[Small Volume of 50% Glucose Solution Pleurodesis for Management of Inoperable Patients with Pneumothorax].

This interim report presents the results of pleurodesis with 50 ml of 50% glucose solution for patients with inoperable pneumothorax. Twenty patients were enrolled, and treatment was performed for 22 sites in total. The degree of lung collapse was mild in 2 cases, moderate in 12 cases, and severe in 8 cases. The mean number of treatments was 1.4 times (range 1~3). Mild chest pain after injection occurred in one case, and additional chest tube insertion was required for pleural effusion in one case. Other side effects, such as fever or dehydration, were not observed. On day one the mean blood glucose level was 145.0 mg/dl (range 103~259), and the mean pleural effusion volume was 284.6 ml (range 5~910). The air leakage was successfully controlled in 20 of the 22 sites( 91%). Pleurodesis in this manner was thought to be useful intervention for inoperable patients with pneumothorax.

[Immunoglobulin G4( IgG4)-related Fibrosing Mediastinitis Localized in the Retrosternal Area:Report of a Case].

An 84-year-old man was referred to our out-patient clinic with an elongated mass localized to the retrosternal area that was incidentally identified by computed tomography. On 18F-fluorodeoxyglucose-positron emission tomography, this lesion showed intense tracer uptake. Thus, a surgical biopsy under thoracoscopy was performed. Histological examination revealed dense fibrous tissue associated with inflammatory cell infiltration. The immunoglobulin (Ig) G4/IgG plasma cell ratio was over 90%. Serum IgG4 levels were normal. According to the Umehara criteria for IgG4-related disease, a final diagnosis of a "possible" IgG4-related fibrosing mediastinitis was made. Oral glucocorticoid treatment with 30 mg/day prednisolone reduced the mass.

[Thymoma Presenting Synchronously with a Mycosis Fungoides;Report of a Case].

A 65-year-old woman presented with mycosis fungoides and an anterior mediastinal tumor. Stage Ⅱa mycosis fungoides was treated with bath psoralen plus ultraviolet A, topical corticosteroids, and oral bexarotene. One month later, a surgical resection was performed for the anterior mediastinal tumor, which was a stage Ⅱ thymoma with membrane invasion. Furthermore, adjuvant radiotherapy was performed for anterior mediastinum. The mycosis fungoides lesion exacerbated after 3 months;thus, chemotherapies were performed. The patient died of respiratory insufficiency due to multiple pulmonary metastases of mycosis fungoides 1 year after the operation.

[Utility of Partial Splenic Embolization Prior to Lung Resection in Patients Demonstrating Platelet Transfusion Refractoriness Due to Hypersplenism].

It is often difficult to control perioperative bleeding in patients with liver cirrhosis and concurrent thrombocytopenia and coagulation factor deficiency. Partial splenic embolization (PSE), an auxiliary treatment strategy in management of liver cirrhosis and hepatocellular carcinoma, can not only increase platelets but also improve liver function. With advances in interventional radiology, PSE is a safer and more reliable procedure compared to a splenectomy. We present the case of a 69-year-old man diagnosed with left lung cancer, with thrombocytopenia, and hepatitis C virus-related cirrhosis. Although he was administered prophylactic platelet transfusion prior to operation, he was noted to be refractory to platelet transfusion. PSE was performed to improve his thrombocytopenia, following which we could safely perform left upper lobectomy of the lung and ND2a-1 lymph node dissection without any major bleeding. PSE is useful induction therapy to provide a wider choice of treatment options for patients with thrombocytopenia.

[Congenital Bronchial Atresia Requiring Differentiation from Intralobar Sequestration].

