Masaya Tamura

The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer

Expression of vascular endothelial growth factor (VEGF)-C and that of its receptors were assessed in non-small cell lung cancer. Immunohistochemistry revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A significant positive correlation was found between VEGF-C in cancer cells and VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer patients, VEGF-C expression was significantly associated with lymph node metastasis, lymphatic vessel invasion, and worse outcomes after the operation. Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear, VEGFR-2 expression in endothelial cells retained the independency as the prognostic indicator. In light of these findings, we conclude that VEGF-C plays an important role in lymphatic invasion/metastasis and tumour progression in non-small cell lung cancer.

Small amount of low-residue diet with parenteral nutrition can prevent decreases in intestinal mucosal integrity

OBJECTIVE To investigate the suitable combination ratio of low-residue diet (LRD) and parenteral nutrition (PN) for nutritional support of surgical patients. SUMMARY BACKGROUND DATA Bacterial translocation (BT) is a severe complication of total parenteral nutrition (TPN). However, it is sometimes impossible to supply sufficient amounts of nutrients to surgical patients by the enteral route. The authors reported previously that concomitant use of LRD with PN provided preferable nutritional support for patients undergoing surgery for colorectal cancer. METHODS Ninety male Donryu rats were used for three experiments. In experiment 1, rats were divided into two groups to receive TPN or total enteral nutrition with LRD. In experiment 2, rats were divided into six groups, receiving variable amounts of LRD. In experiment 3, rats were divided into five groups to receive isocaloric nutritional support with variable proportions of PN and LRD. Intestinal permeability was assessed by monitoring urinary excretion of phenolsulfonphthalein. BT was assessed in tissue cultures of mesenteric lymph nodes and spleen. RESULTS In experiment 1, increases in intestinal permeability and BT were observed in rats maintained on 7-day TPN, but not in those maintained on total enteral nutrition for up to 14 days. In experiment 2, the changes in body weight of rats were correlated with the dose of LRD. However, the intestinal permeability was increased only in rats receiving LRD at 15 kcal/kg per day. In experiment 3, additive LRD corresponding to 15% of total caloric intake prevented increases in intestinal permeability and BT. CONCLUSION Combined nutritional therapy consisting of PN and small amounts of LRD can provide better nutritional support than TPN for surgical patients.

The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer.

AbstractBackground: The aim of the present study was to evaluate the diagnostic utility of levels of circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9 (MMP-9), and VEGF and to verify that the combination assay of these circulating factors is a clinically useful indicator to predict the presence of lymph node metastasis in non–small cell lung cancer (NSCLC). Methods: A series of 78 patients who underwent surgery for NSCLC was used in this study. Serum VEGF-C and VEGF and plasma MMP-9 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression models were used to analyze the influence of VEGF-C, MMP, and VEGF levels on the probability of presence or absence of lymph node metastasis. Results: Patients with lymph node metastasis had higher serum VEGF- C, VEGF, and plasma MMP-9 concentrations than did those without metastasis (VEGF-C, P = .0004; VEGF, P = .001). Serum VEGF- C reached a sensitivity of 85% and specificity of 68% when a cutoff value of 1762.0 pg/mL was applied, while VEGF reached 80% sensitivity and 59% specificity at 316.8 pg/mL. MMP-9 reached a sensitivity of 63% and specificity of 75% when a cutoff value of 51.4 ng/mL was applied. In the ROC curve analysis, VEGF-C (0.761) had the biggest areas under the ROC curve, followed by MMP-9 (0.723) and VEGF (0.694). Combination assay of three markers had higher sensitivity and specificity for prediction than single-marker assays (AUC = 0.837). Conclusions: This study has confirmed that combination assay of three markers to determine VEGF-C, MMP-9, and VEGF expression in circulation detects lymph node metastasis in NSCLC with higher accuracy than single-marker assays.

Extended Thymectomy in Patients with Myasthenia Gravis with High Thoracic Epidural Anesthesia Alone

Successful extended thymectomy was performed in three patients with myasthenia gravis under only high thoracic epidural anesthesia with voluntary breathing. It was not necessary to intubate a tracheal tube during operation for any of the patients. Neither muscle relaxants nor volatile anesthetic agents were required. The mean operating time was 2.0 ± 0.5 hours. The drainage tubes were removed the day after operation in all patients. In two patients the arterial oxygen saturation (SaO2) and the arterial partial pressure of carbon dioxide (PaCO2) and oxygen (PaO2) were stable; in the third patient the SaO2 was temporarily decreased to 92 mmHg when bilateral mediastinal pleura were opened. The right pleural defect was then covered with a large wet towel, which was pressed on the defect, and thoracic drainage was performed. The left pleural defect was repaired with 3-0 Vicryl after suctioning the air in the pleural space, after which the SaO2 recovered. All patients were able to drink water and walk within 1 hour after the operation. This procedure is advantageous in that the use of muscle relaxants and volatile anesthetic agents prevented the laryngeal injury that results from translaryngeal intubation; in turn we avoided causing postoperative respiratory insufficiency. This may be suitable for the operation of some patients with MG, but further studies are required to define the indication.

Diagnostic value of plasma vascular endothelial growth factor as a tumor marker in patients with non-small cell lung cancer.

