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Background Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications. Methods From the 1210 cases of pleural fistulas that were treated at our institution between March 2015 and October 2018, 275 patients with recurrent primary pneumothorax or secondary spontaneous pneumothorax were selected for this study. PG was performed in 127 patients with persistent air leakage during exhalation. In addition, 35 patients with postoperative complications of air leakage persisting for 7 days or longer were included. Results Air leak points were detected in 119 patients (73%), in the apex of the lung in 65 cases, in the basal segment in 13 cases, and in the middle lobe or lingular segment in 9 cases. There were 8 cases of hilar lesions, 12 cases of S6 lesions, 8 cases of upper lobe lesions other than apex, and 4 cases of upper mediastinal lesions. Complications within 30 days were observed in 10 cases (6.2%), with 8 grade 2 cases involving fever, 1 grade 3 case involving infection, and one grade 1 case with abdominal distension. Conclusions The incidence of grade ≥3 adverse events after PG was 0.6%, which is considered acceptable. Our findings suggest that PG is a safe examination method to identify air leaks before surgery for pleural fistulas., Graphical abstract Pleurography (PG) can be easily performed with fluoroscopy in any facility. We performed PG in 162 cases, in which the rate of occurrence of adverse events of grade ≥3 was 0.6%. Air leak was detected by PG in 73% of cases. PG may be useful as a preoperative examination for awake video-assisted thoracoscopic surgery, during which leak testing is difficult. By assessing adhesions with PG, a change to the first port safe position, avoiding adhesions, was possible in 19% of cases. PG may provide useful information for surgical management.

A 65‐year‐old woman was brought to the emergency unit with an approximately 6‐month history of persistent fever and cough. Chest computed tomography (CT) demonstrated a 16‐cm heterogeneous mass with adjacent large cyst (approximately 4.0 cm). The patient underwent CT‐guided biopsy, and benign solitary fibrous tumour (SFT) was immunohistochemically diagnosed. As the symptoms were thought to be due to enlargement of the tumour, surgery was deemed necessary, and the tumour was successfully resected. Based on morphological and immunohistochemical examination of the resected specimen, the final diagnosis was dedifferentiated SFT (DSFT). Follow‐up CT verified disappearance of the pulmonary cyst. The cyst was speculated to be caused by a check valve mechanism, which may also suggest a rapid growth of the tumour. At the time of writing, 2 years post‐operatively, no tumour recurrence has been identified. This represents the first report of intrathoracic giant DSFT with a cystic lesion returning to normal lung parenchyma., A 65‐year‐old woman was brought to the emergency unit with an approximately 6‐month history of persistent fever and cough. Chest computed tomography demonstrated a 16‐cm heterogeneous mass with adjacent large cyst. The tumour was successfully resected, and the final diagnosis was dedifferentiated solitary fibrous tumour.

Background: In many diseases, there is a relationship between the ratio of the diameter of the pulmonary artery (PA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study is to examine whether the PA/Ao ratio at diagnosis of idiopathic pulmonary fibrosis(IPF) and combined pulmonary fibrosis and emphysema (CPFE) is associated with the pulmonary hypertension. At present time, there is no analysis of PA/Ao ratio in CPFE. Methods: The present study included 125 patients diagnosed with IPF or CPFE at a single center from April 2014 to March 2019. The diameters of the PA and Ao on chest CT at initial diagnosis were analyzed retrospectively.The images are classified according to An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline(2018). The diameter of the PA was measured at the subjective bifurcation. The diameter of the Ao was measured at the same slice. These imaging analysis were performed by two pulmologists. Results: The number of IPF and CPFE were 60(48％) and 65 (52％). IPF images were categorized into four types : UIP/ Probable/ Indeterminate/ Alternative Diagnosis, 33/ 37/ 48/ 7 cases, respectively. The mean PA and Ao diameters were 29.75mm and 34.75mm, and the mean PA/Ao ratio of IPF and CPFE were 0.830 and 0.883. The PA/Ao ratio is significantly increased in the IPF group (p the Indeterminate＋Alternative Diagnosis group (0.883 vs 0.825, p Conclusions: The progression of fibrosis or the presence of emphysema in CPFE may suggest pulmonary hypertension in pulmonary fibrosis.

