Biomedical subjects

Yukito Ichinose

Publications and source records attributed to Yukito Ichinose.

At least 19 recordsLinked to original sources

PubMed2006

Persistent and aggressive treatment for thymic carcinoma. Results of a single-institute experience with 25 patients.

OBJECTIVES: The aim of this study is to retrospectively evaluate the role of several therapies, mainly chemotherapy, for thymic carcinoma (TC). METHODS: From July 1973 to July 2005, 25 patients (15 males and 10 females) with histologically proven TC were treated at our department. The median age of the patients was 59 years, with a range of from 30 to 78 years. According to Masaoka's staging system, there was 1 stage I patient, 3 stage II, 7 stage III, 6 stage IVa, and 8 stage IVb patients. The histological subtype was in all cases squamous cell carcinoma, nonkeratinizing type. RESULTS: There were 6 complete surgical resections, 1 incomplete resection followed by chemoradiotherapy, 6 with radiotherapy alone, 3 with radiotherapy plus chemotherapy, and 9 with chemotherapy alone as the initial treatment. Eighteen patients were administered second-line therapy. The regimen obtaining the best response rate was doublet chemotherapy consisting of carboplatin (CBDCA) and paclitaxel. The median survival time and survival rate at 5 years for the patients excluding surgical cases with stage I/II disease were 32 months and 31%, respectively. CONCLUSION: The doublet of CBDCA and paclitaxel thus appears to be a promising regimen for TC and further investigation in a multi-institutional phase II trial is, therefore, strongly called for.

Adult↗

PubMed2006

Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902.

PURPOSE: We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE. PATIENTS AND METHODS: Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle. RESULTS: Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%). CONCLUSION: EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.

Aged↗

PubMed2006

Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer.

BACKGROUND: Angiogenesis plays an important role in tumorigenesis and has attracted interest as a potential target in cancer treatment. PATIENTS AND METHODS: We examined the prognostic value of the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptors (VEGFRs) fms-like tyrosine kinase receptor-1 (flt-1) and kinase insert domain-containing receptor (KDR) in non-small-cell lung cancer (NSCLC). Sixty patients with surgical stage I NSCLC who had not undergone induction therapy or adjuvant therapy were selected from among 170 patients with NSCLC who had undergone surgery from January to December 1995. Specimens obtained at surgical resection were subjected to immunohistological staining, and the relationship between postoperative outcome and the expression of VEGF and its receptors was investigated. All patients included in the analysis had been followed up for 5 years or longer or until death. RESULTS: Patients with tumors expressing VEGF or KDR tended to have poorer outcomes, and VEGF expression and KDR expression were positively correlated. In contrast, flt-1 expression was not correlated with VEGF expression or outcome. Outcomes were poor in patients with tumors positive for both VEGF and VEGFRs. Multivariate analysis identified expression of both flt-1 and KDR and VEGF and KDR as possible independent prognostic factors. CONCLUSIONS: Our results suggest that expression of VEGF and VEGFR are associated with a poor prognosis via autocrine and paracrine growth stimulation of cancer cells. Moreover, tumors expressing both flt-1 and KDR may have greater malignant potential and are associated with a poor prognosis.

Adenocarcinoma↗

PubMed2006

Triplet chemotherapy for malignant pericardial mesothelioma: a case report.

Malignant pericardial mesothelioma (MPM) is a relatively rare neoplasm in Japan, and no standard treatment regimens have been established for this disease. A 47-year-old woman with MPM presenting with cardiac tamponade was treated using four cycles of chemotherapy consisting of cisplatin (CDDP) 40 mg/m2, gemcitabine (GEM) 800 mg/m2 and vinorelbine (VNR) 20 mg/m2 on days 1 and 8 every 4 weeks after pericardial drainage alone. The diagnosis of MPM was confirmed by an immunohistochemical procedure using either positive or negative markers of malignant mesothelioma in addition to conventional cytological examinations using pericardial effusion. The patient experienced no severe non-hematological or hematological toxicities except for grade 3 neutropenia. The patient has returned to her usual activities and has remained well for 24 months after the last chemotherapy without any evidence of disease progression.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

A prospective Japanese study of the association between personality and the progression of lung cancer.

OBJECTIVE: To examine predictive values for the effect of the "Type 1" (hopeless and emotion-suppressive, cancer prone), "Type 4" (autonomous, healthy), and "Type 5" (rational/antiemotional, cancer prone) personalities proposed by Grossarth-Maticek on the prognosis of lung cancer patients. METHODS: 68 lung cancer patients were scored on the Types 1, 4, and 5 personality scales of the Short Interpersonal Reactions Inventory and were followed until the date of death or were censored at a maximum of 5.7 years after entry. RESULTS: The stage at diagnosis tended to be higher in patients with a high Type 1 or a low Type 4 score. A univariate Cox proportional hazards model showed that a high tendency toward Type 1 or Type 5 was related to an increased hazard of death. Adjustment for age, performance status, and stage, however, attenuated the relation to Type 1, leaving only Type 5 as a significantly related personality factor. CONCLUSION: A high Type 5 tendency may predict poor survival in lung cancer patients, whereas Types 1 and 4 may not be independent predictors.