We assessed the diagnostic value of circulating VEGF as a tumor marker in patients with lung cancer and compared its clinical utility with that of other markers such as carcinoembryonic antigen (CEA) and cytokeratin 19 (CYFRA). One hundred and sixty non-small cell lung cancer patients and 70 healthy volunteers were included in the study. Circulating VEGF was assessed by enzyme-linked immunosorbent assay (ELISA). The serum concentrations of both CEA and CYFRA were measured by means of immunoradiometric assays. The diagnostic value of plasma VEGF (VEGFp) was better than that of CYFRA and similar to that of CEA. When the diagnostic value of VEGFp and CEA for the diagnosis of adenocarcinoma was compared, the two markers proved to have nearly equal discriminatory power. In diagnosing squamous cell carcinoma, VEGFp showed less discrimination than CYFRA. When the diagnostic value of VEGFp was analyzed for stage I adenocarcinoma patients, VEGFp was slightly more discriminatory than CEA. The combination assay of VEGFp and CEA had a sensitivity of 75% and a specificity of 60% at a cutoff of 104.4 pg/mL for VEGFp and 5.2 ng/mL for CEA. The combination of VEGF and CEA was superior to CEA alone in the early diagnosis of adenocarcinoma of the lung.

New indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic surgery

The aim of this work was to analyze parameters to determine the possibility for detection of tumor location, and clarify the indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic resection. In a series of 97 patients who underwent video-assisted thoracoscopic surgery, information on standard uptake values (SUVs) and the detectability of tumor location was assessed. In patients whose lesions were <15 mm in diameter and where the distance to the pleura was >10 mm, lesions were not detected. Multivariate analysis to determine the factors related to the possibility of detecting tumor localization revealed that the distance to the pleural surface (P=0.0001), and the ratio of solid portion (P=0.0104) were statistically significant. In the non-solid tumor group, we should perform preoperative marking for tumors located more than 3 mm in depth from the visceral pleura. In the solid tumor group, the linear function (depth=0.4×size-0.9) may be used to separate detectable and undetectable groups. However, the sensitivity was 90.3% even if this formula was applied. Here we advocate the algorithm for detection of indication for preoperative marking using the ratio of solid portion, tumor size and SUV of fluorodeoxyglucose positron emission tomography.

Treatment for Intercostal Arterial Aneurysm in Neurofibromatosis Type 1

We report a valuable case in which a spontaneous intercostal arterial aneurysmal rupture associated with neurofibromatosis type 1, and a re-rupture after embolization of the aneurysm were successfully treated by endovascular embolization without surgery. Our case calls for attention as it indicates that recurrent aneurysmal rupture can occur even after an embolization or surgery. It is important to carefully observe the course of the patient by follow-up computed tomography (CT) or angiography in such cases.

Closed three-port anatomic lobectomy with systematic nodal dissection for lung cancer.

Closed three-port anatomic lobectomy of the lung with systematic nodal dissection was performed in 5 patients with clinical stage IA lung cancer. For removal of the resected specimen, a new technique was developed to avoid making an additional skin incision. No complications or deaths occurred after the operation, and all patients were alive longer than 27 months without recurrence, including 5-year survivors.

Antitumor effect and antiangiogenic potential of the mTOR inhibitor temsirolimus against malignant pleural mesothelioma.

The mTOR inhibitor temsirolimus has antitumor and antiangiogenic activity against several carcinomas, yet few reports document the efficacy of temsirolimus against malignant pleural mesothelioma (MPM). Therefore, we evaluated the efficacy of temsirolimus and the antiangiogenic effect of temsirolimus in the treatment of MPM. We examined the efficacy of temsirolimus alone and the efficacy of the combination of temsirolimus and cisplatin or pemetrexed against four MPM cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The effect of temsirolimus on the production of proangiogenic cytokines by MPM cell lines was examined by enzyme-linked immunosorbent assay (ELISA). Expression of mTOR and proangiogenic cytokines in clinical specimens from MPM patients was determined by immunohistochemistry. Temsirolimus inhibited cell viability and suppressed cell proliferation of all MPM cell lines. Combined treatment with temsirolimus and cisplatin inhibited the viability of all MPM cell lines more effectively than temsirolimus alone. Temsirolimus strongly inhibited the phosphorylation of p70s6k, a downstream molecule of mTOR, in all MPM cell lines and led to an increase in the levels of cleaved caspase-3 in the H226 and Y-meso14 cells. Temsirolimus also inhibited the production of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-AA (PDGF-AA). Phosphorylated mTOR and high expression of VEGF and PDGF were detected in 2 and 3, respectively, out of the 5 MPM specimens. These results suggest that temsirolimus has activity against MPM cells by inhibition of cell proliferation and angiogenesis, and may be beneficial for a subset of MPM patients with high mTOR expression.

Pattern and predictors of false positive lymph node involvement on positron emission tomography in patients with non-small cell lung cancer.

Objectives The aim of this study was to elucidate the optimal parameters for diagnosing false positive (FP) lymph nodes (LNs) in patients with non-small cell lung cancer.Methods We reviewed 292 patients with non-small cell lung cancer (NSCLC). Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging was performed at 1 hour (early) post-FDG injection and repeated 2 hours (delayed) after injection. We analyzed the relationship between the pathology of LNs and the results of PET, and the percent change in the standardized uptake value (%ΔSUV) between the two time-points.Results Eighteen of 46 cases (39.1%) in the FP group showed higher SUVs for their LNs compared with those for primary tumor, whereas 13.2% in the true positive group (p = 0.032) had higher SUVs for their LNs. Thirty-four of 36 cases in the true positive group had %ΔSUV ranging from 0% to 61.5% compared with only 13 of 33 in the FP group. Twenty out of 22 cases (90.9%) where %ΔSUV was over 61.5% or under 0% were considered as FP.Conclusions Patients with higher SUVs for LNs than for primary tumors and patients with extremely high or low %ΔSUVs tended to have FP LNs.