A 51‐year‐old man was referred to our hospital, with a dumbbell‐shaped nodule measuring 40 mm in the right upper lobe of the lung. He was a current smoker with diabetes mellitus and bronchial asthma. The transbronchial biopsy was performed. However, definitive diagnosis was not obtained from the excised specimens. Bacterial culture of bronchial lavage fluid also yielded negative results, including for tuberculosis. After eight months of observation, the tumour had slightly increased in size. Surgery was planned to resect the tumour for definitive diagnosis. Because of the size of the tumour, a lobectomy of the lung was scheduled with the patient's consent. Four small incisions, each less than 1.2 cm long, were made in the chest wall for thoracoscopic surgery. To remove the specimen, we made a 3‐cm longitudinal incision 1 cm below the xiphisternal joint. The patient complained of no chest pain after surgery. The post‐operative course was uneventful., This study describes video‐assisted thoracic surgery (VATS) with minimal chest incisions to prevent chronic post‐operative intercostal neuralgia and paraesthesia, using a small subxiphoid incision only to remove the specimen.

Background The current state of thoracoscopic technology allows less invasive surgical procedures and requires fewer ports and incisions. Totally video-assisted thoracic surgery with a single port has emerged as the least invasive thoracoscopic approach. However, uniportal video-assisted thoracic surgery brings about considerable difficulties, necessitating the development of skillful techniques as well as specific surgical devices. In such situations as dense pleural adhesion and anatomical abnormality, it may be more burdensome, necessitating the conversion to conventional multiportal video-assisted thoracic surgery or even to thoracotomy. To troubleshoot these situations, we herein propose the use of additional technique which could support to sustain the confident operative field for uniportal video-assisted thoracic surgery. This procedure also provides the same cosmetic outcomes as uniportal video-assisted thoracic surgery. Case presentation A previously healthy, 77-year-old female was referred to our hospital, with a lung adenocarcinoma measuring 28 mm in the right upper lobe. Uniportal video-assisted thoracoscopic surgery was planned to resect the tumor. During operation, we found the incomplete interlobar fissure between the upper and the middle lobe and the abnormal lobulation of the upper lobe. Therefore, the modified marionette technique was introduced to make the procedure safer and easier. This technique proposed herein consists of employing the untethered gripping forceps to retract the lung, not requiring additional traumatic trocars. The postoperative course was uneventful and the patient `was discharged in 1 week after a modified uniportal video-assisted thoracic surgery for the right upper lobectomy. Conclusions The modified marionette technique produced sufficient operative views to attain uniportal video-assisted thoracic surgery safely in this case, rendering operative conversion unnecessary.

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.

Background Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients. Results This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032). Conclusions TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS. Electronic supplementary material The online version of this article (10.1186/s13023-018-0790-x) contains supplementary material, which is available to authorized users.

The development of colon cancer represents a major complication in patients with inflammatory bowel disease (IBD). The importance of microRNAs (miRs) in carcinogenesis is becoming clearer because miRs have been implicated in the regulation of cancer-related cellular processes to include apoptosis, differentiation, cell cycle progression, and immune function. In the current study, we sought to identify miR dysregulation specific to progression along the normal-inflammation-cancer axis in colonic specimens from patients with IBD.MiR microarrays and quantitative reverse transcription PCR were used to detect and confirm dysregulated miRs. Receiver operating characteristic curve analysis was applied to evaluate the potential use of miR-224 as a neoplastic disease marker in IBD. For miR-224 target messenger RNA (mRNA) identification, mRNA microarrays were employed in combination with bioinformatic analyses, Western blotting, and luciferase activity measurements.We identified 30 miRs that were differentially expressed between chronically inflamed mucosae and cancers arising from IBD tissues. MiR-224 levels increased successively at each stage of IBD progression and accurately discriminated cancers from normal or chronically inflamed IBD tissues. Moreover, mRNA arrays combined with bioinformatic analyses suggested the participation of miR-224 in cell cycle regulation. Subsequently, cell cycle experiments indicated that miR-224 regulates the G1-S checkpoint. Finally, in silico prediction analyses, confirmed by Western blotting and luciferase assays, identified p21 as a specific direct mRNA target of miR-224.These findings reveal miR dysregulation specific to IBD-associated colorectal carcinoma. MiR-224 is overexpressed in IBD cancers and targets p21, a key cell cycle regulator. Moreover, these results establish the participation of miR-224 in IBD carcinogenesis.

