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The purpose of this prospective study was to assess the ability of plasma vascular endothelial growth factor-A short isoforms (pVEGF-Asi) to predict bevacizumab (BV) efficacy and to explore other circulating biomarkers in metastatic colorectal cancer (mCRC) patients treated with modified FOLFOX6/XELOX plus BV (mFOLFOX6/XELOX + BV).Pre-treatment plasma samples were collected from 100 mCRC patients receiving first-line chemotherapy with mFOLFOX6/XELOX + BV. The plasma levels of 11 angiogenesis-associated molecules, including pVEGF-Asi and 22 cancer-associated gene mutations in circulating tumor DNA, were analyzed. For the primary endpoint, we assumed that the hazard ratio (HR) for progression-free survival (PFS) calculated using a Cox proportional hazards model was1.15, comparing patients with a high versus those with a low pVEGF-Asi level divided according to the median pVEGF-Asi value.The median value of pVEGF-Asi was 37 (range 6.5-262) pg/ml. The HR for PFS between the high and low pVEGF-Asi patient groups was 1.3 [95% confidence interval (CI) 0.8-2.1; log rank, P = 0.25], which was larger than the predefined threshold of 1.15. The multivariate analysis demonstrated that PFS was significantly associated with plasma intercellular adhesion molecule-1 (pICAM-1) (≥190.0 versus190.0 ng/ml; HR 2.1; 95% CI 1.3-3.5), RAS (mutant versus wild; HR 2.5; 95% CI 1.5-4.3), and FBXW7 (mutant versus wild; HR 2.8; 95% CI 1.2-6.8), whereas overall survival was significantly associated with pICAM-1 (HR 2.0; 95% CI 1.1-3.7) and RAS (HR 2.6; 95% CI 1.5-4.6).The addition of BV was unable to compensate for the poor PFS associated with a high pVEGF-Asi level, suggesting that pVEGF-Asi is unlikely to be a good predictive biomarker of the efficacy of mFOLFOX6/XELOX + BV therapy. The clinical significance of circulating ICAM-1, mutant RAS, and mutant FBXW7 levels should be studied further.

Background. In immediate one-stage implant-based breast reconstruction, acellular dermal matrix (ADM) has been usually used due to cover the outside part of the pectoralis major muscle in the world. Unfortunately, ADM is not approved in Japan yet. Therefore we have performed safety one-stage implant-based breast reconstruction without ADM according to several unique technics in our institution and obtain the excellent results. We report single institution experience using the retrospective medical data. Methods. We chose the surgical method of immediate breast reconstruction (autologous and prosthetic) according to patient's preference, breast volume and cancer condition in early breast cancer patients (pts). Two hundred fifty four early breast cancer pts underwent immediate artificial breast reconstruction from January 2014 to March 2017 in our institution. Thirty seven pts were excluded in this analysis because of preplanned the expander insertion. ALLERGAN Natrelle 410 series were used as the silicon breast implant (SBI). We performed three unique steps to determine the one-stage SBI cases as follow. ICG fluorescence imaging to confirm the blood flow state of the chest skin after mastectomy is used as standard method. If there is a defective contrast region, we remove these area. And then, serratus anterior muscle/fascial and external oblique fascial flap is elevated to completely cover the SBI together with the pectoralis major muscle so that the between mastectomy field and the SBI insertion section are isolated. We used sizer to confirm the skin tension and form of breast. After confirming these steps, we adopted cases whether SBI insertion can be safety done. We evaluated the total cosmetic finding based on three categories of inframammary fold position, balance of both breast size and form at half year after operation. If the difference between both inframammary fold positions was under 1cm, if compensatory pad is not necessary with underwear, if the protrusion of the lower pole is sufficient compared with the contralateral side, we gain the point one on each categories in each cases. The total cosmetic evaluation was classified as three categories. Good, fair and poor were defined as gained 3 points, 2 points and 0/1 points, respectively. Results. Among 217 planned immediate prosthetic breast reconstruction pts, 186 pts (85.7%) were succeed one-stage implant-based breast reconstruction. Among 186 pts, the median age was 47 years old (23-75), median body weight was 53kg (35-84), median body mass index was 21.08 kg/m2(16.20-29.41), removed breast volume was 240g (56-522) and implant volume was 220cc (90-425). Implant removed in one case because of complications and infection was occurred in five cases. The revision surgery was performed in one cases because of malposition. Among all pts, the good, fair and poor of total cosmetic evaluation is 84.3%, 13.5% and 2.2%, respectively. Conclusions. Immediate one-stage implant-based breast reconstruction without ADM may be useful and safe procedure according to our unique technics in early breast cancer patients who hope the immediate prosthetic breast reconstruction in Japan. Citation Format: Okumura S, Tatibana S, Narita C, Hyodo I, Sawaki M, Hattori M, Yoshimura A, Ishiguro J, Kotani H, Gondo N, Adati Y, Iwata H, Kamei Y. Immediate one-stage implant-based breast reconstruction without an acellular dermal matrix in Japanese breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-12.

