[Successful Treatment of Spontaneous Esophageal Rupture with Empyema by the Open Drainage and Application of Basic Fibroblast Growth Factor].

A 77-year-old man vomited after alcohol drinking and was sent to our hospital by an ambulance due to sustained chest pain. Chest computed tomography (CT) showed pneumothorax and pleural effusion, and thoracic drainage was performed. Since food residue was found from chest drainage and esophagoscopy and esophagography showed injured potion on the left wall of the lower thoracic esophagus perforating to the left thoracic cavity, a spontaneous esophageal rupture was diagnosed. Establishment of fenestration for open drainage and gastrostomy were performed. After 49 days, the fistula was successfully closed by cleaning of the left thoracic cavity, with application of basic fibroblast growth factor and enteral nutrition through gastrostomy. The fenestration was closed after 53 days and the patient was discharged after 78 days.

[Right Upper Lobectomy for Lung Cancer with Partial Anomalous Pulmonary Venous Connection;Report of a Case].

A 75-year-old woman was pointed out a mass shadow in the right upper lobe by chest computed tomography (CT) 3 month ago. Bronchoscopic examination revealed adenocarcinoma, and right upper lobectomy was performed. Preoperatively, it was revealed that V1+2 returned to the superior vena cava while V3 returned to the normal position. Postoperative course was uneventful and there has been no recurrence 6 months post-surgery.

[Intraphrenic Bronchogenic Cyst;Report of a Case].

Bronchogenic cyst is not a rare disease, but cases of bronchogenic cyst in the diaphragm are rare. We report a case of intraphrenic bronchogenic cyst. A 68-year-old woman was pointed out a 30 mm tumor on the left diaphragm by chest computed tomography (CT) 12 years ago. Because the size of the tumor had been increasing for 12 years, she was hospitalized for surgery. The tumor in the left diaphragm was removed by thoracotomy. Histologically, the tumor was diagnosed as a intraphrenic bronchogenic cyst.

[Multiple Pulmonary Inflammatory Myofibroblastic Tumor].

A 67-year-old man visited hospital because of prolonged cough. Chest computed tomography (CT) revealed multiple tumors in bilateral lungs. Transbronchial lung biopsy did not reveal malignancy. Because antibiotic treatment was ineffective, partial resection of the right lung was performed for establishing the diagnosis. The pathological diagnosis was inflammatory myofibroblastic tumor. The postoperative course was uneventful. After 6 months postsurgery, he complained of breathing difficulty and exacerbation of the lesions was found by chest CT. By methylprednisolone pulse therapy, the symptom was improved, and the size of lesions reduced. Since this event, he has been administered oral prednisolone (PSL) 10 mg/day, and the exacerbation of the disease has not been noted.

[Pulmonary Fetal Adenocarcinoma Requiring Differential Diagnosis of Metastatic Lung Tumor;Report of a Case].

Fetal adenocarcinoma is a rare disease. We report a case of fetal adenocarcinoma requiring differential diagnosis of metastatic lung tumor. A 75- year-old woman was pointed out a 8 mm tumor in the right lower lobe by chest computed tomography(CT) 6 month ago. Because the size of the tumor had been increasing for 6 months, she was hospitalized for surgery. Because of the tumor shape, we suspected that the tumor was metastatic lung tumor of hepatocellular carcinoma for which she had undergone hepatic arterial infusion chemotherapy and radiofrequency ablation. A right lower lobectomy with lymph node dissection was performed and pathological diagnosis was high-grade fetal adenocarcinoma, stage IV.

[Pulmonary Nontuberculous Mycobacteriosis Appeared at the Surgical Margin of the Lung Cancer Surgery;Report of a Case].

A 70-year-old woman had undergone right S8+9 segmentectomy for stage I A lung cancer. Surgical staplers were used for an intersegmental line. Two years after surgery, routine chest computed tomography(CT) showed a 40-mm mass around the staple line in the right lower lobe, and positron emission tomography (PET) was positive. The mass was suspected to be local recurrence of lung cancer, and she was done additional surgery for resection of the remaining right lower lobe. The pathologic diagnosis was lung nontuberculous mycobacteriosis. It was suggested that nontuberculous mycobacteriosis developed at the atelectasis around the staple line. In addition to local recurrence, the possibility of nontuberculous mycobacteriosis should be considered in cases of pulmonary nodules appearing at the staple line after pulmonary resection.

[Pulmonary Chondroma; Report of a Case].

A 66-year-old man was pointed out a nodular shadow in the right lower lobe by chest computed tomography (CT) 4 years ago. Since the size of the shadow has been increasing for 4 years, he hospitalized for surgery. Partial resection of the right lower lobe was performed. Histopathologically, the tumor was composed of cartilage tissue without epithelial components, and was diagnosed as a chondroma. Postoperative course was uneventful and there has been no recurrence at 1 years and 8 months after surgery.

