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Background A mediastinal mediobasal segmental pulmonary artery (A7) from the right main pulmonary artery is extremely rare. Case presentation: We have reported a case of a 71-year-old woman with aberrant A7 who underwent right lower lobectomy for lung cancer (cT1bN0M0, stage IA2). Preoperative three-dimensional computed tomography (CT) angiography revealed an aberrant mediastinal A7 from the right main pulmonary artery. Right lower lobectomy and mediastinal lymph node dissection were performed. Intraoperatively, A7 was observed between the superior and inferior pulmonary veins, and at the front of the lower bronchus near the anterior hilum. The artery was carefully dissected from the caudal side after dissection of the inferior pulmonary vein. Then, the lung parenchyma, which was within the fissure due to poor lobulation between the middle and lower lobes, was safely divided. Conclusions Thoracic surgeons need to evaluate CT angiography or enhanced multidetector CT carefully at preoperative conferences and always keep this anomaly in mind.

The risk of complication following pneumonectomy is high; therefore, the decision to perform pneumonectomy should be carefully evaluated. A retrospective multicenter study of patients with metastatic lung tumors who underwent pneumonectomy was conducted.The database from the Metastatic Lung Tumor Study Group of Japan was retrospectively reviewed. Between 1984 and 2013, 4,742 patients underwent pulmonary metastasectomy. Of the 4,742 patients, 55 patients (1.16%) who underwent pneumonectomy were analyzed, and their survival parameters and prognostic factors were evaluated.Of the 55 patients who underwent pneumonectomy, 34 patients were male and 21 patients were female. The primary tumor sites were colorectal in 28 patients, head and neck in 12 patients, bone in three patients, bladder in three patients, and other regions in nine patients (breast, uterus, liver, soft tissues in two patients, respectively, and pancreas in one patient). The overall 5-year survival rate of patients following pneumonectomy was 28.9%. The rate was significantly lower than that of patients who underwent other metastasectomy which had an overall 5-year survival rate of 53.4% (P0.001). There were 3 hospital mortalities (3/55, 5.45%). Univariate analysis revealed that patients 55 years old or older (P=0.016) and patients who had lymph node metastasis (P=0.032) were significant predictors of poor prognosis. Multivariate analysis indicated that the age group 55 years old or older was an independent prognostic factor (P=0.040).The indication of pneumonectomy should be carefully reviewed, especially for patients 55 years old or older, however characteristics of each primary organ should also be considered.

OBJECTIVES New chemotherapeutic regimens (i.e. FOLFOX or FOLFIRI with molecular targeted drugs) have improved the prognosis of patients with unresectable or recurrent colorectal cancer. To estimate the prognostic impact of these chemotherapies, we examined the chronological change in survival rates of patients who underwent pulmonary metastasectomy for colorectal cancer metastasis. METHODS Using a large database, we conducted a retrospective, multi-institutional study to collect data of 1223 eligible patients from 26 institutions who had undergone pulmonary metastasectomy with curative intent. We divided those patients who underwent metastasectomy in different time periods according to the major trend of chemotherapy regimens for recurrent colorectal cancer: those who underwent metastasectomy between 1990 and 1999 ( N = 451, Group A), between 2000 and 2004 ( N = 433, Group B) or between 2005 and 2007 ( N = 339, Group C). RESULTS Five-year overall survival rates after metastasectomy were 45% in Group A, 56% in Group B and 66% in Group C ( P

Thymoma is the most common thymic epithelial tumor whose classification was first introduced in 1999. Type B2 thymoma is considered a moderate/high-risk tumor; however, extrathoracic metastases are extremely rare with limited reports to date. In this report, we present a rare thymoma metastasis to the semimembranosus muscle, which was resected with a wide margin after confirmation by open biopsy. At the final follow-up after 1 year, no local recurrence has been observed.

Little is known about the association between the atypical adenomatous hyperplasia (AAH)-adenocarcinoma in situ sequence of the lung and endoplasmic reticulum-stress responders such as ATF6, XBP1, and GRP78. Using stored tissues, we examined (i) the percentage of a splicing form (active form) of XBP1 messenger RNA in normal lung tissue (NLT) and adenocarcinoma (ACA; using reverse-transcription polymerase chain reaction); (ii) ATF6 and GRP78 protein expressions in NLT and ACA (using Western blotting analysis); (iii) ATF6, XBP1, and GRP78 protein expressions in NLT, AAH, and ACA, including some adenocarcinoma in situ (using immunohistochemistry); and (iv) the incidence of nuclear translocation of the 3 proteins in these lesions. The percentage of the splicing form of XBP1 messenger RNA showed a borderline difference between NLT and ACA (P = .068). In the Western blotting analysis, the nuclear fractions of ATF6 (including the active form) and GRP78 proteins were higher in ACA than in NLT. In the immunohistochemistry, the values obtained for the incidence of the nuclear translocation of ATF6, XBP1, and GRP78 proteins were as follows, respectively: 13.3%, 2.2%, and 0.5% in low-grade AAH; 37.9%, 2.3%, and 2.2% in high-grade AAH; and 47.2%, 10.6%, and 4.4% in ACA. A significant difference was detected between low-grade AAH and ACA for ATF6. In terms of nuclear translocation, high-grade AAH seemed intermediate between low-grade AAH and ACA. These results support endoplasmic reticulum-stress responses, such as nuclear translocation of these 3 proteins (including their active forms), being in parallel with the progression of the adenoma-carcinoma sequence in the lung.

