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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.

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.

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.

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

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

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

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

Background. In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. Methods. The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. Results. The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 ± 25 mm Hg (mean ± SD) and 80 ± 20 mm Hg in the thoracic aorta; 77 ± 29 mm Hg and 48 ± 21 mm Hg in the trachea; and in the lung, 51 ± 11 mm Hg (chitosan hydrogel), 62 ± 4 mm Hg (fibrin glue, rubbing method), and 12 ± 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. Conclusions. A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations. (Surgery 2001;130:844-50.)

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

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

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

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

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.