We reported a case of bronchial atresia requiring differentiation from the intralobar sequestration. A 42-year-old man was referred to our institution with suspicion of intralobar sequestration, based on a 3-dimensional computed tomography (CT) angiography that showed abnormal blood vessels from the right inferior phrenic artery flowing into the right lower lobe. CT revealed a lesion between S9 and S10 wherein there were refluxed blood vessels from A9 without an accompanying bronchus, with polycysts and emphysematous changes. Ventilation-perfusion scintigraphy revealed a reduction in uptake in the same sites. He was diagnosed as congenital bronchial atresia preoperatively, and we performed a right basal segmentectomy. Pathological examination confirmed the bronchiectasis and emphysematous changes in the lung parenchyma, but malignant findings were not confirmed.

[A Recurrent Case of Thymic Adenocarcinoma Effectively Treated with S-1 Over a Long-Term Period].

A 61-year-old woman with an abnormal radiograph shadow in her anterior mediastinum was admitted to our hospital and underwent an extended thymectomy. The pathological diagnosis of the tumor was a non-papillary adenocarcinoma of the thymus in pathological stage IV b using the Masaoka classification owing to mediastinal lymph node metastasis. We found parasternal lymph node metastases 5 months after her first operation, and subsequently, she underwent surgery and adjuvant radiotherapy. We found systemic lymph node metastases and metastatic lesions in distant organs, including her lungs, brain, and kidney 27 months after her first operation. Systemic chemotherapy, such as carboplatin plus paclitaxel and an ADOC regimen were not very effective, so we performed immunohistochemical staining of the primary thymic adenocarcinoma. The levels of both thymidylate synthase and dihydropyrimidine dehydrogenase were low; therefore, we started S-1 100mg/body (2 weeks of administration, 1 week of withdrawal)31 months after her first operation. She entered complete remission 6 months after the initiation of S-1. We surgically resected her solitary lung metastasis 13 months after initiation of S-1, and then continued the S-1 treatment. There was no recurrence for more than 2 years after the lung surgery. We believe that when the expression levels of thymidylate synthase or dihydropyrimidine dehydrogenase are low in cases of recurrent thymic adenocarcinoma, S-1 may be able to induce an effective response.

Risk factors associated with recurrence of surgically resected node-positive non-small cell lung cancer.

PURPOSE: The aim of this study was to identify risk factors for recurrence in non-small cell lung cancer (NSCLC) patients with lymph node metastases after surgical resection. METHODS: We reviewed 66 consecutive patients with surgically resected NSCLC who had pathologically proven positive lymph nodes (pN1 or pN2). All patients underwent a preoperative 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) evaluation. We analyzed the recurrence-free survival (RFS) and recurrence-free proportion (RFP) according to the clinicopathological factors. RESULTS: A total of 27 patients were pathologically N1 and 39 were N2. The 5-year overall survival rate and the RFS rate were 47.2 and 27.7 %, respectively. The cut-off values for the SUVmax of the tumor and the lymph node ratio (LNR) were determined to be 6.5 and 0.12, respectively, using a receiver operating characteristics curve analysis. Both univariate and multivariate analyses revealed three significant independent factors for RFS: namely, the SUVmax of the tumor, the LNR, and the use of adjuvant chemotherapy. Only the SUVmax was an independent significant predictor of the RFP. CONCLUSIONS: Both the SUVmax and the LNR can serve as prognostic factors for patients with pN + NSCLC. Our study suggests that the LNR could be a stronger prognostic factor than the N classification of the TNM system and the SUVmax may predict recurrence in node-positive NSCLC patients.

[Lung Segmentectomy Using Video-assisted Thoracic Surgery for Lung Cancer in a Patient with Situs Inversus Totalis].

The case was 83-year-old man who had complete situs inversus, and was pointed out to have peripheral adenocarcinoma with the size of 1.8 cm at the left upper lobe( S3). Because of severe emphysema and other multiple comorbidities, left S3 segmentectomy with hilar lymph node sampling was performed using video-assisted thoracic surgery (VATS). Preoperatively, the simulation of operation was performed using the 3 dimension computed tomography images of pulmonary arteriovenous and bronchus (3DCTAB). Postoperative course was uneventful. 3DCTAB was thought to be useful in understanding the anatomical location of pulmonary arteriovenous and bronchus directly, and in performing segmentectomy in the case of situs inversus like this.

