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Objectives Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. Methods This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. Results The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Conclusions Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era.

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

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).

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.

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.

Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology.In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores).In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively).Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc.

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.

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.

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.

Application of ultraviolet light (UV-) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) resulted within 30s in an insoluble, flexible hydrogel. About 20% of the FGF-2molecules were released from the FGF-2-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which no further significant release occurred under in vitro non-degradation conditions of the hydrogel. The FGF-2molecules retained in the chitosan hydrogel remained biologically active, and were released from the chitosan hydrogel upon the in vivo biodegradation of the hydrogel. In order to evaluate its accelerating effect on wound healing, full thickness skin incisions were made on the back of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure in both db/db and db/+ mice. However, the addition of FGF-2 in the chitosan hydrogel further accelerated wound closure in db/db mice, although not in db/+ mice. Histological examination also has demonstrated an advanced granulation tissue formation, capillary formation and epithelialization in wounds treated with FGF-2-incorporated chitosan hydrogels in db/db mice.

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

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.

Heparin-carrying polystyrene (HCPS) consists of low-molecular-weight heparin chains enriched in trisulfated disaccharide structures linked to a polystyrene core. In this study, the interactions between HCPSs of various molecular weights and heparin-binding growth factors, VEGF(165), FGF-2, and HGF, were compared to the interactions of the same factors with native heparin, periodate-oxidized heparin (IO(4)-heparin) and periodate-oxidized alkaline-degraded heparin (IO(4)-LMW-heparin). The binding of each growth factor to heparin-agarose beads (heparin-beads) was more strongly inhibited by HCPSs in a molecular weight-dependent manner than by native heparin or the modified heparins, indicating a stronger interaction between HCPS and these growth factors. HCPSs also inhibit heparin-binding growth factor-induced endothelial cell growth in a molecular weight-dependent manner much more strongly than the native or modified heparins. However, HCPSs did not inhibit the mitogenic activity of VEGF(121), which has a non-heparin-binding nature. Thus, HCPSs exhibit enhanced abilities to interact with each of the heparin-binding growth factors studied and to inhibit heparin-binding growth factor-induced endothelial cell proliferation in a molecular weight-dependent manner. These effects might be ascribed to the heparin-clustering effect of HCPSs.

The authors report a newly devised nerve stimulator and its clinical application in thoracoscopic surgery. The stimulator is a monopolar system, that has a long extension between the electrodes and the handle. The stimulator is inserted into the chest cavity through a portal, and is used to distinguish motor nerves from the surrounding tissue and to determine whether there is nerve involvement with tumor. The tumor is then safely and rapidly resected by thoracoscopic technique and the major nerves are spared. This method was used in two clinical cases, with excellent results obtained, and with no major complications.

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

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.

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

We aimed to identify prognostic factors after pulmonary metastasectomy for colorectal cancer and propose the clinical application of them. Furthermore, we endeavored to provide a rationale for pulmonary metastasesectomy.Several prognostic factors have been proposed, but clinical application of them remains unclear. Moreover, there is no theoretical evidence that pulmonary metastasectomy is indicated for colorectal cancer.We retrospectively analyzed 1030 patients who underwent pulmonary metastasectomy for colorectal cancer from 1990 to 2008. Prognostic factors were identified and the relationship of recurrent sites after pulmonary resection to pulmonary tumor size was assessed.Overall 5-year survival was 53.5%. Median survival time was 69.5 months. Univariate analysis showed tumor number (P0.0001), tumor size (P0.0001), prethoracotomy serum carcinoembryonic antigen (CEA) level (P0.0001), lymph node involvement (P0.0001), and completeness of resection (P0.0001) to significantly influence survival. In multivariate analysis, all remained independent predictors of outcome. In patients whose recurrent sites extended downstream from the lung via hematogenous colorectal cancer spread, pulmonary tumor size was significantly larger than in those with recurrent sites confined to the lung and regions upstream from the lung.We should utilize these prognostic factors to detect patients who might benefit from surgery. Therefore, we should periodically follow up advanced colorectal cancer patients by chest computed tomography to detect small pulmonary metastases before serum CEA elevation. Metastases to the lung or organs upstream from the lung are regarded as semi-local for colorectal cancer. This concept provides a rationale for validating surgical indications for pulmonary metastases from colorectal cancer.

