18F-FDG-PET/CT findings in primary pulmonary mixed squamous cell and glandular papilloma.

A 55-year-old female had an abnormal shadow on chest radiograph. Computed tomography (CT) revealed a 26-mm tumor mass in the left upper lobe. No malignant findings were obtained by bronchoscopic cytology or histopathological diagnostics, but on positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) examination the maximum SUV was 9.01 in accordance with the tumor mass shadow on CT. Video-assisted thoracoscopic surgery was performed as clinically suspected of lung cancer, and the diagnosis was pulmonary mixed squamous cell and glandular papilloma (PMSGP). Primary PMSGP is extremely rare, and this is the first to describe the PET findings of this disease.

ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer.

Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly associated with platinum drug resistance in various solid tumors. However, the impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC) remains unclear. We investigated in vitro cisplatin (CDDP) sensitivity using the collagen gel-droplet embedded culture drug sensitivity test. The ATP7B mRNA expression level in each specimen was also examined using real-time polymerase chain reaction. The relationship between ATP7B expression and in vitro CDDP sensitivity was then evaluated. The ATP7B mRNA expression levels in CDDP-resistant tumors were significantly higher than those in the CDDP-sensitive group (p=0.015; Mann-Whitney U test). Our results suggested that ATP7B expression is a promising chemoresistance marker for cisplatin.

Association of ATP7A expression and in vitro sensitivity to cisplatin in non-small cell lung cancer.

Expression of copper-transporting P-type adenosine triphosphatase A (ATP7A) is reportedly associated with platinum drug resistance in various types of solid tumors. However, the impact of ATP7A expression on platinum drug resistance in non-small cell lung cancer (NSCLC) has yet to be adequately elucidated. In vitro cisplatin (CDDP) sensitivity was investigated using the collagen gel-droplet embedded culture drug sensitivity test, and the ATP7A mRNA expression levels were assessed by real-time polymerase chain reaction in surgically resected specimens of NSCLC. The relationship between the ATP7A expression levels and the in vitro CDDP sensitivity was then evaluated. The ATP7A mRNA expression levels in the CDDP-resistant tumors were significantly higher than those in the CDDP-sensitive tumors (p=0.0167, Mann-Whitney U test). In conclusion, the results suggest that evaluation of ATP7A expression is useful as a marker for cisplatin chemoresistance.

11C-acetate for positron emission tomography imaging of clinical stage IA lung adenocarcinoma: comparison with 18F-fluorodeoxyglucose for imaging and evaluation of tumor aggressiveness.

BACKGROUND: To determine the usefulness of positron emission tomography (PET) with (11)C-acetate (AC) for imaging lung adenocarcinoma and evaluating its tumor aggressiveness, AC- and (18)F-fluorodeoxyglucose (FDG)-PET were compared. METHODS: One hundred and sixty-nine adenocarcinomas with clinical stage IA and 53 benign nodules were examined by both AC- and FDG-PET before surgery. The sensitivity and specificity for discriminating benign/adenocarcinoma were compared between AC- and FDG-PET. The AC and FDG uptakes were examined to determine the relationship with tumor aggressiveness, i.e., pathological tumor stage, lymphatic, vascular, or pleural involvement, and proliferative activity determined by Ki-67 staining score. RESULTS: While the sensitivity of AC-PET was significantly higher than FDG-PET for bronchioloalveolar carcinoma (BAC) and well-differentiated (W/D) adenocarcinoma (p < 0.001 and 0.006, respectively), there was no significant difference for moderately or poorly differentiated adenocarcinoma. The specificity was not different between them. While FDG uptakes were significantly higher in tumors with pathological advanced stages or those with lymphatic, vascular and/or pleural involvements than in tumors with pathological stage IA or those without these tumor involvements (p = 0.04 to p < 0.001), AC uptake did not show significant differences between the respective sub-groups except according to the tumor stage. While both AC and FDG uptakes showed a significant correlation with Ki-67 staining scores (p = 0.03 and p < 0.001, respectively), the correlation coefficient of former was lower than that of latter (p = 0.07). CONCLUSIONS: While AC-PET can image BAC and W/D adenocarcinoma with a higher sensitivity than FDG-PET, it cannot evaluate tumor aggressiveness of clinical stage IA lung adenocarcinoma as well as FDG-PET.