[Current surgical treatment of primary chest wall tumor].

Primary chest wall tumor is relatively rare. According to the annual report by The Japanese Association for Thoracic Surgery in 2012, 447 primary chest wall tumors were resected in 2010. It was only 0.66% of the total number of operations in general thoracic surgery in Japan. From January 1992 to December 2012, 3,022 cases in general thoracic surgery were operated in our department. Of these, 30 patients (1%) with primary chest wall tumor were surgically treated. We retrospectively reviewed the medical records of them and investigated the details of this tumor. The patients group included 11 males and 19 females, with a mean age 57.6 years (range, 16 to 79 years). The majority of these patients were referred to us because of radiographical abnormalities on chest X-ray( 56.7%) or clinical symptoms( 33.3%). The operative procedure was tumor extirpation in 25 cases and chest wall resection in 5 cases. Histologically, 23 cases (76.7%) were benign tumors, 7 cases (23.3%) were malignant tumors. Malignant tumors included aggressive and poor prognostic cases such as malignant fibrous histiocytoma or malignant peripheral nerve sheath tumor, on the other hand, extremely rare tumor with low grade malignancy such as parachordoma arising from the chest wall soft tissue was included. In conclusion, although, the standard therapy for malignant primary chest wall tumors has not been established, aggressive surgical resection remains the treatment of choice and to provide an accurate diagnosis.

Oncogenic KRAS-induced interleukin-8 overexpression promotes cell growth and migration and contributes to aggressive phenotypes of non-small cell lung cancer.

The CXC chemokine interleukin-8 (IL-8) is an angiogenic growth factor that is overexpressed in various cancers, including non-small cell lung cancer (NSCLC). Previously, IL-8 was shown as a transcriptional target of RAS signaling, raising the possibility of its role in oncogenic KRAS-driven NSCLC. Using microarray analysis, we identified IL-8 as the most downregulated gene by shRNA-mediated KRAS knockdown in NCI-H1792 NSCLC cells where IL-8 is overexpressed. NSCLC cell lines harboring KRAS or EGFR mutations overexpressed IL-8, while IL-8 levels were more prominent in KRAS mutants compared to EGFR mutants. IL-8 expression was downregulated by shRNA-mediated KRAS knockdown in KRAS mutants or by treatment with EGFR tyrosine kinase inhibitors and EGFR siRNAs in EGFR mutants. In our analysis of the relationship of IL-8 expression with clinical parameters and mutation status of KRAS or EGFR in 89 NSCLC surgical specimens, IL-8 expression was shown to be significantly higher in NSCLCs of males, smokers, and elderly patients and those with pleural involvement and KRAS mutated adenocarcinomas. In KRAS mutant cells, the MEK inhibitor markedly decreased IL-8 expression, while the p38 inhibitor increased IL-8 expression. Attenuation of IL-8 function by siRNAs or a neutralizing antibody inhibited cell proliferation and migration of KRAS mutant/IL-8 overexpressing NSCLC cells. These results indicate that activating mutations of KRAS or EGFR upregulate IL-8 expression in NSCLC; IL-8 is highly expressed in NSCLCs from males, smokers, elderly patients, NSCLCs with pleural involvement, and KRAS-mutated adenocarcinomas; and IL-8 plays a role in cell growth and migration in oncogenic KRAS-driven NSCLC.

An immunoglobulin G4-related disease mimicking postoperative lung cancer recurrence.

A postoperative lung cancer patient presented with lymphadenopathy, pleural thickening, and 18F-fluorodeoxyglucose (FDG) uptake on a positron emission tomography-computed tomography (PET-CT) scan. Lung cancer recurrence was initially suspected, but bilateral submandibular masses with 18F-FDG uptake indicated the possibility of a systemic disease, such as Mikulicz's disease. High serum immunoglobulin G4 (IgG4) and IgG4-positive plasma cell infiltration in the submandibular glands led to the diagnosis of IgG4-related disease. After systemic steroid therapy, 18F-FDG uptake decreased in both the submandibular glands and the suspected recurrent lesions.