A 34-year-old male with frequent recurrence of right pneumothorax was admitted to our hospital. He was a current smoker and outwardly male without genital aplasia. He was diagnosed as tuberous sclerosis complex (TSC) at 2 year-old and underwent transcatheter arterial embolization for right renal hemorrhage due to renal tumor 2 years ago. Chest Computed Tomography showed that he had multiple tiny round cystic lesions with thin wall in both lungs. The recurrent pneumothorax was expected to be associated with TSC-Lymphangioleiomyomatosis (LAM). Video-assisted thoracic surgery was successfully performed. The operative and histological findings revealed that the bullae were classified into two groups; emphysematous bullae and bullae due to LAM. His postoperative course was uneventful. TSC-LAM is extremely rare, but in some cases the clinical recognition might be escaped due to subtle findings of bullae in early LAM, resulting in diagnosis as spontaneous pneumothorax.

Adrenocortical carcinoma (ACC) in childhood is rare: in 2002, only three new cases were reported in Japan. Although there is no established therapeutic management system, margin-free complete surgical excision of the tumor is very important to a satisfactory outcome. We report a case of ACC with bilateral pulmonary metastasis in a 10-year-old boy. Preoperative chest computed tomography (CT) showed pulmonary metastasis with near-water density. The patient was treated successfully with complete surgical resection of the primary tumor and adjuvant chemotherapy, including mitotane. After bilateral lung surgery for the metastatic lesions, the plasma dehydroepiandrosterone sulfate level became negative.

Lung cancer associated with Sweet's syndrome is extremely rare. There are only seven reports of such cases. As far as could be determined from a comprehensive search, there is no reported operative case of lung cancer with this syndrome in the world literature. A 75-year-old Japanese man was diagnosed as having Sweet's syndrome. A chest computed tomography (CT) scan to screen for malignant lesions associated with this syndrome revealed an abnormal shadow in the lung. Although [(18)F]2-fluoro-2-deoxy-D: -glucose positron emission tomography showed no abnormal uptake, lung cancer was most strongly suspected by chest CT. His erythema improved rapidly with steroid therapy and he underwent a segmentectomy (S(6)) of the right lower lobe. A pathological examination revealed lung adenocarcinoma (pT1N0M0: Stage Ia). The patient was discharged from the hospital without any worsening of Sweet's syndrome. We herein report a first operative case of an early stage lung adenocarcinoma with this syndrome.

Objective: To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of EGFR on lung cancer. Methods: We analyzed mutations in EGFR, KRAS, TP53, and ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines. Results: Mutations in EGFR were found only in adenocarcinoma (35 of 106 adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of EGFR and KRAS genes were observed.Mutations of EGFR were well associated with a positive response to gefitinib. Cells with EGFR mutations were very sensitive to gefitinib as well as siRNA-mediated knockdown of EGFR, those with KRAS mutations responded poorly, and those without mutations of KRAS and EGFR showed moderate responses to both treatments. Conclusions: Our present results imply that (1) mutation analyses of EGFR and KRAS provide valuable information about whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments, and (2) siRNA-mediated knockdown is effective in lung adenocarcinomas with EGFR mutation, probably in those with resistance to gefitinib by acquired mutation in EGFR.

