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

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

Objectives 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

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

Background 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. Methods 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). Results 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). Conclusions 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. © 2016 Wiley Periodicals, Inc.

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).

症例は52歳，女性．検診時の胸部Ｘ線写真で左下肺野に約1cm大の腫瘤影を指摘され近医を受診した．胸部CTで左肺舌区に境界明瞭な結節影を認め，肺動静脈瘻を疑われて当院を紹介された．3D-CTで左肺S4末梢に8mm大の結節影と結節に流入出する肺動静脈を認めたため肺動静脈瘻と診断し，胸腔鏡下に腫瘤を含めた左肺S4部分切除術を施行した．肺動静脈瘻は常染色体優性遺伝疾患であるRendu-Osler-Weber病の部分症状として認められることがあるが，本症例は遺伝性を認めず，単発性であり，口唇などの毛細血管拡張を認めなかった．孤立性肺動静脈瘻の術前評価に3D-CTが有用であった症例に対して胸腔鏡下肺部分切除術を施行し，良好な結果を得たので若干の文献的考察を加えて報告する．

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

症例は64歳，女性．2008年4月頃から咳嗽，喀痰が出現したため近医を受診し，胸部レントゲン写真で両肺野に多発結節影を指摘された．胸部CTでは径5～27mm大，両肺胸膜直下に多発する境界明瞭，辺縁不整な結節影を認めた．一部に石灰化を伴っていた．PET-CTで多発結節影に集積を認めたため転移性肺腫瘍を疑い，確定診断目的で胸腔鏡下に右肺部分切除術を施行した．胸膜直下に暗赤色調で中心部に白色の浅い陥凹を伴う腫瘤を認めた．右肺S3の腫瘤を切除し迅速病理診断に提出し，肺アミロイドーシスの診断を得た．最終組織診断はAL（λ）型の多発性結節性肺アミロイドーシスであった．術後に血液検査などを追加し，シェーグレン症候群の合併を認めた．結節性肺アミロイドーシスの本邦報告例55例では，全身性のものは認めず，シェーグレン症候群を合併する頻度が22％（12/55）と高頻度であった．

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

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

Supplemental oxygenation is important in reversible pulmonary failure. To determine whether the peritoneal cavity can be used as a source of "extrapulmonary respiration," we perfused the peritoneal cavity with oxygenated red blood cells (RBCs) and saline, and measured the amount of oxygenation delivered through the peritoneum of dogs under controlled ventilation. Inflow and outflow catheters were placed in the peritoneal cavity and connected to a perfusion circuit. We investigated the safety of this procedure by examining the relationship between intraperitoneal infusion volume and hemodynamic changes in dogs that underwent peritoneal perfusion with oxygenated RBC (n = 6) and with oxygenated saline (n = 6). The controls comprised dogs that underwent a sham operation (n = 6). We found that an intraperitoneal infusion of less than 1,250 mL was hemodynamically safe. Oxygenation levels (PaO2) increased most obviously with an intraperitoneal infusion of oxygenated RBC. The peritoneum can potentially serve as an "artificial lung" in critically ill patients.

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

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

One-Step Dry-Coated tablets (OSDrC) of a colon-targeting drug were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as the outer layer. Lag time in the 1st fluid, which simulated the stomach, was affected by differences in the pores occurring as a result of Chit dissolution. The dissolution rate of Chit was decreased by the addition of Eud-L. On the other hand, lag times in phosphate buffer (pH 7.4) simulating the small intestine, and in the 2nd fluid simulating the colon, were affected by differences in the pores occurring as a result of Eud-L dissolution and Chit swelling. The lag time of OSDrC with an outer layer of Eud-L:Chit at a ratio of 3:1 in each test medium was greater than the gastric emptying time in the 1st fluid and the small intestine transit time in phosphate buffer (pH 7.4). Furthermore, lag times were similar when test media were changed sequentially. Therefore, it is possible to deliver colon-targeting drugs as OSDrC with an outer layer of Eud-L:Chit at 3:1.

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

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

Pellet formulations as represented by multiparticulate systems are often contained in hard capsules. We examined the use of a different approach to the making of compressed tablets containing pellets, OSDRC-technology. OSDRC-technology employs a double-structure punch (center punch and outer punch) allowing for dry-coated tablets to be assembled in a single run. We examined the effects of the thickness of the outer punch, formability of pellets, and diameter of tablets on pellet filling. The results revealed that thinner outer punches are not always better for filling small tablets with large amounts of pellets. We considered that this was because the core pellets spread in a cone shape within the formulating tablets at filling, requiring a thickness of the outer punch and a particle density of the diluents at which pellets would not exude from the formulating tablets. It was suggested that the formability of core pellets affects the maximum number of layers of pellets, and higher formability would yield better results. However, we found that pellets with poor formability (tensile strength ofor =2 kPa) could be used in tablets. For the tablets, the larger the diameter, the greater the maximum number of layers. We considered this to be due to the friction between the pellets and punch wall. We concluded that OSDRC-technology could be applied to capsule-like forms containing pelletsor =50 wt% through an unconventional approach.

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.

