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OBJECTIVES The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index. METHODS Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (>80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated. RESULTS Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively). CONCLUSIONS Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.

We investigated the role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in predicting the effect of induction therapy in patients with thymic epithelial tumors. Fourteen patients with thymic epithelial tumors who underwent PET-CT before and after induction therapy were retrospectively analyzed. The relationship between the change in the maximum standardized uptake value (SUVmax) in PET-CT, the response evaluation criteria in solid tumors and the pathologic response (Ef0, no necrosis of tumor cells; Ef1, some necrosis of tumor cells with more than one-third of viable tumor cells; Ef2, less than one-third of tumor cells were viable; and Ef3, no tumor cells were viable) was analyzed. The study cohort consisted of 5 males and 9 females. Nine of the patients had thymoma, and 5 had thymic carcinoma. The induction therapy included chemotherapy in 9 cases, chemoradiation therapy in 4 cases and radiation therapy in 1 case. Among the 8 patients with a pathologic response of Ef0/1, 5 were clinically evaluated as having stable disease (SD), while 3 were found to have had a partial response (PR). The SUVmax was elevated in 2 cases, unchanged in 1 and decreased in 5. On the other hand, 3 of the 6 patients with a pathologic response of Ef2, 3 were classified as having SD, while the other 3 had a PR. The SUVmax decreased in all of the patients. In comparison with CT, PET-CT seems to be useful for predicting the pathologic response to induction therapy in patients with thymic epithelial tumors.

Objectives The T descriptor of thymic epithelial tumours proposed by the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group as well as the Masaoka-Koga system is defined by the anatomical extent of primary tumours, regardless of their size. However, the prognostic significance of tumour size in thymic epithelial tumours has not been fully elucidated. Methods We evaluated the prognostic significance of tumour size in 154 consecutive patients with thymic epithelial tumours including 124 thymomas, 21 thymic carcinomas and 9 neuroendocrine tumours, who underwent complete resection between 2001 and 2014. Results Among all tumours, the median tumour size was 4.9 cm. The median thymoma, thymic carcinoma and neuroendocrine tumour sizes were 4.8, 5.7 and 5.8, respectively, although the differences were not significant. In survival analysis, the 5- and 10-year overall survival (OS) and recurrence-free survival (RFS) rates for all patients were 91 and 81%, and 80 and 69%, respectively. Under the stratification of tumour size, no trend was observed for OS, whereas RFS showed stepwise deterioration as tumour size increased. For 119 patients with Stage I disease, RFS showed deterioration as tumour size increased. Multivariate analysis revealed that tumour size >4.0 cm was an independent prognostic factor for worsening RFS (P = 0.03). Conclusions Patients with tumours >4.0 cm showed significantly worse outcomes in RFS compared with those with smaller tumours. This relationship was also noted in patients with Stage I disease.

Background Conditional survival (CS) is defined as living some additional time predicated on living to a certain time point. This study aimed to evaluate the usefulness of CS analyses for postoperative follow-up of surgically treated patients with lung cancer. Methods We retrospectively analyzed survival and clinicopathologic data from 859 patients with non-small cell lung cancer who underwent complete resection. CS is the probability of surviving additional time (y), after an individual has already survived for some time (x), and can be calculated from the following formula: CS(y|x) = S(x + y)/S(x), where S is the overall survival at a specific time. Results The 5-year cumulative overall survival rate was 75%. The additional 5-year survival rates at 1, 2, 3, and 4 years after operation (5Y-CS) were 75%, 77%, 77%, and 81%, respectively. The likelihood of surviving for a total of 5 years, 3 years after surgery was 89%. Age less than or equal to 70 years, female sex, no or light smoking, adenocarcinoma histologic type, pathologic stage I, and normal serum carcinoembryonic antigen levels were the clinicopathologic features associated with a high cancer-specific CS. For patients with favorable factors, the 2Y recurrence-free CS (3) reached 100%, whereas 5Y-CS did not change. Conclusions Estimates of CS probabilities may provide more meaningful information than traditional cumulative survival. Even in patients with favorable factors, a postoperative follow-up visit after 3 postsurgical years may be required.