Clinicopathological features of lung adenocarcinoma with KRAS mutations.

BACKGROUND: KRAS and epidermal growth factor receptor (EGFR) mutations are thought to play an important role in the carcinogenesis of lung adenocarcinoma. However, clinicopathological findings of KRAS mutated adenocarcinoma cases have not yet been fully clarified. The authors analyzed the relationship between the KRAS mutation and corresponding clinicopathological findings, focusing on nonmucinous and mucinous bronchioloalveolar elements. METHODS: EGFR and KRAS mutations were detected in DNA samples extracted from 182 surgically resected tissues of lung adenocarcinomas by the Smart Amplification Process. The relations between gene mutation status and clinicopathological features were analyzed. All adenocarcinoma cases were divided into bronchioloalveolar carcinoma (BAC), adenocarcinoma with bronchioloalveolar features, and adenocarcinoma without BAC components (non-BAC). BAC/adenocarcinoma with bronchioloalveolar features tumors were further assessed for the presence of mucinous features. RESULTS: EGFR and KRAS mutations were found in 76 and 30 cases, respectively. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features was found in 22 cases, which included 10 nonmucinous and 12 mucinous tumors. Of 19 cases with mucinous BAC/adenocarcinoma with bronchioloalveolar features, KRAS mutations were detected in 12, but no EGFR mutation was detected. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features had significantly earlier pathological stages and more favorable prognoses than did non-BAC. Mucinous BAC/adenocarcinoma with bronchioloalveolar features showed less smoking history than did nonmucinous BAC/adenocarcinoma with bronchioloalveolar features and non-BAC. Furthermore, transversion type KRAS mutations were more common in non-BAC. CONCLUSIONS: KRAS mutated adenocarcinomas can be divided into BAC/adenocarcinoma with bronchioloalveolar features and non-BAC types. Non-BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis, and mucinous BAC/adenocarcinoma with bronchioloalveolar features has little relationship to smoking history.

[High-grade fetal adenocarcinoma of the lung; report of a case].

82-year-old man was admitted with an abnormal shadow on the chest roentgenogram. Computed tomography showed a 2.8 x 2.4 cm solid tumor in S3 of the left lung. Transbronchial lung biopsy revealed adenocarcinoma and a left upper lobectomy (ND2a-1) was performed. The tumor consisted mainly of tall columnar clear cells, and no morules were found. Immunohistochemically, the tumor was positive for alpha-fetoprotein (AFP) and p53. Accordingly, we made the histological diagnosis of high-grade fetal adenocarcinoma of the lung, pT2N0M0, stage IB. The patient was not received adjuvant therapy and has been doing well without any tumor recurrence for 3 months postoperatively.

High-grade neuroendocrine carcinoma of the lung shows increased thymidylate synthase expression compared to other histotypes.

BACKGROUND: Thymidylate synthase (TS) expression has been reported in various tumors, including non-small-cell lung carcinoma (NSCLC), but not in high-grade neuroendocrine (HGNE) carcinoma of the lung. METHODS: We measured TS expression in surgically resected pulmonary tumors, comparing HGNE carcinomas of the lung (13 large-cell neuroendocrine carcinomas, 8 small-cell lung carcinomas) with squamous cell carcinoma and adenocarcinoma of the lung using laser-capture microdissection for tissue isolation, real-time polymerase chain reaction (PCR), and immunohistochemistry. We also measured TS mRNA expression in small-cell lung carcinoma (SCLC) and NSCLC cell lines using real-time PCR. RESULTS: At both mRNA and protein levels, TS expression was significantly higher in squamous cell carcinoma compared to adenocarcinoma. Moreover, TS expression was significantly higher in HGNE carcinomas of the lung compared to squamous cell carcinoma. A significant correlation was found between mRNA and protein expression. TS mRNA expression in SCLC cell lines was significantly higher than in NSCLC cell lines. CONCLUSIONS: TS expression was higher in HGNE carcinomas of the lung than in squamous cell carcinoma, which was higher than in adenocarcinoma. This information may be useful in predicting the effects of TS-inhibiting agents in patients with NSCLC and HGNE carcinomas of the lung.

