-
[show abstract]
[hide abstract]
ABSTRACT: There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis.
Japanese Journal of Clinical Oncology 07/2012; 42(10):965-9. · 1.78 Impact Factor
-
Masatsugu Yamamoto, Tatsuya Nagano,
Keiko Okuno,
Kyosuke Nakata,
Kazuhiro Takenaka,
Kazuyuki Kobayashi,
Yumiko Ishikawa,
Akihiro Sakashita,
Yoshikazu Kotani,
Yasuhiro Funada,
Yoshihiro Nishimura
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to prospectively examine the effect of prophylactic antibiotic use on the development of respiratory infections and on the worsening of symptoms after diagnostic fiberoptic bronchoscopy procedures. This study was an open-label, multicenter, controlled, clinical trial. Patients were alternately assigned to a group given prophylactic antibiotics after bronchoscopy (prophylaxis(+) group) and a group not given antibiotic prophylaxis after bronchoscopy (prophylaxis(-) group), and they were followed-up for 1 week. 158 patients were assigned to the prophylaxis(-) group and 153 to the prophylaxis(+) group. Therapeutic antibiotic administration was needed in 3 patients (1.90%) in the prophylaxis(-) group and 5 patients (3.27%) in the prophylaxis(+) group (risk ratio 1.014, 95% confidence interval 0.978-1.052; p=0.446). Worsening of symptoms after bronchoscopy occurred in 57.6% of all patients by day 7, but no significant differences were observed between the 2 study groups. Prophylactic antibiotic use after bronchoscopy did not prevent the development of infectious events and worsening of symptoms, suggesting that prophylactic antibiotics might not be necessary for routine diagnostic bronchoscopic procedures.
The Kobe journal of medical sciences 01/2012; 58(4):E110-8.
-
[show abstract]
[hide abstract]
ABSTRACT: A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patient's enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity.
Case reports in pulmonology. 01/2011; 2011:812972.
-
[show abstract]
[hide abstract]
ABSTRACT: Graft-versus-host-disease (GVHD) with erythroderma can rarely occur in the context of thymoma and is associated with a poor prognosis due to an increased risk of infection-related death. The present study describes a case of a 50-year-old man with malignant thymoma who developed sepsis in addition to skin manifestations similar to that seen in GVHD. This patient experienced marked improvement in skin lesions in response to steroids and combination chemotherapy with carboplatin and paclitaxel, with subsequent resolution of infection. The present study describes the clinical course of this patient, followed by a review of pertinent reports of thymoma associated with GVHD with particular focus on the efficacy of treatment strategies.
Case Reports 01/2011; 2011.
-
[show abstract]
[hide abstract]
ABSTRACT: The present study describes a case of a 60-year-old Japanese man who was histologically diagnosed with lung adenocarcinoma harboring L858R mutation of epidermal growth factor receptor. He was successfully treated with gefitinib, but eventually developed leptomeningeal carcinomatosis. He underwent ventriculoperitoneal shunting for hydrocephalus and received erlotinib in place of gefitinib with concurrent whole brain radiotherapy; this resulted in dramatic improvement in his symptoms and performance status from four to one and he survived for as long as 13.6 months after the initiation of erlotinib therapy. This multidisciplinary approach may be particularly useful in terms of increasing survival and improving quality of life.
Internal Medicine 01/2011; 50(24):3019-22. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been demonstrated that NK012, a novel 7-ethyl-10-hydroxycamptothecin (SN-38)-incorporating polymeric micelle, exerts significantly more potent antitumor activity against various human tumor xenografts than irinotecan (CPT-11) (a water-soluble prodrug of SN-38). Combination therapy of anticancer agents with bevacizumab (Bv), an anti-vascualr endothelial growth factor humanized monoclonal antibody, has more potently inhibited tumor growth than either agent alone. In the current study, the authors examined the antitumor effect of NK012 in combination with Bv against human lung cancer.
Nude mice bearing lung adenocarcinoma (PC-14 or A549 xenografts) were administered NK012 at SN-38-equivalent doses of 5 mg/kg or 30 mg/kg in combination with or without Bv at 5 mg/kg. CPT-11 at a dose of 66.7 mg/kg was administered with or without Bv at a dose of 5 mg/kg in the same experimental model. To evaluate interaction with Bv, the pharmacokinetics and microvessel density in tumors that were treated on each regimen were analyzed.
In vitro, the growth-inhibitory effect of NK012 was 50-fold more potent than that of CPT-11 and was almost equivalent to that of SN-38. In vivo studies revealed that the combination of NK012 plus Bv had significantly greater antitumor activity against human lung cancer xenografts compared with NK012 alone (PC-14, P=.0261; A549, P<.001). The pharmacokinetic profile of NK012 revealed that coadministration of Bv did not interfere with the accumulation of NK012.