Accurate preoperative evaluation of lymph nodes can provide optimal treatment for patients. However, in patients with clinical N1 disease (cN1) non-small cell lung cancer (NSCLC), no suitable predictor has been identified for hilar/intrapulmonary lymph node metastasis (pathological N1 disease; pN1). The purpose of this study was to identify pN1 in cN1 NSCLC patients. We retrospectively reviewed the clinicoradiological features of 109 patients with a discrete type of cN1 NSCLC who had undergone complete resection at our institution from 2004 to 2015. The association between clinicoradiological variables and nodal status was analyzed to identify predictors for pN1. The cohort consisted of 77 males and 32 females, ranging in age from 39 to 84 years. The breakdown by pathological N category was 40 (37%) pN0, 41 (38%) pN1, and 28 (25%) pN2 patients. Maximum lymph node diameter was identified as a significant predictor for pN1, with an odds ratio of 1.25 (P = 0.010). When limited to 63 patients who underwent positron emission tomography (FDG-PET) at our institution, the maximum standardized uptake value (SUVmax) of the lymph node was an independent predictor, with an odds ratio of 1.91 with logistic regression analysis (P = 0.004). The size of lymph node and the SUVmax were significant factors for pN1, with optimal cut-off values of 13 mm and 4.28, respectively. Among the patients with cN1, maximum lymph node size and SUVmax of the FDG-PET were significant predictors for pN1.

症例は34歳，男性．来院の1週間前より咳嗽が出現し，3日前より発熱が出現していた．就寝中に喀血を認めたため当院救急外来を受診した．胸部単純CTにて右肺下葉に低濃度の腫瘤性病変と液体貯留を認め，肺化膿症と診断し緊急入院とした．翌日，原因検索目的に胸部造影CTを施行したところ，胸部下行大動脈より右肺下葉に流入する異常動脈を認め，肺分画症と診断した．感染を合併し肺化膿症となった分画肺が破綻して血胸・肺内出血を来たし，気道系への吸い込みにて喀血となったと考え，緊急に右肺下葉切除を施行した．手術所見から分画肺は正常胸膜と境界がなく，肺葉内肺分画症であった．また一部胸膜が裂けており肺内に凝血塊も認められた．肺分画症は胸部X線写真などで偶然発見されることが多いが，放置すると今回のような重篤な経過をたどる可能性があるため，無症状でも手術適応があると再認識した．

症例は35歳男性．検診の胸部X線写真にて異常を指摘され，他院を受診し胸部CTにて左肺門に約35mmの腫瘤が発見された．超音波気管支内視鏡下生検を施行するも悪性所見は得られず経過観察となっていたが，FDG-PETにて同部位に軽度集積を認め（SUVmax 2.63），悪性腫瘍も否定できないため当院に紹介された．Castleman病，肺カルチノイド，悪性リンパ腫，炎症性偽腫瘍などを疑い手術を施行した．術中迅速病理診断は，明らかな悪性所見を認めず，リンパ増殖性疾患と診断されたため，腫瘍切除術を施行した．最終病理診断はCastleman病であった．肺門部の孤立性腫瘤の鑑別は困難な場合が少なくないが，縦隔に次いで肺門リンパ節はCastleman病の好発部位であるため，当疾患も念頭に置く必要があると思われた．