Background: The introduction of new therapies has made it important to differentiate between adenocarcinoma and squamous cell carcinoma. To allow the use of various immunocytochemical stains on limited materials, we tried transferring cells from a given smear to multiple slides. Using touch-preparation samples of 215 surgically resected non-small cell lung carcinomas of confirmed histologic classification (adenocarcinoma,n = 101; squamous cell carcinoma,n = 114), we performed immunocytochemistry for thyroid transcription factor-1, napsin A, p40, p63, CK5/6 and desmocollin-3, and compared cytologic staining results with the corresponding resection. Methods: We examined: (a) the expressions of the above 6 antibodies on cells transferred from touch imprints of resected specimens, the extent of staining being considered positive if more than 5% of the area was stained, and (b) the sensitivity, specificity, positive predictive value and negative predictive value for each antibody. Results: The histologic corresponding rate with Papanicolaou staining was only 73%. Regarding the differentiation of adenocarcinoma from squamous cell carcinoma, the sensitivity and specificity for napsin A in adenocarcinoma were 80 and 97%, respectively, while those for p40 in squamous cell carcinoma were 84 and 98%, respectively. Conclusion: The immunocytochemical expressions of napsin A and p40 in imprint cytology seem to be of great utility for the accurate histological differentiation of lung cancers.

Background We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients. Methods Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival. Results From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1–3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). Conclusions The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1–3 elevation of bilirubin. Trial registration This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

It is difficult to treat patients with acquired airway stenosis, and the quality of life of such patients is therefore lowered. We have suggested the application of photodynamic therapy (PDT) as a new treatment for airway stenosis and have determined the efficacy of PDT in animal disease models using a second-generation photosensitizer with reduced photosensitivity. An airway stenosis rabbit model induced by scraping of the tracheal mucosa was administered NPe6 (5 mg kg(-1)), and the stenotic lesion was irradiated with 670 nm light emitted from a cylindrical diffuser tip at 60 J cm(-2) under bronchoscopic monitoring. PDT using NPe6 improved airway stenosis (P = 0.043) and respiratory stridor. A significant prolongation of survival time was seen in the PDT-treated animals compared to that in the untreated animals (P = 0.025) and 44% of the treated animals achieved long-term survival (>60 days). In conclusion, PDT using NPe6 is effective for improvement in airway stenosis.

症例は64歳，女性．18年前に左乳癌で非定型的乳房切断術を受けた．病理診断はInvasive ductal carcinoma, solid-tubular type, T1N0M0 stage Iであった．今回，検診で胸部異常影を指摘され当院を受診した．胸部X線写真で右上肺野に第2肋骨と重なる不整型結節影を認めた．CTでは右S1末梢に径1cm大の境界明瞭で辺縁不整な結節影を認めた．乳癌および肺癌関連の腫瘍マーカーはいずれも正常範囲内であった．乳癌の肺転移，あるいは原発性肺癌の診断で，胸腔鏡下肺部分切除術を施行し，迅速病理診断で乳癌の転移性肺腫瘍の診断であった．乳癌は遠隔期にも転移をきたすとされているが，原発巣切除後15年以上経過してからの肺のみの転移手術症例は本邦では本症例を含め10例の報告しかなく稀であるため文献的考察を加えて報告した．

We report 3 cases of solitary papillomas located in peripheral regions of the lung that are extremely rare in the literature. The patients were 75-year-old and 72-year-old men and a 53-year-old woman. One patient complained of recurrent hemoptysis. The other 2 had no symptoms, but abnormal nodular shadows were revealed by chest radiographs during a health check. The maximum diameters of the tumors were 1.0, 1.4, and 1.1 cm, respectively. The 3 tumors gave almost the same histologic findings. Papillomatous fronds lined by a stratified columnar epithelium were seen in the lumens of peripheral bronchi, bronchioles, or alveoli. The stratified columnar epithelium consisted of ciliated, mucous, and basal cells. The neoplastic epithelium extended to the alveolar region and showed a similar appearance to bronchioloalveolar or papillary type adenocarcinomas. For differential diagnosis, it is noteworthy that endobronchiolar papillomatous fronds constantly exist and spreading along alveolar walls is limited in adjacent alveoli in peripheral papillomas. The presence of ciliated cells and basal cells is considered an important finding to suggest benign character of the lesion.