In this study, significant antitumor activity was noted with NK012 in combination with Bv against lung cancer cells. The current results warrant the clinical evaluation of NK012 in lung cancer.
Cancer 10/2010; 116(19):4597-604. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There has been no report about re-challenge chemotherapy (RC) consisting of the same regimen as first-line chemotherapy in non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the efficacy of RC as second-line chemotherapy in patients with relapsed NSCLC. We conducted a retrospective review of 28 consecutive NSCLC patients who were treated with RC and compared their clinical outcomes with those of 38 consecutive NSCLC patients who were treated with docetaxel (DOC) at our hospital between July 1992 and December 2003. The RC group consisted of 21 men and 7 women, with a median age of 62 years (range, 42-76 years). Most first-line regimens were platinum-based and the median administered course was 3 (range, 2-7). All patients had responded to the first-line chemotherapy and had performance status (PS) 1 at relapse. The median interval from the end of first-line chemotherapy to relapse was 5.0 months (range, 1.6-36.1 months). The overall response rate of RC was 29%. The median survival time from the beginning of RC was 17.0 months and the 1-year survival rate was 60%. RC led to a significantly better overall survival rate than DOC (p=0.0342). RC could be an active second-line regimen in patients with relapsed NSCLC who responded to first-line chemotherapy.
Lung cancer (Amsterdam, Netherlands) 09/2010; 69(3):315-8. · 3.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1 and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT-11 administration on Days 0 and 7 and S-1 administration on Days 0-13. Pathological changes in the small intestine were also investigated. The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p = 0.0007) and EBC-1-bearing mice (p < 0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation.
International Journal of Cancer 03/2010; 127(11):2699-706. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with cisplatin [cis-dichlorodiammineplatinum (II) (CDDP)] in mice bearing a small cell lung cancer xenograft in terms of antitumor activity and toxicity, particularly intestinal toxicity.
Cytotoxic effects were evaluated in human small cell lung cancer cell lines [H69, H82, and vascular endothelial growth factor (VEGF)-secreting cells (SBC-3/VEGF and its mock transfectant SBC-3/Neo)]. In vivo antitumor effects were evaluated in SBC-3/Neo-bearing and SBC-3/VEGF-bearing mice after NK012/CDDP or CPT-11/CDDP administration on days 0, 7, and 14. Drug distribution was analyzed by high-performance liquid chromatography or fluorescence microscopy, and the small intestine was pathologically examined.
The in vitro growth-inhibitory effects of NK012 were 198- to 532-fold more potent than those of CPT-11. A significant difference in the relative tumor volume on day 30 was found between NK012/CDDP and CPT-11/CDDP treatments (P = 0.0058). Inflammatory changes in the small intestinal mucosa were rare in all NK012-treated mice but were commonly observed in CPT-11-treated mice. Moreover, a large amount of CPT-11 was excreted into the feces and high CPT-11 concentration was detected in the small intestinal epithelium. On the other hand, a small amount of NK012 was found in the feces and NK012 was weakly and uniformly distributed in the mucosal interstitium.
NK012/CDDP combination may be a promising candidate regimen against lung cancer without severe diarrhea toxicity and therefore warrants further clinical evaluation.
Clinical Cancer Research 07/2009; 15(13):4348-55. · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lung adenocarcinoma with a micropapillary component (MPC) is an aggressive subtype of adenocarcinoma with a papillary component. The aim of this study was to explore the pathobiological properties of a papillary component which generates MPC. We reviewed the 445 cases of resected primary lung adenocarcinoma and confirmed all of the MPC(+) cases (n=150) were found only in the cases of adenocarcinoma with a papillary component (n=228) and no features of the MPC were detected in any of the other histological subtypes without papillary component. Even in the cases of adenocarcinoma with a papillary component, the MPC(+) group (n=150) had significantly poorer outcome than the MPC(-) group (n=78) (P<0.0001). When this MPC(+) cases were divided into grade 0-2 according to the proportion of the tumor occupied by the MPC, the stage I patients with grade 2 MPC had a significantly poorer outcome than the stage I patients with grade 0 or grade 1 MPC. By considering the histological characteristics that MPC has always structural continuity with papillary component, we evaluated the pathobiological profile of (1) MPC, (2) papillary component which generate MPC [PC MPC(+)], and (3) papillary component without MPC [PC MPC(-)]. The mean width of the stalks in the PC MPC(+) was significantly smaller than in the PC MPC(-) (17.64+/-9.53 vs. 26.07+/-10.16mum, P<0.001). Although staining for CD34 and collagen IV showed that MPC lacked both fibrovascular stalks and basement membranes, staining for cleaved caspase 3 showed that apoptotic cells were rare in the MPC (1.0%), and the expression levels of the adhesion molecules E-cadherin, beta-catenin, and CD44 were similar in all three lesions. The immunohistochemical staining scores of hypoxic marker GLUT-1 in the MPC, PC MPC(+), and PC MPC(-) were 69, 26, and 8.6, respectively, and the differences between the MPC and PC MPC(+) and between the PC MPC(+) and PC MPC(-) were significant (P=0.001 and 0.025, respectively). These results indicated that the biological behavior of the papillary component which generates MPC is different from the papillary component without MPC in terms of structural alternation and hypoxic state, and the difference may be related to the aggressive behavior of MPC(+) adenocarcinoma.