Purpose This phase III study compared treatment with weekly paclitaxel and biweekly irinotecan in patients with advanced gastric cancer refractory to treatment with fluoropyrimidine plus platinum. Patients and Methods Patients were randomly assigned to receive either paclitaxel (80 mg/m2 on days 1, 8, and 15, every 4 weeks) or irinotecan (150 mg/m2 on days 1 and 15, every 4 weeks). Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, adverse events, and proportion of patients who received third-line chemotherapy. Results Of 223 patients, 219 were eligible for analysis. Median OS was 9.5 months in 108 patients allocated to the paclitaxel group and 8.4 months in 111 patients allocated to the irinotecan group (hazard ratio [HR], 1.13; 95% CI, 0.86 to 1.49; P = .38). Median PFS was 3.6 months in the paclitaxel group and 2.3 months in the irinotecan group (HR, 1.14; 95% CI, 0.88 to 1.49; P = .33). Response rate was 20.9% in the paclitaxel group and 13.6% in the irinotecan group (P = .24). Common grade 3 to 4 adverse events were neutropenia (paclitaxel group, 28.7%; irinotecan group, 39.1%), anemia (21.3%; 30.0%), and anorexia (7.4%; 17.3%). Treatment-related deaths occurred in two patients (1.8%) in the irinotecan group. Third-line chemotherapy was administered in 97 patients (89.8%) after paclitaxel treatment and in 80 patients (72.1%) after irinotecan treatment (P = .001). Conclusion No statistically significant difference was observed between paclitaxel and irinotecan for OS. Both are reasonable second-line treatment options for advanced gastric cancer.

Background: To evaluate the activity and toxicity of docetaxel in patients with metastatic esophageal cancer. Patients and methods: Eligible patients had histologically confirmed carcinoma of the esophagus with measurable metastatic sites according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients were either chemotherapy-naive or previously treated with one regimen of chemotherapy. Docetaxel 70 mg/m 2 was administered intravenously over 1–2 h, every 21 days. Results: Of 52 patients enrolled in this study, three were excluded because they did not receive docetaxel due to worsening condition after enrollment. Thirty-six patients had received prior platinum-based chemotherapy. The majority of patients (94%) had squamous cell carcinoma. Ten of 49 evaluable patients [20%; 95% confidence interval (CI) 10–34%] showed a partial response. Of the 10 partial responses, six patients had received prior platinum-based chemotherapy. Grade 3 or 4 neutropenia was noted in 43 of 49 patients (88%), and nine of 49 patients (18%) developed febrile neutropenia. Twenty-eight of 49 patients (57%) required lenograstim. Grade 3 anorexia and fatigue occurred in nine (18%) and six (12%) patients, respectively. Median survival time was 8.1 months (95% CI 6.6–11.3) and the 1-year survival rate was 35% (95% CI 21–48%). Conclusions: Docetaxel as a single agent is effective in esophageal cancer, but careful management of neutro

