Significance of Mitochondrial DNA Haplogroup on Epidermal Growth Factor Receptor Mutation in Japanese Patients With Lung Adenocarcinoma.

BACKGROUND/AIM: The frequency of somatic mutations of epidermal growth factor receptor (EGFR) in primary lung adenocarcinoma varies among populations and countries. The aim of the present study was to clarify whether the frequency of EGFR mutations in patients with lung adenocarcinoma depends on their mitochondrial DNA haplogroup, which reflects their maternal lineage. PATIENTS AND METHODS: Using normal lung tissue specimens, the mitochondrial DNA haplogroup was determined by multiplex polymerase chain reaction in 135 Japanese patients who underwent surgery for primary lung adenocarcinoma. RESULTS: The 135 patients were divided into two groups according to the two primitive haplotypes (N group, n=32; M group, n=103). The frequency of EGFR mutations in the N group was significantly higher than that in the M group (69% vs. 48%, p=0.044). The difference was prominent when the analysis was restricted to non-smokers (95% vs. 57%, p<0.01). CONCLUSION: The frequency of EGFR mutations in lung adenocarcinoma patients depends on their mitochondrial lineage.

Tumor enucleation for Castleman's disease in the pulmonary hilum: a case report.

BACKGROUND: The development of Castleman's disease in the pulmonary hilum is extremely rare. Although resection of only the lesion is sufficient because of its benign nature, lobectomy or more extensive procedures performed for the pulmonary hilar tumor have been reported. CASE PRESENTATION: The patient was a 15-year-old male with a tumor in the right pulmonary hilum. Endobronchial ultrasound-guided transbronchial needle aspiration was performed but no specific findings were obtained from the cytological and histological evaluation. 18F-fluorodeoxyglucose positron emission tomography showed moderate accumulation in the tumor, which suggested potential malignancy. Intraoperative frozen section diagnosis did not show any malignant findings. Thus, we performed only tumor enucleation without any lung resection. The pathological diagnosis was hyaline vascular type Castleman's disease. No recurrence has been observed for seven years. CONCLUSION: Because hyaline vascular type Castleman's disease in solitary pulmonary hilar tumor is one of the benign diseases common in young people, intraoperative frozen section diagnosis is recommended to avoid unnecessary lung resection.

Expression of Bone Morphogenetic Protein-7 Significantly Correlates With Non-small Cell Lung Cancer Progression and Prognosis: A Retrospective Cohort Study.

BACKGROUND: Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-ß superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer. METHODS: This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed. RESULTS: In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012). CONCLUSIONS: Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.

Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence.

PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

Coil Intrabronchial Migration in an Arteriovenous Malformation Patient Treated 10 Years Ago.

A 56-year-old male who had received transcatheter coil deposition 10 years ago for an arteriovenous malformation (AVM) was admitted to our hospital because of persistent hemosputum. Chest radiograph and bronchoscopy revealed straightened coil bundles in his air way. Recently, less invasive transcatheter intervention has been performed more frequently for treatment of AVM than surgical resection. In our case, however, chest radiography and bronchoscopy showed that the coils might migrate from the deposited site to the airway. Then, right lower lobectomy was undertaken. In AVM patient who received coil deposition, a long-term follow-up is recommended, and surgical resection should be carried out if necessary.

Potentially overlooked branches of the left pulmonary artery.

BACKGROUND: During pulmonary resection, we sometimes encounter "pitfall branches" of the pulmonary artery, which could cause serious vessel injury. Current computed tomography and computer-processing technology can identify the pulmonary artery along the peripheral bronchus, thereby revealing the true rates of different pulmonary artery branching patterns. Knowledge of these branching patterns allows safe and definitive surgery. METHODS: In 186 cases of left lung resection performed at our institution from January 2006 to September 2011, two general thoracic surgeons and one radiologist independently reviewed computed tomography images and examined the branches of the pulmonary artery arising from the pars mediastinalis. RESULTS: Branching patterns of the lingular artery included 17 (9.2%) cases with mediastinal origin, 50 (26.9%) with interlobar and mediastinal origin, and 119 (63.9%) with interlobar origin. The 2 types of lingular artery of mediastinal origin, which were potentially overlooked during surgery, were observed in 36.1% of cases. This was a higher rate than previously reported. Moreover, a mediastinal basal pulmonary artery (A(5+8+10) abnormal branching) was seen in one case. CONCLUSION: Potentially overlooked branches of the left pulmonary artery arising from the pars mediastinalis are much more frequent than we expected. It is crucial to understand the branching pattern of the pulmonary artery by preoperative computed tomography assessment.

Successful closure of a tracheocutaneous fistula after tracheostomy using two skin flaps: a case report.

A tracheocutaneous fistula may develop when a tracheostomy orifice epithelializes during a prolonged course of healing or undernutrition. Various techniques for closing such fistulae have been reported. However, a standard procedure has not yet been established. We, herein, present a case involving a 35-year-old woman who developed a tracheocutaneous fistula after tracheostomy. We closed the fistula using two skin flaps to cover the tracheal lumen and skin defect, respectively. The advantage of this technique is that it allows the tracheal lumen to be covered by inversed skin epithelium and ensures that the suture line of the skin does not match up with that of the subcutaneous tissue.

A case of resected plasma cell type castleman's disease with intramediastinal lymph nodes spread.

We report a case of resected plasma cell (PC) type Castleman's disease (CD) in a 21-year-old female who had an anterior mediastinal mass with additional surrounding nodules. She was aware of low-grade fever and fatigue for several years. From hematological and biochemical examinations, elevated inflammatory responses and levels of serum IgG (2908 mg/dL) and IL-6 (22.2 pg/mL) were observed. She was diagnosed with PC type CD by needle biopsy under computed tomography (CT) guidance. It was thought that the lesion was localized in the mediastinum. Then, mediastinal adipose tissue including the tumor, additional nodules and thymus were removed. The histological findings of PC type CD were found not only in the main tumor but also in surrounding swollen lymph nodes. Her symptoms improved and inflammatory responses decreased after the operation. No recurrence has been observed for 5 years after the operation.

[Nine myasthenia gravis cases of thoracoscopic extended thymectomy].

The indication of thoracoscopic excision of mediastinal tumor at our department is benign tumor or noninvasive thymoma diagnosed before surgery. For myasthenia gravis, thoracoscopic extended thymectomy is performed with a bilateral thoracic approach using a laparolift, and this procedure is indicated for cases with complication of thymoma with a tumor size up to 5 cm. We performed thoracoscopic extended thymectomy in 9 myasthenia gravis patients between January and October 2011, and achieved favorable postoperative courses with no development of major complications so far. However,surgery required a long time compared to the conventional extended thymectomy employing median sternotomy, showing that further modification of the surgical procedure and improvement of the surgical skill are necessary. We report the details of thoracoscopic extended thymectomy with a bilateral thoracic approach for 9 myasthenia gravis patients performed at our department.

Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas.

Mitogen-activated protein kinase phosphatase 5 (MKP-5)/DUSP10 acts as a phosphatase of stress-activated kinases (JNK and p38), but its activity towards ERK has not been demonstrated. In the present study we observed that MKP-5 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription. These data suggested a novel MKP-5 function as a scaffold protein for the ERK pathway. We analyzed MKP-5 gene expression in several tumors, and found that it is frequently upregulated in colorectal but not in lung and breast cancer, suggesting its association with the malignant phenotype of colon cancer.