Levels of nm23‐H1/nucleoside diphosphate kinase (NDP kinase) expression have been reported to correlate inversely with mctastatic potential in some tumors but not in others. Whether or not nm23 gene product is associated with metastatic potential in lung cancer is not clear as yet. We therefore immunohistochemically examined the expression of nm23 gene products in primary lung adenocarci‐no mas according to cytologic subtypes in order to clarify the association of its expression with the clinical features of the disease. Seventy‐two (64.9%) of the 111 lung adenocarcinomas were positive for nm23 protein. In lung adenocarcinoma of Clara cell type, high levels of nm23 expression were associated with advanced pathologic stage, positive lymph node status, and poorer prognosis (P

To ezamine the clinical relevance of P-glycoprotein, encoded by the human multidrug resistance gene (MDR1), to multidrug resistance in lung cancer, we examined the expression of MDR1 in 107 non-small cell lung cancer (NSCLC) specimens and 20 corresponding specimens of normal lung tissues. We also evaluated the relationship between MDR1 expression and the histopathology and pathological staging of NSCLC. The tumors consisted of 60 adenocarcinomas, 38 squamous cell carcinomas, 8 large cell carcinomas, and 1 adenosquamous carcinoma. MDR1 expression was semi-quantified by use of the reverse transcriptase-polymerase chain reaction method. We subclassified the NSCLC into 3 grades according to the MDR1 expression level (-, +, ++). Sixty-one of the 107 tumor specimens (57%) and 18 of the normal lung tissue specimens (90%) expressed various levels of the MDR1 gene. Only one tumor specimen showed higher MDR1 expression than the corresponding normal lung tissue. The relationship between pathological stage and MDR1 expression levels was not significant. These results suggest that the level of MDR1 expression in lung cells is decreased as cells progress from the normal to the transformed state.

In this study, in order to address the problems with manufacturing orally rapidly disintegrating tablets (ODT) containing functional (taste masking or controlled release) coated particles, such as the low compactability of coated particles and the rupture of coated membrane during compression, a novel ODT containing taste-masked coated particles (TMP) in the center of the tablets were prepared using one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture tablets (PM) were prepared by a conventional tableting method, and the properties of the tablets and the effect of compression on the characteristics of TMP were evaluated. OSDrC was found to have higher tensile strength and far lower friability than PM, but the oral disintegration time of OSDrC is slightly longer than that of PM following high compression pressure. Consequently, OSDrC approaches the target tablet properties of ODT, whereas PM does not. The deformation of TMP in OSDrC due to compression is slight, and the release rate of acetaminophen (AAP) from OSDrC is the same as from TMP. However, TMP on the surface of PM are considerably deformed, and the release rate of AAP from PM is faster than from TMP. These findings suggest that OSDrC technology is a useful approach for preparing ODT containing functional coated particles. Furthermore, we demonstrate that the elastic recovery of tablets can affect differences in the properties of OSDrC, PM and placebo tablets (PC).

Malignant pleural mesothelioma (MPM) has a poor prognosis, and conventional imaging modalities do not reflect the prognosis of MPM. In this study, the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) was evaluated for the differential diagnosis, staging and prognosis in MPM patients. Ninety patients who underwent 18F-FDG PET/CT scanning due to a clinical diagnosis or suspicion of MPM prior to therapy were reviewed. Of 90 patients, 31 were pathologically diagnosed as MPM. Maximum standardized uptake values (SUVmax) were semi-quantitatively obtained from PET/CT 60 min (early phase) and 120 min (delayed phase) after injection of 18F-FDG, and the clinicopathological correlations with the level of SUVmax obtained from PET/CT were examined. The survival curves of MPM patients were plotted according to the methods of Kaplan-Meier. The prognostic implications of the level of SUVmax were estimated by t-test. PET/CT scan showed intense abnormal FDG uptake (SUVmax>2.0) in the pleural lesions of all 31 MPM patients at delayed phase, while it showed abnormal FDG uptake in 30 (97%) patients at early phase. In all 31 MPM patients, the values of SUVmax at delayed phase were higher than those at the early phase. PET/CT also indicated metastasis in the lymph node in 7 patients (23%) and in the systemic lesions in 8 patients (26%) with MPM. Twenty-three MPM patients with high SUVmax, whose prognosis was apparent, showed significantly poorer prognosis in both early and delayed phase (respectively, p=0.03 and p=0.01, t-test). The results showed that 18F-FDG PET/CT at delayed phase is very useful for the diagnosis of pleural diseases, and SUVmax on PET/CT in the delayed phase is a more reliable prognostic factor than that in the early phase. High uptake of 18F-FDG PET/CT may be a predictive factor of prognosis in MPM patients.

