Noriyuki Matsutani

Impact of Hospital Volume on Chest Tube Duration, Length of Stay, and Mortality After Lobectomy

BACKGROUND Numerous studies have suggested an inverse relationship between hospital volume and short-term mortality after various major operations. However, the volume-outcome relationship after lung cancer surgery remains controversial. We investigated the effects of hospital volume on various outcomes after lobectomy for lung cancer, including chest tube duration, postoperative length of stay, and in-hospital mortality. METHODS From a total of 5.85 million inpatients in the Japanese Diagnosis Procedure Combination database, we identified 19,831 patients who underwent lobectomy for lung cancer between July and December in 2007 and 2008. Patients were divided into low (≤24 per year), medium-low (25 to 43), medium-high (44 to 67), or high (≥68) hospital-volume groups. Multivariate regression analyses were conducted to analyze the concurrent effects of various factors on postoperative outcomes. RESULTS Overall in-hospital mortality was 0.69%, and was significantly lower in the high-volume group compared with the low-volume group (0.48% versus 0.94%; odds ratio 0.60; p=0.047). Chest tube removal occurred earlier in the high-volume group than in the low-volume group (mean 4.0 days versus 5.1; p<0.001). Postoperative length of stay was shorter in the high-volume group than in the low-volume group (mean 11.5 days versus 15.9, p<0.001). CONCLUSIONS Higher hospital volume was associated with significantly shorter chest tube duration and postoperative length of stay, and lower in-hospital mortality after lobectomy for lung cancer. However, the differences in outcomes between high-volume and low-volume hospitals may be too small to support regionalization of lung cancer operations to high-volume centers.

Exosomal microRNA in plasma as a non‑invasive biomarker for the recurrence of non‑small cell lung cancer

Predictive biomarkers for the recurrence of non-small cell lung cancer (NSCLC) in patients who have received curative resection are important for cancer treatment. The functional microRNAs (miRNAs/miRs) in the exosomes of plasma and serum samples are of interest as stable and non-invasive biomarkers for recurrence in cancer patients. The aim of the present study was to clarify the usefulness of plasma exosomal miRNAs as biomarkers for the prediction of recurrence in NSCLC following curative resection. First, microarray-based expression profiling of miRNAs derived from exosomes in the plasma of 6 patients was employed to identify a biomarker that distinguishes between patients with and without NSCLC recurrence. In the miRNA microarray analyses, the exosomal miR-21 and miR-4257 levels of the NSCLC patients showed marked upregulation in those individuals with recurrence compared with those without recurrence and healthy individuals. These two miRNAs were thus selected as recurrence-specific biomarkers and their potential was evaluated in a separate cohort of 195 NSCLC patients. In comparison to the levels in 30 healthy individuals, exosomal miR-21 and miR-4257 levels showed a significant increase in the NSCLC patients (P<0.01). When evaluating the clinicopathological significance of these miRNAs, exosomal miR-21 showed a significant association with tumor size and tumor-node-metastasis (TNM) stage (P<0.05). Exosomal miR-4257 showed a significant association with histological type, lymphatic invasion and TNM stage (P<0.05). The disease-free survival (DFS) rates of high exosomal miR-21 patients were significantly worse than those of low exosomal miR-21 patients (P<0.05), and the DFS rates of patients with high exosomal miR-4257 levels were significantly worse than those with low exosomal miR-4257 levels (P<0.01). In the Cox multivariate analysis, plasma exosomal miR-21 and miR-4257 expression showed a significance association with DFS (P<0.05). These results suggest that plasma exosomal miR-21 and mir-4257 expression has potential as a predictive biomarker for recurrence in NSCLC patients who have received curative resection.

Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells.

There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-κB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL-6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF-α and IFN-γ, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-κB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation.