症例は65歳，男性．胸腺腫を合併した重症筋無力症（MGFA分類IIIb期）の診断で当院神経内科に入院．抗コリンエステラーゼ薬内服，血漿交換療法，メチルプレドニゾロン1000mg/日×3日間のステロイドパルス療法を施行し，以後ステロイド50mg/日の内服となった．ステロイド導入後約1カ月の胸部CTでは指摘された腫瘤は画像上消失していた．拡大胸腺摘出術を施行し，術後病理診断は胸腺腫（Muller-Hermelink分類混合型，WHO分類Type B2）の退行性変化であった．術前にステロイド導入を行った胸腺腫合併重症筋無力症においては，胸腺腫の退縮の可能性もあることを念頭に置くことが肝要である．

症例は22歳，男性．平成18年9月頃から呂律が回りづらく徐々に悪化していた．筋力の低下も出現し，当院神経内科紹介され精査を施行され筋緊張性ジストロフィーと診断された．スクリーニングの為撮影した胸部CTにて前縦隔腫瘍を指摘され平成19年2月当科紹介となった．確定診断を得るため摘出生検を施行した．術後は手術室にて抜管可能であったが喀痰が多く，喀出も不良であり高炭酸ガス血症を生じ，胸部X線写真上無気肺を認め気管支鏡下に喀痰吸引を施行した．第4病日より歩行を開始してから喀痰も自己喀出可能となり術後12日目に退院となった．筋緊張性ジストロフィーは周術期管理に関して注意が必要とされ，術前に十分な説明と対処法を考慮しておくことが重要であると考えられた．

Background Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. Methods Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. Results TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P

We report a rare surgical case of a solitary pulmonary nodule due to Mycobacterium kansasii. A 59-year-old man was admitted to our hospital for examination of an abnormal shadow in the left upper lobe incidentally found on a chest radiogram. Computed tomography of the chest showed that the nodule was located in the left segment 1+2 and was irregularly shaped with a diameter of 35 mm. Thoracic fluorine-18 fluoro-deoxy-glucose positron emission tomography showed a high metabolic pulmonary lesion, with a maximum standardized uptake value of 5.1, consistent with findings for lung cancer. A bronchoscopy was performed to establish the diagnosis of lung cancer; however, it failed to show malignant cells. Because we could not confirm the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery was performed. The intraoperative rapid diagnosis of the nodule was epithelioid cell granuloma. Smear test of the resected specimen was positive for acid-fast bacilli, and a culture was also positive for mycobacteria, which were identified as Mycobacterium kansasii. Antibiotic treatment for M. kansasii infection was administered for a year after the surgical resection. Few cases of Mycobacterium kansasii infection present with solitary pulmonary nodules.

Aberrant DNA methylation is an important event in carcinogenesis. Of the various regions of a gene that can be methylated in cancers, the promoter is the most important for the regulation of gene expression. Here, we describe a microarray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip (PMAD). For each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved (unmethylated + methylated) DNA fragments were amplified and labeled with Cy3 and Cy5 respectively, then hybridized to a microarray containing the promoters of 288 cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were normalized to signals from Msp I-cleaved (unmethylated + methylated) DNA fragments (Cy5). Normalized signals from lung cancer cell lines were compared to signals from normal lung cells. About 10.9% of the cancer-related genes were hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study. Further analysis of primary tumors indicated that the frequency of hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD method is effective at finding epigenetic changes during cancer.

Even with advances in non-invasive diagnosis of diseases such as cancer or inflammatory diseases, tissue biopsy coupled with histopathologic examination remains the gold standard in establishing an accurate diagnosis.1–2 Generally, effective tissue diagnosis is fundamentally based on biopsying lesions that are suspicious based on visual inspection. Nevertheless, numerous mucosal conditions, such as dysplasia in ulcerative colitis or Barrett’s esophagus, are not always readily recognizable visually, and thus mandate surveillance protocols that involve random biopsies.3 To effectively sample large organs such as the colon, numerous biopsies are required,4 which can be time consuming. Moreover, due to the size of current forceps and the associated mucosal trauma and to the serial operation of the forceps, the number of random biopsies that can be realistically carried out is limited. Consequently, the current standard of care for cancer surveillance in ulcerative colitis patients is performed with at least 33 sequential biopsies (4-quadrant biopsies every 10 cm), which we estimate cumulatively samples less than 0.3% of colonic mucosa. The low sampling coverage may be ineffective at detecting precancerous or cancerous lesions, especially for early, small lesions that are also the most treatable.