[Surgical treatment and outcome for postoperative recurrent or second primary lung cancer].

From 2000 to 2009, we retrospectively reviewed 62 patients who underwent surgical treatment for postoperative recurrent or 2nd primary lung cancer. Of the 62 patients, 43 were men and 19 were women with an average age of 67.6 years old. The histology of the initial primary lung cancer was adenocarcinoma in 42 patients, squamous cell carcinoma in 18, large cell carcinoma in 1 and small cell carcinoma in 1. The surgical procedures for 1st operation were lobectomy with mediastinal lymph node dissection in 52, bilobectomy with mediastinal lymph node dissection in 4, sleeve lobectomy with mediastinal lymph node dissection in 3, and lobectomy + segmentectomy or wedge resection with mediastinal lymph node dissection in 3. p-stage of the 1st primary lung cancer was IA in 22, IB in 16, II A in 7, IIB in 6, IIIA in 6, IIIB in 4, and IV in 1. On the 2nd operation, 56 patients underwent limited surgery. Five patients underwent a lobectomy twice metachronous bilateral lesions and 1 patient underwent completion pneumonectomy (CP) at the 2nd operation. The average age at 2nd operation was 71.8 years old. Of these, 42 patients were diagnosed 2nd primary lung cancer, 20 patients were recurrent disease histologically. The 5-year survival rate of the patients with metachronous and recurrent disease from the 2nd operation was 54.1%, and 43.1%, respectively. Although lobectomy or CP should be considered the surgical procedure of choice for patients with metachronous lung cancer, with this result, we consider that postoperative good survival can be expected by even the limited operation for cases of postoperative recurrent or 2nd primary lung cancer because of possible early detection. We conclude that limited surgery may be a treatment of choice for recurrent or 2nd primary lung cancer after initial operation.

Semi-comprehensive analysis of gene amplification in thymic malignant tumors using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

Research on the amplification of oncogenes in thymic malignant tumor is limited. In this study, we aimed to determine the gene amplification status of receptor tyrosine kinases and other cell regulator genes in thymic malignant tumors, with a view toward the future introduction of molecular targeted therapy. In addition, we examined the usefulness of multiplex, ligation-dependent probe amplification (MLPA) in the semi-comprehensive detection of these gene amplifications. The participants of this study were nine patients with thymic carcinoma and one patient with atypical carcinoid who underwent resection at our department from 1999 to 2016. Twenty-four oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, BRAF, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR) were analyzed for amplification by MLPA. In cases where amplification by MLPA was suspected, confirmation was performed by fluorescence in situ hybridization (FISH). Immunostaining for detected oncoproteins and p53 were performed in cases with confirmed oncogene amplification. MYC (2/10, 20%) and MDM2 (1/10, 10%) amplifications were detected using MLPA and FISH. Immunostaining in both cases was positive. The MDM2-amplified tumor relapsed and spread rapidly after operation despite the use of post-operative chemo-radiotherapy. MYC amplification may be involved in the carcinogenesis of thymic malignant tumors. In addition, MDM2 amplification may be a concern in the increased malignancy.