The prognostic impact of lymph-node dissection on lobectomy for pulmonary metastasis

OBJECTIVES The prevalence and characteristics of lymph-node metastasis have not been thoroughly investigated in patients with pulmonary metastases from various primary neoplasms. The necessity of performing lymph-node dissection with pulmonary metastasectomy is unknown. METHODS We retrospectively reviewed the database of the Metastatic Lung Tumor Study Group of Japan. Between November 1980 and June 2013, 4363 patients underwent resection of pulmonary metastases. After selecting for patients who underwent lobectomy, 683 patients (16%) were analysed. The presence of lymph-node metastasis, outcomes and prognoses were investigated. RESULTS The primary tumour site was colorectal in 350 patients, head and neck in 73 patients, kidney in 41 patients, uterus in 41 patients and bone/soft tissue in 31 patients. The overall 5-year survival rate after pulmonary metastasectomy was 50.1%, and the 10-year survival rate was 36.4%. Lymph-node metastasis was more frequently found in uterine (27%) and head and neck cancers (29%). Five-year survival rates were 53.8% in patients without lymph-node metastasis, 39.4% in patients with hilar lymph-node metastasis and 30.8% in patients with mediastinal lymph-node metastasis. The extent of lymph-node dissection was not related to survival. Univariate analysis revealed that tumour size, the presence of lymph-node metastasis, the presence of multiple lesions, a disease-free interval of 24 months or less and incomplete resection were significant predictors of poor prognosis. Multivariate analysis confirmed these prognostic factors. CONCLUSIONS Retrospective analysis of lobectomy for pulmonary metastasis demonstrated that lymph-node metastasis is a significant prognostic factor predicting poor outcome. Lymph-node sampling or dissection is therefore warranted to predict patient prognosis.

Significant improvement of chronic pain by Pregabalin after thoracotomy: report of four cases

Unfortunately, many patients may have persistent pain lasting for many months, or even years, following thoracic surgery. No effective treatment has so far been established for chronic pain after thoracotomy. There are no reports of treatment involving Pregabalin for pain after thoracic surgery. This study reports four cases that showed significant improvement with Pregabalin in late-onset (notified during an office visit after discharge) nocturnal insomnia and in stress-induced ulcers caused by intercostal neuralgia after thoracotomy.

Qualitative Analysis of Preoperative High-Resolution Computed Tomography: Risk Factors for Pulmonary Complications After Major Lung Resection.

BACKGROUND Postoperative pulmonary complications after major lung resection are strongly associated with mortality. Qualitative findings of emphysema, bronchiectasis, and bronchial wall thickening on high-resolution computed tomography (HRCT) are indicators of chronic obstructive pulmonary disease and may serve as risk factors for pulmonary complications. METHODS The subjects were 347 consecutive patients who underwent single lobectomy for pulmonary malignancy from May 2010 to December 2014. Correlations of pulmonary complications with preoperative clinical factors and HRCT findings were retrospectively examined using multivariate logistic regression analysis to compare the predictive ability for pulmonary complications using clinical variables that were reported to be risk factors. RESULTS Patients who had pulmonary complications were more frequently male (p < 0.001), with a greater smoking history (p < 0.001), lower rate of steroid use (p < 0.001), more frequent emphysema on HRCT (p < 0.001), more frequent bronchiectasis on HRCT (p = 0.002), more frequent bronchial wall thickening on HRCT (p < 0.001), and higher rate of extended resection (p = 0.006). In multivariate analysis, HRCT findings (odds ratio [OR] 12.01, 95% confidence interval [CI]: 5.582 to 25.83, p < 0.001) and extended resection (OR 7.726, 95% CI: 1.678 to 35.57, p = 0.009) were independent risk factors for pulmonary complications. After matching of risk factors between patients with and without pulmonary complication, emphysema (OR 3.394, 95% CI: 1.781 to 6.469, p < 0.001) and bronchial wall thickening (OR 6.250, 95% CI: 2.414 to 16.18, p < 0.001) were independently associated with pulmonary complications in the model with better performance. CONCLUSIONS Qualitative findings on HRCT are independent risk factors for pulmonary complications after lobectomy. Preoperative HRCT may be useful to predict pulmonary complications.

Pleural defect repair with an overlapping method using fibrin glue-coated collagen fleece

PurposeCollagen fleece coated with fibrin glue (TachoComb; CSL Behring, Tokyo, Japan) is a tissue adhesive and sealant used to stop hemorrhage and air leakage. We assessed the efficacy of overlapping methods combined with the use of TachoComb to repair pleural defects.MethodsUsing a beagle animal model, circular and square defects were created on the pulmonary pleura and then repaired with TachoComb patches of varying minimum overlap widths (MOW). The airway pressure at which air leakage from the repaired region occurred (bursting pressure) was measured in a water sealing test. The ability of TachoComb to withstand temporal changes was assessed by repairing a 6-mm circular defect. The bursting pressure was measured at 5 min, 10 min, 3 h, and 24 h after the repair.ResultsTachoComb patches with an MOW ≥6 mm withstood significantly higher pressures than patches with an MOW ≤3 mm for both circular and square defects. The bursting pressure was found to increase over time for up to 3 h after being applied, indicating that adhesion of the TachoComb patch to the pleural tissue improved during the 3-h period.ConclusionPleural defects repaired using an overlapping method with an MOW of 6 mm were able to withstand airway pressures ≥40 cmH2O.

