[Show abstract][Hide abstract] ABSTRACT: AimInvasive thymomas are rare tumours of the anterior mediastinum. These tumours' clinical features have been the subject of much controversy. Therefore, it is necessary to elucidate the optimal management of invasive thymomas. Patients and MethodsA total of 61 patients with invasive thymoma were retrospectively reviewed. ResultsThe study group comprised 38 males (62.3 per cent) and 23 females (37.7 per cent), with a median age of 55 years (range: 28–79 years). According to the Masaoka staging, 31 patients had stage II disease (50.8 per cent), 21 patients had stage III disease (34.4 per cent), four patients had stage IVa disease (6.6 per cent) and five patients had stage IVb disease (8.2 per cent). A statistically-significant difference in the survival rate was observed between stages II and III (P < 0.001) and between III and IV (P < 0.001). Complete resection was performed in 43 patients (70.5 per cent). Patients who underwent complete resection showed significantly better prognosis than those with incomplete resection (P < 0.001) and inoperable/biopsy (P < 0.001). After initial treatment, a total of 20 patients (32.8 per cent) relapsed. The recurrence rates in stages II, III and IV were 3.2 per cent, 66.7 per cent and 55.5 per cent, respectively. Treatment for recurrence was performed in all 20 patients. Conclusion
The outcome of invasive thymoma was correlated with the Masaoka stage and the extent of tumour resection. Salvage treatment for recurrent thymoma might give a moderate response rate and improve survival. A large-scale study is warranted for evaluating the role of the multimodality therapeutic approach in patients with invasive thymoma.
Surgical Practice 11/2013; 17(4). DOI:10.1111/1744-1633.12026 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
Chemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80mg/m(2)) was administered orally twice daily for 14 days, cisplatin (60mg/m(2)) on day 1, and bevacizumab (15mg/kg) on day 1 and every 3 weeks for 4-6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression.
Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1-6 cycles), and the median number of bevacizumab alone was three (range, 1-31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55-88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively.
S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC.
[Show abstract][Hide abstract] ABSTRACT: A 71-year-old woman was admitted to our hospital, because of an abnormality on her chest radiograph findings. After extensive examination, she was diagnosed with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable disease in any treatment. As the fourth-line treatment, she received oral chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after 5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic toxicities were mild with the S-1 administration. We experienced a case of continuation of tumor shrinkage over a year without serious adverse events by S-1 treatment. Therefore, oral administration of S-1 could be useful for the treatment of recurrent non-small cell lung cancer over a long time.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(11):2147-9.
[Show abstract][Hide abstract] ABSTRACT: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type is the most frequent type of non-Hodgkin's lymphoma to primarily involve the lung. Pulmonary MALT lymphoma, also known as bronchial-associated lymphoid tissue (BALT) lymphoma, is a rare disease and the clinicopathological features have yet to be clearly elucidated.
The present study retrospectively reviewed 13 patients (8 men, 5 women) with BALT lymphoma from 3 institutions between 1989 and 2007 to assess clinicopathological features.
At diagnosis, the median age was 61.6 years (range, 37-80 years), and 11 patients were asymptomatic while 2 had non-specific pulmonary symptoms. Two patients had a history of Sjögren's syndrome. Computed tomography of the chest revealed bilateral disease in 7 patients, lung nodules in 8 patients and air space consolidation with or without air bronchogram in 5 patients. In all cases, disease was localized within the lung at the initial diagnosis. Of the 13 patients, 5 remain untreated, while 8 received various combinations of treatment (surgery alone in 6 patients, surgery plus chemotherapy in 1 patient, and radiotherapy alone in 1 patient). Twelve patients remained alive during the median follow-up of 31.3 months (range, 2-147 months), while 1 patient died from unknown causes.
The present study indicates that BALT lymphoma tends to be limited to the lung on the initial diagnosis and responds well to local therapy such as surgery. Prognosis for this lymphoma tends to be indolent.
