Preparations of trans- and cis-µ-1,2-Peroxodiiron(III) Complexes.

The iron(II) complex with cis,cis-1,3,5-tris(benzylamino)cyclohexane (Bn3CY) (1) has been synthesized and characterized, which reacted with dioxygen to form the peroxo complex 2 in acetone at -60 °C. On the basis of spectroscopic measurements for 2, it was confirmed that the peroxo complex 2 has a trans-µ-1,2 fashion. Additionally, the peroxo complex 2 was reacted with benzoate anion as a bridging agent to give a peroxo complex 3. The results of resonance Raman and 1H-NMR studies supported that the peroxo complex 3 is a cis-µ-1,2-peroxodiiron(III) complex. These spectral features were interpreted by using DFT calculations.

[Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

[Predictor of intrathoracic lymph node metastasis in peripheral non-small cell lung cancers 20 mm or less in greatest dimension].

PURPOSES: To assess the independent predictor of lymph node metastasis( LNM) in peripheral smallsized non-small cell lung cancers (NSCLCs), we conducted a clinicopathologic analysis of patients with small-sized NSCLCs with and without intrathoracic LNM. METHODS: We retrospectively studied 213 patients who had undergone surgical resection of NSCLCs 20 mm or less in diameter. Categories of patient characteristics were divided into 2 groups based on clinicopathologic features, and the incidence of LNM was compared. Univariate and multivariate analyses of factors affecting overall survival( OS) were also conducted. RESULTS: In pN1-2 group (n=19), the incidence of elevated (>5 ng/dl) of preoperative carcinoembryonic antigen (CEA) and larger tumor size (>10 mm) was significantly higher than that in pN0 group (n=194) [p=0.0004, 0.0025]. Preoperatively, 73.7% patients were diagnosed as having lower stage in N-staging. Multivariate analysis identified only pN staging as an independent prognostic factor (p=0.002). CONCLUSIONS: It is likely that preoperative CEA and tumor size are useful in selecting patients with micro-N1-2 disease among those with small-sized NSCLCs. Our results indicate that limited resection should be avoided in patients with elevated CEA or tumors more than 10 mm in size, even if preoperative radiographic findings suggest no intrathoracic LNM.

Antidepressants induce toxicity in human placental BeWo cells.

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs) are broadly used for the treatment of depression. Depression is one of the most common psychiatric disorders in pregnant women and SSRIs are commonly prescribed for depression during pregnancy. The placenta regulates the transport of nutrients and oxygen between the maternal and fetal circulation, and is essential for the survival and growth of the fetus. The present study investigated the effects of antidepressants on human placental BeWo cells. BeWo cell viability was significantly decreased following exposure to sertraline (SSRI), paroxetine (SSRI), fluvoxamine (SSRI), and duloxetine (SNRI), whereas escitalopram (SSRI), venlafaxine (SNRI), and mirtazapine (NaSSA) showed little or no effects. Extracellular lactate dehydrogenase activity was increased by sertraline, paroxetine, fluvoxamine, and duloxetine, indicating toxicity to the cells. Sertraline increased the production of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Sertraline decreased the cellular ATP content in a time and concentration-dependent manner. Caspase-3/7 activity and apoptotic cells, detected using the phosphatidylserine-specific fluorescent probe Apotracker Green, were increased by sertraline. Our findings suggest that antidepressants, such as sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. Sertraline may induce ROS-dependent apoptosis in human placental cells. These results are useful for further studies to determine the optimal dosage of antidepressants for pregnant women.

[Prognosis of surgically treated large cell neuroendocrine carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) is a relatively rare tumor in malignant lung neoplasms. The prognosis of LCNEC is poor and there is no consensus on the treatment for LCNEC. We report our retrospective assessment of 11 patients of LCNEC from 1999 to 2008. Three of 11 patients had malignant exudate at thoracotomy. Seven patients received limited resection. There was a recurrence even after complete surgical resection in its early stage. Four patients received platinum-based chemotherapy for adjuvant therapy or recurrence. The response to platinum-based chemotherapy was relatively good and may be comparable to that of small cell lung cancer. The overall 5-year survival rate was 30.3%. Pulmonary LCNEC represents an aggressive tumor and multimodal treatment is required.