We are developing a new 3D Monte Carlo transport code ‘IMPGYRO’ for the analysis of the heavy impurities in fusion edge plasmas. The code directory solves the 3D equations of motion for the test impurity ions to take into account their gyro motion. Most of the important processes, such as the multi-step ionization process and Coulomb scattering, etc., are also included in the model. The results for the prompt redeposition rate of tungsten ions agree well with the analytic results. In addition, 2D density profiles for tungsten ions of each charge state in a simple slab geometry have been calculated for given background plasma profiles typical of a detached plasma state. Although the code is now still under development, these initial results show that the code has potential as a useful tool, not only for the analysis of the prompt redeposition very close to the wall, but also for the analysis of more large scale impurity transport processes.

Background: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC). Patients and methods: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80–120 mg/day S-1 for 2 weeks with 100 mg/m 2 oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m 2 cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease. Results: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n= 318) was noninferior to CS (n=324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840–1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803–1.142). In the intention-to-treat population (SOX, n=339; CS, n= 337), the HRs in PFS and OS were 0.979 (95% CI 0.821–1.167) and 0.934 (95% CI 0.786–1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%). Conclusion: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS. Clinical trial number: JapicCTI-101021.

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.

Salt/NaCl has been reported to induce necrosis in gastric mucosal cells, however, the mechanisms for gastric injury by salt are not clarified. In this study, we elucidated whether salt is an oxidative stress inducer via mitochondrial injury on rat gastric epithelial cells (RGM-1) in 300, 450, 650 and 1000 mM of NaCl-contained medium. To clarify whether salt-induced reactive oxygen species (ROS) is derived from mitochondria, we also investigated a salt-induced ROS production in manganese superoxide dismutase overexpressing cells (RGM-MnSOD). MnSOD is a specific scavenger for superoxide anion produced from mitochondria. The results showed that cellular injuries in RGM-MnSOD were significantly less severe than that in normal RGM-1. The electron paramagnetic resonance (EPR) studies also provided an evidence that the salt-derived superoxide production in RGM-MnSOD was less than that in normal RGM-1. These results indicated that salt is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer.

Purpose To compare the efficacy, toxicities, and pharmacokinetics of an oral regimen consisting of uracil/tegafur (UFT) and leucovorin (LV) between Japanese patients and patients in the United States with previously untreated metastatic colorectal cancer. Patients and Methods Forty-four Japanese patients and 45 patients in the United States were enrolled in concurrent nonrandomized phase II trials. UFT 300 mg/m2/d and leucovorin 75 mg/d were administered orally for 28 days followed by a 7-day rest period. The total daily dose of each drug was divided into three equal doses. Treatment was repeated every 5 weeks until disease progression. Blood samples for the pharmacokinetic study were obtained after the initial dose on day 1 of the first course. Results The response rate for the Japanese patients and the patients in the United States was 36.4% (95% CI, 22.4% to 52.2%) and 34.1% (95% CI, 20.5% to 49.9%), respectively. The only major toxicity was diarrhea, and other toxicities were mild in both populations. The incidence of grade 3 or higher diarrhea in the Japanese and Americans was 9% and 22%, respectively. Although the area under the curve and maximum concentration of fluorouracil were found to be slightly higher in the Japanese patients than the patients in the United States, and area under the curve–adjusted body surface area appeared to be comparable between the two groups. Conclusion The efficacy and pharmacokinetic parameters of UFT and LV are comparable in Japanese and American patients; however, a difference in toxicity profile, specifically diarrhea, was noted. This oral regimen of UFT and LV is considered to have similar activity against metastatic colorectal cancer and to have acceptable toxicity in patients in both countries.

