Ryuzo Kanno

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery

OBJECTIVE A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

Chyothorax associated with massive osteolysis (Gorham’s syndrome)

We report a 15-year-old boy with bilateral chylothorax complicating Gorhams syndrome. Thoracic duct ligation failed to prevent fluid reaccumulation. The patient died of lymphocytopenia. Autopsy revealed vascular proliferation in the parietal and visceral pleura as well as in the ribs, which seemed to cause persistent chylothorax responsible for the poor prognosis of this patient. We reviewed treatments provided to 22 patients reported in the literature with Gorhams syndrome and chylothorax.

Long-term outcomes after video-assisted thoracic surgery (VATS) lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer

BackgroundVideo-assisted thoracic surgery (VATS) lobectomy is a standard treatment for lung cancer. This study retrospectively compared long-term outcomes after VATS lobectomy versus lobectomy via open thoracotomy for clinical stage IA non-small cell lung cancer (NSCLC).MethodsFrom July 2002 to June 2012, 160 patients were diagnosed with clinical stage IA NSCLC and underwent lobectomy. Of these, 114 underwent VATS lobectomy and 46 underwent lobectomy via open thoracotomy.ResultsThe 5-year disease-free survival (DFS) rate was 88.0% in the VATS group and 77.1% in the thoracotomy group for clinical stage IA NSCLC (p = 0.1504), and 91.5% in the VATS group and 93.8% in the thoracotomy group for pathological stage IA NSCLC (p = 0.2662). The 5-year overall survival (OS) rate was 94.1% in the VATS group and 81.8% in the thoracotomy group for clinical stage IA NSCLC (p = 0.0268), and 94.8% in the VATS group and 96.2% in the thoracotomy group for pathological stage IA NSCLC (p = 0.5545). The rate of accurate preoperative staging was 71.9% in the VATS group and 56.5% in the thoracotomy group (p = 0.2611). Inconsistencies between the clinical and pathological stages were mainly related to tumor size, nodal status, and pleural invasion. Local recurrence occurred for one lesion in the VATS group and six lesions (five patients) in the thoracotomy group (p = 0.0495).ConclusionsThe DFS and OS were not inferior after VATS compared with thoracotomy. Local control was significantly better after VATS than after thoracotomy. Preoperative staging lacked sufficient accuracy.

Endoscopic closure of bronchopleural fistula after pneumonectomy by submucosal injection of polidocanol

We report two cases of a bronchopleural fistula with, and without, empyema treated by endoscopic submucosal injection of polidocanol (sclerotherapy) and application of cyanoacrylate. Case 1: A 60-year-old man underwent left pleuropneumonectomy for lung cancer. He developed bronchopleural fistula with empyema at 32 days after the operation. We performed sclerotherapy around the fistula. The air leakage stopped at 2 weeks after the sclerotherapy, and the fistula was closed. He was eventually cured of the empyema by pleural drainage. Case 2: A 61-year-old man underwent left pneumonectomy for lung cancer. He developed bronchopleural fistula without empyema at 50 days after the operation. We performed sclerotherapy and application of cyanoacrylate. After this therapy, the air leakage stopped immediately, and the bronchopleural fistula was closed. The sclerotherapy and application of cyanoacrylate are not only technically easy, but also very effective for treatment of bronchopleural fistula. Sclerotherapy and cyanoacrylate may be advocated as a first therapeutic step.

Expression of Liver-Type Fatty-Acid-Binding Protein, Fatty Acid Synthase and Vascular Endothelial Growth Factor in Human Lung Carcinoma

Objective: A key enzyme of fatty acid synthesis, fatty acid synthase (FAS), is expressed in human cancers, including squamous-cell carcinoma of the lung, and long-chain fatty acids are intracellularly transported and/or taken up from blood by fatty-acid-binding proteins (FABPs). Since the liver-type (L-) FABP, a member of the FABPs, is detected in a subset of gastric adenocarcinomas, the expression of FAS, L-FABP and vascular endothelial growth factor (VEGF) was investigated in human lung carcinomas to elucidate the mechanisms of production and transportation of fatty acid(s) in cancer. Methods: Expression of L-FABP, FAS and VEGF in 199 surgically resected lung carcinomas was examined immunohistochemically. Possible associations of the expression of each protein with major clinicopathological factors were analyzed. Results: L-FABP was detected in 60% (120 of 199) of the lung carcinoma cases; detection was increased in large-cell carcinoma (80%) and adenosquamous carcinoma (83%), but low in squamous-cell carcinoma (47%) and in small-cell carcinoma (57%). Overall expression of FAS was 67.3% (134 of 199 cases) and that of VEGF was 86.8% (158 of 199 cases), respectively. Expression of L-FABP was not correlated with the FAS status, but there was a tendency to co-expression of L-FABP and VEGF. There was no association between L-FABP, FAS or VEGF expression and clinicopathological data. Conclusions: L-FABP, FAS and VEGF are highly expressed in human lung cancer, and expression of L-FABP is associated with that of VEGF but not that of FAS, suggesting that L-FABP might be involved in the uptake of fatty acid(s) from the bloodstream.

Expression of peanut agglutinin-binding carbohydrates correlates with nodal involvement in human lung adenocarcinoma.

The expression of 15 kinds of lectin-binding carbohydrates was examined histochemically in lung adenocarcinoma. The relation between expression of lectin binding carbohydrates and clinicopathologic factors was studied. The expression of peanut agglutinin (PNA) binding carbohydrates showed a high lymph node metastatic rate. Relation between PNA-binding carbohydrate expression and lymphatic vessel invasion was also recognized. Multivariate analysis showed that PNA-binding carbohydrate expression was an independent predictive factor of lymph node metastasis (odds ratio: 2.8) and of lymphatic vessel invasion (odds ratio: 5.2). The expression of PNA-binding carbohydrates would be a significant predictive factor for lymph node metastasis of lung adenocarcinomas.

