Jun Nakajima

Surgical outcomes for pulmonary metastases from hepatocellular carcinoma

BACKGROUNDnAlthough favourable prognosis following aggressive treatment of extrahepatic metastases from hepatocellular carcinoma (HCC) has been reported, surgical outcomes for pulmonary metastases are unclear.nnnMETHODS AND MATERIALSnSixty-one patients (2.6%) of 2297 registered with the Metastatic Lung Tumor Study Group of Japan between 1990 and 2006, who underwent surgery for pulmonary metastases from HCC, were retrospectively reviewed from the registry.nnnRESULTSnThe overall 5-year survival rate was 32.2%. The prognosis was significantly better for < or =2 lesions than for > or =3 lesions (p=0.046), for < or =3 lesions than for > or =4 lesions (p=0.0070), and for < or =4 lesions than for > or =5 lesions (p=0.029). No other factors that influence outcomes were identified. A stepwise regression analysis showed three or less pulmonary metastases to be an independent factor for better prognosis (p=0.048).nnnCONCLUSIONnWith careful patient selection, comparatively good outcomes can be expected following surgical resection of pulmonary HCC metastases. Among them, patients with multiple metastases, if number of metastases is small such as four or less, can be expected to survive long after surgery.

Active specific immunotherapy and cell-transfer therapy for the treatment of non-small cell lung cancer

Lung cancer is an intractable disease urgently requiring more effective treatment approaches. The potential of immunotherapy in this context remains promising, although presently there are no satisfactory protocols available for lung cancer. However, encouraging evidence of clinical benefits from immunotherapy is beginning to accumulate in several lung cancer trials. Better understanding of tumor-specific immune responses, identifying tumor-associated antigens, and manipulating the immunoregulatory environment of the tumor is likely to further increase the efficacy of immune-mediated cancer therapies. Here, we review recent advances in cellular immunotherapy and vaccines for lung cancer, emphasizing an important paradigm shift in the analysis of clinical benefit away from tumor response towards patient response.

Hypoxia increases the motility of lung adenocarcinoma cell line A549 via activation of the epidermal growth factor receptor pathway.

Tumor hypoxia is associated with a malignant phenotype of cancer cells and poor patient prognosis. To investigate the role of hypoxia in tumor progression, we studied the effects of hypoxia in the A549 lung adenocarcinoma cell line. First, we showed that hypoxic treatment decreased cell–cell adhesion and induced a scattering of cancer cells. Concomitant with these morphological changes, the motility of cancer cells was increased, as demonstrated by the Boyden chamber assay. Then, we used oligonucleotide array analyses to identify the genes causally related to the hypoxia‐induced motile phenotype. The results showed that the expression of approximately 100 genes was induced more than 5‐fold by hypoxia. These included (among others) epidermal growth factor receptor (EGFR), as well as other well‐known hypoxia‐induced genes, such as vascular endothelial growth factor. Immunohistochemical analyses of primary lung adenocarcinomas confirmed the induction of EGFR in tumor cells in the vicinity of necrotic areas, a histological indicator of tumor hypoxia. Remarkably, the EGFR inhibitor AG1478 (10 M) completely blocked the increased cell motility induced by hypoxia. Thus, the present study demonstrates the importance of the EGFR pathway in the increased motility of cancer cells that occurs in a hypoxic tumor environment. (Cancer Sci 2007; 98: 506–511)

A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer.

Cancer-specific gene promoter methylation has been described in many types of cancers, and various semi-quantified results have shown their usefulness. Here, we show a more sensitive and specific second-generation system for profiling the DNA methylation status. This method is based on bisulfite reaction of DNA and real-time PCR using two TaqMan MGB probes labeled with different fluorescence, followed by clustering analysis. Primers were designed with CpG-less sequences, and TaqMan MGB probes were designed to contain three or four CpG sites and to be shorter than conventional TaqMan probes. We have added new criteria for primer and probe design for further specificity. We confirmed the reliability of this system and applied it to analysis of lung cancers. Using 10 promoters, 90 primary lung cancers were clustered into six groups consisting of cases having similar smoking status and pathological findings. EGFR mutation and p16 promoter DNA methylation were exclusive, as previously reported; however, DNA methylation in other genes was unrelated to EGFR mutation. This system was also useful to distinguish double primary lung cancers from a single cancer with intrapulmonary metastasis. As above, our system has widespread availability in clinical use and biological research.