Adult↗

PubMed2006

Phase I study of amrubicin hydrochloride and cisplatin in patients previously treated for advanced non-small cell lung cancer.

OBJECTIVE: A single-center phase I trial was designed to determine both the dose-limiting toxicities and the maximum tolerated dose (MTD) for amrubicin hydrochloride in combination therapy with cisplatin for advanced non-small cell lung cancer (NSCLC) patients with prior chemotherapy. METHODS: Eligible patients received amrubicin and cisplatin on days 1 through 3 every 3 or 4 weeks. Cisplatin was administered at a fixed dosage of 20 mg/m(2) while the administered dose of amrubicin was started at 20 mg/m(2). Each group comprised 3 or 6 patients. When dose limiting toxicities were noted in three or more of six patients at a particular level, that level was estimated to be the MTD. RESULTS: Fifteen patients were enrolled in this study, including 5 males and 10 females, with a median age of 57. The dose limiting toxicities included grade 4 neutropenia which lasted 4 or more days and febrile neutropenia. The non-hematologic toxicities were well managed and rarely severe. The MTD of amrubicin in this combination regimen was estimated to be 30 mg/m(2).A partial response was observed in 4 of 15 patients (27%). CONCLUSIONS: The recommended dose was thus determined to be 25 mg/m(2) amrubicin with 20 mg/m(2) cisplatin for 3 consecutive days. A phase II study is currently underway.

Aged↗

PubMed2006

Methodological aspects of current problems in target-based anticancer drug development.

Differently from the conventional antineoplastic agents, target-based drugs are designed a priori, based on our knowledge of various physiological molecules that has been obtained by the development of molecular biology. This "Copernican revolution" in drug development may imply a paradigm shift in this field. However, contrary to the initial expectations, many drugs developed by this approach are now faced with difficulties, mainly because of the fundamental and theoretical limits of this approach. All of the physiological functions are not always known in all target molecules. In low-molecular-weight drugs, i.e., "inhibitors," targets disperse, due to the structural similarities in physiological molecules. This double-faced "out-of-focusing" causes many problems in various steps of drug development, drug design, clinical trials, and administration to patients. Many drugs are now being abandoned because of unexpectedly lower response rates or unforeseeable adverse effects, and the variety of the drugs exhibits a kaleidoscopic appearance. The double-faced "out-of-focusing" derives from the methodological limits in molecular biology, i.e., elementalism, and limits in our techniques for drug development. To overcome these currently inevitable limits, it appears essential to elucidate the specific changes in target molecules that chiefly promote tumor growth and, consequently, strongly predict response to the administered drugs. Precise and efficient detection of responder populations is the key to the development and establishment of target-based anticancer therapies.

Antibodies, Monoclonal↗

PubMed2006

Establishment of a clinical pathway as an effective tool to reduce hospitalization and charges after video-assisted thoracoscopic pulmonary resection.

OBJECTIVE: The purpose of this study was to assess the effect of establishing a clinical pathway based on the length of hospitalization, hospital charges, and the outcome for video-assisted thoracoscopic pulmonary resection (VATPR). METHODS: We retrospectively analyzed consecutive patients who were diagnosed as having primary lung cancer, metastatic lung cancer, or a nodule that was suspected to be malignant and thus was operated on using VATPR during the 1-year period before (n = 105) and after (n = 113) pathway implementation. RESULTS: The mean economic cost and total hospital stay before and after pathway implementation were about dollars 14439 and dollars 13093 (US), and 29.4 and 18.6 days, respectively. These figures were significantly lower after pathway implementation than before establishment of the pathway. CONCLUSION: A clinical pathway is thus considered useful for reducing the length of total hospital stay and the costs associated with VATPR while maintaining high-quality postoperative care.

Adolescent↗

PubMed2006

Initial experience with video-assisted thoracoscopic surgery for pulmonary metastasis in the prone position.

We performed video-assisted thoracoscopic surgery for pulmonary metastasis with the patient in the prone position because the use of the full lateral decubitus position was not possible owing to a deformity of the upper extremity, which existed because of a previous operation for osteosarcoma. In cases where the lateral decubitus position cannot be used, the prone position is both safe and effective for treating dorsal lesions of the lung by means of video-assisted thoracoscopic surgery.

Adult↗

PubMed2006

Wide sleeve resection of lower trachea through anterior approach with omentopexy.

A 61-year-old man with tracheal adenoid cystic carcinoma (case 1) and a 28-year-old woman with benign tracheal stenosis (case 2) were treated with sleeve resection of the lower trachea through a median sternotomy and prophylactic omental wrapping. The resected tracheas were 4.5 cm (case 1) and 4.0 cm (case 2) in length. Both patients had an uneventful course after surgery despite postoperative irradiation in case 1 and preoperative infection with methicillin-resistant Staphylococcus aureus in case 2.

Adult↗

PubMed2006

[A case of adenocarcinoma of the lung significantly responding to TS-1 plus cisplatin combination chemotherapy].