Bronchial carcinoids are relatively rare, low-grade malignancies. Here we report a case of a bronchial carcinoid found by repeated pneumonia in the lingular division of the left lung. A 34-year-old man was referred to our hospital because of an abnormal shadow detected in an annual checkup. A chest computed tomography (CT) showed an infiltrative shadow in the lingular division. Two months later, a follow-up CT showed the shadow had remarkably improved. Two years after the 1st detection, an annual checkup revealed an abnormal shadow in the same lesion again. A chest CT showed not only an infiltrative shadow in the lingular division, but also a solid mass with calcification in the lingular bronchus. A bronchoscopy revealed an obstruction of the left upper lobe bronchus by a vascularized polypoid tumor. A transbronchial biopsy indicated a presence of a carcinoid, and a resection of the left upper lobe was performed. A histopathological examination showed that it was a typical carcinoid. The patient has been free of recurrence for 2 years since surgery. This is a case with repeated pneumonia and atelectasis caused by a bronchial carcinoid.

A 63-year-old woman with cystic bronchiectasis who had been treated in our institute was admitted for recurrent prolonged hemoptysis. Bronchoscopic examination showed bloody discharges in the left basal bronchus and a bulging polypoid lesion covered with intact bronchial mucosa in the left B8. In comparison with the bronchoscopic examination 6 years ago, the lesion was larger and the mucosal color changed more injected. A bronchial arteriogram revealed a convoluted and dilated left bronchial artery. Because bronchial artery embolization failed, a left lower lobectomy was performed. The diagnosis of secondary racemose hemangioma of the bronchial artery was pathologically established. A racemose hemangioma of the bronchial artery is characterized by an enlarged and convoluted bronchial artery. The bronchoscopic findings of this disorder have been rarely reported. This case may provide valuable information about serial bronchoscopic findings and the progression of secondary racemose hemangioma in the bronchial artery.

To assess whether early lung cancer prediction might be informed by an mRNA assay for 5-fluorouracil pathway genes in peripheral blood mononuclear cells (PBMNCs), we examined specimens taken from 51 adenocarcinoma patients and 38 controls (including six patients with benign tumors). PBMNCs and tumor-tissue specimens were taken for measurement of the mRNAs of various 5-fluorouracil pathway genes [thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT)]. By quantitative RT-PCR, all four mRNAs were detected in both PBMNCs and tumor tissues. In PBMNCs, TS mRNA/GAPDH mRNA levels were significantly higher in adenocarcinoma patients than in the controls, and significantly higher for pathological stages 2–4 and lymph-node involvement pN1–pN3 than for pathological stage 1 and pN0, respectively. No correlation between PBMNCs and tumor-tissue specimens was found for the level of any mRNA. Thus, the measurement of TS mRNA in PBMNCs might aid the diagnosis of lung adenocarcinoma.

Endobronchial aspergillosis is still an insufficiently recognized concept.Ten patients who did not have obvious predisposing factors and parenchymal fungal infection were analyzed. They were confirmed to have endobronchial Aspergillus by histology and culture, and were classified according to the presence of bronchiectasis, allergic reaction, and asthmatic symptom.Bronchiectasis was detected in all 10 patients, IgE elevation (370 IU/ml) in 7, Aspergillus specific IgE-RAST in 8, eosinophilia in 7, and asthmatic symptom in 5. Cases were classified into allergic bronchopulmonary aspergillosis (ABPA) (5 cases), ABPA not fulfilling Rosenberg's criteria (2 cases), and endobronchial aspergilloma (3 cases).We proposed classifying endobronchial aspergillosis without obvious systemic predisposing factors into "ABPA", "ABPA without asthma", "ABPA-S (seropositive)", and "Endobronchial aspergilloma". A fifth subtype of endobronchial aspergillosis containing "saprophyte" is warranted.

