Yoshihiko Kanai

Identification of CCDC6-RET Fusion in the Human Lung Adenocarcinoma Cell Line, LC-2/ad

Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non–small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion–positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

Management of massive hemoptysis in a thoracic surgical unit

OBJECTIVE Massive hemoptysis is a life-threatening condition. Surgery is effective but we are sometimes reluctant to operate on patients with this condition. We reviewed our experience with patients who underwent emergency surgery for massive hemoptysis to verify the indications for non-emergency surgical intervention. METHODS We reviewed chest computed tomography (CT) and angiographic and pathological findings and the postoperative course of 25 patients who underwent emergency pulmonary resection in our department between 1979 and 2001 due to life-threatening hemoptysis. RESULTS CT revealed a persistent cavity within the radiological opacity before massive hemoptysis in 12 patients (48%). Of the 21 patients who underwent angiography, nine showed focal bleeding in one bronchial branch and the others showed bleeding in multiple branches. Of these nine patients, seven did not undergo embolotherapy mainly due to minor vascularity. In the remaining patients, embolotherapy was not indicated in six due to multiple bleeding feeders and recurrence after embolotherapy was seen in six. Pathological findings showed that eight of the 12 patients with multiple systemic shunts had a fungal infection. Operative morbidity and hospital mortality were 32 and 4%, respectively. There was no recurrence in patients who underwent surgical treatment. CONCLUSIONS Early pulmonary resection is indicated in patients with hemoptysis of multiple branches from the cavity and chest wall, such as in fungal infections. When a bronchial branch is the only bleeding focus, superselective embolotherapy should be considered prior to surgery even if the localized focus of the bronchial branch shows minor vascularity on the angiography.

Dangerous mediastinal basal pulmonary artery during left upper lobectomy

Anatomical variations in the pulmonary vessels present a potential risk for intraoperative bleeding and damage to the pulmonary circulation during pulmonary resection. Here, we present a patient who underwent left upper lobectomy for lung cancer. The patient had a dangerous mediastinal basal pulmonary artery variation that could be mistaken for the mediastinal lingular pulmonary artery and be divided during left upper lobectomy.

Massive haemothorax after pulmonary endostapling preloaded with bioabsorbable tissue reinforcement material

Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement.

Extralobar pulmonary sequestration presenting as hemothorax

Symptomatic extralobar pulmonary sequestration (EPS) is extremely rare. Herein, we report two male patients (3 and 16 years of age) with EPS presenting as hemothorax. Thoracotomic resections of the sequestrated lungs were uneventful. Pathologic examinations revealed hemothorax caused by circulatory disorders within the EPSs.

Extraction bag lavage cytology during video-assisted thoracoscopic surgery for primary lung cancer

OBJECTIVES Sample extraction from the thoracic cavity through an intercostal space during video-assisted thoracoscopic surgery can result in cancer cell contamination by tumour crushing and tumour cell extravasation, and may have adverse effects on the surgical outcome. Lavage cytology of the sample extraction bag was investigated to clarify the risk of cancer cell spillage and identify the clinicopathological features associated with susceptibility to cancer cell spillage during extraction. METHODS Lavage cytology of the sample extraction bag was investigated in 464 patients with negative pleural lavage cytology who underwent lung resection for primary lung cancer via video-assisted thoracoscopic surgery between January 2010 and December 2012. The surgical procedures, pathological findings and clinical course were evaluated by hospital record review. RESULTS The incidence of positive bag lavage cytology (BLC) was 13.6%. Statistically significant factors associated with susceptibility to BLC positivity were tumour size, standardized uptake value of positron emission tomography, pathological features such as pathological N score, pleural invasion, vascular invasion and papillary-predominant adenocarcinoma. Among patients with Stage I lung cancer, the survival rate was significantly lower in the BLC-positive group than in the BLC-negative group. CONCLUSIONS BLC positivity can be related to oncological characteristics such as tumour invasiveness and adhesiveness as opposed to tumour size and surgical margin, and may help to determine the prognosis of Stage I lung cancer. The sample extraction bag must be carefully manoeuvred through the intercostal space to prevent cancer cell dissemination to the chest wall or thoracic cavity.

Establishment of highly metastatic KRAS mutant lung cancer cell sublines in long-term three-dimensional low attachment cultures

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3–4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.

Muscle plombage for extensive bronchial necrosis after right lower lobectomy

Bronchial stump necrosis is a lethal complication after pulmonary resection. We report a patient who had extensive necrosis of the intermediate bronchus after right lower lobectomy. The large bronchial defect was successfully fixed with latissimus dorsi muscle and replaced by bronchial epithelialization.

Peripherally located endobronchial hamartoma mimicking aspergilloma: a case report

We herein report the case of a 75-year-old man with a pulmonary hamartoma that mimicked aspergilloma on chest computed tomography (CT). A CT scan performed to assess an asymptomatic lesion detected on a screening chest radiograph showed a 1.3-cm diameter nodule with an air crescent sign in the left lower lobe. A diagnosis of aspergilloma was made and the patient treated with an antifungal agent for 1 year, following which he underwent radical surgery because of failure of the radiologic lesion to resolve. Pathologic examination of the resected specimen showed an endobronchial hamartoma within the B9 periphery. Peripherally located hamartomas can develop within the peripheral bronchi resulting in an air crescent appearance on radiological images.

Pleural solitary fibrous tumor with bullae: is it a microinvasive tumor?

We report a rare pleural solitary fibrous tumor with bullae. Chest computed tomography showed a nodular lesion with bullae adjacent to the left diaphragm. Thoracoscopic resection followed by a pathology study showed that the tumor was a solitary fibrous tumor beside the visceral pleura. We suggest that the bullae containing dilated bronchioles were caused by a checkvalve mechanism next to the microinvasive component in the solitary fibrous tumor.