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Video-assisted resections of non-small cell lung cancer (NSCLC) are now performed worldwide; however, its validity as an oncologic surgical modality still remains to be elucidated.A consecutive series of 139 clinical stage IA NSCLC patients who underwent video-thoracoscopy combined with an access thoracotomy (VATS) or a standard open surgery (OR) were prospectively investigated regarding their status after undergoing a nodal dissection and their disease-free survival.Both the VATS (72 patients) and OR groups (67 patients) contained comparable populations in terms of age, sex, histological type, and surgical morbidity, and showed comparable operation time and estimated blood loss. The number of dissected nodes on the right/left side was 25.3/19.5 in the VATS group and 25.6/22.9 in the OR group (P = 0.923/0.313). A pathologic examination revealed the proportion of upstaged patients was 18% in the VATS group and 27% in the OR group (P = 0.439). The disease-free survival rates for both groups were almost completely identical, with rates at 5 years of 76.5% and 79.2%, respectively (P = 0.908).VATS is therefore considered to be an adequate oncologic surgery for clinical stage IA NSCLC, and is also appropriate for the postoperative adjuvant era.

There have been only a few reports about a surgical resection of pulmonary metastasis from malignant head and neck tumor. Here we investigate the survival after a pulmonary metastasectomy, and discuss the prognostic factors. We retrospectively reviewed 25 patients who underwent a pulmonary metastasectomy from malignant head and neck tumor at Kyushu University Hospital from 1981 through 2008. We assessed the five year overall survival by the Kaplan-Meier method and the log-rank (Mantel-Cox) test using the Stat View software program. The three- or five-year overall survival after a metastasectomy was 53.3% and 50.0%, respectively. We investigated the clinico-pathological prognostic factors including gender, age, histology, disease free interval, number or size of pulmonary metastatic tumors, and the operative procedure. Both age (older than 60 years) (P=0.0189) and pulmonary metastases from squamous cell carcinomas in either oral cavity or pharyngeal region (P=0.0002) were identified to be adverse prognostic factors. To obtain a long survival, a positive surgical resection is considered to be an effective and standard treatment for pulmonary metastasis from malignant head and neck tumor. It is also necessary, however, to elucidate fully the primary site and histology of such pulmonary metastasis.

IntroductionThis study first verified the T classification, which is the major point of the revision regarding the seventh Tumor, Node, and Metastasis classification, from a viewpoint of the clinicopathological findings at the primary tumor site in non-small cell lung cancer.MethodsThe medical records of 1393 patients with non-small cell lung cancer who underwent a complete resection at this hospital from 1974 to 2003 were thoroughly reviewed for pathologic findings and survival.ResultsAccording to greatest dimension of the primary tumors, the 5-year postoperative survival was 77.8% for T1a (≤2 cm), 63.3% for T1b (≤3 cm), 46.4% for T2a (≤5 cm), 38.8% for T2b (7 cm). The differences among those new T categories were all statistically significant. The incidence of lymphatic permeation within the primary tumor was 17.2% for T1b and 29.8% for T2a (T1b versus T2a, p < 0.05). The incidence of vascular invasion within the primary tumor was 24.9% for T1b, 35.3% for T2a, and 54.2% for T2b (T1b versus T2a and T2a versus T2b, p < 0.05). On the other hand, the incidence of pleural invasion of the primary tumor was 18.1% for T1a, 29.4% for T1b, 49.3% for T2a, 47.3% for T2b, and 87.5% for T3 (T1a versus T1b, T1b versus T2a, T2b versus T3, p < 0.05). Significant differences were observed among the newly revised T subsets in at least one incidence of lymphatic, vascular, or pleural invasion.ConclusionThe new T classification, which is based mainly on the tumor size, is therefore considered to be appropriate for the pathologic findings of the primary tumor.

Background The 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) has recently become an important non-invasive tool for the diagnosis and staging in several cancers. The standardized uptake value (SUV) of primary tumor has been reported to relate to cancer progression and prognosis, however, biological mechanism is still unclear. Method Seventy-nine patients with non-small cell lung cancer (NSCLC) who had undergone preoperative FDG-PET and a surgical resection were enrolled in this study. NSCLC tissue samples prepared from the surgical specimens were subjected to an immunohistochemical analysis for the expression of Ki-67 and vascular endothelial growth factor (VEGF) proteins. The relationships between the expression status of these proteins and SUVmax of primary tumors were evaluated. Result Concerning the relationship with various clinicopathological findings, SUVmax of primary tumors was associated with histology, tumor proliferation, pleural or vascular invasion, and pathological stage. A significant correlation was observed between the SUVmax and either the Ki-67 or VEGF expression (P

