再生不良性貧血の1例

Thymoma often leads to complications such as autoimmune disease, and symptoms of autoimmune disease are sometimes observed in patients even after thymothymectomy. Here, we encountered a case of aplastic anemia after thymothymectomy. A 73-year-old woman was admitted to our hospital for the treatment of an anterior mediastinal tumor. We performed thymothymectomy by median sternotomy. Histopathological findings showed type B1 thymoma when classified according to the World Health Organization system, and stage I thymoma when classified according to the Masaoka system. Six months after the surgery, the patient had pneumonia, and her hemogram showed pancytopenia; however, it had been normal before surgery. Puncture of the bone marrow showed the presence of fatty marrow, a cell density of 10-20%, and a myeloid/erythroid ratio of more than five. The patient was diagnosed with a very severe grade of aplastic anemia. Cyclosporine and supportive therapy were administered. However, the patient died of multiple organ failure 4 months after the onset of aplastic anemia.

The occurrence of aplastic anemia after thymothymectomy is a very rare complication. However, this complication is likely to be fatal since the patient becomes immunocompromised. Therefore, it is important to be careful regarding not only the recurrence of thymoma in the patient, but also the occurrence of autoimmune disease during follow-up after thymothymectomy.

胸腺腫には自己免疫性疾患が合併しやすく，時に胸腺腫摘出後に症状が顕在化することがある．胸腺腫摘出後に再生不良性貧血を発症した症例を経験したので報告する．

73歳，女性．前縦隔腫瘍にて紹介され，胸骨正中切開で胸腺胸腺腫摘出術を施行した．正岡分類I期，WHO分類はB1であった．術後半年後，肺炎を発症した．術前には正常範囲内であった血液検査で，汎血球減少を認めた．骨髄穿刺にて骨髄の細胞密度は10∼20%，脂肪髄かつ骨髄球/赤芽球の比は5以上であった．Grade 5の再生不良性貧血と診断した．シクロスポリンAを中心とした加療を行ったが，発症4ヵ月後に多臓器不全にて永眠された．

胸腺腫摘出後の再生不良性貧血は非常に稀な病態であるが，易感染性となり致死的となりうる．胸腺腫摘出後の経過観察の際には再発のみならず，自己免疫疾患の合併にも注意を必要とする．


A randomized, open label study of the efficacy of prophylactic 24-h low-dose landiolol for atrial fibrillation in transthoracic esophagectomy


Indocyanine Green Fluorescence Intraoperative Imaging for Hepatic Hydrothorax With a Small Diaphragmatic Defect

Seminars in Thoracic and Cardiovascular Surgery


有瘻性膿胸に対してEWS を用いた気管支充填術と瘻孔内フィブリン糊注入 の併用が有効であった1例


肺アスペルギローマ術後肺瘻に対してPushampSlide法とロープウェイ法を応用したEWS による気管支充填術が有用であった1例


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

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

Annals of Thoracic and Cardiovascular Surgery


Effects of perioperative oral management in thoracoscopic lung lobectomy : Retrospective study

胸腔鏡下肺葉切除術における周術期口腔機能管理の効果に関する検討―後ろ向き研究―


Primary Pulmonary Synovial Sarcoma Showing a Prolonged Survival with Multimodality Therapy

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


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

肺癌・食道癌の周術期における口腔ケアの現状とその効果

The Japanese Journal of Thoracic Surgery


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

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

The Journal of Medical Investigation : JMI


急速に増大する巨大気腫性肺囊胞に対して囊胞内吸引後にEWSとフィブリン糊注入で軽快した1例

The Journal of the Japan Society for Respiratory Endoscopy


胸腔鏡下右上葉切除術の手術時間に影響する因子の検討

胸腔鏡下右上葉切除術の手術時間に影響する因子の検討

The Journal of the Japanese Association for Chest Surgery


Chest Wall Metastasis of Anaplastic Lymphoma Kinase-positive Lung Adenocarcinoma 22 Years After Lobectomy

肺葉切除22年後に胸壁転移を認めたALK融合遺伝子陽性肺癌の1例

Background. When a new tumor appears after a long period of remission following surgery for lung cancer, it is difficult to determine whether the tumor is a recurrence or a new tumor. We herein report a case of a chest wall tumor that developed 22 years after pulmonary lobectomy diagnosed by an anaplastic lymphoma kinase (ALK) gene mutation. Case. An 80-year-old man underwent left-lung upper lobectomy for lung adenocarcinoma (pT4N2M0 Stage III) 22 years prior. We treated him with adjuvant chemotherapy after the surgery and did not detect a recurrence for 10 years. However, we noticed a chest wall mass 22 years after the surgery and diagnosed it by a biopsy as adenocarcinoma. The new specimen was stained with anti-thyroid transcription factor-1 (TTF-1) and anti-ALK antibodies, and the pathological specimen from the first surgery was also stained with anti-ALK antibody. We therefore diagnosed the chest wall tumor as a recurrence of the lung adenocarcinoma. We treated him with crizotinib, and the tumor shrank. However, we stopped the treatment because of the development of drug-induced interstitial pneumonia. We switched him to a platinum combination regimen, and follow-up is ongoing. Conclusions. When a lesion is suspected to be a recurrence long after surgery, an examination of gene mutations, such as that of ALK, may be useful.