Background and Objectives The distinction of primary lung from metastatic breast cancer is crucial in patients presenting with a solitary pulmonary nodule after mastectomy, because treatment strategies are completely different. Definitive diagnosis of these nodules, however, is often difficult. We assessed the feasibility of our diagnostic approach for these nodules and estimated the frequency of primary lung cancer occurrence in patients after mastectomy. Methods We evaluated solitary pulmonary nodules appearing in 48 patients after mastectomy. For histological examination, CT-guided needle aspiration biopsy (CT-NAB) or trans-bronchial lung biopsy (TBLB) was performed. Besides conventional morphopathological examination, differential diagnosis was performed by immunohistochemical examination and evaluation using a molecular marker (mammaglobin 1). Results Biopsy specimens were obtained using minimally invasive methods, namely CT-NAB and TBLB, in 91.7% of patients. From 48 patients, differential diagnosis was obtained by morphopathological methods alone in 32, and by immunohistochemical and molecular marker examination in the remaining 16. Final diagnosis was metastatic breast and primary lung cancer in 40 (83.3%) and 8 patients (16.7%), respectively. Conclusions Our results show the clinical feasibility of our stepwise approach to the differential diagnosis of primary lung cancer and breast cancer relapse presenting as a solitary nodule in patients after mastectomy. J. Surg. Oncol. 2008;98:510–514. © 2008 Wiley-Liss, Inc.

38歳女性．8歳の時，中間気管支幹内の定型カルチノイドで右中下葉切除術を受けた．30年経って血痰が生じ，中間幹断端近傍に径40mmの腫瘤と気管分岐部リンパ節腫脹をみとめ，残存肺全摘（残存右上葉切除）とリンパ節郭清を施行した．術後病理診断は定型カルチノイドのリンパ節再発と転移であった．本症例は，定型カルチノイドでも手術時のリンパ節郭清と長期の経過観察が必要なことを示唆している．

Objectives The tumour-node-metastasis classification has been widely used as a guide for estimating prognosis, and is the basis for treatment decisions in patients with malignant tumours. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group have proposed a new staging system for thymic malignancies. However, its validity has not been fully established. In this study, we assessed the system's utilities and drawbacks. Methods We reviewed 154 consecutive patients with thymic epithelial tumours who underwent complete resection at our institution, and compared their characteristics and outcomes when classified according to the proposed system with those when classified under the Masaoka-Koga system. Results The proportion of patients with Stage I disease increased remarkably to 77.3% when using the proposed system because of the reclassification of Masaoka-Koga stages II and III diseases. Among 69 patients with Type A, AB or B1 thymoma, 68 tumours (98%) were reclassified as Stage I disease. Moreover, the proportion of Stage III and IV tumours increased in concordance with Types B2, B3 thymomas and thymic carcinoma. Under the proposed new system, the recurrence-free survival rates showed significant deterioration with increasing stage, while the overall survival curves did not. Conclusions The newly proposed classification for thymic malignancies does not serve as a prognostic prediction model for overall survival but served as a significant imbalance of stage distribution in our cohort. However, it appears to be beneficial, especially in clinical settings and recurrence-free survival analysis.

Spontaneous regression (SR) of cancer is a rare phenomenon. SR is recognized as complete or partial disappearance of the disease after inadequate or no treatment. Although reports of this phenomenon have been documented for several malignancies, it is rare in patients with lung cancer. In most documented cases, diagnoses of SR were made based on only the radiologic findings. We herein report a case of complete SR of non-small cell lung cancer (NSCLC) that was pathologically proven using a resected specimen. Moreover, despite the local complete SR, the patient subsequently experienced an adrenal metastasis after surgery. To the best of our knowledge, this is the first report of a patient with NSCLC in whom complete regression of the primary site was observed, but in whom a distant metastasis became apparent. Both phenomena were pathologically proven. Our report suggests that both SR and tumor progression can proceed simultaneously.

Primary lung cancer metastasizes to various organs, but rarely metastasizes to the breast. We report a case of breast metastasis from primary lung cancer, which was confirmed by the detection of the same epidermal growth factor receptor (EGFR) gene mutation.

We present a very rare case of simultaneous thymic carcinoids with similar size, one of which showed spontaneous regression. A 68-year-old man was admitted to the hospital because of two similar abnormal masses at his anterior mediastinum on chest computed tomography, one of which had decreased from 25 to 16 mm in diameter. A total thymectomy was performed and the pathologic examinations revealed that both tumors were atypical carcinoids. There have been seldom reports of multiple thymic carcinoids, and this case might suggest that total thymectomy is the best way to treat thymic carcinoid because of the possibility of multicentric origins.