Therapeutic outcomes in thymectomied patients with myasthenia gravis.

PURPOSE: Transsternal thymectomy is well established in the treatment of myasthenia gravis (MG). The objectives of this study were to evaluate the influence and prognostic factors of thymectomy as treatment for MG. PATIENTS AND METHODS: Surgical results of 54 patients with MG who underwent transsternal thymectomy were retrospectively reviewed. We investigated clinical outcomes of extended transsternal thymectomy in MG, and we analyzed the data to clarify the effect of prognostic factors on clinical outcome. RESULTS: A total of 54 patients, including 28 males and 26 females, were analyzed. At their last visit, 5 patients (9%) were in complete remission; 36 (67%) reported clinical improvement; and 18 (33%) had no change. There were no operative or late deaths. Clinical improvement was not detected by a patient's age, sex, presence or absence of thymoma, or acetylcholine receptor (AchR) antibodies titer. Patients in which the duration of illness before operation was equal to or less than 24 months (p = 0.018), and patients in the advanced Myasthenia Gravis Foundation of America (MGFA) stage (p = 0.014), showed a greater degree of clinical improvement. CONCLUSION: Transsternal thymectomy for MG is safe and effective. Those patients with severe symptoms and a shorter duration of illness showed more benefits from thymectomy.

Expression of maspin in non-small-cell lung cancer: correlation with clinical features.

PURPOSE: Maspin is a member of the serpin (serine protease inhibitor) family and has been shown to be a suppressor of tumor growth and metastasis in several types of tumors. The objective of this study was to evaluate whether maspin is a prognostic factor in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We investigated maspin expression in 181 patients with curatively resected NSCLC by means of immunohistochemistry. We also determined whether expression of maspin correlates with the microvessel density (MVD) level. RESULTS: The incidence of strong maspin expression in patients with squamous cell carcinoma was significantly higher than that in patients with other histology (46 of 70 [65.7%]; P < .0001). There was no significant difference between maspin expression status and MVD. Prognosis was defined as progression-free survival (PFS) and overall survival (OS). There was no difference in PFS or OS between patients with strong and weak maspin expression among all patients. However, for squamous cell carcinoma, the PFS and OS rates for patients with strong maspin expression were significantly higher than those for patients with weak maspin expression (PFS, P = .004; OS, P = .001). In multivariate analysis on squamous cell carcinoma, strong maspin expression was an independent favorable prognostic indicator (PFS, P = .03; OS, P = .01). CONCLUSION: Strong maspin expression was an independent factor in predicting a favorable prognosis in squamous cell carcinoma of lung.

11C-Acetate can be used in place of 18F-fluorodeoxyglucose for positron emission tomography imaging of non-small cell lung cancer with higher sensitivity for well-differentiated adenocarcinoma.

OBJECTIVES: Although positron emission tomography (PET) using F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for slow-growing tumors, C-acetate (AC)-PET has been reported to be able to detect them. To determine the usefulness of AC-PET for imaging non-small cell lung cancers (NSCLCs), the sensitivity and specificity were compared between the AC-PET and FDG-PET with a multicenter study. MATERIALS AND METHODS: A total of 284 pulmonary lesions (227 NSCLCs and 57 benign lesions) were examined using both AC-PET and FDG-PET before surgery at seven Japanese institutes. The AC- or FDG-uptake in each lesion were quantitatively measured using the contrast ratio of the standard uptake value between the lesions and the contralateral lung. RESULTS: The sensitivity of AC-PET for diagnosing NSCLC was 0.71, which was significantly higher than the value of 0.57 obtained by FDG-PET (p < 0.001). No significant difference in the specificity was seen between AC- and FDG-PET. For the 146 well-differentiated adenocarcinomas, the sensitivity of AC-PET was 0.62, which was significantly higher than the value of 0.37 obtained by FDG-PET (p < 0.001). Of the 51 moderately- or poorly-differentiated adenocarcinomas and 30 nonadenocarcinomas, there was no significant difference of sensitivity between AC- and FDG-PET. CONCLUSIONS: AC-PET could be used in place of FDG-PET for imaging NSCLC, with higher sensitivity for well-differentiated adenocarcinoma compared with FDG-PET.

Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer.