Application of ultraviolet light irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30 seconds in an insoluble, flexible hydrogel. The FGF-2 molecules retained in the chitosan hydrogel remain biologically active and are released from the chitosan hydrogel upon in vivo biodegradation of the hydrogel. To evaluate the accelerating effect on wound healing of this hydrogel, full-thickness skin incisions were made in the backs of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. The mice were later killed, and histological sections of the wound were prepared. The degree of wound healing was evaluated using several histological parameters such as the rate of contraction, epithelialization, and tissue filling. Application of the chitosan hydrogel significantly advanced the rate of contraction on Days 0 to 2 in db/db and db/+ mice. Although the addition of FGF-2 into the chitosan hydrogel in db/+ mice had little effect, application of the chitosan hydrogel-containing FGF-2 further accelerated the adjusted tissue filling rate (Days 2 to 4 and Days 4 to 8) in db/db mice. Furthermore, the chitosan hydrogel-containing FGF-2 markedly increased the number of CD-34-positive vessels in the wound areas of db/db mice on Day 4. Thus, the application of chitosan hydrogel-containing FGF-2 onto a healing-impaired wound induces significant wound contraction and accelerates wound closure and healing.

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

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

症例は15歳, 男性. 2000年5月学校検診で胸部異常影を指摘された. 胸部X線写真で心陰影に重なり下行大動脈左側縁から左肺野へ突出する半円状の腫瘤影を認めた. CT, MRIでは左後縦隔に胸椎左縁に接する瓢箪形の充実性腫瘤影を認め, 左後腹膜腔の副腎部にも孤立性腫瘤影を認めた. 縦隔内神経原性腫瘍を考え胸腔鏡補助下小開胸開腹により腫瘍摘出術を施行した. 後縦隔の交感神経幹に沿って連続する3個の腫瘍と後腹膜腔左腎上部に1個の計4個の腫瘤を認め, これを一期的に摘出した. いずれの腫瘍も病理学的に神経節細胞腫であった. 後縦隔及び後腹膜腔に多発した神経節細胞腫は稀であるため文献的考察を加えて報告した.

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

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

The purpose of this study is to develop novel dividable coated tablets that retain their characteristics even after they are divided.We prepared dividable one-step dry-coated tablets (dividable-OSDRC) using our own manufacturing process with double structure punches. The release pattern of the dividable-OSDRC with hydroxypropyl methylcellulose (HPMC) or methacrylic acid copolymer LD (Eudragit) as an outer layer was investigated before and after the division, and dissolution profiles were statistically compared using difference factor f1 and similarity factor f2.The dividable-OSDRC with HPMC for sustained-release (compression pressure, 150 MPa; crashing strength, 6.1 N; friability, 0.05%; CV of divided tablet weight, 7.8%) showed statistically equivalent release patterns between the one-half and the whole (f1, 13.9; f2, 55.5) and between the one-half and the two-halves (5.5, 72.5). The surface area of the tablets affected the sustained-release profiles. Furthermore, the tablets made with Eudragit LD for timed-release (150 MPa. 12.8 N, 0.18%, 9.6%) also showed approximated release patterns before and after the division.We proved that dividable-OSDRC maintain their release characteristics after they are divided. We conclude that the dividable-OSDRC could be used as a new platform for the controlled release of drugs.

65歳の女性.高血圧で通院中に胸部異常影を指摘され当院を紹介された.胸部X線写真上, 左中肺野に約10cm大の辺縁明瞭な円形腫瘤影を認めた.胸部CT・MRIでは左前縦隔から左胸腔内のほぼ半分を占める内部不均一な嚢胞状腫瘤であった.前胸壁から穿刺吸引細胞診を施行し, 胸腺癌あるいは肺癌の診断であったため左開胸により摘出術を施行した.開胸すると腫瘍は左前縦隔に存在する縦隔腫瘍で胸膜播種と左上葉への浸潤を認め, 左肺上葉を合併切除し, 播種巣を可及的に切除した.腫瘍は13×9×5.5cm大で線維性被膜を有し, 内腔に著明な出血壊死を伴うTypeB3 (WHO分類), IVa期胸腺腫であった.術後化学療法及び残存胸腺に対する放射線照射を追加したが, 2年後に左胸腔内再発を来たし, 術後4年6ヵ月で亡くなった.ほぼ全体が嚢胞状変性を来した胸腺腫は検索し得た限り自験例を含め47例のみであり比較的稀と考え報告した.

This study was conducted in order to clarify the compression characteristics, and to confirm the superiority of the physical properties, of the newly invented One-Step DRy-Coated tablets (OSDRC). We compared both the compression characteristics and the physical properties of OSDRC with those of physical-mixture tablets (PM) that were prepared with the same ingredients, quantity, and compression pressures. We selected potassium chloride (KCl) and acetaminophen (AAP) as the model drugs, since the former is known for its appropriate compression characteristics and the latter for its brittleness. The advantage of OSDRC is that they are capable of maintaining any kind of drug in their core, because the core is tightly surrounded by the outer layer, even when the drugs in the core have poor compression characteristics, which causes difficulties in forming a solid core tablet using conventional dry-coated tablet methods. The radial tensile strength of OSDRC was the same as, or superior to, that of PM containing of AAP. The results were in accordance with the compression process analysis performed according to Kawakita's equation. The friability of OSDRC was also superior to that of PM. These preferable characteristics were attributable to the high intensity of the OSDRC outer layer surface in comparison to that of PM. It was difficult to clarify the difference between OSDRC and PM in their physical properties when KCl was applied, since the tabletability of the whole tablet was high due to KCl's physical properties. The OSDRC containing AAP in their cores showed a controlled release pattern, though no other materials that have been known to influence drug release was present. It was considered that this controlled release pattern was caused by a reduced AAP particle surface area due to compression. It was confirmed with these experiments that the compression characteristics and the physical properties of AAP-OSDRC were superior to those of PM. These results indicated that it is possible to produce tablets that have materials with poor compression characteristics in the core portion, and high tabletability materials for the outer layers. In other words, it is possible to produce capsule-like tablets using the OSDRC compression method.

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.