背景．肺癌術後に長期間無再発生存し，遠隔臓器に病変の出現を認めた場合，再発であるか新規病変であるのかを判断するのは困難である．今回われわれは肺葉切除の22年後に出現した胸壁腫瘍に対し，anaplastic lymphoma kinase(ALK)融合遺伝子を検索することにより肺癌の胸壁転移と診断した1例を経験したため，報告する．症例．80歳男性．58歳時に肺腺癌(pT4N2M0 Stage III)に対して左肺上葉切除術を施行した．術後補助化学療法を行い，10年間再発を認めず経過観察を終了した．術後22年目に前胸部の無痛性腫瘤が出現し，生検で腺癌の所見であった．TTF-1陽性，ALK融合遺伝子陽性から肺腺癌の転移が疑われ，初回手術の病理標本もALK融合遺伝子陽性であったことから，胸壁転移と診断した．Crizotinibにて治療し腫瘍は縮小したが，薬剤性間質性肺炎を発症し中止した．プラチナ併用レジメンに変更して加療し，現在も経過観察を継続している．結論．術後遠隔期に再発転移を疑う病変が出現した場合，病理組織診断に加えALK融合遺伝子などの遺伝子変異検索を行うことで診断に至る可能性がある．


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

Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs. J. Med. Invest. 63: 149-151, February, 2016.


Acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer : Analysis of two cases

発症予測が困難であった肺癌術後間質性肺炎急性増悪の2例

Acute exacerbation of interstitial pneumonia (IP) is one of the most severe and fatal postoperative complications in lung cancer patients underlying IP. We treated two patients suffered from acute exacerbation of IP after pulmonary resection for lung cancer. We analyzed their clinical findings. Thoracoscopic lobectomy with mediastinal lymph node dissection was performed in these cases. The patients were diagnosed with acute exacerbation 4 or 5 days after operation and treated with steroids. Both patients had not been diagnosed as IPs before surgery, however, IPs were diagnosed by retrospective analysis of pathological examination for the removal lungs. Chest CT before surgery showed an interstitial shadow in the lung field faintly in these cases. It should be considered that patients who show a faint interstitial shadow in chest CT could potentially cause an acute exacerbation of IP after lung cancer operation.


Utility of respiratory-gated small-animal PET/CT in the chronologic evaluation of an orthotopic lung cancer transplantation mouse model.

Our aim in this study was to clarify the effects of respiratory-gated PET in the evaluation of lung cancer according to the (18)F-FDG uptake in an orthotopic transplantation mouse model. We created such a model, and we performed PET/CT. The mice were divided into two groups according to tumor volume: a small-tumor group (<20 mm(3)) and a large-tumor group (>20 mm(3)). We reconstructed the following conditions based on list-mode data: non-gated (3D) images and gated (4D) images, divided based on the respiratory cycle (expiration phase, stable phase, and inspiration phase). We calculated the maximum standardized uptake values (SUVmax) in each phase. We used the % difference [= (4D SUVmax - 3D SUVmax)/3D PET SUVmax × 100 (%)] to evaluate the differences in the 4D SUVmax and 3D SUVmax. The 4D SUVmax values were significantly higher than the 3D SUVmax, regardless of the tumor size. The % difference for the small tumors was greater than that for the large tumors, and it was highest in the stable phase. We conclude that the SUVmax in the stable phase under respiratory-gated PET are the most reliable. The SUVmax observed under non-gated PET are considered to be more frequently underestimated in cases involving small tumors than in those involving large tumors. In the chronologic study evaluating the time course of tumor development, the size of the tumor is small in early stage, and respiratory-gated PET is effective in reducing the underestimation of such tumors caused by respiratory motion.


甲状腺未分化癌に対するsorafenibによる治療経験

甲状腺未分化癌に対するsorafenibによる治療経験

Official Journal of the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery

日本内分泌・甲状腺外科学会雑誌


人工呼吸器管理中の慢性有瘻性膿胸に対してEWSを用いた気管支充填術を施行した1例


肺癌の術中胸膜浸潤診断の正確性についての検討

肺癌の術中胸膜浸潤診断の正確性についての検討


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

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


Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.

This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.

Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion.


Evaluation of Powered ECHELON FLEX for pulmonary lobectomy

肺葉切除における電動式自動縫合器の使用経験

Objective : It has been accepted to use staplers for open and video-assisted thoracic surgery, however there was a risk in stapling of the pulmonary vasculatures. A newly developed stapler, powered ECHELON FLEX (Ethicon) is an electrically-powered stapler. It may reduce tip movement during cutting and stapling, which results in reduction of the risk of trauma to surrounding tissue. The aim of this study was to evaluate powered ECHELON FLEX for pulmonary lobectomy. Methods : We reviewed 16 patients who underwent pulmonary lobectomy with powered ECHELON FLEX in our institution from December, 2013 to April, 2014. Results : There were 25 stapling for the pulmonary artery, 17 stapling for the pulmonary vein, 16 stapling for the bronchus, and 33 stapling for the pulmonary parenchyma. Though two case of oozing from the stamps of a pulmonary artery and pulmonary parenchyma, there were no serious complications related to use of the staplers. Conclusions : The powered ECHELON FLEX can be used for pulmonary lobectomy safely.