Aim: Randomized phase III study for the first-line treatment of advanced gastric cancer (AGC) (G-SOX PIII) demonstrated the non-inferiority of S-1 plus oxaliplatin (SOX) for S-1 plus cisplatin (CS) on PFS (HR for SOX vs. CS 1.004, 95% confidence interval [CI] 0.840-1.199; Higuchi, JCO 2013;30:Suppl, Abstract 60) and on OS (HR 0.958, 95% CI 0.803-1.142). Reporting of separate analyses for individual progression types is recommended (European Medicines Agency. Appendix 1 to the guideline on the evaluation of anticancer medicinal products in man). Thus, we aimed to assess the association between progression types and OS in this study. Methods: Tumor lesions were assessed every 6 weeks until disease progression and independently reviewed according to the RECIST v1.0. We applied the Cox regression including two time-dependent covariates, i.e., progressive disease with new lesions (PDNL) or without new lesions (PDwoNL) in each treatment group, and estimated their effects compared to no progression (Non-PD). Results: The results of analysis are shown in the table below. PDNL and PDwoNL were identified for 88 and 166 patients in SOX group (317 patients), and 95 and 146 patients in CS group (324 patients), respectively. The hazards of death in Non-PD were different between treatment groups (HR 0.582). However, association between progression types and OS were similar in both treatment groups. Both progression types were strong prognostic factors for OS, and greater effects were seen in PDNL (HR 8.277 in SOX, 5.997 in CS). Conclusions: The progression accompanied by new lesions gives a strong negative impact on OS in patients treated with S-1 and platinum for AGC. Examining progression types would be useful for evaluating efficacy of anticancer treatment on OS. HR (95%CI) P SOX vs. CS in Non-PD 0.582 (0.371-0.914) 0.019 in PDwoNL 1.111 (0.868-1.589) 0.403 in PDNL 0.803 (0.593-1.089) 0.158 SOX PDwoNL vs. Non-PD 5.447 (3.609-8.221) PDNL vs. Non-PD 8.277 (4.250-8.462) CS PDwoNL vs. Non-PD 2.854 (2.038-3.995) PDNL vs. Non-PD 5.997 (4.250-8.462) Disclosure: Y. Yamada: honoraria: Yakult Honsha, Taiho, Chugai, Pfizer, Takeda, Bristol-Myers, Dainippon Sumitomo, Johnson & Johnson, Novartis, Daiichi Sankyo Research Funding: Yakult Honsha, Otsuka, Chugai, Pfizer, Astra Zeneca, Novartis, Daiichi Sankyo, Bayer, Merck; K. Higuchi: I have received honoraria from Yakult Honsha; M. Gotoh: I have received honoraria from Yakult Honsha; N. Fuse: I have received honoraria from Taiho and research funding from Yakult Honsha and Taiho. N. Sugimoto: I have received honoraria and research funding from Yakult Honsha and Taiho; T. Nishina: I have received honoraria and research funding from Yakult Honsha and Taiho; A. Tsuji: I have received honoraria from Yakult Honsha and Taiho; K. Yamaguchi: I have received honoraria from Chugai, Bristol-Myers, Takeda, and Merck; H. Yasui: I have received honoraria from Yakult Honsha, Medicon, Chugai, Taiho, and Bristol-Myers. S. Hironaka: I have received honoraria from Yakult Honsha and Taiho; C. Hamada: I have received consultant fees and honoraria from Yakult Honsha, Taiho, and Chugai; I. Hyodo: I have held an advisory Role for Yakult Honsha and Taiho. I have received honoraria from Yakult Honsha and Taiho. All other authors have declared no conflicts of interest.