Efficacy and tolerability of nanoparticle albumin-bound paclitaxel in combination with carboplatin as a late-phase chemotherapy for recurrent and advanced non-small-cell lung cancer: A multi-center study of the Fukushima lung cancer association group of surgeons

The present retrospective multi-center study aimed to evaluate the efficacy and feasibility of nanoparticle albumin-bound (nab)-paclitaxel plus carboplatin as a second or late-phase chemotherapy in patients with non-small cell lung cancer (NSCLC). A total of 25 patients with recurrent or advanced NSCLC who had received previous chemotherapy were treated with nab-paclitaxel (70-100 mg/m2, intravenously) on days 1, 8 and 15 every 28 days with a carboplatin area under the concentration-time curve of 4-6 on day 1. The overall response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicities were statistically evaluated. Of the 25 patients, there were 9 cases of recurrent disease following surgery, 16 cases of advanced disease, 13 cases of adenocarcinoma, 11 cases of squamous cell carcinoma and 1 case of large cell carcinoma. A total of 13 patients received second-line chemotherapy and 12 received fourth-line or later chemotherapy. One patient exhibited a complete response, 7 had a partial response, 10 exhibited stable disease and 7 had progressive disease. The overall response rate was 32.0% and the disease control rate was 72.0%. The median PFS and median OS following nab-paclitaxel treatment were 4.0 and 14.0 months, respectively. Frequent treatment-associated adverse events were myelosuppression, peripheral neuropathy, gastrointestinal symptoms and baldness, the majority of which were grade 1-2. Grade 3-4 neutropenia, thrombocytopenia and anemia occurred in 7 (28.0%), 3 (12.0%) and 2 (8.0%) patients, respectively. No patients experienced grade 3-4 sensory neuropathy and no grade 5 adverse effects were observed. Nab-paclitaxel plus carboplatin as second-phase or later chemotherapy provided a small but significant survival benefit for patients with recurrent or advanced NSCLC, with tolerable adverse effects. To the best of our knowledge, the results of the present study demonstrated for the first time that nab-paclitaxel plus carboplatin is a promising and feasible late-phase chemotherapeutic agent for NSCLC.

Identification of the Decay-Accelerating Factor CD55 as a Peanut Agglutinin–Binding Protein and Its Alteration in Non–Small Cell Lung Cancers

Purpose: Peanut agglutinin (PNA) recognizes tumor-associated carbohydrates. In this study, we aimed to identify the core protein harboring PNA-binding sugars in the human lung and to explore the relationship with the pathology of primary non–small cell lung cancers (NSCLC). Experimental Design: PNA lectin blotting was used to detect PNA-binding proteins in the microsomal fraction of lung tissue from 24 patients with NSCLC. The 55- to 65-kDa core peptide PNA-binding protein was characterized by enzymatic treatment and identified by immunoprecipitation and affinity chromatography. The expression level and increase in size of the 55- to 65-kDa PNA-binding protein/decay-accelerating factor (DAF) were compared between normal and tumor regions of the tumor tissue by Western blotting and quantitative PCR. Results: The 55- to 65-kDa PNA-binding protein was observed in human lung. This was a glycosylphosphatidylinositol-anchored membrane protein carrying O-linked carbohydrates. This core protein was identified as DAF, one of the complementary regulatory proteins. DAF was enlarged to 65 to 75 kDa in NSCLC tumor lesions due to sialylation in the sugar moiety. At the transcription level, DAF levels were significantly lower in tumor regions, suggesting its down-regulation in NSCLC cells. Conclusions: DAF was identified as a new PNA-binding protein in the human lung. The down-regulation and heavy sialylation of DAF was associated with pathology in NSCLC, and these alterations make this protein a potential marker for NSCLC.

Recurrent Intrapulmonary Solitary Fibrous Tumor With Malignant Transformation

Intrapulmonary solitary fibrous tumor (SFT) of the pleura; the so-called inverted pattern, which appears to grow into the lung parenchyma, is extremely rare. We experienced a 66-year-old woman with an intrapulmonary SFT that recurred locally with malignant transformation 2 years after wedge resection of the left upper lobe for the primary tumor. Subsequently, she underwent a lobectomy of the residual left upper lobe. Six years after the second operation she was well, without rerecurrence. Complete excision and long-term follow-up of intrapulmonary SFTs of the pleura are important, even when the primary tumor displays benign histopathologic features.

Concomitant metastatic lung tumor and hamartoma

A 65-year-old woman who had undergone surgery for rectal cancer was referred to our hospital with an abnormal shadow on chest X-ray. Chest computed tomography (CT) revealed a 3-cm-diameter mass with ill-defined margins in the left lower lobe and a well-defined, 1-cm-diameter, round nodule in the right upper lobe. Transbronchial lung biopsy (TBLB) of the left lung tumor revealed metastatic adenocarcinoma originating from the rectal cancer. The patient underwent synchronous partial resection of the right upper lobe and left lower lobectomy under video-assisted thoracoscopic surgery (VATS). The pathological diagnosis of the right lung tumor was chondromatous hamartoma, and the left lung tumor was metastasis originating from the rectal cancer. The patients postoperative course was uneventful, and she was well and free of disease 4 years after pulmonary metastasectomy.