Feasible combination chemotherapy with nedaplatin and irinotecan for patients with non-small cell lung cancer and multiple high-risk factors

We retrospectively analyzed the outcome of high-risk patients with non-small cell lung cancer (NSCLC) treated with nedaplatin (NP) and irinotecan (CPT) combination chemotherapy. Between July 2002 and January 2006, 31 NSCLC patients with multiple high-risk factors were treated with NP at 50 mg/m2 and CPT at 50 mg/m2 on days 1 and 8 every 4 weeks. Among them, the patients had a total of 85 risk factors, including poor performance status (2 or 3) in 27, cardiac or pulmonary failure in 15, symptomatic bone or brain metastasis in 9, and advanced age (> or = 75 years) in 8, as well as other factors. A total of 83 courses of the chemotherapy were administered and 24 patients were able to receive 2 to 4 courses. With regard to toxicities, 7 (8.4%) and 11 courses (13%) were associated with grade 4 neutropenia and grade 3 febrile neutropenia, respectively. One patient suffered acute myocardial infarction. Each of the toxicities was controllable and there were no treatment-related deaths. One patient achieved CR, 13 achieved PR, 14 SD and 3 PD, and the overall response rate was 45.2%. Of 26 patients with stage IIIB or IV, the median survival time was 232 days, the 1-survival rate was 38.5%, and 3 patients survived for more than 3 years. In conclusion, chemotherapy with NP and CPT appears to be safe and highly effective for high-risk patients with NSCLC.     

PIK3CA gene amplification in Japanese non-small cell lung cancer

We have investigated 92 non-small cell lung cancer tissues and found 11 PIK3CA amplification. PIK3CA amplification incidence was significantly higher in male, smoker and squamous cell carcinoma patients. Among 11 patients with PIK3CA amplification, two patients harbored a PIK3CA mutation. There was significant difference in survival between the patients with PIK3CA normal copy number and the patients with PIK3CA amplification.     

Peroral endoscopic myotomy for esophageal achalasia: Indication and technique

Since the inception of peroral endoscopic myotomy (POEM) in 2008, more than 2000 POEMs have been performed to date in the world. The technique has been standardized to include the following 5 steps: mucosectomy, submucosal tunnel creation, esophageal myotomy, cardiomyotomy, and mucosectomy closure. Minor technique variations do exist as far as the equipment utilized as well as with the orientation and completeness of the myotomy. This article describes the equipment used during POEM as well as the essential steps to have a safe and successful procedure.     

Does magnifying endoscopy improve the diagnosis of erosive esophagitis?

Background and Aims:  Low-grade erosive esophagitis (i.e. Los Angeles grade A) is the most predominant type of esophagitis in Japan. It is unclear whether all the mucosal breaks detected by conventional endoscopy are indicative of esophageal mucosal erosion. Hospital-based, cross-sectional, cross-over, observational study was assigned to investigate the value of magnifying endoscopy for diagnosis of erosive esophagitis.
Methods:  From August to December 2006, 178 consecutive patients with upper gastrointestinal symptoms were enrolled at three university hospitals and one national medical center in western Japan. Before endoscopy, all participants were requested to answer questionnaires concerning their symptoms. Experienced endoscopists performed an endoscopic diagnosis of each patient first with a conventional standard view and then with a magnifying view. Endoscopic diagnostic concordance between conventional and magnifying endoscopic view for erosive esophagitis was calculated. Relationship between a variety of symptoms and erosive esophagitis was also evaluated.
Results:  Erosive esophagitis was identified using conventional and magnifying endoscopy in 14.6% and 17.4% of patients, respectively. Eleven false-negative and six false-positive diagnoses using conventional endoscopy occurred among the 178 enrolled patients. The weighted kappa value of diagnostic concordance for erosive esophagitis between the two endoscopic views was 0.76. The prevalence of erosive esophagitis in patients with reflux-, dysmotility-, and ulcer-like symptoms was 20.7%, 24.1%, and 15.2%, respectively.
Conclusions:  Magnifying endoscopy did not significantly improve the diagnostic sensitivity of erosive esophagitis over non-magnifying, conventional endoscopy. Erosive esophagitis was frequently identified in patients that did not have reflux symptoms.     

Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy

Several studies have suggested that epidermal growth factor receptor (EGFR) gene mutation, EGFR gene amplification, and some other biomarkers may be predictors of gefitinib sensitivity. We analyzed EGFR mutation and EGFR copy number in 22 gefitinib-treated non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied 143 gefitinib-na?ve Japanese NSCLC cases. The erbB2 copy number was also studied in 59 gefitinib-na?ve NSCLC cases. In gefitinib-treated patients, the presence of EGFR mutation was associated with a higher response rate to gefitinib and a longer overall survival, but the increased EGFR gene copy number was not. In gefitinib-na?ve cases, EGFR mutation but not EGFR gene copy number was significantly correlated with gender, pathological subtypes, and smoking status. The erbB2 copy number was not significantly correlated with the EGFR mutation or EGFR copy number in 59 cases. In conclusion, EGFR mutation was a better predictor of clinical outcome in gefitinib-treated patients than the EGFR gene copy number.     

Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations have been reported to correlate with the sensitivity to the tyrosine kinase inhibitor treatment for advanced lung cancers. Since several reports have shown that invasive thymoma overexpress the EGFR protein, we examined the EGFR expression and mutation statuses in thymoma and thymic carcinoma tissues. METHODS: EGFR mutation statuses from 99 thymic epithelial tumor samples were evaluated by a rapid and sensitive TaqMan assay using Applied Biosysytems 7500 real-time PCR system. Probes were designed according to the 13 different EGFR mutations reported previously in lung cancers. A total of 38 thymoma samples were directly sequenced for the EGFR gene. Protein expressions were evaluated for 56 thymic epithelial tumors by immunohistochemistry. RESULTS: EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using TaqMan PCR assay. Of the 38 samples 3 showed a heterozygous silent mutation without changes in the protein, a G to A transition at the nucleotide 2361 in exon 18. EGFR expression was significantly higher in invasive thymomas (stages III-IV, 15/19 were positive) than in early stage thymomas (stages I-II, 7/33 were positive) (P < 0.0001). All four carcinomas and all seven B3 thymomas showed EGFR positive staining. CONCLUSIONS: Although EGFR mutation at the tyrosine kinase domain is unlikely to be a therapeutic target for thymoma, the information about EGFR expression would contribute to the further identification of the therapeutic target for advanced thymomas.     

A planar catechin analogue having a more negative oxidation potential than (+)-catechin as an electron transfer antioxidant against a peroxyl radical

The hydrogen transfer reaction of antioxidative polyphenol with reactive oxygen species has proved to be the main mechanism for radical scavenging. The planar catechin (P1H(2)), in which the catechol and chroman structure in (+)-catechin (1H(2)) are constrained to be planar, undergoes efficient hydrogen atom transfer toward galvinoxyol radical, showing an enhanced protective effect against the oxidative DNA damage induced by the Fenton reaction. The present studies were undertaken to further characterize the radical scavenging ability of P1H(2) in the reaction with cumylperoxyl radical, which is a model radical of lipid peroxyl radical for lipid peroxidation. The kinetics of hydrogen transfer from catechins to cumylperoxyl radical has been examined in propionitrile at low temperature with use of ESR, showing that the rate of hydrogen transfer from P1H(2) is significantly faster than that from 1H(2). The rate was also accelerated by the presence of Sc(OSO(2)CF(3))(3). Such an acceleration effect of metal ion indicates that the hydrogen transfer reaction proceeds via metal ion-promoted electron transfer from P1H(2) to oxyl radical followed by proton transfer rather than via a one-step hydrogen atom transfer. The electrochemical ease of P1H(2) for the one-electron oxidation investigated by second-harmonic alternating current voltammetry strongly supports the two step mechanism for hydrogen transfer, resulting in the enhanced radical scavenging ability.     

The results of liver cryosurgery for synchronized liver metastasis from colorectal cancer

We examined our results of liver cryosurgery for synchronized liver metastasis from colorectal cancer. Twelve patients whose prognosis after the cryosurgery was clear were eligible. All of the patients received not only a resection of the colorectal primary lesion, but they also received a cryosurgery for liver metastases under the same laparotomy. These patients had been treated in this manner from 1981 to 1987. Ten of the 12 patients died from recurrent cancer. The range in survival time of 12 cases was from 6 months to 117 months, and the average survival length was 25.4 months. The examination of the results suggested that there were no cryosurgery induced anti-immunological response observed among the patients. The survival lengths of the patients with untreated cancer were good.     

Phase II study of OK-432 intrapleural administration followed by systemic cisplatin and gemcitabine for non-small cell lung cancer with pleuritis carcinomatosa

We conducted a phase II study of OK-432 intrapleural administration followed by systemic chemotherapy using cisplatin with gemcitabine to determine their combined effects on non-small cell lung cancer (NSCLC) with pleuritis carcinomatosa. Between December 1999 and October 2001, 15 patients were registered in the study. Fourteen patients had an Eastern Cooperative Oncology Group performance status (PS) of 1, and one patient had a PS of 2. Ten patients had adenocarcinoma, one had squamous cell carcinoma, and four had malignant mesothelioma. Patients underwent thoracocentesis and received an OK-432 intrapleural injection. They were then treated every three weeks with chemotherapy consisting of 80 mg/m2 cisplatin on day 1 and 1000 mg/m2 gemcitabine on days 1 and 8. Thirteen patients received two or more courses of chemotherapy. Grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred in five, two and three patients, respectively. Non-hematological toxicities were mild, except for one patient who experienced a grade 3 elevation of transaminase and two patients who experienced grade 3 nausea. Of the 15 patients, one achieved partial response (PR), 13 a stable disease (SD) rating, and one a progressive disease (PD) rating, and the overall response rate was 6.7%. The median survival time was 13.5 months and the one-year survival rate was 60.0%. In conclusion, OK-432 intrapleural administration followed by cisplatin and gemcitabine systemic chemotherapy did not reduce patients' tumors but did prolong their survival time. A large-scale phase II study of the efficacy of this combination therapy is required.