A 60-year-old man with a 7-year history of multiple pulmonary nodules presented to our hospital because the nodules were seen to have increased in size on review of films on a regular medical checkup 1 week earlier. Computed tomography (CT) revealed multiple pulmonary nodules with calcification in the lungs. The largest nodule measuring 2.5 cm in the maximum dimension was lobulated and ill-defined. The patient underwent 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to evaluate the multiple nodules and to search for a primary lesion. 18F-FDG-PET/CT revealed increased uptake in only two nodules with a standardized uptake value of 4.61 and 2.10, respectively. The two foci with increased 18F-FDG uptake were resected and pathologically proven to be pulmonary epithelioid hemangioendothelioma (PEH). PEH can transform into malignancy with metastasis. An 18F-FDG-PET/CT finding may be an indicator to decide on PEH resection.

[背景]小児における気道狭窄治療は困難であり，効果的で侵襲の少ない治療法の確立が望まれている。われわれは，気道狭窄治療に対する新しい治療法として低侵襲治療法の一つである光線力学的治療（PDT）を提案し，本法の有効性を検討した。[方法]ウサギ気管粘膜を擦過して作成した気道狭窄モデルに光感受性物資であるフォトフリンを投与し，その組織集積性を調べた。またウサギ気道狭窄モデルにフォトフリンを用いたPDTを施行し，気管支鏡下に観察しその効果を検証した。[結果]フォトフリンの気道狭窄部肉芽組織への高い集積を認め，正常気管に対し4倍，他臓器に対し10倍以上の集積を認めた。また，PDTにより気道狭窄および喘鳴症状の改善を認め，未治療の狭窄モデルに対して生存期間の有意な延長を認めた。[結論] 光感受性物質は肉芽組織へ高濃度に集積し，PDTにより気道狭窄は改善した。これらの結果からPDTは肉芽性気道狭窄に対する新たな治療法として機能することが示唆された。

We report a postoperative patient who developed neurally mediated syncope, which was diagnosed using head-up tilt testing after the patient developed syncope in the intensive care unit. The patient had been misdiagnosed as having epilepsy since her childhood. Therefore, in patients with presumed epilepsy who present with syncope and have a nondiagnostic electroencephalogram, cardiac causes of syncope, such as neurally mediated syncope, should be considered.

Airway stenosis in childhood is resistant to conventional treatments. Endoscope-assisted photodynamic therapy (PDT) is a potent candidate for the therapeutic modality owing to the easy approach to the tracheal lesion and low degree of invasiveness. The aim of the present study was to examine whether a photosensitizer preferentially accumulates in the lesion of airway stenosis in order to explore the possible applicability of PDT. The tracheal mucosa of rabbits was scraped off, and the rabbits were intravenously administered with Photofrin. The tissue concentration of Photofrin was quantitatively measured by fluorometric analysis. Granulation formation was seen in the mucosa-deprived lesion, causing airway stenosis. Photofrin concentration in the granulation tissue was four-fold higher than that in the intact trachea and 10-fold higher than that in the liver, spleen, skin and muscle. Photofrin preferentially accumulated in the lesion of airway stenosis. A preliminary experiment on PDT using transtracheal illumination showed an amelioration of airway stenosis, resulting in reduction in respiratory stridor.

Background: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors. Methods: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)]. Results: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs. Conclusions: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0+/-8.1) than in normal lung tissues (1.0+/-0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

Background: Prolonged endotracheal intubation in children often induces intractable airway stenosis. The aim of the present study was to establish a new model of airway stenosis for developing an effective method of treatment. Material and methods: The rabbit trachea was annularly incised, and the tracheal mucosa was scraped with a nylon brush. The trachea was then closed. Nine days after scraping, the trachea was microscopically examined. Results: All of the examined rabbits showed tracheal stenosis, ranging from 22% to 82% in diameter and from 48% to 97% in cross-sectional area. The stenotic lesion was confined within the scraped region, not including the sutured region. Histologic examination showed inflammation in the stenotic lesion with submucosal hyperplasia caused by proliferation of fibroblasts and thickening of collagen fibers. Conclusion: This method can be easily carried out and assures induction of airway stenosis. This model may be useful for developing methods for treating airway stenosis in the early stage.

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1alpha, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1alpha expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1alpha protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1alpha messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1alpha protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the 'high score' group for HIF-1alpha protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1alpha protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1alpha mRNA scores correlated significantly with scores for HIF-1alpha protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1alpha protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma.