Smoking is an independent prognostic factor of lung adenocarcinoma. Benzo[a]pyrene (B[a]P) is one of the strongest carcinogens and it is present in both the environment and cigarette smoke. In this study, the effect of B[a]P on the proliferative activity of lung adenocarcinoma cells was investigated. A lung adenocarcinoma cell line, A549, was cultured with B[a]P for various periods, and its proliferative activity was examined by an MTS assay. To investigate the intracellular events related to the proliferative activity, the gene expression profile was investigated by a microarray analysis and a quantitative RT-PCR, and the protein expression and activation status of Akt, ERK 1/2 and the epidermal growth factor receptor (EGFR) were examined by a western blot analysis. Following the culture with B[a]P for 24 weeks, the serum-independent proliferative activity was increased. A microarray analysis revealed that a reversible upregulation of the EGFR and epiregulin genes was recognized in the B[a]P treated cells, in which the overexpression of the phosphorylated EGFR protein was also recognized. The EGFR tyrosine kinase inhibitor reduced the cellular proliferation and the level of phosphorylation of ERK1/2, which is a downstream signal of the EGFR, in the B[a]P-treated A549 cells. Moreover, the B[a]P treatment increased the mRNA expressions of the ligands for EGFR such as amphiregulin and epiregulin. B[a]P increases the proliferative potential of lung adenocarcinoma cells through the EGFR signaling pathway.

DNA polymerase lambda, pol lambda, is a eukaryotic member of the X-family DNA polymerases that is involved in two modes of DNA repair, i.e. base excision repair (BER) or non-homologous end joining (NHEJ). Using immunohistochemical approaches, we have observed pol lambda expression in human tissues, particularly in the respiratory system of lung cancer patients. pol lambda proteins were distributed in the nuclei of the epithelial cells in the bronchi, bronchioles and alveoli. Intriguingly, the level of pol lambda expression in the bronchiolar epithelia significantly correlated with the amount of habitual smoking in the individuals. Conversely, pol lambda expression in cancer tissues did not correlate with the smoking status of the patients. Pol lambda expression was sometimes discrepant between the tumor tissues and adjacent bronchioles. More importantly, tumors without pol lambda expression that occurred in heavy smokers significantly tended to be at an advanced clinical stage. Pol lambda may thus be involved in the DNA repair processes counteracting DNA damage caused by tobacco smoke in the respiratory system.

Summary Objective In the present study, we investigated the relationship between the urinary excretion rate of the oxidized nucleoside 8-hydroxydeoxyguanosine (8-OHdG) and clinical factors in lung cancer patients. Methods The present study included 100 patients, who underwent a lung surgery. The patients included 62 men and 38 women with a mean age of 65.5 years ranging from 35 to 82. The diagnosis included 81 primary lung cancers, 9 metastatic lung cancers and 10 benign lung diseases. Urine samples collected for 24 h were analyzed for the content of 8-OHdG using an ELISA assay. Results The urinary excretion rate of 8-OHdG in smokers was significantly higher than that in never-smokers. Specifically, the 8-OHdG excretion rate of current smokers was higher than that of patients who had quit smoking for longer than 1 month. Excluding current smokers, the urinary excretion rate of 8-OHdG did not relate to age or gender, but to the malignant potential of the disease. The urinary 8-OHdG level increased in the order of metastatic lung cancer, primary lung cancer and benign disease. In lung cancer patients, furthermore, the mean urinary 8-OHdG level of patients with stages II–IV disease was significantly lower than that of patients with stage I disease. Conclusions Smoking significantly increased the urinary excretion rate of 8-OHdG, suggesting that smoking causes an increased rate of oxidative DNA modifications. On the other hand, the capacity to repair oxidative DNA modifications might be impaired to some extent in cancer patients.

症例は48歳男性．20年前に右肋骨腫瘤を指摘されていた．受診1ヵ月前より持続する右胸痛あり．胸部単純写真にて，右上肺野に境界明瞭な円形のスリガラス陰影を認めた．胸部CT検査では，右第2肋骨に辺縁が骨で覆われた最大径10cmの腫瘤があり，内部のCT値は筋肉より軽度高値であった．MRIでは，腫瘤の内部はT1強調画像にて低信号，T2強調画像にて低～高信号が不均一に混在し，造影後は全体的に増強された．以上より，疼痛を伴う線維性骨異形成が最も考えられ，右胸壁腫瘍切除および再建術を施行した．切除標本の病理学的検索では，不規則な形の線維骨形成および紡錘形細胞の増殖を認め線維性骨異形成の診断であったが，悪性所見は認められなかった．

PID control has widely used in the field of process control and a lot of methods have been used to design PID parameters. When the characteristic values of a controlled object are changed due to a change over the years or disturbance, the skilled operators observe the feature of the controlled responses and adjust the PID parameters using their knowledge and know-how, and a lot of labors are required to do it. In this research, we design a learning type PID control system using the stochastic automaton with learning function, namely learning automaton, which can autonomously adjust the control parameters updating the state transition probability using relative amount of controlled error. We show the effectiveness of the proposed learning type PID control system by simulations.