A 65-year-old woman whose parents were from Okinawa Prefecture, had productive cough and bilateral diffuse nodular lesions on chest X-ray. She had been shown a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. Video-assisted thoracoscopic lung biopsy showed marked peribronchiolar infiltration of lymphocytes and stenosis of bronchioles. HTLV-1 associated bronchiolo-alveolar disorder (HABA) was diagnosed. The symptoms, hypoxemia and chest X-ray findings improved with oral erythromycin. However, expiratory chest CT showing mosaic perfusion, pulmonary function test demonstrating increased thoracic gas volume, and ventilation scintigraphy resulting in decreased clearance during 8 years, all of those findings indicated progression of air trapping. Abnormalities on chest CT partially improved, but bronchiolar lesions have deteriorated. Expiratory chest CT, body phlethysmography and ventilation scintigraphy were recommended to clarify the course of HABA.

We report a case of bird-related chronic hypersensitivity pneuminitis exhibiting the fluctuation of serum markers for interstitial lung disease along with the changes in life environment. A 65-year-old man had had an abnormal chest radiograph for 2 years and had complained of a non-productive cough. He had had 30 parakeets 20 years previously and had used feather products for 15 years. In autumn and early winter wild birds had visited persimmons trees in the neighboring garden. Antibodies to bird-related antigens in the broncho-alveolar lavage fluids and sera were positive and the thoracoscopic lung biopsy specimens histologically revealed airway-centered fibrosis. We then determined he was having bird-related chronic hypersensitivity pneumonitis. After avoidance of feather products, all of serum SP-A, SP-D and KL-6 decreased. But three markers elevated and radiographic findings worsened accompanied with the increase of visiting wild birds in next autumn. After pruning persimmon trees and starting corticosteroid with cyclosporine, disease activity gradually improved.

Objective System l-amino acid transport mediates the uptake of aromatic neutral amino acids and nutritionally essential amino acids from extracellular fluids. Little is known about the role of l-amino acid transporter 1 (LAT1), a member of the system l-amino acid transporter family, in non-small-cell lung carcinomas (NSCLCs). Patients and methods We examined (i) LAT1 mRNA levels in 40 normal lung tissues (NLTs) and 237 NSCLCs using semiquantitative RT-PCR, (ii) LAT1 protein expression in 295 NSCLCs using immunohistochemistry, and (iii) whether LAT1 mRNA and protein expressions were related to clinicopathologic findings and outcome. Results The LAT1 mRNA level was significantly higher in all NSCLCs (6.81±1.13) than in NLT (1.00±0.18). The LAT1 mRNA level showed no association with clinicopathologic findings or outcome. LAT1 protein was detected with a diffuse or granular appearance within the cytoplasm and/or on the plasma membrane of tumor cells. When tumors were graded as positive if staining indicating a plasma membrane expression of LAT1 protein made up more than 10% of the tumor, the frequency of this membrane expression was found to be associated with tumor histology, differentiation grade, pathologic stage, T classification, pleural invasion, lymph-vessel invasion, and overall survival rate. Conclusion Detection of a plasma membrane expression of LAT1 protein would appear to be of value in informing the prognosis in NSCLC cases.

Supplemental oxygenation is essentially important in critically ill patients with potentially reversible pulmonary insufficiency. An extracorporeal membrane oxygenator and percutaneous cardiopulmonary support have been used for these patients. However, these techniques are associated with so many complications that an additional new therapeutic modality is required. The purpose is to investigate if the peritoneal cavity can be used as "extrapulmonary respiration" that is analogous to peritoneal dialysis and utilizes the efficacy of liposome-encapsulated hemoglobin (artificial oxygen carrier; TRM-645).Rats weighing an average of 300 g (n = 18) received an incision in the right chest to generate pneumothorax, which resulted in severe and lethal hypoxia. Oxygenated TRM-645 and human red blood cells (MAP group) were administered into the peritoneum in the experimental rats' pneumothorax model. No treatment except the right pneumothorax was administered to the sham group.Survival times from the pneumothorax were significantly longer in the TRM-645 and MAP groups than in the sham group (32.0 +/- 6.9 and 22.0 +/- 4.9 min vs 9.2 +/- 1.9 min, P0.01). In addition, an arterial blood gas analysis showed that the oxygenation in levels significantly improved.The abdomen (peritoneum) can potentially become an "artificial lung" that can be employed in critical care settings. TRM-645 provides an alternative to the use of washed human red blood cells.