Setting of fees for robotic surgery for lung cancer not covered by insurance

肺癌ロボット手術の私費料金設定

In Japan, the only robot surgery covered by health insurance is prostatectomy. Robot surgery for pulmonary cancer has not been approved as advanced health care, and hospitals are required to set out-of-pocket fees for surgery on their own. We calculated the fee not covered by insurance to be 1.28million yen, taking into account expenses for : (1) the use of medical equipment, (2) maintenance, (3) labor costs, and (4) medical materials and drugs. Since the fees for surgery plus hospitalization are actually incurred by patients, whether or not the hospitalization fee should be included in out-of-pocket medical fees is decided by each health care institution. In any case, it is necessary to provide patients with a summary of medical fees prior to surgery. Hospitals are required to collect data on pulmonary robot surgical cases while operating the system with medical fees incurred by individual patients.


[Sentinel node identification of lung cancer].

【いますぐ役立つ診断・治療デバイス】 呼吸器領域 肺癌におけるセンチネルノード同定(解説/特集)

Sentinel node identification is important for small-sized non small cell lung cancer patients who are candidates for segmentectomy in determining their eligibilities. Intraoperative sentinel node identification using indocyanine green or preoperative computed tomography lymphography by transbronchial injection of iopamidol are suitable for daily medical practices, because these methods take about only 10 minutes to identify sentinel nodes in addition to routine surgical or bronchoscopic procedures.

The Japanese Journal of Thoracic Surgery


特集:Sentinel node navigation surgery Ⅱ．各論 3．肺癌におけるsentinel node navigation surgery


Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [18F] FDG PET-CT.

Positron emission tomography-computed tomography (PET-CT) with [18F] fluorodeoxyglucose (FDG) has recently been applied for evaluating tumor response to anticancer therapy. The aim of the present study was to evaluate the utility of FDG PET-CT in monitoring non-invasively and repeatedly the inhibitory effect of cisplatin (CDDP) on an orthotopic lung cancer model. Validation of in vivo FDG uptake in human lung cancer Ma44-3 cell line in an orthotopic SCID mouse model was carried out. Next, we assessed the use of FDG PET-CT to monitor the response of orthotopic lung cancer to the anticancer effect of CDDP. SCID mice were divided into the CDDP group (7 mg/kg single dose intraperitoneally) and the control group. Tumor volume and maximal standardized uptake value (SUV max) were calculated for all mice. All mice were sacrificed for histopathologic analysis. Validation of FDG PET-CT showed that tumor volume and SUV max were significantly correlated with postmortem tumor length measured in specimens (P=0.023) and (P=0.012), respectively, and there was a significant correlation between SUV max and tumor volume (P=0.048). Response monitoring showed that significant growth inhibition by CDDP in the form of SUV max of the CDDP group was significantly lower than that of the control group on day 8 (P=0.02) and on day 13 (P=0.003). Tumor volume of the CDDP group was significantly lower than that of the control group on day 13 (P=0.03). The present study supports using FDG PET-CT in monitoring tumor progression and therapeutic response of lung cancer in an orthotopic model non-invasively and repeatedly.


Methylation and expression profiles of MGMT gene in thymic epithelial tumors

A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.


Demonstration of the skip metastasis pathway for N2 non-small cell lung cancer.

Journal of Thoracic and Cardiovascular Surgery


Usefulness of lymphangiography with near infrared fluorescence system in treatment of postoperative chylothorax

乳び胸治療における近赤外蛍光システムを用いたリンパ官造影の有用性


進行肺癌に合併した続発性気胸に対する胸腔内フィブリン糊注入療法の経験

進行肺癌に合併した続発性気胸に対する胸腔内フィブリン糊注入療法の経験

The Journal of the Japanese Association for Chest Surgery


Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model.

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20 mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO(®)) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model.

The Journal of Medical Investigation : JMI


Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation

Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.

European Journal of Cardio-Thoracic Surgery


18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.

OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.


Fluoroscopy-assisted thoracoscopic resection after computed tomography-guided bronchoscopic metallic coil marking for small peripheral pulmonary lesions.

OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of <20 mm diameter according to our treatment protocol from September 2004. RESULTS: We could install coils in the objective bronchi in all cases. The average time required for the marking procedure was 38.9 (15-120) min. Pneumothorax was recognized in 1 (1.7%) case as a complication, but no fatal complications occurred. We could also install coils for each lesion in 4 cases (9 lesions) with multiple lesions. In 14 cases with the VBN system, the examination time and CT number were significantly reduced (P < 0.05 and <0.001, respectively), compared with those of 40 cases without the VBN system. The average interval between the CM and the operation was 5.6 (0-30) days. We never experienced a case of migration preoperatively. Sixty-two (98.4%) lesions were definitively identified, and WWRs were performed using three trocars in 58 (92.1%) cases during thoracoscopic surgery. Lobectomy was initially performed in only 1 case owing to coil migration. Thirty-seven of 40 cases (92.5%) were in line with the treatment protocol. There were no local-regional recurrences in all cases undergoing WWR. CONCLUSIONS: We could prospectively show that our method was suitable to perform WWR with a sufficient margin for small GGO lesions of <20 mm. Moreover, we reconfirmed that the advantages of our method were safety, permitting flexibility in scheduling operations and a high ability to deal with multiple lesions. Additionally, our method became a minimally invasive and mature technique by using a new VBN system.


Therapeutic hypothermia for severe cerebral air embolism complicating pleural lavage for empyema.