[背景] 新生児や乳児での長期にわたる挿管により気道狭窄が生じ, その治療は非常に困難である。本研究は, 気道狭窄治療法の新規開発に利用できる気道狭窄モデルを確立することを目的とした。 [方法] ウサギ気管を切開し, 気管内腔をナイロン製のブラシで擦過後, 切開部を縫合し経過観察した。まず, 経時的に狭窄部の病理学的変化の観察を行い, 次に擦過後9日目に喉頭気管を摘出し, 組織学的観察をおこなった。 [結果] 全例で気道狭窄を認め, 擦過後9日目には径で22～82%, 断面積で48～97%の狭窄を認めた。組織学的には著明な炎症像および線維芽細胞・膠原線維の増生による粘膜下組織の肥厚を認め, 炎症反応の程度と狭窄度に相関が認められた。縫合部には狭窄所見を認めなかった。 [結論] 本方法により, ウサギ気管に狭窄を誘導することができた。本方法は, 簡便かつ確実で, 特に発症早期の狭窄に対する予防・治療の検討に有用である。

Aims: The third edition of the World Health Organization (WHO) classification of lung tumours has been published and is expected to become the standard nomenclature. The aim of this study was to assess the usability and prognostic significance of the WHO classification in comparison with other recent classifications. Methods and results: One hundred and forty-seven resected pulmonary adenocarcinoma cases were reviewed and histologically classified according to the WHO classification (1999) and the classification by Noguchi (1995). Papillary carcinomas as described by Silver and Askin (1997) were also identified. Since the papillary type in the WHO classification is not strictly defined, we compared the following two kinds of WHO classification: (i) WHO-N; WHO classification adopting Noguchi Type F as the definition of the papillary type, namely, pure papillary adenocarcinoma without a bronchioloalveolar component; (ii) WHO-SA; WHO classification adopting papillary carcinoma by Silver and Askin as the definition of the papillary type, namely, tumour with papillary structure constituting at least 75% of the lesion. The bronchioloalveolar carcinoma of the WHO classification showed a better prognosis than other subtypes in both overall and Stage I disease limited survival analysis. In analysis limited to Stage III disease, only the papillary type of WHO-SA showed a significantly worse prognosis. Conclusions: WHO-SA is recommended for prognostic correlation.

PURPOSE: This study was undertaken to identify prognostic factors that can be used to predict prognosis after surgery for lung metastases from colorectal carcinoma. METHODS: We reviewed retrospectively the clinical course of 37 patients who underwent surgical resection of primary colorectal cancer and metastatic lung disease at the National Defense Medical College Hospital between September 1986 and July 1999. We analyzed the prognostic factors with special reference to the clinicopathologic factors of primary tumors. RESULTS: Multivariate analysis indicated that the existence of an extranodal cancer deposit in the primary lesion (hazard ratio = 4.55, P = 0.009) and three or more lung metastases (hazard ratio = 2.9, P = 0.04) were significant indicators for poor prognosis. We divided the patients into two groups: Group A (n = 12) had neither of these two parameters, and Group B (n = 25) comprised all other patients. This two-ranked classification was significantly related to both survival rates (3-year and 5-year survival rate, 90.9 and 90.9 percent in Group A and 16.1 and 8.1 percent in Group B, respectively; P = 0.0003) and disease-free survival after thoracotomy (3-year and 5-year disease-free survival rate, 52.9 and 39.7 percent in Group A and 5.3 and 5.3 percent in Group B, respectively; P = 0.002). CONCLUSION: An extranodal cancer deposit at the primary tumor site is a new significant prognostic factor after resection of lung metastases from colorectal cancer. A two-ranked classification by extranodal cancer deposit and the number of pulmonary lesions can provide useful prognostic information for the treatment of lung metastasis. Surgical resection of pulmonary metastasis is expected to be very useful for patients in Group A.

Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant heparin-carrying polystyrene on tumour growth and metastasis. Non-anticoagulant heparin-carrying polystyrene has a higher activity to inhibit vascular endothelial growth factor-165-, fibroblast growth factor-2- or hepatocyte growth factor-induced human microvascular endothelial cell growth than heparin, ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin, which is probably due to the heparin-clustering effect of non-anticoagulant heparin-carrying polystyrene. Non-anticoagulant heparin-carrying polystyrene inhibited human microvascular endothelial cell, B16 melanoma and Lewis lung cancer cell adhesion to Matrigel-coated plates. Non-anticoagulant heparin-carrying polystyrene also showed strong inhibitory activities in the tubular formation of endothelial cells on Matrigel and B16-melanoma and Lewis lung cancer cell invasion in a Matrigel-coated chamber assay. In vivo studies showed that growth of subcutaneous induced tumours and lung metastasis of B16-melanoma and Lewis lung cancer cells were more effectively inhibited by non-anticoagulant heparin-carrying polystyrene than ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin. Furthermore, non-anticoagulant heparin-carrying polystyrene markedly reduced the number of CD34-positive vessels in subcutaneous Lewis lung cancer tumours, indicating a strong inhibition of angiogenesis. These results suggest that non-anticoagulant heparin-carrying polystyrene has an inhibitory activity on angiogenesis and tumour invasion and may be very useful in cancer therapy. British Journal of Cancer (2002) 86, 1803–1812. doi:10.1038/sj.bjc.6600307 www.bjcancer.com © 2002 Cancer Research UK