Invasive Lymphangioma of the Lung Manifesting as a Large Pulmonary Mass with Hemoptysis: Report of a Case

Solitary lymphangioma of the lung is rare. We report a case of invasive lymphangioma of the lung, diagnosed in a 9-year-old girl who presented with intractable hemoptysis and a large pulmonary mass, 10u2009cm in diameter. We performed left lower lobectomy and lingular segmentectomy to remove the mass completely and the patient has been well for 3 years since. Pathologically, the mass was partly polycystic and partly solid. Irregular and dilated vascular and lymphatic vessels, as well as fibrosis of the interstitium, were spreading into the adjacent lung parenchyma, demonstrating their invasive nature. A new monoclonal antibody, D2-40, which reacts with lymphatic endothelium, proved useful for establishing the pathological diagnosis. We suggest that these pathological findings might be consistent with the intermediate type of localized lymphangioma of the lung and diffuse lymphangiomatosis.

Video-assisted thoracic surgery lobectomy preserves more latissimus dorsi muscle than conventional surgery.

Video-assisted thoracic surgery (VATS) lobectomy for early lung cancer has become technically feasible. We sought to determine if VATS preserved chest wall muscle postoperatively better than thoracotomy. Consecutive patients who underwent lobectomy between 2004 and 2006 for clinical Stage IA non-small cell lung cancer through VATS (VATS group) or posterolateral thoracotomy (PLT group) at our institution were eligible for the study. The cross-sectional areas of bilateral latissimus dorsi muscle (LDM) at the lower end of the scapula were obtained by computed tomography preoperatively and one year after surgery. These were quantified with image analysis by two researchers in a blinded manner. Fourteen patients in the VATS group (mean age, 68 years; 8 men, 6 women) and 24 patients in the PLT group (mean age, 62 years; 14 men, 10 women) were assessed. Postoperative/preoperative ratios of the LDM cross-section areas on the surgical side were 89+/-20% (Mean+/-S.D.) in the VATS group and 57+/-16% in the PLT group (P<0.001). Those on the non-surgical side were 89+/-23% in the VATS group and 97+/-16% in the PLT group (P=0.23). We conclude that VATS may prevent atrophy of LDM on the surgical side better than conventional thoracotomy.

Pulmonary Intimal Sarcoma Treated by a Left Pneumonectomy with Pulmonary Arterioplasty Under Cardiopulmonary Bypass: Report of a Case

Intimal sarcoma of the pulmonary artery is a rare disease. This neoplasm was characterized by an aggressive extension to the lumen of the pulmonary artery, thus mimicking a pulmonary thromboembolism. We herein report a 44-year-old woman who was diagnosed as having primary intimal sarcoma of the left lung preoperatively by transbronchial biopsy. The tumor originated in the pulmonary artery in the left lung, extending to the main pulmonary trunk via the pulmonary arterial lumen, thus resulting in stenosis of the main pulmonary trunk. A complete resection of the tumor with the left pneumonectomy and the pulmonary arterioplasty was successfully performed under cardiopulmonary bypass with vacuum assisted venous drainage.

Chest wall desmoid tumor with life-threatening intrathoracic extension

Fig. 1. The tumor, originating from the right posterior chest wall and involving the 8th, 9th and 10th ribs, had invaded the right thoracic cavity and was causing compression of the right lung and leftward displacement of the mediastinum. The patient had no history of pregnancy or surgical trauma in her chest wall. Preoperatively, the patient’s vital capacity was 940 ml (34% of normal) and echocardiogram revealed pulmonary hypertension (estimated right ventricular pressure: 62 mmHg).