Pulmonary and thymic lymphoid hyperplasia with characteristic clinicoradiological manifestations were seen in a 71-year-old woman who was diagnosed with primary Sjogren’s syndrome. A hazy opacity 12 mm in diameter and an anterior mediastinal nodule 20 mm in diameter were incidentally detected on computed tomography. Thoracoscopic biopsy revealed lymphoid hyperplasia in the lung accompanying thymic lymphoid hyperplasia. Immunohistochemically, the pulmonary lesion was considered to be nodular lymphoid hyperplasia (NLH), not lymphoma. A previously undescribed finding in the NLH was the hazy opacity containing an air bronchiologram, not a solid nodule. This finding might suggest a common causal relation for NLH, thymic hyperplasia, and primary Sjogren’s syndrome.

Case. A 54-year old woman was found to have an abnormal shadow in a regular checkup chest X-ray film. We suspected a bronchial artery aneurysm based on a contrast-enhanced chest CT. Aortography, bronchial arteriography and pulmonary arteriography showed a bronchial artery aneurysm, 2 cm in diameter, connecting the right bronchial artery, inferior phrenic artery, and pulmonary artery. Bronchoscopy revealed dilatation and hypervascularity of moniliform submucosal vessels below the right truncus intermedius. She underwent bronchial artery embolization several times, but new feeding vessels developed each time. We considered this case required surgical resection. Bronchoscopy after aneurysmectomy revealed decrease of moniliform submucosal vessels. Histological examination revealed a three-layer structure leading to both the pulmonary and bronchial arteries. Conclusion. We diagnosed idiopathic bronchial artery aneurysm connecting to a pulmonary artery.

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.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.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.

We report herein the case of a 30-year-old man who developed a primary leiomyosarcoma (LMS) 11 years after undergoing a median sternotomy for mediastinal seminoma followed by 50 Gy radiotherapy. He was given two courses of chemotherapy, resulting in 90% tumor regression, after which resection of the tumor with adjacent chest wall structures was carried out. Reconstruction was performed using a methylmethacrylate prosthesis prepared preoperatively. Post-operatively, he received two additional courses of chemotherapy and has had no sign of recurrence for 45 months.

It is not well understood what kind of histologic resolution is obtained with corticosteroid medication in sarcoidosis, or how we are able to judge cure in that disease. We examined the cases of sarcoidosis who were under steroid medication and received lobectomy and lymphadenectomy for combined lung cancer. Steroid treatment had been introduced for the relief of visual disturbance, not for the pulmonary lesion. Administration of corticosteroid improves clinical, laboratory, bronchoalveolar lavage and radiological findings, but it is difficult to make histological granulomatous inflammation completely disappear. Improvement of radiological and clinical problems in sarcoidosis is not the same as complete cure in patients with steroid-treated sarcoidosis.

Amplification of chromosomal DNA is thought to be one of the mechanisms that activates cancer-related genes in tumors. In a previous genome-wide screening of DNA copy number aberrations in a panel of non-small cell lung cancer (NSCLC) cell lines using an in-house bacterial artificial chromosome-based array, we identified a novel amplification at 14q11.2 in HUT29 cells derived from human lung adenocarcinoma. To identify the most likely target for the 14q11.2 amplification, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed NSCLC cell lines for the expression levels of 28 genes present within the 1-Mb amplified region. Significant overexpression in the HUT29 cell line with amplification, relatively frequent overexpression in additional NSCLC cell lines compared with an immortalized normal lung epithelial cell line, and reported information about the function of each candidate gene prompted us to characterize the BCL2-like2 (BCL2L2) gene, a prosurvival member of the BCL2 family, as the most likely target for the 14q11.2 amplicon. Immunohistochemical analysis of 61 primary cases of lung adenocarcinoma demonstrated that BCL2L2 overexpression was significantly associated with tumor stage and differentiation status, and tended to be associated with a poorer prognosis. Downregulation of BCL2L2 expression using small interfering RNA dramatically inhibited the growth of HUT29 cells, but showed no effect on anticancer reagent-induced cell death of the same cell line. These findings demonstrate that overexpressed BCL2L2, through amplification or other mechanisms, promotes the growth of NSCLC, especially the adenocarcinoma subtype, and might be a therapeutic target.