Internal Medicine 02/2009; 48(5):301-6. DOI:10.2169/internalmedicine.48.1438 · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We herein report an extremely rare case of a patient chylothorax at an interval of 20 years after thoracic vertebrae fractures, who underwent a successful thoracoscopic thoracic duct ligation and pleurodesis. A 51-year-old man was referred to our hospital with shortness of breath on effort about 1 month after participating in archery. Twenty years previously, he was involved in a traffic accident. At that time, the patient sustained trauma to the spine and suffered a spinal injury, thus resulting in paralysis in the lower part of his body. A chest roentgenogram and computed tomogram revealed a large amount of bilateral pleural effusion. After thoracentesis was performed, a diagnosis of chylothorax was made and the patient was hospitalized. Conservative management by a low-fat diet proved to be unsuccessful. The patient did not request pleurodesis, because pleural adhesions might impair pulmonary function. As a result, we decided to perform surgery. On the right side, we performed video-assisted thoracoscopic surgery by clipping the thoracic duct and applying an absorbable sealing material. Thereafter, pleurodesis was performed and OK-432 was instilled. Thereafter, the pleural fluid flow was almost completely stopped. On the left side, pleurodesis was effective. The patient has since remained symptom free and has been followed up on an outpatient basis for 9 months after the 100th postoperative day. We assumed that the chylothorax in this case was related to the earlier traffic accident.
Surgery Today 02/2008; 38(1):56-8. DOI:10.1007/s00595-007-3557-x · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a phase I dose escalation study to determine the maximum tolerated dose, recommended dose, and safety profile of a biweekly gemcitabine and carboplatin combination regimen in the treatment of patients with completely resected nonsmall cell lung cancer (NSCLC).
Patients with completely resected pathologically documented stage IB, II, or IIIA NSCLC, performance status (ECOG) 0-1, with adequate bone marrow, renal, liver, and cardiac functions, were treated with gemcitabine and carboplatin. The starting dose was gemcitabine 800 mg/m2 on days 1 and 15 and carboplatin area under the time-concentration curve (AUC) 4 mg/mL/min on day 1. Gemcitabine was increased to 1000 mg/m2 (level 3). Carboplatin was increased to AUC 5 (level 2, 3). The regimen was performed every 4 weeks. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle.
Nine patients were enrolled in this study. All patients were assessed for safety. Grade 3 leukopenia occurred in 1 patient (11%) and grade 3/4 neutropenia occurred in 3 patients (33%). No other grade 3/4 toxicity was observed. No dose-limiting toxicity was experienced at dose levels 1, 2, and 3 of this schedule.
Maximum tolerated dose was not reached in this study. Considering treatment continuation, the recommended dose for a phase II study is gemcitabine 1000 mg/m2 on days 1 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. Biweekly administration of gemcitabine and carboplatin is a feasible and well-tolerated regimen for the treatment of patients with completely resected NSCLC as adjuvant chemotherapy.
American journal of clinical oncology 11/2007; 30(5):498-502. DOI:10.1097/01.coc.0000264179.23080.bc · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this phase I study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity of the biweekly paclitaxel and carboplatin combination chemotherapy in frail patients with advanced non-small cell lung cancer (NSCLC).
Seventeen unresectable and previously untreated NSCLC patients participated in this study. Frail patients (>80 years old with PS 0-1 and adequate organ functions, or <80 years old with PS 2 or <80 with PS 0-1 and one inadequate organ function of bone marrow, liver, or kidney) of NSCLC were enrolled in this study. Both paclitaxel and carboplatin were administered on day 1 and repeated biweekly. The starting dose of paclitaxel 120 mg/m2 and carboplatin was AUC 3 /d on day 1 every 2 weeks for 4 to 8 cycles.
Seventeen frail patients received a total of 1 to 10 cycles. The major hematologic toxicity was neutropenia. Nonhematologic toxicities, including numbness and constipation, were generally mild and reversible. The MTD of paclitaxel were determined as 140 mg/m2. The recommended phase II study dose of paclitaxel was determined as 120 mg/m2 with area under the curve 3 biweekly for 1 day. An objective response was observed in 8 of 17 patients (47%) with frail patients.
The combination chemotherapy of biweekly paclitaxel and carboplatin appears to be tolerable and sufficiently effective in frail patients with NSCLC. A phase II trial is underway.