Cerebral air embolism during pleural lavage is a rare, but potentially fatal complication. We present a case of severe cerebral air embolism that developed during pleural lavage for empyema and was successfully treated by therapeutic hypothermia. A 77-year old male patient with empyema developed severe cerebral air embolism during pleural lavage via a chest tube. Cranial computed tomography and cranial magnetic resonance imaging showed many small bubbles and widespread infarction in the territory of the right middle cerebral artery. The patient received therapeutic hypothermia maintained at 33°C for 24 h and could leave the hospital without delayed sequelae.

Interactive Cardiovascular and Thoracic Surgery


内科的治療抵抗性の乳児気管支肉芽に対してHo:YAGレーザー焼灼術を施行した1例

The Journal of the Japan Society for Respiratory Endoscopy


当科における気管支鏡検査へのLung pointの経験

当科における気管支鏡検査へのLung pointの経験


YAGレーザー使用時の気管支鏡破損の1例

YAGレーザー使用時の気管支鏡破損の1例


Computed tomography lymphography by transbronchial injection of iopamidol to identify sentinel nodes in preoperative patients with non-small cell lung cancer : A pilot study

The objective of the present study was to assess the safety and feasibility of computed tomography lymphography by transbronchial injection of a water-soluble extracellular computed tomography contrast agent. From April 2010 to May 2011, patients with clinical stage I non-small cell lung cancer who were candidates for lobectomy were enrolled in the present study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. Computed tomography images of the chest were obtained 0.5 and 5 minutes after 2 or 3 mL of iopamidol was injected through a microcatheter. Sentinel nodes were identified when the maximum computed tomography attenuation value of the lymph nodes on the postcontrast computed tomography images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. The ultrathin bronchoscope could access the targeted bronchus, and iopamidol was delivered into the peritumoral area in all 13 patients without any complications. Sentinel nodes were identified in 12 (92.3%) of the 13 patients. The average number of sentinel nodes was 1.5 (range, 1-2). Pathologic examination revealed metastatic lymph nodes in 2 patients. Metastatic nodes were included with the sentinel nodes. Computed tomography lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify the sentinel nodes in patients with clinical stage I non-small cell lung cancer.

Journal of Thoracic and Cardiovascular Surgery


A Pediatric Case of Removal of a Bronchial Foreign Body Using a Laryngeal Mask Airway

摘出時にラリンジアルマスクを使用した小児気管支異物の1例

Background. We report a pediatric case of remove of bronchial foreign body using a laryngeal mask airway and flexible bronchoscopy. Case. A 18-month-old girl accidentally inhaled a peanut. Afterwards she entered another hospital with a chief complaint of wheezing and received antibiotic treatment. On the next day, an abnormal shadow was pointed out, which was suspected to indicate a foreign body, in the left main bronchus. Chest computed tomography (CT) scan was carried to our hospital. On the same day, after the airway was cleared using a laryngeal mask airway (LMA size 2.0) under general anesthesia, a flexible bronchoscope (external diameter 4.0 mm) was inserted. The foreign body was successfully removed with a balloon-tip catheter. The foreign body was a peanut. Conclusion. By using a laryngeal mask airway, we could maintain available ventilation and enable a smooth procedure using a flexible bronchoscope while removing a pediatric bronchial foreign body.

背景.摘出時にラリンジアルマスクを使用した小児気管支異物の1例を経験したので報告する.症例.1歳6カ月の女児.ピーナッツを食べた際に誤嚥.その後,喘鳴が出現し,前医に入院.抗菌薬を投与されていたが,翌日施行された胸部CTにて気管支異物を疑われ,当院に搬送された.CTにて左主気管支に異物と思われる陰影を認め,気管支異物と診断し,同日全身麻酔下に異物除去を施行した.ラリンジアルマスク(サイズ2.0)を使用して気道を確保した後,外径4.0mmの軟性気管支鏡を挿入し,バルーン付きカテーテルにて摘出した.異物はピーナッツであった.結論.小児気管支異物に対して,ラリンジアルマスクの使用により,異物摘出時の有効な換気と軟性気管支鏡のスムーズな操作性を担保することができた.


Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer.

To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions.

The Journal of Medical Investigation : JMI


5-Aminolevulinic acid-induced fluorescence diagnosis of pleural malignant tumor.

BACKGROUND: It is known that endogenously synthesized protoporphyrin IX (PpIX) following the administration of 5-aminolevulinic acid (5-ALA) is an effective photosensitizer for photodynamic diagnosis (PDD). We tested in vivo and in vitro susceptibility of human lung cancer and mesothelioma cells to photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) as a photosensitizer. METHODS: Human lung cancer cell lines A549, Ma44-3, FT821 and human mesothelioma cell lines MSTO-211H, NCI-H290, Y-MESO-14 were incubated with 0.03% 5-ALA for 4h. After incubation, protoporphyrin IX (PpIX) fluorescence was detected using a fluorescence microscope. Pleural carcinosis was induced in severe combined immunodeficiency disease mice using the previous cell lines to test the efficacy of PDD in vivo. The mice were sacrificed 4h after oral administration of 400mg/kg of 5-ALA. We counted the visible tumors under white light then fluorescence light. RESULTS: In vitro, clear red fluorescence was observed in all cell lines. The mean fluorescence intensity was stronger in A549 and FT821 cells than Ma44-3 cells (165.59±26.49, 157.62±18.93 vs. 104.01±17.58). Also, MSTO-211H and NCI-H290 cells had stronger fluorescence intensity than Y-MESO-14 cells (142.51±26.85, 165.16±12.91 vs. 92.31±8.69). In vivo, the tumor detection rate of fluorescence diagnosis was 1.1-4.5 times higher than that of white light. The mean number of metastases detected by the PDD was significantly higher than that of white light for FT821 (p=0.004), Ma44-3 (p=0.006) and Y-MESO-14 cell lines (p=0.005), but not for A549, NCI-H290 and MSTO-211H cell lines. Small lesions were detected by fluorescence diagnosis even though the lesions were invisible macroscopically under white light. CONCLUSION: Our results suggest the possibility of clinical application of fluorescence diagnosis with intrapleural malignant tumors.


Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure.

Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.


[Lung cancer in patient with a common trunk of left pulmonary veins; report of two cases].

左上下肺静脈が共通幹を形成していた肺癌の2例

A 69-year-old man and a 53-year-old man with lung cancer of left upper lobe underwent pulmonary resection. A preoperative chest computed tomography (CT) scan showed the left superior and inferior pulmonary veins forming a common trunk. In the former case, the common trunk was misidentified as the superior pulmonary vein. The latter was recognized preoperatively by using 3-dimensional CT, and successfully performed left superior segmentectomy. This variation type is surgically important because of a potential risk of intraoperative bleeding and damage to pulmonary circulation during pulmonary resection.

The Japanese Journal of Thoracic Surgery


Diagnosis of the presence of lymph node metastasis and decision of operative indication using fluorodeoxyglucose-positron emission tomography and computed tomography in patients with primary lung cancer.

PET/CT is superior to CT scan in lymph node staging. However, because the false-positive rate is high in PET-positive lymph nodes measuring less than 1 cm in diameter, we think that clinical background should be considered and other modalities or histological examinations should be undertaken if necessary. J. Med. Invest. 57: 305-313, August, 2010.


[Clinical analysis of elderly patients with primary lung cancer].

胸部外科の指針 高齢者原発性肺癌における臨床的検討

We clinically reviewed 33 surgery patients and 15 non-surgery patients aged 80 years or older with primary lung cancer treated at our hospital. The surgery group consisted of 21 males and 12 females (82.0 +/- 1.9 years old). The surgical procedures were 1 pneumonectomy, 19 lobectomies (1 bronchoplasty), 4 segmentectomies and 9 partial resections. The cancer types were 17 adenocarcinomas, 14 squamous cell carcinomas and 2 others. The stagings were 24 in stage I, 4 in stage II and 5 in stage III. There were no direct surgical deaths within 30 days post operatively. There have been 9 other disease-related deaths to date (27%). The non-surgery group consisted of 9 males and 6 females (81.7 +/- 1.5 years old). Treatment procedures consisted of radiationtherapy in 11, chemotherapy in 2 and best supportive care in 3. The cancer types were 2 adenocarcinomas, 11 squamous cell carcinomas and 2 others. The stagings were 7 in stage I, 4 in stage II and 4 in stage III. There have been 3 other disease-related deaths to date (20%). We must carefully select the therapeutic approach for elderly lung cancer patients, because the other disease-related death rates of both groups were high. The 5-year survival rate of stage I patients in the surgical group was relatively good (60.2%). There were long-term survival (7 5-year survivors) in the surgical group. Since there were some cases of radiation pneumonia in the group receiving radiation therapy, it would be better to perform surgery for elderly patients with lung cancer, especially those with stage I disease. For elderly patients, it is important to consider quality of life as well as the survival rate.


Undiminished regulatory T cells in the thymus of myathenia gravis patients

The thymus has been implicated as a possible site of origin that triggers autoimmunity in myasthenia gravis (MG). Although several groups have suggested that the decrease in the number of regulatory T (Treg) cells contributes to the onset of MG, the exact role of Treg cells in MG remains unclear. To address this point, we examined the number and distribution of Treg cells in a large number of patients with MG. Immunohistofluorescence analysis of Foxp3 along with CD4 and CD8 was performed in thymic sections of MG (+) (n = 24) and MG (-) patients (n = 27). Circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG (n = 15) and age-matched healthy subjects (n = 15) were also analyzed. Foxp3(+)CD4(+)CD8(-) cells were predominantly found in the thymic medulla and their number declined with age. There was no significant difference in the number or the distribution of Foxp3(+)CD4(+)CD8(-) cells in the thymus between MG (+) and MG (-) patients. The number of circulating CD4(+)CD25(+) cells in the peripheral blood of patients with MG was not significantly altered compared to that in healthy subjects. The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis.


Gefitinib耐性後に切除した肺腺癌術後肺転移の1例

Gefitinib耐性後に切除した肺腺癌術後肺転移の1例

The Journal of the Japanese Association for Chest Surgery


Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model.

Fluorescence diagnosis of lymph node metastasis of non-small cell lung cancer has not been reported previously. This study was conducted to evaluate the feasibility of fluorescence detection using 5-aminolevulinic acid and mono-L-aspartyl chlorine e6 for lymph node metastasis in a lung cancer mouse model. Human lung cancer cell line Ma44-3, which forms metastatic lymph nodes in the mediastinum, was injected into the left lungs of 6 severe combined immunodeficiency disease mice. Two weeks after implantation, 2 groups of 3 mice received oral administration of 5-aminolevulinic acid (100 mg/kg) or intraperitoneal administration of mono-L-aspartyl chlorine e6 (5 mg/kg). Both lungs and mediastinal organs were removed en-bloc and illuminated with blue light (405 nm) to evaluate the detectability of lung tumors and metastatic lymph nodes in the mediastinum. These organs were evaluated histopathologically. Clear red fluorescence was observed in the lung tumors of all mice. Metastatic lymph nodes had formed in 5 of 6 mice and were detected by fluorescent detection in all 5 mice even though one of the lymph nodes was invisible macroscopically under white light. In conclusion, fluorescence diagnosis of lymph node metastasis is possible in a mouse model. The successful result with small lymph node metastasis suggests the possibility of clinical application.