Summary Purpose To determine the antitumor activity and toxicity of paclitaxel administered as a three-hour infusion and to estimate the incidence of hypersensitivity reactions using a short-course prophylaxis regimen in patients with advanced gastric cancer. Patients and methods Sixty patients with advanced measurable gastric cancer and performance status 0 to 2, who had received at most one prior chemotherapy regimen, were treated with paclitaxel 210 mg/m2 over three hours following a short-course premedication with dexamethasone, diphenhydramine and ranitidine administered 30 min prior to the delivery of paclitaxel. Cycles were repeated every three weeks. Twenty-six patients (43%) had received prior chemotherapy for metastatic disease and six patients had received adjuvant chemotherapy. The response rate to prior chemotherapy was 50% (13 of 26). Results Objective responses were observed in 14 of 60 patients (23%; 95% confidence interval (95% CI): 13%–36%). Six of twenty-eight (21%) patients with no prior chemotherapy and 7 of 26 (27%) previously treated patients for metastatic disease developed a PR. There were no complete responses. The median duration of response was 152 days. The study treatment was well tolerated. Twenty-two of sixty patients (37%) experienced grade 3 or 4 neutropenia, which was the most common and serious toxicity. Grade 3 peripheral neuropathy occurred in one patient. Hypersensitivity reactions were observed in only nine patients (15%) and were all grade I. Conclusions A three-hour infusion of paclitaxel is both an active and safe treatment for gastric cancer using the short-course premedication schedule. Paclitaxel appears to be non-cross resistant to other active agents for gastric cancer

A combination of radiotherapy and chemotherapy is a usual treatment method for malignant head and neck tumors, however chemoradiotherapy is associated with hematopoietic impairment and serious stomatitis in patients. The clinical effects and evaluation of hematopoietic activity (e.g., leukocyte count) and the degree of stomatitis under adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer were investigated for preoperative cancer therapy. In order to evaluate the clinical effects of Ancer 20 injection with regard to hematopoietic activity and the degree of stomatitis, a clinical study was performed for 18 patients with oral cancer in our department. The 18 patients, who had oral squamous cell carcinomas (5 of the tongue, 4 of the mandibular gingiva, 3 of the maxillary gingiva, 1 of the floor of the mouth, 3 of the buccal mucosa, and 2 others), were treated with this combination of adjuvant therapy with Ancer 20 injection, from March, 1991 to March, 1997. They were injected with Ancer 20 (twice a week, 40 micrograms) during the cancer treatment period. We investigated hematopoietic activity, (e.g., leukocyte and platelet counts) and the degree of stomatitis periodically, before and after the combined radiotherapy and chemotherapy treatment period. It was found that in the patients who were treated with Ancer 20 injection, the decrease in leukocyte and platelet counts was prevented and the condition of stomatitis was improved. These results suggest that Ancer 20 injection may generally improve various dysfunctions due to hematopoietic impairment by radiotherapy combined with chemotherapy, and improve immunological factors. We conclude that Ancer 20 injection is a useful adjuvant treatment for oral cancer.

We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25 (mean+/-SD) in the high grade malignant group (n=9) that demonstrated diffuse large cell (DL) components and 2.53+/-0.46 (mean+/-SD) in the low grade malignant group (n=12) that did not demonstrate DL components. Among 12 patients who underwent HP eradication therapy, the blood sFas antigen level lowered after eradication in 7 out of 10 patients who showed complete response or partial response, while sFas antigen level did not decrease in the 2 patients who showed no change or progression of the disease. In the high grade malignant group, 2 of 3 patients who underwent HP eradication treatment showed a mild decrease in the sFas antigen level as well as an improvement on endoscopic and histological examinations, but these sFas level were not normalized. The blood sFas antigen level tended to coincide with pathological activity and malignancy, suggesting that the sFas antigen level may be a prognostic indicator and useful index for the response of HP eradication treatment in gastric MALT lymphoma.