Several lines of evidence have suggested that the long arm of chromosome 12 may carry a tumor-suppressor gene(s) that plays a role in pancreatic ductal carcinogenesis. We have previously found a significant association between loss of heterozygosity of the 12q arm and a poor prognosis in pancreatic cancer patients. In this study, we introduced a normal copy of chromosome 12 into some pancreatic ductal carcinoma cells. Both anchorage-dependent and -independent proliferations as well as invasiveness were similar throughout the hybrid clones when compared with their corresponding parental cells. In sharp contrast, significant suppression of tumorigenesis was observed after inoculation of the hybrid clones into nude mice. Measurements made up to 1 month later showed that there was a significant delay in the growth of tumors into which the introduced normal copy of chromosome 12 had been restored. More significantly, using our dorsal skin chamber and an intravital microscopy system experiment in SCID mice, we demonstrated and visualized directly that implantation of the hybrids failed to promote the angiogenic phenotype encountered in the parental cells. Gene expression profiling using the complementary DNA microarray system identified a set of 24 genes differentially expressed between the hybrids and parental cells. An additional set of 18 genes was also identified that were differentially expressed between the hybrid clone that lost its growth-suppression activity and one that retained such activity. Another set of 25 genes mapped on 12q was detected that showed high expression levels in the hybrid clones retaining growth-suppressive activity. In summary, this study provides the first functional evidence of the existence of an additional tumor-suppressor gene(s) on chromosome 12, whose absence is responsible for the pathogenesis in pancreatic ductal carcinogenesis.

症例は29歳, 男性. トラック運転中に居眠りをして大型トラックに追突, ハンドルで前胸部を強打した. 近医に搬送され気管分岐部裂傷の診断を得て, 当科に紹介された.気管支鏡検査上, 気管分岐部竜骨の左右主気管支接合部が損傷し直径約8mmの裂孔が認められた.受傷約24時間後に手術を開始.竜骨の損傷が比較的広範なため, 明らかな損傷部のみのdebridementと単純縫合閉鎖では術後縫合不全や肉芽性狭窄の危険性が高いと考え, 気管分岐部を切除しMontage型再建術を行った.術後, 気管・気管支吻合部合併症をきたすことなく良好に経過し第29病日に退院した.気管分岐部損傷に対する分岐部切除再建術の報告はこれまでないが, 竜骨の広範な破壊を伴う症例に対しては, 積極的にこの術式を考慮してよいと考える.

目的. 東北大学呼吸器外科および仙台厚生病院にて切除された2220症例の肺癌患者を対象に, 臨床像ならびに喫煙が予後に及ぼす影響における男女差の検討を行なった. 方法. 1952年から2000年において, 当施設にて切除された原発性肺癌手術症例のうち喫煙指数が把握できた2220例 (男性1617例, 女性603例) を対象とした. 結果. 女性では男性に比し, 腺癌の比率が高く, 男性は扁平上皮癌と大細胞癌の比率が高かった. 男女とも非喫煙者の5年生存率は喫煙者より有意に良好であった. 男女とも喫煙指数の増加によって腺癌の比率の減少が認められた. 癌死の割合が最も少なく, 非癌死の影響を観察するのに適切であると考えられる病理病期IA期症例にて検討したところ, 男性では全死因にて喫煙者の予後が有意に不良であったが, 肺癌死のみで生存曲線を比較すると非喫煙者と同等の予後であった. 結論. 喫煙と関連してI期腺癌男性患者にて非癌死が増加することが示された. I期腺癌女性患者において喫煙の影響は明らかとはならなかったが, 喫煙者の全死因での生存率は不良であり, 肺癌切除後の予後改善という観点からも両性での禁煙指導の重要性が示された.

症例は37歳男性.2001年7月より左側胸部痛があり近医を受診し, 胸部X線写真上, 左下肺野に腫瘤影を指摘されるも放置していた.その後同年10月より左側胸部腫脹が出現し, 疼痛も増悪したため再度近医を受診し, 当科紹介された.理学的所見としては左側胸部に皮膚発赤, 腫脹, 発熱を伴った弾性硬の腫瘤を触知し, 血液学的検査にて軽度炎症所見を認めた.胸部CTでは左側胸部に直径約10cmの腫瘤が存在し, 更に腫瘤は連続性に後縦隔, 左下葉の一部にまで達していた.気管支鏡では確定診断が得られず, 経皮的吸引細胞診を施行し, 肉腫が疑われ, 手術を施行した.病理の結果放線菌症との診断が得られ, Amoxicillin経口投与にて退院した.術前診断に苦慮した, 稀な進行期放線菌症の一例を経験したので報告する.