A case of anaplastic carcinoma of thyroid administered peroral fluorinated pyrimidine for long-term survival during three years

経口フッ化ピリミジン系抗癌剤の補助療法にて3年の長期生存を得ている甲状腺未分化癌の1例

We report a case of anaplastic carcinoma of the thyroid administered peroral fluorinated pyrimidine, providing longterm survival during three years. Three years ago, a 70-year-old woman diagnosed with anaplastic carcinoma of the thyroid was admitted for chemoradiation therapy after tumor resection and tracheostomy. The tumor was confirmed to remain on the margin of resected specimens by postoperative histopathology. Combination chemotherapy, including docetaxel, 5-fluorouracil, cisplatin, and radiotherapy, was performed for four weeks. After completion of radiotherapy, CT scan showed residual tumor and lytic clavicular bone findings. But the patient did not desire the same heavy chemotherapy, wishing rather to undergo chemotherapy as an outpatient, if possible. She received chemotherapy with S-1 which was peroral fluorinated pyrimidine for 9 months. In this period, PET-CT showed that accumulation of FDG and lytic clavicular bone findings were continuously confirmed. She was changed to tegafur-uracil(UFT)from S-1, because of myelosuppression. She is alive at this writing in good physical condition. CT shows no tumor growth and no remote metastasis.

Japanese Journal of Cancer and Chemotherapy


Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo.

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer. (c) 2009 UICC.


Recurrent thymoma with a pleural dissemination invading the intervertebral foramen.

We report a rare case of recurrent thymoma with pleural dissemination invading the intervertebral foramen. A woman with Masaoka's stage IVa thymoma with myasthenia gravis (MG) underwent macroscopically complete resection. After 45 months, she developed back pain. Computed tomography (CT) of the chest demonstrated a mass in the right thoracic cavity invading the intervertebral foramen between thoracic vertebrae 10 and 11. She underwent complete resection of the tumor and postoperative radiotherapy. The resected specimen was histologically diagnosed as a pleural dissemination from thymoma. There has been no local recurrence.

European Journal of Cardio-Thoracic Surgery


Surgically treated pleomorphic carcinoma of the lung

We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.

The Japanese Journal of Thoracic Surgery


Clinical analysis of tracheoplasty and bronchoplasty in primary lung cancer

気管・気管支形成手術の現況 2．気管・気管支形成 原発性肺癌における気管・気管支形成手術の臨床的検討

In our department, there were 482 thoracic surgeries for primary lung cancer between 1994 and 2007. We clinically reviewed cases that underwent tracheoplasty or bronchoplasty (n = 22, 4.6%). The patients consisted of 21 males and 1 female (66.5 +/- 12.0 years-old). All patients were smokers. The tissue forms were 19 squamous cell carcinomas, 2 adenocarcinomas, 1 large cell carcinoma, 1 adenoid cystic carcinoma and 1 carcinoid, including 2 multiple carcinomas. Sleeve resections involved the trachea in 1, upper lobes in 13, lower lobes in 3, upper-middle lobes in 2 and intermediate bronchus in 1. Wedge resections were performed in the upper lobes in 2. Fourteen reconstructions were performed. We ordinarily sutured the trachea and bronchus in any case, using a single outside knot. There was no leakage at the anastomosis. There were 2 hospital deaths. There were 4 cancer deaths, including 2 local recurrences. There were 4 patients demonstrating stenosis post operatively. There were 3 stenoses among 4 preoperative radiation therapies. We considered that radiation therapy disturbed the repair of the anastomosis. There were 8 pneumonia patients who developed post operatively. There were 2 operative hospital deaths among 3 angio-bronchoplasties without coverage. Recently, we have routinely covered the anastomosis at the reconstruction site and have not experienced any major complications.


Aberrant methylation of tumour-related genes in thymic epithelial tumours.

BACKGROUND: Thymoma is an uncommon neoplasm derived from epithelial cells of the thymus. Few studies have addressed the genetic alterations that occur in the tumourigenesis of thymoma. METHODS: We examined aberrant DNA methylation of DAP-K, p-16, MGMT and HPP1 genes in 26 thymomas and 6 thymic carcinoma to clarify the association between aberrant DNA methylation and clinicopathological features. RESULTS: Fifteen (47%) of 32 thymic epithelial tumours showed aberrant methylation. Aberrant methylation was more frequent in thymic carcinoma (86%) than in thymoma (29%). Moreover, the frequency of tumours with methylation of multiple genes in thymic carcinoma was higher than in thymoma (60% vs 20%). In thymoma, the frequency of tumour methylation, including the type A tumour component (28%), was lower than that of tumours with type B tumour component (42%). MGMT methylation was detected in 23% of thymoma and in 83% of thymic carcinoma. The frequency of methylation of the MGMT gene in both tumours was high compared with the other 3 genes. CONCLUSIONS: Aberrant DNA methylation was more frequent in thymic carcinoma than in thymoma, and the frequency of DNA methylation in thymic epithelial tumours is roughly parallel to their malignant behaviour.


Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer

Systematic nodal dissection has been recommended for patients with resectable non-small cell lung cancer because of its staging accuracy. However, in patients with clinical stage I non-small cell lung cancer whether systematic nodal dissection provides more benefits than mediastinal lymph node sampling or not is controversial. In this retrospective study, we evaluated the effect of mediastinal lymph node sampling in patients with clinical stage I NSCLC. One hundred and nineteen consecutive patients with clinical stage I NSCLC, who underwent curative operation between January 1994 and December 2000, were retrospectively reviewed (dissection group = 58: sampling group= 61). Systematic nodal dissection was defined as complete removal of mediastinal lymph node, and mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4, and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors. The total number of removed mediastinal lymph nodes in patients who underwent systematic nodal dissection was 22.1 +/- 9.7, which was significantly higher than that in patients who underwent mediastinal lymph node sampling of 11.4 +/- 7.0 (p < 0.001). Postoperatively N2 disease was detected in 8 patients (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the median follow up of 79 months, the cancer specific survival rate at 5 year was 78.0% in the dissection group and 76.2% in the sampling group (p = 0.60). Mediastinal lymph node sampling showed the similar effect to systematic nodal dissection in patients with clinical stage I non-small cell lung cancer.

The Journal of Medical Investigation : JMI


Photodynamic therapy using a second generation photosensitizer, Talaporfin

Background: Photodynamic therapy (PDT) using Talaporfin is an attractive treatment for centraltype early lung cancer. It was noted that some patients had altered levels of arterial oxygen saturation as indicated by pulse oximeter (SpO2) and arterial oxygen saturation levels in blood gas analysis (SaO2) during PDT. The present experiments were designed to provide an explanation for these findings. Methods: The influence of Talaporfin on SpO2 using in vitro and in vivo experiments, and clinically, was examined. Results: Our in vitro and in vivo experiments showed a linear relationship between Talaporfin concentration in the plasma and the SpO2 level (R = 0.9957 and 0.9837). The apparent SpO2 level decreased according to the increase of Talaporfin concentration in the plasma. In two patients with PDT, SpO2 levels at 4 6 h and 24 h after Talaporfin administration were 93% and 97%, respectively. Conclusions: Talaporfin raised blood absorbance at 660nm with a pulse oximeter. It appeared that the presence of the drug falsely decreased the level of SpO2 since SpO2 did not actually change.


The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer.

A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT-PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC.


Clinical analysis of operative and hospital deaths in primary lung cancer

胸部外科の指針 原発性肺癌における手術死亡および在院死亡

In our department, there were 313 thoracic surgeries for primary lung cancer from January 1994 to December 2003. We clinically reviewed for the operative and hospital death (n=18, 5.8%). The patients were 16 males and 2 females (70.6 +/- 5.6 years old). The surgical procedures were 4 pneumonectomies, 13 lobectomies (3 bronchoplasties) and 1 partial resection. The mean interval until postoperative death was 122.5 +/- 156.1 days. There were 5 direct operative deaths within 30 days (1.6%). There were 4 cancer deaths, 2 hemoptyses, 2 operative bleeding, 2 thromboses, 2 cerebral hemorrhages, 1 pyothorax, 1 pneumonia, 1 respiratory failure, 1 multiple organ failure after chemotherapy and 2 unexplained deaths. The patients with pneumonectomy or aged significantly had high mortality. For postoperative complications such as hemoptysis or bleeding, perioperative management that takes these issues into consideration is needed. Furthermore, we must carefully review the preoperative evaluation and combined treatment, because there were many cancer deaths among cases showing early recurrence and metastasis.


Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma.

OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.

Journal of Thoracic and Cardiovascular Surgery


Fluoroscopy-assisted thoracoscopic resection of pulmonary nodules after computed tomography--guided bronchoscopic metallic coil marking.

OBJECTIVE: To localize small and deeply situated pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, we developed a marking procedure that uses a metallic coil. METHODS: Nine patients underwent video-assisted thoracoscopic surgery for the removal of 11 pulmonary lesions. Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic metallic coil marking was performed with an ultrathin bronchoscope, with simulation by means of virtual bronchoscopy. During thoracoscopy, a C-arm-shaped roentgenographic fluoroscope was used to detect the radiopaque nodules. RESULTS: The marking procedure took 15 to 60 minutes from insertion to removal of the bronchoscope. There were no complications from the marking, and all 11 nodules were easily localized by means of thoracoscopy. The metallic coil showed the nodules on the fluoroscopic monitor, which aided in nodule manipulation. Nodules were completely resected under thoracoscopic guidance, except in one case in which a minithoracotomy was performed at an early stage of the trial. The pathologic diagnosis was primary adenocarcinoma in 9 patients, pulmonary metastasis from colon cancer in 1 patient, and pulmonary lymph node in 1 patient. Two cases of bronchioloalveolar adenocarcinoma with an invasive component and a well-differentiated adenocarcinoma were converted to open thoracotomy to perform curative lobectomy. CONCLUSIONS: In this pilot study computed tomography-guided transbronchial metallic coil marking with an ultrathin bronchoscope with virtual bronchoscopic simulation might be a useful method for the fluoroscopy-assisted thoracoscopic resection of pulmonary nodules.


Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 +/- 0.009 versus MMI-166, 0.069 +/- 0.008 mg; P = 0.005; metastatic area: control, 93,495 +/- 55,747 versus MMI-166, 22,747 +/- 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients.


Photodynamic therapy for submucosal tumor of the central bronchus

A 75-year-old man was referred to our hospital because of the emphysema and tumor of the right intermediate bronchus. Thoracic CT scan and bronchoscopic examination demonstrated a spherical tumor of the right intermediate bronchus covering a normal mucosa. The biopsy specimen obtained from this tumor was histologically diagnosed as "glandular type of adenocarcinoma in the bronchus". Surgical treatment was not feasible because of poor pulmonary function. Therefore, the patient underwent Photodynamic therapy (PDT) using porfimer sodium (Photofrin) and an excimer dye laser. After 4 months, the tumor disappeared and there has been no recurrence for 3 years 3 months. PDT can affect a submucosal tumor of the central airway, and is safe for patients with poor pulmonary function. Our report recommends that PDT should be applied not only to early lung cancer but also submucosal tumor of the central bronchus.


甲状腺髄様癌術後肝転移に対し肝動脈化学塞栓療法が有効であった1例

甲状腺髄様癌術後肝転移に対し肝動脈化学塞栓療法が有効であった1例


Extramedullary plasmacytoma immunoglobulin D (λ) in the chest wall and the subglottic region


Establishment of patient-like SCID mouse model by orthotopically implanting primary cultured cells from surgically-resected lung cancer tissues

In our previous studies, we established a lymphogenous metastatic SCID mouse model using orthotopic implantation of human lung cancer cell lines. However, the lymphogenous metastatic potential of each cell line in our models does not reflect that of a primary tumor. In this study, we made orthotopic implanted models using primary cultured cells from surgically-resected lung cancer tissues. Tissues of 5 patients with non-small cell lung cancer (NSCLC) were applied to a primary culture method using a collagen gel coated flask. Suspensions of 2.0x10(4) cancer cells were injected into the left lung of SCID mice. We could maintain primary culture cells from 2 (FM205 and FT821 cells) of 5 lung cancers, and made orthotopically implanted SCID mouse models. The size of both tumors in implanted sites of the lung increased with time. The FM205 cells microscopically were metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 16 weeks. The FT821 cells were microscopically metastasized to the mediastinum by 4 weeks after implantation and macroscopically metastasized by 6 weeks. The lymphogenous metastatic potential of these primary culture cells was similar to that of clinical tumors. As the lymphogenous metastatic potential of this model reflects that of the clinical tumor, it is useful for elucidating the mechanism of lymphogenous metastasis and selecting anticancer drugs suitable for an individual patients.


Microscopic analysis of chromium accumulation in the bronchi and lung of chromate workers

It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma. The authors used a microscopic X-ray fluorescence analyzer with transmitted X-ray mapping imaging (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected lung tissue specimens and 90 biopsy specimens from chromate workers. The maximum chromium accumulation (mean +/- standard deviation) in 10 resected lung tissue specimens was 197 +/- 238 counts per second (cps)/mili ampere (mA) (range, 4-649 cps/mA). Chromium accumulation was scattered in six tissue specimens and diffuse in one specimen. Chromium accumulation in the proximal bronchi was less than in the bronchioles or subpleural regions of the lung. Chromium accumulation was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was 6.5 +/- 9.2 cps/mA (range, 0-46.5 cps/mA). Chromium detected in bronchial tissue specimens was deposited in the bronchial stroma but not in the epithelium. The maximum chromium accumulations in dysplasic (n = 3), squamous metaplastic (n = 10), and normal bronchial epithelia (n = 9) in chromate workers and in normal bronchial epithelia (n = 3) in non-chromate workers were 20.2 +/- 5.4, 18.3 +/- 12.2, 13.2 +/- 13.4, and 3.0 +/- 1.8 cps/mA, respectively. The amount of chromium accumulation significantly increased according to the progression of malignant change of the bronchial epithelium (P = 0.003). Previous studies found that lung carcinoma with chromate exposure exhibited a variety of genetic abnormalities. Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma.


Pulmonary Resection in Renal Cell Carcinoma Metastasis : the Influence of Histologic Atypia of the Metastatic Focus on Preoperative or Perioperative Diagnosis

臨床と研究 腎癌肺転移巣の組織学的異型度が画像診断に及ぼす影響

The Japanese Journal of Thoracic Surgery


Two patients managed by palliative care for symptoms due to cervical lymph node recurrence of esophageal carcinoma

食道癌頸部リンパ節再発による症状に対して緩和ケアを実践した2症例

Our department aggressively performs initial treatment for esophageal carcinoma with multidisciplinary approaches, and not only positively treats patients with recurrence or metastasis but also manages those in an advanced stage by following the wishes of patients and their families as much as possible. However, many patients with esophageal carcinoma develop digestive tract and tracheal problems with progression of the disease, and the palliation of symptoms and continuation of home care often become difficult. In such patients, it is important to secure and maintain the route of hydration and nutrition when oral fluid and food intake becomes difficult, and to control respiratory symptoms for the promotion of home care and palliation of symptoms in the terminal stage. In this report, we present 2 patients managed by palliative care until death while supporting home care by maintaining enteral nutrition using gastrostomy for esophageal narrowing due to cervical lymph node recurrence, and controlling the cough reflex and dyspnea associated with the development of a cervical lymph node-tracheal fistula through morphine hydrochloride administration.