BACKGROUND. To propose ‘never-smoking nonsmall cell lung cancer (NSCLC)’ as a separate entity, the clinicopathologic differences of operable NSCLC between never-smoking patients and patients with a history of smoking were investigated. METHODS. The medical records of 1405 patients with primary NSCLC who underwent a complete resection at the study institution from 1974 through 2004 were reviewed for clinicopathologic variables and postoperative survival. RESULTS. The proportion of never-smoking patients with NSCLC has been significantly increasing over 30 years, from 15.9% in the 1970s to 32.8% in the 2000s. A significantly greater proportion of female patients or adenocarcinoma patients was found in the ‘never-smoking NSCLC’ group in comparison to the ‘smoking NSCLC’ group (85.8% vs 11.2% and 87.8% vs 49.1%, respectively). The proportion of pathologic stage IA disease for the ‘never-smoking NSCLC’ group was significantly higher than that for the ‘smoking NSCLC’ group (40.1% vs 25.4%; P < .0001). With regard to both overall and cancer-specific survival, the ‘never-smoking NSCLC’ patient group was significantly superior to the ‘smoking NSCLC’ group. In addition to smoking status, the factors found to be significantly associated with the postoperative survival rate were sex, histologic type, T classification, and N classification by univariate analyses. A multivariate analysis revealed never-smoking status to be an independent prognostic factor in addition to pathologic T and N classification. CONCLUSIONS. The differences in the clinicopathologic factors and survivals between the ‘never-smoking NSCLC’ patient group and the ‘smoking NSCLC’ group suggest that NSCLC in never-smokers should be considered a separate disease entity. Cancer 2008. © 2008 American Cancer Society.

Aims Gefitinib shows prominent anti-tumor activity against advanced or recurrent non-small cell lung cancer (NSCLC). However, most gefitinib-responsive patients ultimately relapse. We reviewed postoperatively recurrent NSCLC patients who received gefitinib treatment, and analyzed both the clinical features and manifestations of treatment failure in patients who initially responded to gefitinib. Methods From 2002 to 2006, gefitinib was administered to in 34 postoperative recurrent lung adenocarcinoma patients. There were 13 men and 21 women with a mean age of 65years. Twenty patients had never smoked while 14 were former smokers. Epidermal growth factor receptor (EGFR) gene mutation was measured using surgical specimens of the primary tumor. Results The study group showed 1 complete response, 16 partial responses, 7 stable diseases and 8 progressive diseases. Mutations of EGFR gene were detected in 20 of 34 patients. Only the presence of EGFR gene mutations was significantly associated with the clinical response of gefitinib in our limited study ( p =0.036). In 9 of 12 responders, gefitinib treatment failed due to the appearance of new lesions. Conclusions Gefitinib was significantly effective for patients with mutations of the EGFR gene and most responders failed due to the appearance of new lesions without progression of the pre-existent target lesions.

BACKGROUND. The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS. A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS. Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level

A patient presenting with Pancoast syndrome was definitely diagnosed to have pulmonary leiomyosarcoma. The patient underwent a right upper lobectomy combined with resection of the chest wall, including the 1st to 3rd ribs. The disease recurred rapidly at the local and distant sites. No previous reports about pulmonary sarcoma presenting as a Pancoast tumor were found in the literature. The possibility of primary pulmonary leiomyosarcoma should be considered, and early detection and surgical resection are necessary when a round or oval tumor with necrosis is observed in the apex of the lung.

The most effective treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. Nevertheless, up to 20% of patients, even those with stage I NSCLC, relapse after surgery and die. The prognostic nutritional index (PNI) is used to assess immunonutritional conditions or is a predictor of postoperative recurrence in patients with digestive malignancies. However, the usefulness of the PNI for lung cancer is still unknown. We retrospectively analyzed clinicopathological features of stage I NSCLC patients to identify predictors of recurrence and to investigate effects of preoperative PNI levels.We selected 141 consecutive stage I NSCLC patients who were treated from August 2005 to August 2010. We measured their preoperative PNI levels in uni- and multivariate Cox regression analyses of recurrence-free survival.A low PNI was significantly associated with sex (P=0.0117), preoperative serum carcino embryonic antigen levels (P=0.0228), and postoperative recurrence (P0.0001). In multivariate analysis, PNI (RR: 9.243; 95% CI: 3.662-25.823; P0.0001), pleural invasion (RR: 8.664; 95% CI: 2.510-38.056; P=0.0005), and intratumoral blood vessel invasion (RR: 3.151; 95% CI: 1.259-7.681; P=0.0152) were independent prognostic factors. The low-PNI group had a significantly shorter recurrence-free survival than the high-PNI group, regardless of pathological T factors (T1a, P=0.0422; T1b, P0.0001; T2a, P=0.0098).The preoperative PNI level is a simple and novel predictor of recurrence in stage I NSCLC patients, and might help identify patients who will need multimodality therapy such as induction or adjuvant therapy.