Lung cancer (Amsterdam, Netherlands) 05/2009; 67(3):282-9. · 3.14 Impact Factor
-
Takeo Ito,
Genichiro Ishii,
Kanji Nagai, Tatsuya Nagano,
Masakazu Kojika,
Yukinori Murata,
Naho Atsumi,
Yutaka Nishiwaki,
Eishi Miyazaki,
Toshihide Kumamoto,
Atsushi Ochiai
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to identify clinicopathological and biological prognostic markers for patients who had undergone complete resection of pathological stage IB squamous cell carcinoma (SqCC) of the lung. A total of 136 consecutive stage IB SqCC patients fulfilled eligibility criteria, and their clinicopathological factors were evaluated. Tissue microarrays were also constracted, and immunohistochemical staining with 24 antibodies was performed. Correlations between clinicopathological factors, antibody immunohistochemical reactions, the patients' overall survival (OS) and relapse-free survival (RFS) were evaluated. The univariate analysis showed that 70-year-old and over elderly group had a shorter OS time and RFS time than the younger group (p=0.0086 and p=0.0091, respectively). The univariate analysis for immunohistochemical staining showed that the podoplanin-negative group had a shorter OS time and RFS time than the podoplanin-positive group (p=0.0106 and p=0.0308, respectively). Multivariate analysis revealed a significant correlation between both the 70-year-old and over elderly group and the podoplanin-negative group and poor outcome (OS, p=0.007 and p=0.008, respectively; RFS, p=0.008 and p=0.024, respectively). The results showed that patient age and a novel biological prognostic marker, podoplanin, are useful for predicting a poor outcome of patients after complete resection of stage IB SqCC of the lung.
Lung Cancer 03/2009; 63(3):418-24. · 3.43 Impact Factor
-
Akikazu Kawase,
Genichiro Ishii,
Kanji Nagai,
Takeo Ito, Tatsuya Nagano,
Yukinori Murata,
Tomoyuki Hishida,
Mitsuyo Nishimura,
Junji Yoshida,
Kazuya Suzuki,
Atsushi Ochiai
[show abstract]
[hide abstract]
ABSTRACT: Recent studies have reported increased podoplanin expression by cancer cells and stromal cells, but little is known about its expression and biological significance in adenocarcinoma of the lung. We examined podoplanin expression by both cancer cells and stromal cells in 177 consecutive lung adenocarcinoma cases and analyzed relations between podoplanin expression and both clinicopathological factors and outcome. Podoplanin expression was observed on the apical membrane of the cancer cells in only 9 of the 177 (5.1%) cases. By contrast, cancer-associated fibroblasts (CAFs) were found to express podoplanin in 54 cases (30.5%). Podoplanin (+) CAFs were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. The univariate analyses and log-rank test showed that podoplanin expression was significantly associated with shorter survival time (p < 0.001 and p < 0.001, respectively). We divided the cases into 3 groups according grade based on the proportion of CAFs expressing podoplanin [a grade 0 group (n = 123), a grade 1 group (n = 36) and a grade 2 group (n = 18)]. The result showed that conventional prognostic factors were significantly correlated with the grade of podoplanin expression by CAFs. Furthermore, the grade 2 group tended to have a shorter survival time than the grade 1 group (p = 0.092). The results of this study highlight the importance of podoplanin expression by CAFs and provide new insights into the biology of the cancer microenvironment in adenocarcinoma of the lung.
International Journal of Cancer 09/2008; 123(5):1053-9. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In U.S.A., Pulse CO-Oximetry has emerged as a quick, simple, and non-invasive diagnostic modality to measure the concentration of COHb in arterial blood. To investigate its efficiency, we measured COHb levels by employing Pulse CO-Oximetry and by CO-Oximeter in arterial blood.
Normal healthy volunteers with a habit of smoking, smoked three cigarettes consecutively for nine minutes.
Through this experiment, it was confirmed that the COHb level by Pulse CO-Oximetry rose after smoking (6.9 +/- 2.7%: mean +/- SD) and fell after oxygen inhalation (2.5 +/- 2.2%). The correlation coefficient of COHb levels between Pulse CO-Oximetry and blood sample was 0.34.
The correlation coefficient between the COHb level by Pulse CO-Oximetry and that in the blood sample was not so high, but Pulse CO-Oximetry has the potential of changing the way victims of CO exposure are diagnosed and treated, because of its easiness.
Masui. The Japanese journal of anesthesiology 06/2008; 57(5):621-3.