大腸癌肺転移36例の肺切除後予後について原発巣因子による検討を行った. 36例の5生率は35.9%で,肺切除後の予後因子としてリンパ節転移n2以上,癌先進部の簇出中等度以上,リンパ節以外の非連続性癌進展病巣(ex)陽性が有意であった.この3因子中,全因子陰性か1因子のみ陽性のp-Low群(n=17)は2因子以上陽性のp-High群に比べ肺切除後予後が有意に良好で(5生率75.1%: 0%, p=0.0002),術後無再発生存も長かった(50%無再発生存期間1, 848日: 202日, p

There has been an increase in the detection rate of small early lung cancer due to recent improvements in imaging technology. However, conventional imaging modalities such as computed tomography (CT) alone are not capable of differentiating small pulmonary nodules. New modalities such as F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with CT (PET/CT) have contributed to the evaluation of lung cancer staging, although the differential diagnosis of pulmonary nodules showing ground-glass opacity (GGO) with PET/CT is controversial. In Japan, cancer screening with whole body FDG-PET has been available for asymptomatic individuals, and it has been reported that a wide variety of cancer types are detectable by FDG-PET at potentially curable stages. We present the case of a 62-year-old male with early lung cancer, which was revealed by repeated health screening. A PET/CT scan revealed definite intense FDG uptake (SUVmax 1.2) in the pulmonary nodules of the right upper lobe, while no definite FDG uptake was observed in the lesion in the previous annual screening. Right upper lobectomy was performed, and the pathological diagnosis was well-differentiated adenocarcinoma. Five-year survival has been noted since the thoracotomy, and the patient is doing well without recurrence. This is a significant case of early lung cancer with GGO lesions, which revealed intense FDG uptake during an annual repeated health screening with FDG-PET/CT.

Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.

Lung carcinoma with rhabdoid cells: a clinicopathological study and survival analysis of 14 cases Aims: We determined the clinicopathological features of primary lung carcinomas with rhabdoid cells by defining the immunophenotype of rhabdoid cells and analysing survival. Methods and results: Rhabdoid cells are distinctive in having an eccentric nucleus and a large intracytoplasmic inclusion on routinely stained sections. Based on the number of rhabdoid cells, 45 cases of large cell carcinoma were divided into the following three types: lung tumour with a rhabdoid phenotype (LTRP) (n=4), lung carcinoma with a small number of rhabdoid cells (LCSR) (n=10), large cell carcinoma containing no rhabdoid cells (LCNR) (n=31). LTRP is composed of at least 10% rhabdoid cells. In LCSR the percentage of rhabdoid cells is less than 10%. LTRP and LCSR are associated with locally advanced disease. Immunohistochemical stains were positive for epithelial markers in all LTRP and eight LCSR, for neuroendocrine markers in one LTRP and three LCSR. The outcome is worse for patients with LTRP than LCSR or LCNR. LCSR shows a trend close to LCNR. Stage-matched survival analysis, however, revealed no statistically significant difference among the histological subtypes. Conclusions: Rhabdoid cells are heterogeneous except for epithelial markers and vimentin positivity. Less than 5% of rhabdoid cells has a negligible effect on prognosis.

BACKGROUND Adenocarcinoma of the lung occasionally has acidophilic nuclear inclusions (ANIs). Some studies have reported that the incidence of ANIs was higher in well differentiated tumor types and have suggested that adenocarcinoma patients with ANIs might have a more favorable prognosis; however, to the authors' knowledge, statistically significant prognostic findings were not reported. The objective of the current study was to assess the prognostic significance of ANI in patients with pulmonary adenocarcinoma and, moreover, to characterize ANI immunohistochemically and ultrastructurally. METHODS Surgically resected tumor specimens from 147 patients with primary pure adenocarcinoma of the lung were examined. Only obvious ANIs surrounded by a clear halo on hematoxylin and eosin-stained slides were counted; the authors classified cases with ≥ 10 ANIs per 10 high-power fields (/10HPF) as frequent-ANI cases, cases with < 10 ANIs/10HPF as infrequent-ANI cases, and cases without ANIs as non-ANI cases in the current study. RESULTS Nineteen frequent-ANI cases (12.9%) and 16 infrequent-ANI cases (10.9%) were found; the remaining 112 cases (76.2%) were considered to be non-ANI cases. The majority of ANIs immunohistochemically contained surfactant apoprotein and ultrastructurally corresponded to invagination of the inner nuclear membrane, showing a tubular or amorphous configuration. Frequent-ANI patients showed significantly better prognosis than the other two groups on both overall univariate analysis and univariate analysis limited to patients with International Union Against Cancer Stage I disease (P = 0.0096 and P = 0.0095, respectively). However, on the multivariate analysis only disease stage was shown to be a significant prognostic factor and frequent-ANI showed borderline significance (P = 0.0956). CONCLUSIONS Frequent ANIs appear to be of limited value in clarifying the prognosis of patients with lung adenocarcinoma. Cancer 2001;91:1896–904. © 2001 American Cancer Society.