Predictors of long-term compensatory response of pulmonary function following major lung resection for non-small cell lung cancer.

Long‐term pulmonary function which might include compensatory response (CR) significantly influences quality of life of long‐term survivor after major lung resection. We investigated long‐term pulmonary function after major lung resection.

Therapeutic potential of recombinant thrombomodulin for lung injury after pneumonectomy via inhibition of high-mobility group box 1 in mice.

BACKGROUND Surgical acute respiratory distress syndrome (ARDS) is an extremely critical condition which may occur after major lung resection. Despite advances in minimally invasive surgical procedures and progress in the therapeutic management of this disease, prognosis remains poor. In this study, we investigated the contribution of high-mobility group box 1 (HMGB1) in a surgical ARDS model and evaluated the possible therapeutic effect of recombinant thrombomodulin (rTM) for the treatment of surgical ARDS. METHODS C57BL/6J mice underwent left pneumonectomy. rTM was injected at 12 hours before surgery, followed by 12 hours for 3 days after surgery. Lipopolysaccharide (LPS) was administered at 2 hours after surgery. We conducted a histologic analysis and measured HMGB1, IL-6, IL-1&bgr;, and TNF-&agr; in bronchoalveolar lavage fluid on day 3 after pneumonectomy. Data were compared between the treatment groups. RESULTS On histologic analysis, left pneumonectomy followed by LPS administration induced both severe inflammatory cellular infiltration and alveolar wall congestion with hemorrhage. rTM administration rescued these histologic changes. The level of HMGB1, IL-6, IL-1&bgr;, and TNF-&agr; in bronchoalveolar lavage fluid was significantly increased by LPS administration after pneumonectomy and significantly decreased by rTM administration with LPS and pneumonectomy (p < 0.001). Also, LPS alone showed no statistical differences in HMGB1 or proinflammatory cytokine level compared with pneumonectomy (PNX) group. In addition, the survival outcome was also improved by rTM administration. CONCLUSIONS LPS administration after left pneumonectomy could induce the severe lung injury. PNX and LPS have similar contribution to this model and may play a synergistic role in this process. rTM may have the potential therapeutic effect for surgical ARDS via suppression of HMGB1 and the secretion of proinflammatory cytokines induced by the administration of LPS after left pneumonectomy.

Predictors of post-recurrence survival in patients with non-small-cell lung cancer initially completely resected.

OBJECTIVES Despite recent progress in diagnostic technology and therapeutic approaches to non-small-cell lung cancer (NSCLC), 30-75% of patients develop tumour recurrence after resection. However, the details of post-recurrence survival (PRS) are not well understood. We aimed to investigate the predictors of PRS in patients with NSCLC initially completely resected. METHODS A series of 568 NSCLC patients who had undergone complete resection between 2000 and 2009 were evaluated retrospectively. Patients who had developed recurrent NSCLC after complete resection were subjected to the current analysis. We examined PRS using the Kaplan-Meier method and multivariate Cox regression analyses. RESULTS Of the 568 patients, 138 (24.3%) were identified as having disease recurrence. The 2-year and 5-year PRS rates were 44.6 and 25.9%, respectively, while the median PRS time was 22.5 months. Non-adenocarcinoma histology [hazard ratio (HR) = 2.825, 95% confidence interval (CI): 1.825-4.367, P < 0.001], serum carcinoembryonic antigen (CEA) at recurrence ≥5.0 mg/dl (HR = 2.205, 95% CI: 1.453-3.344, P < 0.001) and no systemic chemotherapy (HR = 2.137, 95% CI: 1.304-3.247, P = 0.002) were independent prognostic factors for PRS. CONCLUSIONS The current results showed that non-adenocarcinoma histology, elevated serum CEA at recurrence and no systemic chemotherapy were independent unfavourable post-recurrence prognostic factors. The current data can be informative for patient follow-up after complete resection and further clinical investigation may give us more information about PRS and accurate treatment strategy for recurrent NSCLC after initial complete resection.