Dual time point FDG PET for evaluation of malignant pleural mesothelioma.

OBJECTIVE: To evaluate whether 2-deoxy-2-18F-fluoro-D-glucose (FDG) positron emission tomography (PET) is more useful in differentiating malignant from benign pleural lesions, and whether delayed FDG PET imaging can improve the diagnostic performance in patients with suspicion of malignant pleural mesothelioma (MPM). METHODS: Thirty-three patients who were suspected of having MPM were examined with FDG PET. PET imaging (whole body) was performed at 60 min (early) post-FDG injection and repeated at 120 min (delayed) after injection only in the thoracic region. We evaluated the FDG uptake visually and semiquantitatively. The semiquantitative analysis using the standardized uptake value (SUV) was determined for both early and delayed images (SUVearly and SUVdelayed, respectively). RESULTS: The final diagnosis was MPM in 17 patients and benign pleural disease in 16 patients. The sensitivity, specificity, and accuracy to detect MPM on both early and delayed PET were all 88%. The mean value of SUVdelayed in MPM was significantly higher than that of SUVearly (P < 0.001). The mean values of SUVearly and SUVdelayed in MPM were significantly higher than the corresponding values in benign pleural disease (P < 0.01, respectively). CONCLUSION: FDG PET seems to be a useful imaging modality for differential diagnosis of MPM. In addition, the diagnostic performance on delayed PET was the same as that on early PET, although SUVdelayed was significantly higher than SUVearly in patients with MPM.

Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients.

The Wnt family genes encode multifunctional signaling glycoproteins that are involved in the regulation of a wide variety of normal and pathological processes including tumorigenesis. In order to clarify the clinical significance of the intratumoral Wnt1 expression in non-small cell lung cancer (NSCLC), we performed an immunohistochemical study on the Wnt1 expression in NSCLCs in relation to the tumor proliferation. The intratumoral Wnt1 protein expression appeared in a cytoplasmic staining pattern. Of the 151 NSCLCs studied, 61 carcinomas (40.4%) were Wnt1-positive. Regarding the tumor biology of the intratumoral Wnt1 expression, the Ki-67 proliferation index was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0062). Furthermore, regarding the expression of c-Myc, one of the proliferation-regulating Wnt targets, the percentage of c-Myc-positive tumor cells was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0019). The Ki-67 proliferation index was significantly higher in c-Myc-positive than in c-Myc-negative tumors (P=0.0239). The overall survival was significantly lower in patients with Wnt1-positive NSCLCs than in patients with Wnt1-negative NSCLCs (P=0.0003). A Cox regression analysis demonstrated that the Wnt1 status was a significant prognostic factor for NSCLC patients (hazard ratio 1.983; P=0.0061). Our results revealed that the Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc.

Dual-time-point FDG-PET for evaluation of lymph node metastasis in patients with non-small-cell lung cancer.

OBJECTIVE: The objective of this study was to retrospectively evaluate whether delayed additional F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can improve the certainty of this modality in evaluating lymph node metastasis in patients with non-small-cell lung cancer (NSCLC). METHODS: Eighty-three patients with NSCLC were examined. FDG-PET imaging (whole body) was performed at 1-h (early) post-FDG injection and repeated 2 h (delayed) after injection only in the thoracic area. The PET images were evaluated qualitatively for regions of focally increased metabolism. If a lymph node was visible on the PET image, the semi-quantitative analysis using the standardized uptake value (SUV) was determined for both early and delayed images (SUV(early) and SUV(delayed), respectively). Retention index (RI) was then calculated on the basis of the following equation: (SUV(delayed) - SUV(early)) x 100/SUV(early). The RI value of more than 0% was taken to be the PET criterion for malignancy. RESULTS: For early and delayed PET, sensitivities for lymph node staging were 54% and 62%, respectively, specificities were 89% for both, and accuracies were 78% and 81%, respectively. The results of combined delayed PET and RI showed a sensitivity of 62%, specificity of 96%, and accuracy of 86%. CONCLUSIONS: Dual-time-point FDG-PET (combined delayed PET and RI) showed better (although not statistically significant) specificity, positive predictive value, and accuracy than early or delayed PET alone for lymph node staging in NSCLC.

En bloc partial vertebrectomy for lung cancer invading the spine after induction chemoradiotherapy.