【目的】肺癌検診におけるCTの有用性の検討【対象・方法】最近4年間に当院に人間ドック目的で入院した男性1335人, 女性19人の合計1354人. 年齢は22歳から66歳で平均48.3歳である. 検査項目は問診, 喀痰細胞診, 直接胸部単純写真 (以下胸単), 胸部X線CT (以下CT) である. CT導入前の胸単のみの検診1281人と比較する.【結果】 CTを用いた検診では1354人中5人 (0.37%) の肺癌が発見された (10万人対369). 内訳は高分化型腺癌3例, 低分化型腺癌1例, AAH 1例であった. 低分化型腺癌の1例はMissed caseである. いずれも胸単では指摘できなかった. 一方, CT導入前の胸単のみの検診では肺癌は発見できなかった.【考察】胸部CT検診の早期肺癌発見における有用性の報告は多くの施設によりなされている. 今回我々の検討では, 対象は比較的若年層であり, 通年検診症例である. CT導入前の肺癌発見が1281例中0例に対し, 導入後は1354例中5例であり1例を除き早期肺癌であった. 費用効果などあらゆる側面からCTの有用性を検討すべきであり, また対象とする集団の年齢構成や職種などにより適切な検診方法を検討すべきである.

1999年1月から同年12月までに乳腺外来を受診し視触診, マンモグラフィ, 超音波検査等で強く悪性疾患を疑った61例に対して乳腺MRIを施行した。そのうち腫瘤性病変に対して組織学的診断の得られた58例 (良性疾患8例, 乳癌50例) を対象に, dynamicstudyによる腫瘤影の特徴, 時間信号強度曲線について良悪性疾患別に比較し, 造影MRI検査における造影パターンの解析の有用性を検討した。対象症例すべてが造影MRIで濃染した腫瘤を認め, 信号強度のピーク時間の平均値は良性疾患では約7分, 乳癌例では約2分であった。PRE (preripheral ring enhancement) は乳癌50例中40例 (80.0%) に認められたのに対して, 良性疾患では全例で認められなかった。乳腺疾患の画像診断は主にマンモグラフィ, 超音波検査が用いられてきたが, 乳腺腫瘤の治療方針を決定していく上で, dynamic MRIにおける造影パターンの解析が一助となると考えられる。

von Recklinghausen病に合併した悪性神経鞘腫の肺転移に対し, 胸腔鏡下切除を施行し得た1例を経験したので報告する.症例は32歳の女性で, 小児期よりvon Recklinghausen病と診断され, 1994年12月に右下腿の悪性神経鞘腫に対して, 術前化学療法, 放射線治療の後, 広範囲腫瘍摘出術を施行した.1997年9月の胸部X線写真で右中肺野にcoin lesionを認め, 転移性肺腫瘍の診断で1997年11月に胸腔鏡下肺部分切除術を施行した.術後の病理組織診断は, 悪性神経鞘腫の肺転移であり, 断端に肉腫細胞を認めず, 術後1年9ヵ月の現在までに新たな肺転移の出現を認めていない.悪性神経鞘腫の転移臓器としては肺が最も多く, その予後は著しく不良であるが, 本症例は比較的予後が期待できると考えられた.

Background The cut-and-sew Maze procedure has historically been the most efficacious therapy for patients with atrial fibrillation (AF) that is refractory to medical management, but is not widely used as a stand-alone treatment for AF. New ablation technologies can create pulmonary vein (PV) isolation without cardiopulmonary bypass. Methods and Results The `thoracoscopic mini-Maze' procedure includes bilateral PV isolation, ablation of the epicardial ganglionated plexi and excision of the left atrial appendage using small bilateral thoracotomies with thoracoscopic assistance. Between January 2006 and April 2007, 20 thoracoscopic mini-Maze procedures were performed at 2 institutions and over a mean follow-up of 16.6 months, 18 (90%) patients are in sinus rhythm. Perioperative bleeding complications occurred in 3 patients (15%) and there was 1e (5%) late instance of atrial flutter that required a right-sided ablation. None of the patients died or needed a pacemaker. Conclusions Early experience with the thoracoscopic mini-Maze procedure suggests that sinus rhythm can be re-established in most patients in the short-term and with more experience the rate of complications should reduce, which is required prior to defining the role of this therapy in the future treatment of AF. (Circ J 2008; 72: 434 - 436)

Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189. © 1999 Cancer Research Campaign