The aim of this study was to report the incidence of lung cancer in patients with hematological malignancy (HM), as well as patient characteristics and outcome. We investigated 1503 consecutive patients treated for HM and 1208 patients who underwent surgical resection for lung cancer. Lung cancer with HM was observed in 12 patients (0.8 % of HM cases and 1.0 % of lung cancer cases), including eight men who were smokers and four women who had never smoked. The average Brinkman index was 1010, which suggested heavy smokers. In synchronous cases, all four patients preceded to HM treatment; however, three patients died from HM. In metachronous cases, during a mean 52.7 months after treatment of lung cancer, three patients had HM. At a mean 41.4 months after HM treatment, five patients had lung cancer and underwent surgery without serious postoperative events. A second cancer tended to be detected within 5 years after treatment of the first cancer. Men with a history of heavy smoking might be at risk for combined lung cancer and HM. Careful follow-up is recommended within 5 years after treatment of the first cancer. Most lung cancer detected synchronously with HM had poor prognosis. In metachronous cases, surgical resection of lung cancer after treatment of HM was feasible and safe.

Background Although stage IA non-small cell lung cancer has an optimistic survival rate, up to 10% of these patients relapse after surgical procedures and die. We retrospectively analyzed clinicopathologic features of patients with stage IA non-small cell lung cancer to identify recurrence predictors and to investigate effects of preoperative serum Krebs von den Lungen-6 (PS-KL-6) concentrations. Methods We selected 204 consecutive patients with stage IA non-small cell lung cancer treated from December 2003 to December 2009 for this study and tested their PS-KL-6 concentrations in univariate and multivariate Cox regression analyses of recurrence-free survival (RFS). Results High PS-KL-6 concentration (PS-KL6 High ) was significantly associated with sex ( p = 0.0006), smoking status ( p = 0.0438), histology ( p = 0.0049), and postoperative recurrence ( p = 0.0058). Both intratumoral blood vessel invasion ( p = 0.0345) and PS-KL6 High ( p = 0.0021) were identified as independent predictors of shorter RFS. Relative risk of patients with PS-KL6 High was 3.478 compared with patients with low PS-KL-6 concentration (PS-KL6 Low ; 95% confidence interval: 1.576 to 8.013). Among patients with tumors larger than 2 cm (T1b), the PS-KL6 High group had significantly shorter RFS than the PS-KL6 Low group ( p = 0.0040). Conclusions PS-KL-6 concentration is a simple and novel predictor of recurrence in patients with stage IA non-small cell lung cancer and might help to identify patients who will need more careful follow-up among T1bN0M0 series.

A 61-year-old man consulted a nearby doctor with the chief complaint of lassitude in June 2010. Blood tests revealed a hemoglobin level of 3.7 g/dL. The observation of significant anemia resulted in a full medical workup. On computed tomography (CT) findings, a large mass (17 × 10 cm in diameter) was found in the abdominal region. The lumen was distended with accumulation of air and fluid. In addition, I continued with a bladder wall, but did not recognize the abnormality that was apparent to a bladder lumen. There was no evidence of ileus. A diagnosis of appendix cancer or sarcoma was made preoperatively. During surgery, the bladder was observed to have some permeation, but the bladder wall contained a lesion of small intestinal origin with only slight permeation. The neighboring small intestine was surrounded by the tumor, with 3 sites of penetration. Histopathologic diagnosis indicated a high-risk gastrointestinal stromal tumor (GIST) with mitotic figures (44/50 high power fields). In accordance with the recommended guidelines, imatinib was administered for 1 year. Two sites of recurrences were observed by CT after discontinuing imatinib. A second operation was performed without increase because of the absence other lesions. Separate lesions in the sigmoid colon and jejunum were removed surgically. The tumor in the sigmoid colon was a lesion with high denaturation for mesenchymal system tumor such as GISTs by pathologic diagnosis. The lesion in the small mesentery was a suture granuloma. In this case, the combination of surgical management with chemotherapy resulted in good quality of life with no recurrence despite the presence of a high-risk GIST.

A single-center phase I trial was designed to determine both the dose-limiting toxicities and the maximum tolerated dose (MTD) for amrubicin hydrochloride in combination therapy with cisplatin for advanced non-small cell lung cancer (NSCLC) patients with prior chemotherapy.Eligible patients received amrubicin and cisplatin on days 1 through 3 every 3 or 4 weeks. Cisplatin was administered at a fixed dosage of 20 mg/m(2) while the administered dose of amrubicin was started at 20 mg/m(2). Each group comprised 3 or 6 patients. When dose limiting toxicities were noted in three or more of six patients at a particular level, that level was estimated to be the MTD.Fifteen patients were enrolled in this study, including 5 males and 10 females, with a median age of 57. The dose limiting toxicities included grade 4 neutropenia which lasted 4 or more days and febrile neutropenia. The non-hematologic toxicities were well managed and rarely severe. The MTD of amrubicin in this combination regimen was estimated to be 30 mg/m(2).A partial response was observed in 4 of 15 patients (27%).The recommended dose was thus determined to be 25 mg/m(2) amrubicin with 20 mg/m(2) cisplatin for 3 consecutive days. A phase II study is currently underway.