American journal of clinical oncology 10/2007; 30(5):487-91. DOI:10.1097/COC.0b013e31804b458f · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 63-year-old woman was referred and admitted to our department for further examination of protein-losing enteropathy (PLE), which was diagnosed by alpha-anti trypsin test. Her symptoms were frequent vomiting, watery diarrhea and hypoproteinemia. Although intensive examination for PLE was performed in her previous hospital, the origin of the disease was not detected. Abdominal computed tomography revealed diffuse enlargement and swelling of the intestine wall and a 5-cm diameter mass with unclear margin, which involved the mesenteric arteries and veins. Total colonoscopy showed a diffuse edematous lesion with hemorrhage at the terminal ileum. Enteropathy-type T-cell lymphoma (ETL) was diagnosed based on a biopsy of the lesion and CD45 gating analysis. Immediate start of chemotherapy (CHOP) led to a transient regression of the tumor even though her symptoms were not improved. During the second cycle of CHOP, the patient died of massive hemorrhage throughout the intestine. The pathological study revealed that intraepithelial CD3-positive clonal T-cells were present in the lesion, indicating that this case could be associated with celiac disease. In light of the histological findings, we concluded that this was a case of ETL associated with celiac disease, which is extremely rare in Japan.
Internal Medicine 02/2007; 46(15):1219-24. DOI:10.2169/internalmedicine.46.6377 · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The silencing of tumor suppressor genes (TSGs) by aberrant hypermethylation occurs frequently in human cancer. Recently the RUNX3 gene was identified as a TSG inactivated by hypermethylation. We examined RUNX3 expression by reverse transcription-PCR and the methylation status of this gene by methylation specific-PCR in 43 lung cancer cell lines and 120 primary non-small cell lung cancer (NSCLC) tumor samples. RUNX3 expression was absent in 10 (50%) of 20 small cell lung cancer (SCLC) cell lines, 8 (50%) of 16 adenocarcinoma (AdC) cell lines, and 1 (33.3%) of 3 squamous cell carcinoma (SqC) cell lines. The frequency of RUNX3 methylation was significantly higher in AdC (7/16, 43.8%) than SCLC cell lines (1/20, 5%; p=0.032). RUNX3 expression was restored by treatment with 5-aza-2'-deoxycytidine and/or trichostatin-A in AdC cell lines. These results indicated that RUNX3 expression was regulated by aberrant hypermethylation in AdC cell lines. RUNX3 methylation was detected in 30 (25%) of 120 primary NSCLC tumors. RUNX3 methylation was significantly more frequent in non-smokers (16/43, 37.2%) than smokers (12/71, 16.9%; p=0.014), and in patients with AdC (26/72, 36.1%) than in patients with SqC (3/45, 6.7%; p<0.001). These results indicated that silencing of the RUNX3 gene plays an important role in the pathogenesis of lung cancer, and aberrant methylation is an important mechanism of inactivation of the RUNX3 gene in lung AdC.
[Show abstract][Hide abstract] ABSTRACT: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC).
We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples.
EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022).
These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.
Clinical Cancer Research 10/2005; 11(19 Pt 1):6816-22. DOI:10.1158/1078-0432.CCR-05-0441 · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a phase II study to examine the efficacy and safety of weekly docetaxel and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). Forty chemotherapy-naive patients (10 with stage IIIB and 30 with stage IV NSCLC) with an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions were enrolled. Chemotherapy consisted of cisplatin (80 mg/m2) on day 1, and docetaxel (35 mg/m2) on days 1, 8 and 15, delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. There were 18 partial responses, with an overall response rate of 45% (95% confidence interval 29.6-60.4%) in 40 treated patients. The median survival period was 19.9 months, median progression-free survival was 5.5 months and 1-year survival rate was 69.4%. Hematologic toxicities were mild and included grade 3 or 4 neutropenia in 37.5%. There were no severe infections or septic deaths. Non-hematologic toxicities were generally mild. Grade 3 or 4 transaminase elevations were observed in two patients. Grade 3 events included two cases each of vomiting, and one case each of hypokalemia, diarrhea and creatinine elevations. Weekly docetaxel and cisplatin is an effective and safe combination in the treatment of patients with advanced NSCLC.