Comparison Between Stereotactic Radiotherapy and Sublobar Resection for Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to compare outcomes of primary treatment with stereotactic body radiation therapy (SBRT) versus sublobar resection (SLR) for clinical stage I non-small cell lung cancer (NSCLC) in patients with medical comorbidities. METHODS: Consecutive patients who underwent SBRT (n = 106) or SLR (100 wedge resection, 41 segmentectomy) because of medical comorbidities associated with stage I NSCLC were enrolled. Lesions located in the outer third of the lung field on computed tomography were defined as external, and others were defined as internal. A propensity score-matched analysis was also performed that compared SBRT and SLR results. Charts were reviewed to determine local tumor recurrence, disease-specific survival (DSS), and overall survival (OS). RESULTS: A propensity score-matched analysis, recurrence-free survival (RFS) became significant in favor of surgery (p = 0.036). For large nodules of greater than 2.0 cm in diameter, RFS was significantly better in the surgery group (p = 0.042). No significant differences in OS, DSS, or RFS were observed with small nodules of less than 2.0 cm in diameter. In the external group, a higher recurrence rate was seen for SBRT group. For internal group, there was no statistical difference between each treatment. Local recurrence rate was higher in the SBRT group (p = 0.0082) in the external group. CONCLUSIONS: In a matched comparison of stage I NSCLC in patients with medical comorbidities, RFS was in favor of surgery comparing SBRT, but there were no significant differences in OS or DSS. The tumor size and tumor location should be considered before deciding whether to perform SBRT or surgery.

Mean Computed Tomography Value to Predict the Tumor Invasiveness in Clinical Stage IA Lung Cancer.

BACKGROUND: The purpose of this study was to validate the ability of the mean computed tomography (m-CT) value to predict tumor invasiveness and recurrence, and further, to compare with other measurements such as consolidation/tumor ratio and solid tumor size. METHODS: A retrospective study was conducted of 494 patients with clinical stage IA lung cancer who had peripherally located lung adenocarcinoma. Receiver operating characteristic curve analysis was used to compare the ability to predict tumor invasiveness and recurrence between m-CT value, consolidation/tumor ratio, and tumor size. Multiple logistic regression analyses were performed to determine the independent variables for the prediction of pathologic, less invasive lung cancer. Disease-free survival was measured from the date of the operation until any recurrence. RESULTS: The m-CT values were 643.6 ± 9.4 Hounsfield units in the noninvasive cancer group and 365.9 ± 11.4 Hounsfield units in the invasive cancer group (p < 0.0001). The invasive cancer group was strongly associated with a high CT attenuation value, high consolidation/tumor ratio, large solid tumor size, large tumor size, and high standardized uptake value. Multiple logistic analyses, including the preoperatively determined variables, revealed that standardized uptake value and m-CT are independent predictive factors of less invasive lung cancer. In addition, the hazard ratio of the m-CT value was higher than that of the standardized uptake value value. CONCLUSIONS: The evaluation of m-CT value is useful in predicting less invasive lung cancer. The m-CT value can potentially determine operative procedure, particularly limited resection for peripheral lung adenocarcinoma.

[Surgical fixation of the ribs for flail chest injuries].

The record of 20 patients presenting with flail chest injury from 1998 to 2005 was reviewed to determine surgical indication and timing. There were 4 groups with each indication as followed: 1) 8 patients with surgical indication for injury regions other than fractured ribs, 2) 5 without improvement of flail chest after internal pneumatic stabilization for more than 10 days, 3) 4 performed surgical fixation positively for flail chest with respiratory failure, 4) 3 with strong deformation of the thorax without respiratory failure. Eight patients (40%) required artificial respiration for more than 6 days after surgical stabilization. The reasons of prolonged artificial respiration included unconsciousness in 4 patients, pneumonia in 2, and others in 2. In the group consisting of 8 patients taking more than 6 days to be extubated after surgical fixation, the injury severity score (ISS) was significantly higher (p = 0.006) than that of the other group. In patients with no improvement of flail chest after internal pneumatic stabilization for more than 10 days, surgical fixation reduces the period of internal pneumatic stabilization and the risk of pneumonia. For the elderly who can develop complications easily, early indication of surgical fixation should be considered. In patients with unconsciousness or ISS > or = 25, the extubation delays frequently after surgical fixations.