[Anormalous Systemic Arterial Supply to the Basal Segments of the Lung Presented with Chest Back Pain;Report of a Case].

A 58-year-old woman visited our hospital due to left chest back pain. Chest computed tomography (CT) showed 19 mm nodule in the left lower lobe with the abnormal artery supply from the descending aorta and it was diagnosed as the anomalous systemic arterial supply to the basal segments of the lung. She had undergone partial resection of the left lower lobe by video-assisted thoracoscopic surgery. Histopathology showed the inflammatory change with fibrosis and lymphocites in the nodule, and fungus-like bacterial masses with macrophages and neutrophils. At 7 days after the operation, the patient discharged without any problems. In order to perform less invasive treatment, early surgical intervention should be considered to prevent the spread of inflammation in the thoracic cavity.

[Tracheal Injury Successfully Treated without Surgery;Report of a Case].

A 73-year-old man was injured after crashing his automobile into a concrete wall, and was admitted to our hospital with breathing difficulties. Chest computed tomography showed extensive mediastinal emphysema, right traumatic pneumothorax, and a suspected tracheal injury at the membranous region. Because of the associated tracheomalacia, the site of the tracheal injury was difficult to find by bronchoscopy. In addition, as the patient's respiratory condition was stable, surgical treatment was not chosen. Due to the continuous air leakage from the right lung, the patient underwent surgery after mediastinal and subcutaneous emphysema improved. The postoperative course was uneventful.

Definitive concurrent chemoradiotherapy in a patient with stage IV non-small cell lung cancer due to cervical lymph node metastases.

In the American Society of Clinical Oncology guideline, it is mentioned that systemic therapy is a standard treatment, but there is no cure for patients with stage IV non-small cell lung cancer (NSCLC). Recent technical advances have facilitated the delivery of curative-intent radiation doses to some stage IV patients. In this report, we introduce a long-term disease-free survivor after concurrent chemoradiotherapy (CRT) and discuss considerations for this treatment. The patient was a 61-year-old woman diagnosed with stage IV adenocarcinoma of the lung classified as cT4N3M1c; the M1c classification was because of multiple synchronous pathologically proven cervical lymph node metastases (CLNM). We administered concurrent CRT to all lesions with a dose of 60 Gy in 30 fractions over 6 weeks. Concurrent chemotherapy consisted of two cycles of carboplatin and pemetrexed. Adjuvant chemotherapy was performed with five cycles of carboplatin and pemetrexed followed by three cycles of pemetrexed alone. As of 43 months after CRT, the patient was still alive without disease. In conclusion, our patient with stage IV NSCLC due to CLNM achieved long-term disease-free survival by concurrent CRT as with patients with locally advanced NSCLC. Patient subgroups should be explored to achieve long-term disease-free survival after definitive CRT in patients with stage IV NSCLC due to CLNM.

[Mediastinal Hemangioma Mimicking a Mature Cystic Teratoma;Report of a Case].

A 16-year old young man was referred to our hospital due to abnormal mass of mediastinum on chest radiography. Chest computed tomography scan revealed 45 mm mass in diameter with low density areas and ring shaped calcification at right upper mediastinum. However, chest magnetic resonance imaging showed no existence of fat nor calcification. Although no typical findings was observed, surgical resection was performed because mature cystic teratoma was undeniable. At complete video-assisted thoracoscopic surgery, tumor was found to be in the upper mediastinum covered with mediastinal pleura and with dense fibrous structures around it, and was resected with surrounding fat tissue. Histological diagnosis was hemangioma associated with lymphangiogenesis and arteriovenous malformation-like region in the surrounding fat tissue.

Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

AIM: Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III ß-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. PATIENTS AND METHODS: Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. RESULTS: The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0.0011). CONCLUSION: Customized adjuvant chemotherapy based on biomarker examination significantly improved the survival of patients with NSCLC, regardless of p-stage.

SCOP/PHLPP1ß in the basolateral amygdala regulates circadian expression of mouse anxiety-like behavior.

While disruption of the circadian clock triggers a spectrum of affective abnormalities, how the clock regulates mammalian emotionality remains unclear. Here, we characterized the time-of-day-dependent regulation of mouse anxiety-like behaviors. We show that anxiety-like behaviors are expressed in a circadian manner in mice and demonstrate that the clock machineries in the dorsal telencephalon (dTel) are required for the time-of-day-dependent regulation of anxiety-like behaviors. We identify suprachiasmatic nucleus circadian oscillatory protein (SCOP/PHLPP1ß) as an essential intracellular signaling molecule mediating this temporal regulation downstream of the clock. Using viral-mediated, basolateral amygdala (BLA)-specific knockout of Scop, we demonstrate that deletion of SCOP in the BLA exerts anxiolytic effects on the elevated plus maze at early subjective night, thereby blunting the circadian variation in the anxiety-like behavior. We conclude that the circadian expression of SCOP in the BLA plays a key role in generating circadian rhythmicity in the anxiety-like behavior. Our results demonstrate SCOP as a regulator of anxiety-like behaviors and reveal its key roles in the anxiogenic functions of the BLA.

Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung cancer cells.

BACKGROUND: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours. Aim of the present study is to establish gene therapy against RRM1-overexpressing tumours. METHOD: An adenoviral vector that encoded a short hairpin siRNA targeting the RRM1 gene (Ad-shRRM1) was constructed. Two RRM1-overexpressing non-small cell lung cancer (NSCLC) lines, MAC10 and RERF-LC-MA, were used. Finally, a human tumour xenograft model in nude mice was prepared by subcutaneously implanting tumours derived from RERF-LC-MA cells. RESULTS: Ad-shRRM1 effectively downregulated RRM1 mRNA and protein in both types of NSCLC cells and significantly reduced the percentage of viable cells as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (p<0.005). Caspase 3/7 analysis revealed that transfection with Ad-RRM1 increased the percentage of apoptotic cells in culture containing either type of RRM1-overexpressing cell (p<0.001). Treatment with Ad-shRRM1 exerted a potent antitumour effect against the RRM1-overexpressing RERF-LC-MA xenografts (p<0.05). Furthermore, Ad-shRRM1-mediated inhibition of RRM1 specifically increased sensitivity to gemcitabine of each type of RRM1-overexpressing tumour cell. Combination treatment with Ad-shRRM1 and GEM exerted significantly greater inhibition on cell proliferation than Ad-shRRM1 or GEM treatment alone. CONCLUSION: RRM1 appeared to be a promising target for gene therapy, and Ad-shRRM1 had strong antitumour effects, specifically anti-proliferative and pro-apoptotic effects, against NSCLC cells that overexpressed RRM1. Combination therapy with Ad-shRRM1 and GEM may become a new treatment option for patients with NSCLC.

[Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer.

G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non-small-cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki-67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87-positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki-67 index was significantly higher in GPR87-positive compared to GPR87-negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87-positive compared to those with GPR87-negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.

Spontaneous whole-lung torsion after massive pleural effusion and atelectasis.

We present a case of whole-lung torsion after massive pleural effusion and atelectasis. A 79-year-old woman with a history of recent pneumonia and pleurisy presented to our hospital and complained of left leg edema and pain that was considered to be vasculitis. A sagittal computed tomography (CT) scan showed that her whole right lung had a 120-degree counterclockwise torsion toward the hilum. We obtained and compared a CT image from the previous doctor. By comparing the CT scans, we determined that lung torsion had progressed gradually. To our knowledge, this is the first report that confirms the progress of whole-lung torsion with CT images.

Mechanism study of copper-mediated one-pot reductive amination of aryl halides using trimethylsilyl azide.

Reaction mechanisms of the copper-mediated amination of aryl halides with trimethylsilyl azide (TMSN3) were analyzed on the basis of the time-course study using reaction monitoring FT-IR, trapping an intermediary aryl azide by the Huisgen reaction, and the analysis of the generated N2 gas during the reaction. This amination would proceed through multiple pathways via aryl radicals and copper(I) azide.

[Plication of diaphragm for eventration of diaphragm caused by megacolon; report of a case].

A 70-year-old woman with severe respiratory distress was admitted to our hospital by ambulance. Chest X-ray revealed marked elevation of left diaphragm and invagination of megacolon. Colectomy was performed to improve the respiratory distress, but continuous mechanical ventilation was necessary after operation due to hypoxia and hypercapnea. Therefore, plication of diaphragm was additionally performed. With 10 rows of nonabsorbable sutures, 6 to 8 pleats were formed. The following day of operation, she was successfully relieved from the ventilator.

Teratoma with naturally occurring malignant transformation in a child.

We present a 12-year-old girl with a teratoma with malignant transformation (TMT) of the mediastinum. Computed tomography showed a cystic mass (5.0 cm × 4.0 cm) with a thick solid portion, in the anterior mediastinum. Six months later, the solid portion of the mass had enlarged, and surgical resection was performed. The resected tumor was 7.0 × 5.0 × 4.0 cm in size. The cystic portion was a mature teratoma, and the solid portion predominantly comprised a viable embryonal rhabdomyosarcoma. There were no immature teratomatous elements or other germ-cell components. The histopathologic diagnosis was a mature teratoma with embryonal rhabdomyosarcoma, a so-called TMT. The tumor recurred, despite adjuvant chemotherapy. The patient died of progressive disease 16 months postoperatively. To the best of our knowledge, no naturally occurring TMT of the mediastinum has previously been reported in a child. Surgical resection at an early stage is necessary.