OBJECTIVE: The optimal surgical treatment for non-small cell lung cancer (NSCLC) with vertebral body invasion remains both controversial and challenging. We reviewed our experiences of NSCLC with vertebral body invasion, in which we have performed induction chemoradiotherapy followed by lung resection with en bloc partial vertebrectomy. METHODS: Six NSCLC patients with vertebral invasion underwent an operation following chemoradiotherapy from January 2001 to July 2006. Vertebral invasion was evaluated by the chest CT and MRI findings. Either carboplatin-paclitaxel (n=3) or carboplatin-docetaxel (n=3) was used. Two cycles of chemotherapy were performed with concurrent radiation (50 Gy) treatment. RESULTS: In all of the six cases, a complete resection with en bloc partial vertebrectomy was performed with no operative mortality. The histological complete response rate and major response rate were 16.7% (1/6) and 83.3% (5/6), respectively. The 5-year overall survival rate was 67.7%. In addition, no local failure was observed after surgery. CONCLUSIONS: Surgery after chemoradiotherapy (carboplatin/paclitaxel or docetaxel and 50 Gy radiation) for NSCLC with vertebral invasion could thus be performed with acceptable morbidity.

A surgical case of primary lung cancer with peripheral intrapulmonary lymph node metastasis.

We report on a case of a patient with lung adenocarcinoma and peripheral intrapulmonary lymph node (IPLN) metastasis who was misdiagnosed as having intrapulmonary metastasis. A subpleural nodular shadow visualized by radiography was diagnosed as an intrapulmonary metastasis originating from primary lung cancer. Preoperative evaluation indicated that this case was a clinical T4N1 lung adenocarcinoma with metastasis in the same lobe. However, postoperative evaluation showed that it was a peripheral IPLN metastasis, and this was actually a case of pathologic T2N1 adenocarcinoma. It may have been possible to treat this case non-surgically with the possibility of radical cure. This case suggests that a nodule is present in the same lobe with lung cancer, and it must be borne in mind that IPLN metastasis may be misdiagnosed as intrapulmonary metastasis.

Thoracoscopic partial resection without using a stapler. (complete republication).

Thoracoscopic partial pulmonary resection for small peripheral nodules without using a stapler has been introduced to our hospital. After partial resection was performed with electrocautery, two different methods of surface sealing were used: a coagulation method (C method) with Soft Coagulation alone, and a coagulation-suturing method (CS method) with Soft Coagulation combined with continuous suturing. The clinical outcomes of the two methods were retrospectively compared in this study. The C method was used in 19 lesions of 18 cases, and the CS method was used in 20 lesions of 19 cases. Primary lung cancer was the most frequent diagnosis (22 lesions of 21 cases). There were no differences between the two groups in the size and depth of the lesions. Operative time was longer with the CS method than with the C method. Postoperative air leakage was a complication in 4 cases with the C method, and one of them required re-do surgery, whereas only one case with the CS method had temporary air leakage. Postoperative computed tomography showed cavitation in 3 C method cases and 5 CS method cases, all without related symptoms. There were no local recurrences at resected sites. In conclusion, the C method was technically easy to perform, but air leakage may be prolonged after surgery. The CS method may have the advantage of causing less air leakage than the C method, but mastering the technique is important to shorten operative time.

Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor--an expression in non-small-cell lung cancer.

PURPOSE: The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A). RESULTS: Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491). CONCLUSION: The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.

Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer.