The monoclonal antibody D2-40 is a new selective marker for lymphatic endothelium. The lymphatic microvessel density (LMVD) using D2-40 has not yet been evaluated in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate LMVD using D2-40 in NSCLC. We investigated LMVD in 77 patients with NSCLC who underwent curative tumor resection. We also determined the relation between LMVD and clinicopathologic factors, VEGF-C and Ang-2 and microvessel density (MVD) using factor VIII-related antigen. The median number of D2-40-positive vessels in the highest LMVD was 25 (range, 5-71). LMVD was significantly associated with tumor status, lymph node metastasis, stage, lymphatic invasion, VEGF-C protein and MVD (p=0.0149 for tumor status; p<0.0001 for nodal status; p<0.0001 for stage; p=0.0153 for lymphatic invasion; p=0.0030 for VEGF-C, and p=0.0029 for MVD). Furthermore, LMVD using D2-40 expression was shown to be an independent predictor of lymph node metastasis by multivariate analysis (p=0.0070). These data indicate that a high LMVD by D2-40 may be an indicator of lymph node metastasis in NSCLC.

Endoscopic drainage of an infected giant bulla.

A 42-year-old man was hospitalized because of an infectious giant bulla. The infected giant bulla did not improve by the administration of antibiotics. Some infectious bullae were considered to be difficult to allow for simple cutaneous drainage, so endoscopic drainage was performed to remove the infection. Our experience with endoscopic abscess drainage is excellent in patients in whom conventional therapy fails. We consider the endoscopic drainage an alternative to percutaneous drainage in patients who have an infectious bulla.

Dedifferentiated liposarcoma of the pleura: report of a case.

We report a case of dedifferentiated liposarcoma of the pleura in a 59-year-old man who presented with pain in the right chest wall, 3 years after a routine chest X-ray showed a large tumorous mass. The resected tumor was composed of three distinct histological features: well-differentiated liposarcoma with low-grade leiomyosarcomatous and low-grade osteosarcomatous components. To our knowledge, this is the first report of dedifferentiated liposarcoma of the pleura.

The prognostic value of overexpression of Skp2 mRNA in non-small cell lung cancer.

Skp2 putatively plays a critical role in regulating cell cycle progression. A high level of Skp2 expression is observed in a variety of cancer. No previous report describes the prognostic value of Skp2 mRNA in non-small cell lung cancer (NSCLC). Therefore, the purpose of this study was to examine overexpression of Skp2 mRNA in NSCLC and identify the association of Skp2 expression level with patient survival. We investigated Skp2 expression in 79 patients with NSCLC by means of reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The Skp2 expression was significantly associated with tumor status, lymph node metastasis, stage, vascular invasion, histology and Skp2 protein. With regard to prognosis, the overall and stage I survival rates for patients in the high Skp2 mRNA group were significantly poorer when compared with the low Skp2 mRNA group. Furthermore, expression of Skp2 mRNA was an independent predictor of prognosis by multivariate analysis. Skp2 expression might play an important role in the development and progression in NSCLC and Skp2 gene expression can serve as a useful prognostic marker in NSCLC patients.

Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer.

BACKGROUND: Integrin-linked kinase (ILK) promotes tumor growth and invasion. Increased ILK expression is correlated with progression of several tumor types, but the expression of ILK has not been investigated in patients with non-small cell lung cancers (NSCLCs). METHODS: We investigated ILK expression in patients with NSCLC by means of immunohistochemistry. RESULTS: ILK expression was significantly associated with tumor grade, T status, lymph node metastasis and stage. (p = 0.0169 for tumor grade; p = 0.0006 for T status; p = 0.0002 for lymph node metastasis; p < 0.0001 for stage). The 5-year survival rates for patients with strong and weak or no ILK expression levels were 20% and 59%, respectively: the difference was statistically significant (p < 0.0001). A multivariate analysis of survival revealed that ILK expression, T status, N status and vascular invasion were statistically significant prognostic factors (p = 0.0218 for ILK; p = 0.0046 for T status; p < 0.0001 for N status; p < 0.0001 for vascular invasion). CONCLUSIONS: Our study demonstrates that increased expression of ILK is a poor prognostic factor in patients with NSCLC.

Optimum drainage method in descending necrotizing mediastinitis.