Background: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM. Methods: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m 2 , GEM 800 mg/m 2 and VNR 20 mg/m 2 on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy. Results: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively. Conclusions: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.

Summary Background and Objectives: To determine the prognostic factors for long-term survivors (LTS) with stage IV non-small cell lung cancer (NSCLC) who had undergone various treatments. Patients and methods: From 1990 to 1999, 222 NSCLC patients with stage IV disease, who had been treated in our department, were reviewed. As the initial treatment, 135 patients (48%) were treated with chemotherapy alone, 52 patients with a combination of chemotherapy and radiotherapy, 19 patients underwent an operation with or without any other therapeutic modalities and 16 were received radiotherapy alone. Results: Seventeen (7.7%) patients survived for more than 2 years, and all but one had adenocarcinoma. Among these LTS, eight patients received surgery as the initial therapy, and 16 (94.1%) received some type of local-control therapy, including surgery or radiotherapy, during the course of their disease. Regarding the clinical characteristics between LTS and others (non-LTS), an early N status, a single metastatic site, a good performance status, and surgery for initial therapy were all found to be significantly important factors for LTS. A multivariate analysis using a logistic regression model also showed an early N status and surgical treatment to be significantly associated with LTS. Conclusions: Selected patients with an early N status may be appropriate candidates for aggressive multimodality treatment including surgery, in order to provide a long-term survival for stage IV NSCLC.

Objective Visceral pleural invasion caused by non–small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis. Methods From January 1992 through December 1998, 143 consecutive patients with peripheral non–small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated. Results Forty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion ( P = .004), even patients with stage I disease ( P = .02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival ( P = .02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses ( P = .03), as were sex ( P = .03), age ( P = 002), and the stage of the disease ( P Conclusions This study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis.

Background and Objectives Surgery is a standard treatment in patients with clinical stage IB/II non-small cell lung cancer (NSCLC). We often have difficulty in treating of elderly patients due to their insufficient physiological function. To better manage such elderly patients, the clinical characteristics and prognosis of patients with these stages, who were 75 years of age or older, were reviewed. Methods From 1972 to 1999, 112 elderly patients with these stages were treated in our department. These patients comprised 88 men and 24 women. The histological types were 50 adenocarcinomas, 51 squamous cell carcinomas, 8 large cell carcinomas, and 3 adenosquamous carcinomas. Results Seventy-four patients (66%) underwent a surgical resection, including 60 surgery alone, 14 combined modality therapy. Radiotherapy, with or without chemotherapy, was given to 30 patients (27%), and chemotherapy alone to 5 (4.5%). In addition, 3 (2.7%) were given no therapy. The survivals of the surgery group at 2 and 5 years are 53% and 21% and those of the radiotherapy group are 35% and 3%, respectively. A multivariate analysis in radiotherapy group shows the predominant prognostic factor to be adenocarcinoma. The 2-year survival of the radiotherapy group in patients with adenocarcinoma is 58%, while that of patients with squamous cell carcinoma is 22%. Conclusions These above observations suggest that radiotherapy is an alternative strategy for patients who cannot undergo surgery, especially with adenocarcinoma. J. Surg. Oncol. 2004;87:134–138. © 2004 Wiley-Liss, Inc.

Bronchiolitis obliterans (BO) after lung transplantation prevents a satisfactory prognosis, and recent studies suggested that interleukin-10 (IL-10) gene transfer to distant organs could inhibit BO in rodent models. Although delivery of the therapeutic gene to a local airway would be favored to minimize systemic effects, current limitations include lower gene transfer efficiency to airway epithelium. As recombinant Sendai virus (SeV) can produce dramatically efficient gene transfer to airway epithelium, we determined if SeV-mediated IL-10 gene transfer to the local airway would inhibit bronchial fibrous obliteration in murine tracheal allografts. Administration of cyclosporine A (CsA) significantly promoted not only recovery of the injured airway epithelium but also SeV-mediated IL-10 expression (CsA- versus CsA+ =228+/-78 versus 3627+/-1372 pg/graft with 5 x 10(7) pfu), thereby suggesting the requirement of epithelia for efficient gene transfer. Even at the highest expression, no significant leakage of IL-10 was evident in the systemic circulation, and the induction of interferon-gamma was completely diminished on day 7 by IL-10 gene transfer. As a result, luminal loss was significantly prevented in allografts treated with SeV-IL-10 (luminal opening, all control groups: 0% respectively, and SeV-IL-10 5 x 10(7) pfu: 25.7+/-10.5%), an effect that was enhanced by short-term CsA treatment (SeV-IL-10 5 x 10(7) pfu with CsA: 63.7+/-12.7%). We propose that SeV is a useful vector that can target airway epithelium to prevent BO avoiding putative systemic effect.