Long-term survival has become achievable after bone-marrow transplantation, but various pulmonary diseases due to chronic graft-vs.-host disease have been recognized. Particularly, bronchiolitis obliterans is a life-threatening complication with no effective remedy. Bilateral pneumothorax associated with bronchiolitis obliterans is rare, but it requires careful attention. In a 42-year old man with intractable pneumothorax after bone marrow transplantation and surgical procedures, extensive thoracolysis was effective as an acute treatment for this disease.

We report a rare surgical case of a bronchial hamartoma in subsegmental bronchus. A 70-year-old man was incidentally pointed out an abnormal chest shadow without any complaints. Chest computed tomography revealed a round nodule with diameter of 15 mm in the right upper lobe. The bronchoscopic examination revealed complete obstruction of right B2a by the tumor. Right S2 segmentectomy was done to make a definite diagnosis and to prevent possible obstructive pneumonia. Histopathological examination revealed that the tumor was a benign cartilage bronchial hamartoma.

局所進展型非小細胞肺癌症例4例に対し, シスプラチン (CDDP) +ビノレルビン (VNB) による術前化学療法を2～3コース施行し, PR2例, MR2例の臨床的効果を得た.手術適応ありと評価された3例に対し手術を施行し, Ef2 2例, Ef3 1例の組織学的効果を得た.術前化学療法の副作用として, 全例にGrade 3の白血球減少を認めたがG-CSF製剤の使用により速やかに改善した.輸血を必要とした血色素量減少を認めたのは1例であった.また放射線照射を加えた3コース目を実施した症例ではGrade 3の悪心・嘔吐を認めたが, CDDP+VNBによる術前化学療法の毒性は概ね許容範囲内であった.今後更に症例を重ね, 有用性を検討していきたい.

We report a rare surgical case of synchronous multiple primary lung cancers with synchronous multiple colon cancers. A 74-year-old woman was incidentally pointed out abnormal chest shadows. Chest computed tomography revealed 2 nodules in the right upper and middle lobe. Transbronchilal lung biopsy (TBLB) was done, and the tumor in the middle lobe was diagnosed as adenocarcinoma. In addition, positron emission tomography pointed out colon cancer. Colon fiber revealed multiple colon polyps and colon cancers. Immunostaining with thyroid transcription factor (TTF)-1 and Napsin-A for TBLB specimen was done to distinguish their association. With the diagnosis as primary lung cancer, we performed right upper and middle lobectomy with lymph node dissection. These tumors were pathologically diagnosed as synchronous multiple primary lung cancers with adenocarcinoma and squamous cell carcinoma. Several months later, colon regions were resected through colonoscopic endometric mucosal resection and left hemicolectomy.

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.

MicroRNA (miRs) have emerged as salient regulators in cancer homeostasis and, recently, as putative therapeutics. Cholangiocarcinomas (CCA) are aggressive cancers with survival usually measured in months. mRNA arrays followed by pathway analysis revealed that miR-494 is a major modulator of the cell cycle progression from gap 2 (G₂) to mitosis (M). We performed fluorescence activated cell sorting (FACS) as well as differential interference contrast (DIC) microscopy, and confirmed that miR-494 induces a significant arrest in G₂/M in CCA cells. Furthermore, we verified that miR-494 modulates the protein level of six genes involved in the G₂/M transition: Polo-like Kinase 1 (PLK1), pituitary tumor-transforming gene 1 (PTTG1), Cyclin B1 (CCNB1), cell-division cycle 2 (CDC2), cell-division cycle 20 (CDC20) and topoisomerase II α (TOP2A). Next, we identified direct binding of miR-494 to the open reading frame (ORF) and downregulation of PTTG1 and TOP2A. In summary, our findings suggest that miR-494 has a global regulatory role in cell cycle progression, exerted by concerted effects on multiple proteins involved in gap 1 (G₁) to synthesis (S), as described previously, as well as G₂ to M progression. Therefore, it appears that the simultaneous effects of a single miR species on multiple targets along the same canonical pathway is advantageous for the usage of miRs as therapeutics. In addition, our data suggest that miRs act within a narrow range. miR expression above the upper threshold does not appear to induce further effects, which is reassuring in terms of off-target effects of miR surrounding noncancerous tissue.