Descending necrotizing mediastinitis (DNM) is a rare but often fatal disease. Transcervical mediastinal drainage and transthoracic mediastinal drainage are the most commonly employed drainage methods for treating patients with DNM. It remains controversial as to whether transcervical mediastinal drainage alone would be adequate for the treatment of DNM, which is a life-threatening disease. Between 1996 and 2004, 13 patients with DNM were treated at our department. We performed transcervical mediastinal drainage in 6 patients with localized DNM, in whom the infection remained limited to above the level of the carina. A more aggressive approach, that is, transthoracic mediastinal drainage, was employed in the remaining 7 patients who had extensive DNM, with the infection extending below the carina. The overall mortality rate was 8%. All the 6 patients treated by transcervical drainage survived without major postoperative complications. Six out of the 7 patients treated by transthoracic drainage survived, while one died of pneumonia. Our results suggest that transcervical mediastinal drainage may be adequate for treating patients with localized DNM in whom the infection does not extend beyond the carina, while transthoracic mediastinal drainage must be adopted for patients with more extensive disease.

Pulmonary artery perforation by a tube thoracostomy.

A 74-year-old woman was hospitalized in another institution because of a left-sided empyema and bronchopneumonia. A trocar-type chest tube was inserted. Upon withdrawal of the trocar, blood was seen flowing from the draining system and she developed hypotension. The patient was then transferred to our hospital and a diagnosis of pulmonary artery perforation was made. The patient was treated successfully with left pneumonectomy. Pulmonary artery perforation following chest tube placement is a rare and serious complication. When blood is seen following chest tube insertion a pulmonary artery perforation should be considered.

Successful management of a patient with stage IIIA non-small cell lung cancer using sensitivity-based induction chemotherapy--report of a case.

To select the most appropriate drug treatment for different patients with lung cancer, we have been measuring the chemosensitivity of lung cancer tissues to various drugs using the collagen gel droplet embedded culture drug sensitivity test (CD-DST). A 57-year-old Japanese male with stage IIA squamous cell carcinoma of the lung received sensitivity-based induction chemotherapy consisting of docetaxel (70 mg/m2) given on days 1, 22, and 43. He was treated as an outpatient, and no serious side effects were observed. After the chemotherapy, the left upper bronchus was reopened by the reduction of the tumor, and a left pneumonectomy with simultaneous partial resection of the pericardium was performed. After discharge, the patient received 2 cycles of adjuvant chemotherapy, consisting of weekly docetaxel doses (35 mg/m2) for 3 consecutive weeks, followed by one week without treatment. Although the 3-year survival rate of stage IIIA NSCLC patients is under 30%, three years after administration of the chemotherapy no other recurrence site has been detected, and the patient is in good health. Using CD-DST, sensitivity-based induction chemotherapy with docetaxel was successful in the patient reported here.

G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer.

BACKGROUND: G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. RESULTS: In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). CONCLUSIONS: These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs.

Overexpression of Ang-2 mRNA in non-small cell lung cancer: association with angiogenesis and poor prognosis.

Overexpressed Angiopoietin-2 (Ang-2) derived mainly from cancer cells was reported to promote tumor angiogenesis. The aim of this study was to evaluate the expression of Ang-2 in non-small cell lung cancers (NSCLCs). We investigated Ang-2 expression in 77 patients with NSCLC who underwent curative tumor resection by means of reverse transcription-polymerase chain reaction (RT-PCR). We also determined whether or not expression of Ang-2 mRNA correlates with immunohistochemical assays of Ang-2 protein and microvessel density (MVD) level. The level of Ang-2 mRNA expression was presented by the relative yield of each gene to the S14 mRNA, respectively. Ang-2 mRNA expression in NSCLC was significantly greater than that in non-cancerous normal lung (p=0.0178). The Ang-2 mRNA expression was significantly associated with lymph node metastasis, stage, Ang-2 protein, and microvessel density (MVD) level (p=0.0009 for lymph node metastasis; p=0.0002 for stage; p<0.0001 for Ang-2 protein; p<0.0001 for MVD). With regard to prognosis, the overall and stage I survival rates for patients in the high Ang-2 mRNA expression group were significantly poorer when compared with the low Ang-2 mRNA expression group (p<0.0001 for overall; p=0.0201 for stage I). Furthermore, expression of Ang-2 mRNA was an independent predictor of prognosis by multivariate analysis (p=0.0028). These data indicate that Ang-2 may contribute to tumor angiogenesis and progression and that Ang-2 gene expression can serve as a useful prognostic marker in NSCLC.