The mediastinal gastroenteric cyst is a rare developmental cyst. In general, the majority of mediastinal gastroenteric cysts are recognized in infancy and are commonly located in the posterior mediastinum. In addition, gastroenteric cysts occasionally contain pancreatic tissue; however, no studies have reported that these cysts influenced the diabetes mellitus status of the patient. We report here an extremely rare case of an adult gastroenteric cyst with pancreatic tissue originating from the anterior mediastinum, influencing the severity of diabetes mellitus in a patient. This case report presents two remarkable findings. First, the location of the gastroenteric cyst (anterior mediastinum) and the patient's age at the time of detection (adulthood) were extremely rare. Secondly, the present case is also unusual in terms of glycometabolism. As this tumour decreased in size, the glycosylated haemoglobin value increased, which suggested a worsening of the patient's diabetes mellitus. The diabetes mellitus further worsened after removal of the tumour.

Epithelial-mesenchymal transition (EMT), when epithelial cells convert to mesenchymal cells, influences cancer invasion and metastasis. Smad interacting protein 1 (SIP1) is an EMT trigger, which is inversely correlated with E-cadherin in some carcinomas. To elucidate the role of SIP1 in esophageal squamous cell carcinoma (ESCC), the status of EMT and the clinicopathological features were evaluated. Immunohistochemical (IHC) analyses of 111 human ESCC tissue specimens for SIP1 and E-cadherin were performed, and the relationships between the expression and clinicopathological features were evaluated. IHC analyses of esophageal tumors showed the expression of SIP1 and E-cadherin to be significantly inversely correlated. Significant correlations between the SIP1 expression and clinicopathological variables such as differentiation, depth of invasion, vascular invasion, and pathological stage were also seen. Conversely, tumors with a weak expression of E-cadherin tended to exhibit greater histological differentiation. Logistic regression analyses revealed a positive SIP1 expression, lymphatic invasion, and vascular invasion to be factors predicting lymph node (LN) metastasis. Univariate survival analyses revealed a positive SIP1 expression predicted a poorer overall survival than a negative expression. These results suggest that SIP1 is correlated with LN metastasis and may therefore be an independent marker for metastasis in patients with ESCC.

A 65-year-old man was admitted to our hospital with nausea, vomiting and appetite loss. First upper endoscopic examination and X-ray examination showed a peptic ulcer and a pyloric stenosis. Fiberscope could not go through the pyloric ring. Computed tomography examination and biopsy showed no evidence of malignancy. Though we considered surgical resection of the stenosis at first, he could eat a staple food with therapy of proton pump inhibitor. So we followed up with upper endoscopic examinations. Second, third and forth upper endoscopic examinations showed no evidence of malignancy. Fifth upper endoscopic examination showed an ulcer scar on the pyloric ring and a 0-IIc carcinoma in the antral greater curvature. Distal gastrectomy with D2 lymph node dissection and B-II reconstruction. Pathologically, a mucosal carcinoma with no lymph node metastasis and U1-III peptic ulcer were diagnosed.

To identify the risk factors for postoperative biliary complications after hepatic resection for hepatocellular carcinoma.The subjects were 123 patients who underwent hepatic resection for hepatocellular carcinoma between January 2006 and December 2010. Perioperative factors related to postoperative bile leakage were studied.Postoperative bile leakage occurred in eight (6.5%) of the patients. Univariate analysis showed that liver fibrosis or cirrhosis (p=0.007), long operation time (5 hours) (p=0.002), major hepatic resection (p=0.024) and hepatectomy including Couinaud's segment 4 (p=0.0078) or segment 5 (p=0.023) were associated with an incidence of bile leakage. From multivariate analysis, operation time (relative risk=6.10, p=0.026) or resection of segment 4 (relative risk=6.86, p=0.017) were found to be independent risk factors for bile leakage.Prolonged operation time and hepatectomy including segment 4 led to a high risk for postoperative bile leakage in this series of patients.

We here report a rare case of synovial sarcoma of the chest wall. A 71-year-old Japanese woman noticed a left anterior chest wall mass after twice having had surgery for lung cancer. An aspiration biopsy diagnosed synovial sarcoma. She then underwent a surgical resection. Pathology examination revealed a biphasic-type synovial sarcoma. When the prepared RNA from the tumor was subjected to a polymerase chain reaction, SYT-SSX1 fusion gene transcripts were demonstrated. Patients with the SYT-SSX1 fusion gene have a worse clinical outcome than patients with SYT-SSX2-positive tumors. After a second surgery, performed in 1 year later, there was no evidence of recurrence for 30 months; however, careful observation may be required.

Posttransplantation lymphoproliferative disorders (PTLDs) are well-recognized complications of prolonged immunosuppression in recipients of both solid organ and bone marrow transplants, and they occur in 2% to 10% of these patients. 1 Most PTLDs are non-Hodgkin lymphomas ; therefore, a mucosa-associated lymphoid tissue (MALT) lymphoma has not been considered an entity manifestation of PTLD. Recently, Hsi et al. 2 reported 5 MALT lymphomas after solid organ transplantation, and they concluded that MALT lymphomas could be a rare form of PTLD. 2 However, in that series, all the MALT lymphomas originated in either the stomach or parotid gland but not in the lungs. This report presents the first case of a patient with a pulmonary MALT lymphoma after living donor liver transplantation (LDLT).