Objectives: The increasing age of the population has raised the importance of determining the minimally required surgical treatment for elderly lung cancer patients. Despite a number of previous studies, the therapeutic impact of a radical mediastinal lymphadenectomy (RLA) associated with a pulmonary resection for lung cancer remains controversial. Herein, we investigated the impact of lymph node dissection on the overall survival for elderly lung cancer patients and assessed whether the non-performance of an RLA could be justified in the surgical treatment for these elderly patients. Methods: We analysed the data for 160 patients aged 70 years and older (113 males, 47 females) who underwent curative-intent surgery for non-small-cell lung cancer. They were divided into two groups, according to the method used for the intra-operative mediastinal lymph node dissection, the radical systematic lymphadenectomy (RLA, n = 76) and the non-radical lymphadenectomy (NLA, n = 94) groups.A Coxproportional hazardsmodel and the Kaplan—Meier methodwere usedfor the survival analyses.Propensity-based analyses were also used to reduce the effect of non-randomisation and possible bias in indication of treatment between the two groups. Results: RLAs had no protective effect on mortality; the hazard ratio for the RLA group in comparison to the NLA group was 0.97 (95% confidence interval (CI): 0.32— 2.89) in the multivariate analysis and 1.43 (95% CI: 0.42—4.91) in the propensity-based stratifying analysis. The 3-year survival probability was 81.3% (95% CI: 67.1—89.8) for the NLA group, which was marginally better than that of the RLA group (77.5% (95% CI: 63.3—86.8)). There was no significant difference in the overall survival between the two groups (p = 0.26). The 3-year survival probability of the NLA group at each quartile ofthe propensity scorealso tendedto bebetterthan thatoftheRLAgroup,whichdidnotshowany significantdifference.Conclusions:Therewas no survival benefit shown for RLA associated with pulmonary resections in the present cohort, even in the propensity-based analyses. Although some reports recommend a systematic mediastinal lymphadenectomy for proper staging and better survival, a pulmonary resection with nonperformance of radical lymphadenectomy could be an acceptable surgical treatment for the increasing number of elderly lung cancer patients. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Aortic cannulation is a difficult technique for young cardiovascular surgeons. A convenient training method for this procedure is introduced in this paper. After two gloves are worn on a hand, they are removed together, then a piece of mandarin-orange peel is inserted between the gloves. The inner glove is filled with water and the mouth of the inflated gloves is securely tied with a strong ligature. Then this "glove balloon" is set inside a container to stabilize it. Purse-string stitches are placed on the orange peel. After the center of the purse string is incised with a number 11 blade, a cannula is introduced. This "glove-and-peel method" will help young cardiovascular surgeons to become accustomed to aortic cannulation.