PURPOSE: The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin (IL)-24, is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells including lung cancer cells. However, only one clinical study has documented that MDA-7/IL-24 expression is down-regulated with progression of melanoma. Thus, the present study was conducted to assess the clinical significance of MDA-7/IL-24 expression in non-small cell lung cancer. EXPERIMENTAL DESIGN: A total of 183 consecutive patients with resected pathologic stage I-IIIA, non-small cell lung cancer were retrospectively reviewed, and immunohistochemical staining was used to detect MDA-7/IL-24 expression. RESULTS: MDA-7/IL-24 expression was high in 97 (53.0%) patients and low in the other patients. There was no significant correlation between MDA-7/IL-24 status and any patients' characteristic including pathologic stage. There was no significant difference in tumor angiogenesis or proliferative activity according to MDA-7/IL-24 status, but MDA-7/IL-24-high adenocarcinoma showed a significantly higher incidence of apoptotic tumor cell death than MDA-7/IL-24-low adenocarcinoma. MDA-7/IL-24-high patients seemed to show a favorable postoperative prognosis as compared with MDA-7/IL-24-low patients (5-year survival rates, 75.9% and 62.0%, respectively), although the difference did not reach a statistical significance (P = 0.061). Subset analyses showed that positive MDA-7/IL-24 expression was a significant factor to predict a favorable prognosis in adenocarcinoma (P = 0.033), which was confirmed by a multivariate analysis; there was no difference in the prognosis according to MDA-7/IL-24 status in squamous cell carcinoma. CONCLUSIONS: MDA-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma.

Large cell carcinoma with neuroendocrine morphology of the lung.

We experienced a surgical case of large cell carcinoma with neuroendocrine morphology (LCCNM) of the lung. A 76-year-old man was admitted to our hospital because a routine chest X-ray examination had revealed a nodular shadow in the left lung field. 18F-fluorodeoxyglucose positron emission tomography showed accumulation of fluorodeoxyglucose in an area corresponding to the shadow. Transbronchial lung biopsy failed to give a definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Needle biopsy was performed, and the tumor was diagnosed as large cell neuroendocrine carcinoma by rapid intraoperative pathological examination. As sampling of hilar lymph nodes revealed no metastasis, left upper segmentectomy was performed for severe obstructive pulmonary disease. Immunohistochemical examination finally diagnosed the tumor as LCCNM. The patient is doing well without recurrence at ten months after surgery.

Expression of angiopoietins and its clinical significance in non-small cell lung cancer.

Angiopoietin (Ang)-1 and -2 have been recently identified as potent angiogenic factors which function in concert with vascular endothelial growth factor (VEGF), but no detailed clinical study on Ang expression has been reported. To assess the clinical significance of Ang expression in non-small cell lung cancer (NSCLC), a total of 236 patients with pathological stage-I-IIIA disease were retrospectively reviewed. Expression of Ang-1, Ang-2, or VEGF was examined immunohistochemically; intratumoral microvessel density (IMVD) was examined with immunohistochemical staining against CD34, a marker of pan-endothelial cells (CD34-IMVD), and that against CD105, a marker of proliferative endothelial cells (CD105-IMVD). Positive expression of Ang-1 and that of Ang-2 were seen in 101 (42.8%) and 40 patients (16.9%), respectively. There was no significant correlation between Ang-1 expression and CD34-IMVD or CD105-IMVD. In contrast, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (56.7 versus 38.5; P = 0.032). More interestingly, such an angiogenic effect of Ang-2 was seen only when VEGF expression was high; when VEGF expression was high, the average CD105-IMVD for Ang-2-positive tumor was significantly higher than that for Ang-2-negative tumor (89.1 versus 63.6; P = 0.045); when VEGF expression was low, the average CD105-IMVD for Ang-2-positive tumor and that for Ang-2-negative tumor were almost the same (27.4 and 27.1, respectively). Moreover, positive expression of Ang-2, not Ang-1, was a significant factor to predict a poor postoperative survival (5-year survival rates for Ang-2-positive patients and -negative patients were 53.5 and 70.3%, respectively; P = 0.027), which was confirmed by a multivariate analysis. The influence of Ang-2 status on postoperative survival was enhanced when VEGF expression was high. That said, the 5-year survival of Ang-2-positive and VEGF-high patients was extremely low (41.4%) as compared with that for Ang-2-negative and VEGF-low patients (66.6%), as compared with that for Ang-2-positive and VEGF-low patients (63.6%), and as compared with that for Ang-2-negative and VEGF-low patients (71.8%). In conclusion, positive Ang-2 expression was significantly correlated with a poor prognosis, as well as with aggressive angiogenesis in resected NSCLC that was enhanced in the presence of high VEGF expression.

Glomeruloid microvascular proliferation is superior to intratumoral microvessel density as a prognostic marker in non-small cell lung cancer.