A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer.We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay.This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach.Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.

MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3′-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo. Conclusion: Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics. (HEPATOLOGY 2011)

Claudin-7 is a tight junction protein that plays an important role in tumorigenesis, tumor invasion and metastasis. We examined the clinical significance of claudin-7 expression in 75 postsurgical non-small cell lung cancer (NSCLC) patients. Claudin-7 expression was measured immunohistochemically and was found to be high in 25 patients (33.3%) and low in 50 (66.7%). Survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high NSCLCs (P=0.024). In particular, survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high squamous cell carcinomas (P=0.011). A reduced expression of claudin-7 was associated with poor outcome in NSCLCs. Claudin-7 may thus be a useful biomarker and a potential therapeutic target in patients with NSCLC.

S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca(2+)-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis. We observed frequent overexpression of S100A4 in pancreatic cancer cell lines and further analyzed RNAi-mediated knockdown to address the possibility of its use as a therapeutic target for pancreatic cancer. The specific knockdown of S100A4 strongly suppressed cell growth, induced G2 arrest and eventual apoptosis, and decreased cell migration. Furthermore, microarray analyses revealed that knockdown of S100A4 induced expression of the tumor suppressor genes PRDM2 and VASH1. Our present results suggest the possibility that the inhibition of S100A4 can be utilized in antitumor applications for patients with pancreatic cancer.

There are several reports describing [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) findings in patients with lymphomatoid granulomatosis (LYG). We report a case of grade I LYG that showed increased uptake of FDG. The patient was a 63-year-old Japanese male who underwent an FDG-PET/computed tomography (CT) scan in screening for a malignant lesion. Increased uptake of FDG [maximum standard uptake value (SUV(max)), 3.7] was observed in the right hilar region in FDG-PET and enhanced CT revealed a round, abnormal mass that also showed increased FDG uptake. The patient had no previous symptoms. A tumor biopsy was performed and the histological diagnosis was grade I LYG. Therefore, increased SUV(max) in FDG-PET might be useful for diagnosing of LYG.

We report a patient with primary lung adenocarcinoma who had Ewing's sarcoma and was successfully treated with ifosfamide. A 56-year-old Japanese man was referred to the Orthopedic Department of our hospital with a complaint of pain on his hip, ischuria, and dyschezia (vesicorectal disorder). MRI showed a mass in the sacrum. Open biopsy revealed Ewing's sarcoma (T2N0M0G4, Stage II B). Chest CT to screen showed an abnormal shadow in the left pulmonary lower lobe (S10). Bronchoscopic examination revealed primary lung adenocarcinoma(cT2N0M0, Stage I B). Because of a severe hip pain, treatment for Ewing's sarcoma by high-dose ifosfamide (day 1: 4 g/m2/day --day 2-7: 2 g/m2/day: total 14 g/m2) was given in one course before lung surgery. The lung adenocarcinoma became small, the reduction ratio of the tumor was 26.5% and the tumor changed into a cavity. No serious adverse effect was observed.

To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of EGFR on lung cancer.We analyzed mutations in EGFR, KRAS, TP53, and ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines.Mutations in EGFR were found only in adenocarcinoma (35 of 106 adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of EGFR and KRAS genes were observed. Mutations of EGFR were well associated with a positive response to gefitinib. Cells with EGFR mutations were very sensitive to gefitinib as well as siRNA-mediated knockdown of EGFR, those with KRAS mutations responded poorly, and those without mutations of KRAS and EGFR showed moderate responses to both treatments.Our present results imply that (1) mutation analyses of EGFR and KRAS provide valuable information about whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments, and (2) siRNA-mediated knockdown is effective in lung adenocarcinomas with EGFR mutation, probably in those with resistance to gefitinib by acquired mutation in EGFR.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.