A 67-year-old man was admitted to our hospital, complaining of productive cough and chest pain. Chest radiograph and computed tomography revealed a huge mass invading the mediastinum, enlargement of right hilar and cardiophrenic lymph nodes and nodules in right lower lobe and left upper lobe. Multiple space occupying regions in the liver were also observed. Cytology for exfoliated sputum revealed adenocarcinoma, so he was diagnosed with advanced lung cancer (clinical stage T 4 N 2 M 1, stage IV). He was enrolled in a clinical phase II study, and received combination chemotherapy with TS-1 and cisplatin. TS-1 was administered on days 1-21. Cisplatin was administered on day 8. Every cycle was repeated every 5 weeks. The patient then received 6 cycles of chemotherapy,and yielded a partial response (87% decrease in size determined by RECIST criteria version 2. 0). Grade 2 leukopenia and neutropenia were observed, and non-hematologic toxicities were also mild. The disease progressed after the end of chemotherapy, and he was given 5 regimens of chemotherapy, including gefitinib. He died of brain metastases. Time to progression of his disease for combination chemotherapy using TS-1 and cisplatin chemotherapy was 240 days. Survival time was 709 days. This combination chemotherapy was effective in the present case, and might prolong survival. We think it is valuable to confirm the efficacy of TS-1 and cisplatin combination chemotherapy.

Adenocarcinoma↗

PubMed2006

[Combination chemotherapy with S-1 and cisplatin for non-small cell lung cancer].

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.

Administration, Oral↗

PubMed2006

The use of a water seal to manage air leaks after a pulmonary lobectomy: a retrospective study.

BACKGROUND: The methods for managing chest drainage tubes during the postoperative period differ among thoracic surgeons and, as a result, the optimal method remains controversial. PATIENTS AND METHODS: We reviewed 170 consecutive patients undergoing a pulmonary lobectomy for either primary lung cancer or metastatic lung cancer from January 1998 to December 2002. After the operation, the chest drainage tube was placed on a suction pump with a negative pressure of -10 cmH(2)O in 120 patients before 2001, while such drainage tubes were kept on water seal in 47 cases mainly since 2001. RESULTS: Regarding the preoperative and postoperative variables, postoperative air leak as well as the video-assisted thoracic surgery (VATS) procedure were more frequently observed in the water seal group than in the suction group (p=0.01580, p<0.001, respectively). In comparing these different populations, each Kaplan-Meier curve, which presented the duration of the postoperative air leak seemed to be similar between the two methods. CONCLUSION: These observations suggest that applying chest tubes on water seal seems to be an effective method for preventing postoperative air leak in clinical practice. However, a prospective randomized trial using a larger series of patients is warranted for this subject.

Aged↗

PubMed2006

[Adjuvant chemotherapy for non-small cell lung cancer].

Recently, several randomized trials with a large number of enrolled patients have shown that postoperative adjuvant treatment improves survival among patients with completely resected non-small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to be effective for patients with postoperative stage I to IIIA NSCLC in western countries. On the other hand, uracil-tegafur was also shown to improve survival among patients with stage I adenocarcinoma in Japan. We reviewed the results of recent randomized trials and meta-analyses, and discuss the current role and problems related to adjuvant chemotherapy in NSCLC.

Adenocarcinoma↗

PubMed2005

Malignant schwannoma of the upper mediastinum originating from the vagus nerve.

BACKGROUND: Malignant schwannoma of the upper mediastinum originating from the vagus nerve is extremely rare. CASE PRESENTATION: A 46-year-old female was admitted for a left cervical mass which was associated with both hoarseness and Horner's syndrome. Chest computed tomography showed a mass extending from the left upper mediastinum to the left supraclavicular area. A fine needle aspiration cytological examination suggested primary lung cancer stage IIIB large cell carcinoma. After administering induction chemo-radiotherapy, a complete surgical resection was performed. The tumor was found to involve both the left vagus nerve and the left sympathetic nerve. Histological examination of the resected specimen revealed the tumor to be malignant schwannoma. CONCLUSION: Despite incorrect preoperative diagnosis, the multimodality treatment administered in this case, including induction chemo-radiotherapy and surgery, proved to be effective.

Journal Article↗

PubMed2005

Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas.

PURPOSE: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. EXPERIMENTAL DESIGN: We examined EGFR mutations at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non-small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non-small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin-1 mRNA levels, and increased EGFR gene copy numbers. RESULTS: Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 16 of 17 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (12.6%) with wild-type EGFR (P < 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P = 0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P = not significant). CONCLUSIONS: The presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations.

Adenocarcinoma↗

PubMed2005

Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma.

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM. METHODS: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m(2), GEM 800 mg/m(2) and VNR 20 mg/m(2) on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy. RESULTS: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively. CONCLUSIONS: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.

Adult↗

PubMed2005

Long-term survival after an aggressive surgical resection and chemotherapy for stage IV pulmonary giant cell carcinoma.

BACKGROUND: Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective. CASE PRESENTATION: We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation. CONCLUSION: This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy.

Journal Article↗