Glomeruloid microvascular proliferation (GMP) is a focal proliferative budding of endothelial cells (ECs) resembling a renal glomerulus. Whereas some experimental and clinical studies have suggested recently that GMPs indicate an aggressive angiogenic phenotype, the incidence and clinical significance of GMPs remains unclear. Thus, we conducted a retrospective study on GMPs in a total of 236 patients with completely resected pathological (p-) stage I-IIIA NSCLC. ECs were highlighted with immunohistochemical staining using an anti-CD34 antibody, and GMPs were defined as focal glomerulus-like aggregates of closely associated and multilayer CD34-positive ECs. Expression of vascular endothelial growth factor, angiopoietin (Ang)-1, and Ang-2 was also examined immunohistochemically. GMPs were positive in 60 (25.4%) patients, and the incidence was not correlated with age, gender, histological type, or p-stage. The mean intratumoral microvessel densities for GMP-negative tumor and GMP-positive tumor were 178.2 and 184.1, respectively, showing that the incidence of GMPs was not correlated with intratumoral microvessel density (P = 0.676). There was no correlation between vascular endothelial growth factor expression and the incidence of GMPs, but GMPs were more frequently seen in Ang-1-positive tumor than in Ang-1-negative tumor. The 5-year survival rate of GMP-positive patients was 54.2%, which was significantly lower than that of GMP-negative patients (72.3%; P = 0.016). The 5-year survival rate of higher-MVD patients (71.5%) seemed to be lower than that of the lower-MVD patients (63.7%), but the difference did not reach a statistical significance (P = 0.137). A multivariate analysis confirmed that the presence of GMPs was a significant prognostic factor (P = 0.003), whereas MVD was not. In conclusion, GMPs indicate an aggressive angiogenic phenotype associated with a poor prognosis in NSCLC.

Clinical significance of p21 expression in non-small-cell lung cancer.

PURPOSE: The clinical significance of p21 expression remains unclear, whereas many experimental studies have demonstrated that p21, the product of the WAF1/CIP1/SDI1 gene, plays an important role in regulation of the cell cycle as an inhibitor of cyclin-dependent kinases. The purpose of this study was to clarify the clinical significance in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 233 consecutive patients with completely resected pathologic stage I to IIIA NSCLC were retrospectively reviewed. Expression of p21 and the status of p53 were examined immunohistochemically. Proliferative activity was also evaluated immunohistochemically. The incidence of apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining. RESULTS: Expression of p21 was positive in 120 patients (51.5%). The 5-year survival rate of p21-positive patients was 73.8%, significantly higher than that of p21-negative patients (60.7%; P =.006). Aberrant expression of p53 was positive in 98 patients (42.1%). When combined with p53 status, the prognostic value of p21 status was enhanced: the 5-year survival rate of p21-positive and p53-negative patients was 80.7%, markedly higher than that of p21-negative and p53-positive patients (50.0% for both; P =.001). Multivariate analysis confirmed that positive expression of p21 was a significant factor for predicting a favorable prognosis. There was no significant correlation between p21 expression and p53 status, proliferative activity, or incidence of apoptosis. CONCLUSION: p21 expression was shown to be an independent prognostic factor in NSCLC.

Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer.

PURPOSE: The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non-small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression. EXPERIMENTAL DESIGN: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I-IIIA, NSCLC. RESULTS: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor. CONCLUSIONS: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC.

Clinical experience of sleeve lobectomy with bronchoplasty using a continuous absorbable barbed suture.

Anastomosis in bronchoplasty is usually performed using interrupted sutures, which are considered safe, reliable, and secure. However, placing interrupted sutures can be complex and time-consuming. There have been recent reports of continuous suturing using standard suture materials in bronchoplasty. We have experienced four cases of sleeve lobectomy with bronchial anastomosis in continuous fashion using a novel absorbable barbed suture device, the V-Loc™ wound closure device (Covidien, USA), which facilitates secure wound closure without knot-tying. Two patients underwent sleeve upper lobectomy and two underwent sleeve upper-middle lobectomy. Surgical approach was completely thoracoscopic in one patient and open in three. There were no intraoperative difficulties such as cutting or loosening, and a leak test was negative in all cases. One patient had pneumonia postoperatively and developed anastomotic stenosis 4 months after surgery, which did not require treatment. All patients were alive, without local recurrence, at a mean follow-up of 11.5 months postoperatively.