Postoperative toxic shock syndrome (PTSS) caused by toxin-producing Staphylococcus aureus has incidentally been reported to be experienced following various surgical procedures or wounds. This syndrome includes sudden high fever, headache, muscle ache, a sunburn-like rash, hypotension, and tachycardia, while also often showing a rapid progression and a fatal outcome. To date, no such cases have ever been reported after thoracic surgery. We herein describe a highly probable case of PTSS in a 61-year-old man who underwent a pulmonary resection for lung cancer. The patient recovered after immediate and intensive antibiotic and steroid therapies. PTSS can occur incidentally even in the field of thoracic surgery; therefore, thoracic surgeons should be aware of this possible onset in order to recognize and treat this disease in a timely manner.

A 51-year-old female was referred to our clinic for investigation of abnormal chest X-ray findings during a routine health examination. Chest computed tomography showed a middle mediastinal tumor, and she was admitted to hospital for surgical treatment. The tumor was removed using thoracoscopic surgery, without significant blood loss. Pathological examination showed that the tumor was composed of blood vessels with relatively thick vascular walls containing smooth muscle. Immunohistochemical staining was positive for CD34 and Factor VIII, and negative for D2-40. Based on these findings, the tumor was diagnosed as a cavernous hemangioma. We herein present this very rare case of middle mediastinal cavernous hemangioma.

The response characteristics of a squid axon have been investigated by several authors. The Hodgkin-Huxley equations (or H-H model) are in good agreement with the experimental results. The H-H model shows the chaotic response under the subthreshold stimuli. For muscle fibre, Falk and Fan formulated the Falk-Fatt equations (or F-F model), which art: nonlinear equations similar to those of Hodgkin and Huxley. However, the response characteristics of the F-F model have not been studied in detail. In the present study several aspects of the F-F model are studied. The F-F model is solved with trains of periodic current stimulations. Chaotic responses are observed under a special condition on pulse amplitude, frequency and width. Further, to investigate the general characteristics of the F-F model, an average firing rate is computed and phase variables are drawn in the phase plane. Finally, the relationship between the F-F model shows the chaotic response and the H-H model shows the n/m phase-locked os...

The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local therapy.

Purpose Increased numbers of patients with both lung cancer and atherosclerotic vascular disease (AVD) may be expected in the future. The aim of this study was to report the incidence of lung cancer in patients with AVD and to discuss patient characteristics and management. Method A total of 638 patients who underwent AVD treatment were investigated. Results Lung cancer was observed in 17 (2.7%) of 638 patients studied. The proportion of smoking history was significantly higher in patients with lung cancer (p = 0.0091).The pack-year index in patients with lung cancer was significantly higher than that in patients without lung cancer (p = 0.0073). Although 4 of 6 (66.7%) patients with concomitant lung cancer and AVD had stage I or II lung cancer, 5 of 7 (71.4%) patients with lung cancer diagnosed after AVD treatment had stage III or IV lung cancer. In patients with lung cancer found after AVD treatment, only 1 of 7 patients underwent surgical resections. The time until lung cancer was 12 to 198 months with a mean of62.5 months after AVD treatment. In concomitant cases, priority was given to AVD treatment in all 5 cases, and there were no serious events after the postoperative course. Conclusions Both patients with a smoking history and heavy smokers were at high risk for lung cancer, and most lung cancers found after AVD treatment were in the advanced stages and had poor prognoses. Therefore, we recommend careful and routine follow-up for screening lung cancer after AVD treatment.

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named “BioKnife”), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus–deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.

Maintaining blood flow in and supplying various anti-inflammatory or angiogenic cytokines to the bronchial stump are very important factors involved in its healing. Pericardial fat pad tissue samples surgically obtained from 20 patients were assessed, and their angiogenic ability was investigated. The messenger RNA level of all angiogenic cytokines, including vascular endothelial growth factor, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-A (PDGF-A), angiopoietin-1 (Ang-1), Ang-2 and hepatocyte growth factor (HGF) were detected in the pericardial fat pad tissue. The protein levels of all cytokines except PDGF-A increased with time from day one to day seven after primary culture of the pericardial fat pad tissue. In particular, both HGF and Ang-2 protein levels on day seven were significantly higher than those on day one (P=0.0475 and P=0.0417, respectively). On the other hand, the protein level of FGF-2 decreased in time and was significantly lower on day seven than on day one (P=0.0296). The present study demonstrated the angiogenic ability of the pericardial fat pad. These results suggest that reinforcement of the bronchial stump by the pericardial fat pad is a worthwhile and justified procedure, and may prevent bronchopleural fistula after pulmonary resections.

Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors.This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed.The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5 years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19 days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP ≥ 500 ng/ml in comparison to those with AFP 500 ng/ml (p 0.05). No other factors were associated with the survival after pulmonary metastasectomy.The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.