The various methods of treating the numerous types of anterior mediastinal neoplasms are undergoing refinements; however, prior to the commencement of any treatment, an accurate histologic diagnosis must be established. We conducted a retrospective analysis of biopsies performed through a parasternal anterior mediastinotomy (PAM) on 21 patients with an anterior mediastial mass suspected of being malignant by computed tomography (CT) and other clinical information. Patients with possible localized thymomas were excluded. Mediastinotomy, which enables relatively large tissue samples to be taken, was performed through the bed of the second or third costal cartilage under local anesthesia. In 19 of the 21 patients (90%), the histologic diagnosis made from the mediastinotomy biopsy was identical to the final diagnosis. Conversely, although the tissue obtained from needle biopsy was sufficient for a histologic diagnosis in 11 of 12 patients, the histologic diagnosis made from the needle biopsy was the same as the final diagnosis in only 5 of 10 patients (50%). Thus, diagnostic accuracy was significantly higher in the mediastinotomy biopsies than in the needle biopsies (P = 0.0318). Moreover, the mediastinotomy biopsy specimens revealed subtypes of lymphomas and germ cell tumors. All of the patients from whom a mediastinotomy biopsy had been taken began appropriate therapy without delay according to the histologic diagnosis. These results suggest that the PAM approach should be chosen as the preferred method of biopsy for suspected malignant anterior mediastinal tumors.

Recent reports of cancers that produce colony-stimulating factors (CSF) and which are associated with leukocytosis indicate that most are granulocyte CSF-producing tumors. A 71-year-old man with metastatic chest wall tumors from large cell lung cancer with marked leukocytosis and eosinophilia was reported. His maximal leukocyte count was 48300/microliter with 37.5% eosinophils. Granulocyte-macrophage CSF (GM-CSF) activity detected by enzyme-linked immunosorbent assay (ELISA) in serum was 112 pg/ml (normal range < 2.0 pg/ml), but G-CSF was normal. Immunohistochemical detection of GM-CSF protein on a chest wall tumor sample was positive. Irradiation of the chest wall tumor was performed and the leukocyte count decreased temporally. However, he died of respiratory failure due to progressive tumor growth 56 days after admission. Based on these results it appears that autocrine production of GM-CSF is a possible cause of this leukemoid reaction.

BACKGROUND Stereotactic radiation therapy is highly effective in the treatment of small brain metastases, regardless of the histology. This suggests that small extracranial malignancies may be curable with similar radiation therapy. The authors developed a novel treatment unit for administering such therapy. METHODS The unit consisted of a linear accelerator (linac), an X-ray simulator (X-S), computed tomography (CT), and a table. The gantry axes of the three machines were coaxial and could be matched by rotating the table. Patients were instructed to perform shallow respiration with oxygen. The motion of the tumor was monitored with the X-S. When the motion was slight enough, the table was rotated to the CT. To include all geometric movement on the CT images, each scan was made while the patient was performing shallow respiration. After the CT positioning, the table was rotated to the linac, and non-coplanar treatment was given. Beginning in October 1994, 45 patients with 23 primary or 43 metastatic lung carcinomas were treated. Radiation doses at the 80% isodose line were 30-75 gray in 5-15 fractions over 1-3 weeks with or without conventional radiation therapy. RESULTS The treatment was performed with no or minimal adverse acute symptoms. The daily treatment time was short. During a median follow-up of 11 months, local progression occurred in 2 of 66 lesions. Interstitial changes in the lung were limited. CONCLUSIONS With this unit and procedure, focal radiation therapy similar to stereotactic radiation therapy is possible for extracranial sites. The preliminary experience appeared safe and promising, and further exploration of this approach is warranted. Cancer 1998;82:1062-70. © 1998 American Cancer Society.

Vascular endothelial growth factor (VEGF) is a well known factor that induces angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been identified. We examined the isoform patterns of VEGF mRNA using reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. All the colon cancers examined expressed VEGF121. The isoform patterns were classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3, VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1 expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The patients with liver metastases showed the type 3 isoform expression pattern at a significantly higher incidence (12 of 16, 75%) than those without liver metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was significantly associated with M1 stage (P=0.019). The patients with colon cancer and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox-Mantel). The colon cancers with the type 3 pattern showed a significantly higher involvement of veins (P=0.006). These observations suggest that the aberrant type 3 expression pattern of VEGF189 mRNA isoforms is correlated with liver metastasis, M stage, and poor prognosis in colon cancer. Images Figure 2 Figure 3

肺転移を切除した稀な胃癌5例について, 原発巣と転移巣を臨床病理学的に比較するとともに免疫組織化学的に糖鎖抗原 (SLX, CA19-9) の発現を検討した.再発転移形式で分類すると, 肺の転移巣再切除が可能と思われたのは3例であった.これらは肺を主たる標的臓器として転移巣を形成する傾向があったと考えられ, 共通点は転移巣の病理組織が分化型 (腸型) であり, CA19-9が陽性を示したことであった.このうち1例に5年生存が得られた.この1例は原発巣よりも転移巣でSLXの減弱がみられた.胃癌の結節状肺転移の形成や予後に糖鎖抗原が関与している可能性が示唆された.