Soybean products intake has been suggested to have protective effects against breast cancer. As for lung cancer, we previously reported that soy consumption showed inverse association with the risk of non-small cell lung cancers (NSCLC) with epidermal growth factor receptor mutations among Japanese. However, other possible heterogeneity of its effect on the etiology of NSCLC by background characteristics is still unclear. In this study, we investigated the impact of soy consumption on the development of NSCLC among larger number of Japanese women, with the association of smoking status, reproductive factors, as well as histology. We conducted a case-control study with 420 NSCLC women cases and 840 age-sex matched control subjects. Dietary exposures were evaluated based on a semi-quantitative food frequency questionnaire, including items on lifestyles, menstrual and reproductive history. Soy consumption was categorized into two groups: a lower third group, “Low consumption group (LCG)” which intake of soy was less than 30.3 mg/day, and others, “High consumption group (HCG)” which intake of soy were 30.3mg/day or more. We assessed the impact of soy consumption on lung cancer by calculating odds ratios (ORs) and their 95% confidence intervals (CIs) of HCG, relative to LCG with adjustment for potential confounding factors using logistic regression model. In the overall analysis, we observed inverse association with high consumption of soy products [OR: 0.87, 95%CI: 0.65–1.16]. When stratified by smoking status, HCG in never smokers showed significantly inverse association showed an OR below unity [OR: 0.69, 95%CI: 0.50–0.96] in spite of the increased OR among HCG in ever smokers [OR: 2.02, 95%CI: 1.11–3.68]. As for reproductive factors, ORs of HCG were consistently below unity among women with pre-menopause [OR: 0.55, 95%CI: 0.29–1.04], menopause after 50 years old [OR: 0.57, 95%CI: 0.34–0.94], and no delivery [OR: 0.57, 95%CI: 0.15–1.06]. It is interesting to note that on histology based analysis, we found inverse association between high consumption of soy products and adenocarcinoma [OR: 0.57, 95%CI: 0.34–0.94] among never smokers, despite the increased ORs were seen among ever smokers [OR: 3.35, 95%CI: 0.17–67.7]. In this study, consumption of soybean products generally demonstrated an inverse association with NSCLC. In addition, the results indicated the interaction between soy consumption and smoking status for the impact on the development of NSCLC. We also found associations among soy consumption, reproductive factors and lung cancer, which indicated that female hormonal factors might be involved in the etiology of NSCLC. Further epidemiological evaluation is warranted. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B107.

There were a few reports of patients with lung cancer developing at the wall of giant bullae complicated with hemorrhage. A 40-year-old male with complaints of hemoptysis was referred to our hospital, and a solitary pulmonary mass was pointed out on his chest roentgenogram. Computed tomography (CT) demonstrated a well-circumscribed solid mass measuring 7.0 × 6.5 × 6.0 cm in the right upper lobe of the lung. At the chest CT 1 year before, only a giant bulla without mass was found. From the interval change of CT findings with his clinical course, the mass was suspected as acute hemorrhage in the giant bulla. A right upper lobectomy of the lung was performed to control his hemoptysis. The surgical specimen showed the giant bulla filled with blood clot, and a partial wall of the bulla was irregularly thickened. Pathological examination revealed that the thickened wall was composed of large-cell carcinoma. In patients with bullous diseases complicated with hemorrhage, we should be aware of a possibility of developing lung cancer in the bullae.

Background Late pulmonary metastasis from urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Case presentation A 76-year-old man was referred to our hospital due to an abnormal shadow on chest X-ray. He had a history of left nephrectomy with a diagnosis of UC in the renal pelvis 29 years previously. Computed tomography showed a mass lesion in the right middle lobe of the lung that measured 4.9 cm in diameter. A transbronchial biopsy revealed the tumor to be metastatic pulmonary UC, and he underwent right middle lobectomy of the lung. Conclusion Long-term postoperative follow-up of patients with UC might be necessary after radical nephrectomy.

目的．非小細胞肺癌におけるリンパ節転移巣の大きさや形態と予後との関係について検討した．方法．1996年1月から1998年12月までに一肺葉以上切除と縦隔リンパ節郭清を行った201例のリンパ節標本について，転移巣の最大径と形態を評価した．形態については，sinus permeation（SP）/stromal change（SC）/extracapsular invasion（ECI）の有無について検討した．結果．pN0は145例，pN1は20例，pN2は36例であった．2 mm以下の微小リンパ節転移（micrometastasis；mi）は，pN1で5例とpN2で4例認められ，2 mmを超える転移群（macrometastasis；ma）と生存比較したが，pN1mi vs pN1maではp＝0.439，pN2mi vs pN2maではp＝0.319と有意差は認めなかった．しかしmi 9例中，SP/SC/ECIを認めなかった4例はすべて4年以上無再発生存した．結論．非小細胞肺癌における微小リンパ節転移や形態を組み込んだ病期分類の細分化を行うことにより，より明瞭な予後の指標を示すことができると考える．