We developed a method for predicting true-negative lymph node metastases in clinical IA non-small lung cancer (NSCLC) by the combined evaluation of computed tomography (CT), 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and the maximum standardized uptake value (SUVmax) of primary tumors. The subjects of this study were 94 patients with clinical stage IA NSCLC who underwent both preoperative CT and FDG-PET. We analyzed the relationship between the SUVmax of primary tumors and various clinicopathological factors to find the best method available for assessing true-negative lymph node metastasis. The pathological stages were IA (n = 80), IB (n = 4), IIA (n = 5), IIIA (n = 4), and IV (n = 1). Pathologic lymph node metastasis was recognized in nine patients and the SUVmax of these tumors ranged from 3.3 to 20.3. A SUVmax of 3.0 was defined as the cut-off point and patients were dichotomized according to this point. Tumors with SUVmax of 3.0 or less were associated with a significantly lower incidence of pleural and vascular invasion and were characterized by the degree of differentiation. The SUVmax of primary tumors reflects the grade of malignancy; therefore, the combined evaluation of FDG-PET/CT findings with the SUVmax of primary tumors may help predict lymph node metastasis negativity.

In this study, we investigated prognostic factors associated with survival after distantly metastatic recurrence in surgically resected non-small cell lung cancer (NSCLC), and clarified the influence of local treatment on the prognosis for oligometastatic recurrence.From 1994 through 2004, 418 consecutive patients with NSCLC underwent complete resection; 138 experienced a postoperative recurrence by December 2005. Of those, we reviewed 93 patients with only distant metastases for clinicopathological information, treatment modality, and survival.For the 93 patients with distant metastasis alone, the 2- and 5-year survival rates after recurrence were 43.9% and 38.7%, respectively. Of those patients, 44 first received local treatment, including radiotherapy in 31 and a surgical resection in 13. Their recurrent disease (oligometastases) was limited with the potential to be controlled with local treatment. The targeted metastatic organs were brain in 14 patients, bone in 14, lungs in 12, and other organs in 4. Significant prognostic factors for postrecurrence survival included adenocarcinoma histology, long disease-free interval (DFI) (1 year or longer), and the performance of local treatment for oligometastases.Local therapy such as radiotherapy and surgery, might be considered first-line treatment in patients with postoperative oligometastatic recurrence, especially those with a DFI ≥ 1 year.

This report presents an extremely rare case of a rapidly growing giant pericardial cyst which was surgically removed 20 years after the first detection. A 38-year-old asymptomatic male was referred because of rapidly growing mass on the right diaphragm. This lesion was detected about 20 years earlier and checked by a chest roentgenogram once a year. However, this lesion showed rapid growth over the last year, therefore surgical removal was performed. A pathological examination revealed this lesion as a giant pericardial cyst without inflammatory, hemorrhage or malignant cells. Therefore, there was no pathological explanation for the rapid growth of this cyst. In conclusion, general thoracic surgeons should be aware of the possibility of rapid growth, even if the diagnosis is a pericardial cyst.

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, exhibit up to a 70% response rate against non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the EGFR gene (EGFR). The mechanism of intrinsic resistance of EGFR mutation-positive NSCLC against EGFR-TKIs is not known. The current study assesses the relationship between the molecular expression of EGFR signals and the response to gefitinib treatment in patients with pulmonary adenocarcinoma to elucidate the mechanism of intrinsic resistance to gefitinib.The present study included 30 patients with pulmonary adenocarcinoma who were treated with gefitinib for a postoperative recurrence. The correlation between the response to gefitinib treatment and various clinical and molecular features was evaluated.EGFR mutations were detected in 20 (66.7%) of the 30 patients. The response to gefitinib treatment was a complete response in 1 case, partial response in 12 cases, stable disease in 4 cases, and progressive disease in 13 cases. Both univariate and multivariate analyses showed the presence of an EGFR mutation, and the expression of phospho-EGFR (p-EGFR) significantly correlated with a better response to gefitinib treatment. Ten of the 16 p-EGFR positive patients were disease controlled, but all 4 p-EGFR negative patients were intrinsically resistant to EGFR-TKIs (P = 0.025). Other factors including sex, smoking status, serum carcinoembryonic antigen and cytokeratin-19 fragment levels, EGFR, Met proto-oncogene, phospho-Met, and hepatocyte growth factor expression were not associated with the response to gefitinib treatment.These results suggest that, even if EGFR mutations were observed, a p-EGFR negative state might be a cause of intrinsic resistance to EGFR-TKIs.

This report presents the case of a patient with mediastinal liposarcoma treated by radiofrequency ablation (RFA) in an open thoracotomy setting. This procedure is safe and feasible, and it appears to be an effective option for patients with soft tissue sarcoma originating from the mediastinum, especially for patients who are not well suited to undergo a further surgical resection. This report on a new type of RFA treatment for mediastinal liposarcoma may therefore be informative for general thoracic surgeons.