On health examination, a nodular opacity of size of 25 mm was detected in a 54-year-old man. High-resolution computed tomography scans showed irregular-shaped ground glass opacity with bubble-like appearance in the right lung. The low-magnified histological findings after right upper lobectomy demonstrated squamous cell carcinoma that progressed along the alveolar septum and resembled the growing pattern of bronchioloalveolar carcinoma. As the mechanism of the formation of air density on computed tomography, the presence of check valve phenomenon was estimated. Squamous cell carcinoma of the lung that multiplies along alveolar walls shows localized ground glass opacity including air density areas similar to those in bronchioloalveolar carcinoma on high-resolution computed tomography.

BACKGROUND Angiogenesis is essential for solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator in vivo. Conversely, there have been few studies of the association between angiogenic factor expression and angiogenesis in esophageal carcinoma. The authors examined VEGF expression and microvessel density in esophageal squamous cell carcinomas to clarify the association of VEGF expression with the clinicopathologic features of the disease. METHODS Surgical specimens from 75 primary esophageal squamous cell carcinomas were examined for VEGF expression and microvessel density by immunocytochemical staining. Original anti-VEGF polyclonal antibody was used to determine VEGF expression, and antifactor VIII antibody was used to determine microvessel density. The isoforms of VEGF mRNA were determined by reverse transcriptase-polymerase chain reaction. RESULTS Thirty-five (46.7%) of the 75 esophageal carcinomas were positive for VEGF protein. There was a close correlation between microvessel density and VEGF positivity (P = 0.0002). High VEGF levels were significantly associated with well differentiated tumors, advanced stage (depth of invasion and blood vessel invasion), high incidence of distant metastases after surgery, and poorer prognosis. CONCLUSIONS The results of this study suggest that VEGF expression is associated with tumor progression and poor prognosis by stimulating angiogenesis in esophageal squamous cell carcinoma. Cancer 1997; 79:206-13. © 1997 American Cancer Society.

大腸癌肺転移を切除した20例の原発巣と転移巣について, 糖鎖抗原 (SLX, CA19-9) の発現を免疫組織化学的に調べ, 予後や転移との関連について検討した.原発巣と肺転移巣の糖鎖抗原の発現はほぼ同等であった.SLXを発現している群では原発巣切除後の生存率が発現していない群より不良であった.CA19-9と肺転移個数とに関連がみられ, 転移個数では4個までと5個以上で生存率に差を認めた.原発部位別では, 結腸癌は全例が糖鎖抗原陽性であり, 直腸癌は60%が陽性-であった.大腸癌の好肺転移性や予後と糖鎖抗原発現との関連が示唆された.

A method of endoscopic treatment via rigid bronchoscopy for treatment of tracheobronchial obstruction due to malignant tumor was discussed.Five cases involving the trachea, one case involving the tracheobronchus and 5 cases involving the main stem bronchi were treated with a Dumon bronchoscope (EFER, France) under general anesthesia from 1992 to 1995.Three cases of Nd : YAG laser irradiation to the endoluminal mass and 6 cases of Dumon stent to the extrinsic compression were performed successfully, and each airway obstruction was rapidly relieved. The quality of life was improved in these cases, however 2 other cases had a difficulty in stent fixation.Endoscopic treatment with a rigid scope is a safe and successful procedure because it maintains a good airway with a large open tube and is more comfortable for the patients, especially for those with a significant or life-threatening obstruction of a major airway.Bronchoscopists should use rigid bronchoscopes as well as flexible bronchoscopes in treating airway obstructions.

OBJECTIVES: Gastric cancer is the most common malignant tumour in Japan. Because gastric cancer metastases to the lung generally occur as lymphangitic carcinomatosis or numerous lesions, metastasectomy is rarely indicated. Therefore, the role of resectable pulmonary metastasectomy in gastric cancer is still unclear. The objective of this study was to determine the surgical outcomes and prognostic factors for survival after pulmonary resection of resectable metastatic gastric cancer. METHODS: The database of the Metastatic Lung Tumor Study Group of Japan was retrospectively reviewed. Between March 1980 and March 2011, 3831 patients underwent pulmonary metastasectomy. Fifty-one patients undergoing surgery for metastatic gastric cancer were analysed, and the survival parameters and prognostic factors after pulmonary metastasectomy were determined. RESULTS: The median time to recurrence after lung resection was 6 months (range, 0–29 months). The overall 5-year survival rate after pulmonary metastasectomy was 28%, and the median survival time was 29 months. Both univariate and multivariate analysis found that a disease-free interval