A 60-year-old man was given a diagnosis of pulmonary and ocular sarcoidosis. His radiological abnormalities and visual disturbance resolved after two years. Ten years later, at age 70, squamous cell carcinoma was detected in the right lower lobe of the lung. Lymphocyte CD4/8 ratio in bronchoalveolar lavage fluid has remained at a high level for the previous 10 years and was 7.41 immediately before the operation. Chest CT and gallium scintigram could not detect abnormalities in mediastinal or hilar nodes. The tumor and right lower lobe were resected with hilar and mediastinal lymph nodes. Histological examination revealed that there were numerous epithelioid cell granulomas in mediastinal and hilar lymph nodes. BALF analysis reflects residual granulomatous inflammation, even if the radiological findings do not show any abnormalities.

BACKGROUND Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis. High expression of TS is thought to be associated with poor prognosis in some kinds of cancers. However, this association has not been clarified for nonsmall cell lung carcinoma. In the current study, the authors investigated the clinicopathologic significance of TS mRNA levels and the correlation with cellular proliferation in patients with lung adenocarcinoma. METHODS The expression levels of TS mRNA were measured in 47 lung adenocarcinoma tissues using the Taq-Man real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method and examined the clinicopathologic significance of TS expression. To clarify the correlation between TS expression level and cell proliferation, the Ki-67 labeling index was also examined using immunohistochemical staining. RESULTS A positive correlation was observed between the expression levels of TS mRNA and stage of disease, lymph node metastasis, or tumor differentiation (P = .015). The higher expression group of TS mRNA showed a significantly poorer prognosis than the group with lower expression (P = .042). Moreover, there was a strong correlation noted between the expression levels of TS mRNA and the Ki-67 labeling index (P = .009). CONCLUSIONS The results of the current study demonstrated that TS may be associated with stage of disease, lymph node metastasis, tumor differentiation, prognosis, and tumor cell proliferation. These results suggest that the expression levels of TS mRNA may be useful for predicting the malignant potential in patients with lung adenocarcinoma. Cancer 2006. © 2006 American Cancer Society.

To comparatively assess the interpretation performance of hard-copy versus soft-copy presentations for detecting subtle pulmonary lesions and to estimate soft-copy cost-effectiveness.Computed radiography was used to obtain images with a 1,600x 1,200 matrix having 8 bits of gray-scale definition. The two separate image formats (hard and soft copy), which consisted of 60 chest radiograph combinations, were shown to five board-certified radiologists. The costs of hard copies, chemicals, waste disposal, and labor were calculated.The mean accuracies and Az values were 0.63 (hard) vs. 0.64 (soft) and 0.657 (hard) vs. 0.729 (soft), respectively. Reading one set of hard copies took on average 8.0 sec less than reading soft copies (30.3 vs. 38.3 sec). Estimated savings resulting from replacement of hard copy with soft were US$128,004 per year or US$6.20 per patient at our hospital.Conversion from hard copy to soft copy, using image processing, is feasible and cost-effective.

A pulmonary nodule was incidentally detected in a 50-year-old man during a routine health evaluation. High-resolution computed tomography (HRCT) showed that the lesion had the appearance of a collection of multiple tiny nodules. Histologic examination of the resected specimen revealed a single hamartoma resembling a bunch of grapes. Pulmonary alveoli and bronchioles were entrapped within the hamartoma with tumor buds appearing in a multicentric manner, thereby producing the unusual HRCT findings. Review of chest radiographs taken over the previous 20 years indicated that the tumor doubling time was 4968 days.