Fumiho Sano

Prognostic impact of lymphovascular invasion compared with that of visceral pleural invasion in patients with pN0 non–small-cell lung cancer and a tumor diameter of 2 cm or smaller

BACKGROUND Both visceral pleural invasion (VPI) and lymphovascular invasion (LVI) have been shown to be adverse prognostic factors for early-stage non-small-cell lung cancer (NSCLC). Positive VPI upstages the T category of tumors ≤ 2 cm (T1a) to T2a, whereas LVI is not adapted as a descriptor for the Tumor, Node, Metastasis classification system. This study was conducted to evaluate the prognostic impacts of VPI and LVI in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. METHODS We reviewed records of a total of 142 patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm, who underwent lobectomy with hilar and mediastinal lymph node dissection between January 2001 and December 2009. We conducted univariate and multivariate analyses to evaluate the impact of VPI, LVI, and other clinicopathologic factors on survival. RESULTS Visceral pleural invasion and LVI were diagnosed as positive in 18 (12.7%) and 22 (15.5%) patients, respectively. Male sex, squamous cell carcinoma, positive VPI, and positive LVI were risk factors for overall survival. Squamous cell carcinoma, positive VPI, and positive LVI were risk factors for relapse-free survival. In multivariate analysis, squamous cell carcinoma and positive LVI were independent risk factors for overall survival, and positive LVI was an independent risk factor for relapse-free survival. CONCLUSIONS Positive LVI was more important than VPI as a prognostic factor in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Adjuvant chemotherapy should be considered for such patients, to improve the treatment outcomes.

Assessment of volume reduction effect after lung lobectomy for cancer

BACKGROUND Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. METHODS We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. RESULTS Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. CONCLUSIONS A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function.

Similar radiopathological features, but different postoperative recurrence rates, between Stage I lung cancers arising in emphysematous lungs and those arising in nonemphysematous lungs

OBJECTIVES The aim of the present study was to clarify the differences between lung cancer arising in emphysematous lungs and that arising in nonemphysematous lungs with regard to radiopathological features and the postoperative recurrence rate. METHODS We retrospectively reviewed a prospective database of 212 patients who underwent major lung resection for clinically diagnosed Stage I primary lung cancer. Emphysematous lungs were identified on the basis of quantitative computed tomography (CT). The biological features of the primary tumour were diagnosed according to the presence or absence of a ground-glass component on high-resolution CT and the maximum standardized uptake value in [(18)F]-fluorodeoxyglucose positron emission tomography, in addition to conventional characteristic factors. RESULTS The risk factors for postoperative recurrence were underlying emphysema, a high maximum standardized uptake value, the absence of a ground-glass component, the pathological grade and lymph node metastasis, whereas the risk factors for lymph node metastasis were a high maximum standardized uptake value, the absence of a ground-glass component and the pathological grade. Surprisingly, these risk factors were entirely matched between patients with and without emphysematous lungs, regardless of the fact that patients with emphysematous lungs had a higher recurrence rate. CONCLUSIONS Similar clinicopathological features, but different postoperative recurrence rates, were found between Stage I lung cancers arising in emphysematous lungs and those arising in nonemphysematous lungs. It may be valuable to search for underlying molecular mechanisms that promote metastasis from primary tumours arising in emphysema, such as paracrine effects between the tumour and pulmonary emphysema.

Pulmonary emphysema and tumor microenvironment in primary lung cancer

BACKGROUND To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. METHODS The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). RESULTS Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). CONCLUSIONS The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis.

Enhanced tumor growth in the remaining lung after major lung resection

BACKGROUND Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. METHODS We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. RESULTS The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. CONCLUSIONS Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery.

Simultaneous stapling of the lobar bronchus and pulmonary artery: is it actually dangerous?

We performed a left caudal lobectomy on a 3-month old male swine. During the lobectomy, the lobar bronchus and pulmonary artery were stapled simultaneously using an endostapler. According to a postmortem examination 42 days after the operation, the stumps were surrounded by granulation tissue with prominent accumulation of inflammatory cells. With respect to the bronchus, the stapled tissue remained as it was just after stapling, without degradation of the cartilage, smooth muscle or epithelial layers. In contrast, with respect to the pulmonary artery, the stapled tissue disappeared, which resulted in the formation of a new vascular stump with recruitment of a new adventitial layer and fibrotic tissue. Therefore, despite the simultaneous stapling, the vascular stump was separated from the bronchial stump. Our results suggest that the process of stump healing after stapling of the bronchus is different from that after stapling of the pulmonary artery: bronchial stump healing consists of extraluminal covering of the fibrotic tissues, while pulmonary arterial stump healing consists of intraluminal reformation of the intima and media. On the basis of the results, we believe that a bronchovascular fistula will not develop after simultaneous bronchovascular stapling unless the anterior wall of the bronchus has fallen away due to major stump necrosis.