Patients with cancer receive an explanation of their disease and the recommended treatment when they are asked to give informed consent (IC). In the course of this process patients suffer severe distress, including anxiety and depression, but physicians tend to underestimate it. The goal of this study was to reveal the magnitude of such stress and any changes to this during the IC process by means of the Hospital Anxiety and Depression (HAD) scale, a self-assessment scale. Of 171 in-patients newly diagnosed with lung cancer, 119 were assessable for serial HAD scale scores on admission, immediately after the IC process, and at 1 and again at 2 weeks after the IC. Both anxiety and depression scores increased significantly immediately after IC. Female patients had significantly higher anxiety and depression scores than males at 1 week after the IC. The patients with poor performance status demonstrated high anxiety scores on admission and immediately after the IC, and substantial depression persisted longer in these patients. The prevalence of high scores of more than 11 (judged as adjustment disorder or more severe state) immediately after the IC was 50% for anxiety and 31% for depression. The prevalence decreased significantly within 1 or 2 weeks, but 41% and 14% of the patients still showed high anxiety and depression scores, respectively. Physicians should be aware of these facts and pay special attention to their patients' psychological distress in routine clinical practice.

Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of 14 HCC cases that achieved total tumor necrosis in response to L-TAE. The HCCs of all cases were resected 45 +/- 17 days after L-TAE and were confirmed to be totally necrotic. Ultrasonography showed a mean tumor size of 2.5 +/- 1.0 cm, often with a halo formation around the tumor. Angiographically, neovascularity and clear tumor stains were observed in all cases. Computed tomography portography showed nodular perfusion defects in all the cases examined. There were portal invasions in two cases. On Lipiodol-computed tomography, Lipiodol was densely and homogeneously retained within the whole tumor. The number of tumors was single in all diagnostic images. Macroscopic view of HCCs were single nodular type in nine cases and single nodular type with extra growth in four cases. Clear capsular formation was seen in each HCC nodule. Soft x-rays were taken to observe the exact distribution of Lipiodol in the operative specimens. Microscopic intrahepatic metastases were found histologically in four cases. Histologic examination showed the trabecular pattern with broad blood spaces in which Lipiodol was positive with Sudan III staining. Necrosis was seen not only in the main tumor, but also in the capsular invasions and microscopic metastases with Lipiodol deposition. The characteristics of the cases with total tumor necrosis were as follows. Deposition of Lipiodol throughout the tumor was essential, and clinically the cases showed a single HCC tumor with a diameter of more than 5 cm and arterial hypervascularity. The pathologic findings included expansive growth with capsular formation and trabecular-type HCC with abundant blood spaces. These findings are important for evaluating the radical efficacy of L-TAE.

Summary Local tumor compression is the main mechanical cause of posterior interosseous nerve palsy. The reported cases of these tumors do not include that of pigmented villonodular synovitis. Here, we report a case of a 53-year-old male with a 9-year history of painless swelling in his left elbow and a few months of progressive weakness in his left hand. Imaging identified the mass, and histological examination of the biopsy specimens revealed pigmented villonodular synovitis. The mass was compressing the nerve at the arcade of Frohse, and we performed a complete resection of the mass. Following removal of the mass, the patient regained complete function in his left upper extremity, and no local recurrence has been detected after 2 postoperative years. The possibility of pigmented villonodular synovitis should be considered in the differential diagnosis of posterior interosseous nerve palsy.

Serum levels of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were measured in 38 patients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 43 with hepatocellular carcinoma (HCC) using enzyme-linked immunosorbent assays. All the patients showed significantly higher serum levels of these circulating adhesion molecules than 40 normal controls. The serum E-selectin level showed no relationship to the levels of the other adhesion molecules. Serum VCAM-1 levels were well correlated with serum ICAM-1 levels in CH and LC patients. In HCC patients, however, the close correlation between VCAM-1 and ICAM-1 was lost, because the patients with large tumors (100 cm2) showed relatively high ICAM-1 levels. The amount of ICAM-1 shed from the tumor cells was calculated in the HCC patients as follows: actual serum ICAM-1 level minus basal ICAM-1 level released from the noncancerous liver (obtained from the regression line between ICAM-1 and VCAM-1 in CH and LC patients). Although there was no relationship between the actual ICAM-1 level and the tumor size in HCC patients, the predicted ICAM-1 shedding was closely correlated with tumor size. When in situ expression of these adhesion molecules was evaluated in 10 HCC tissues using immunohistochemistry, the tumor cells exhibited enhanced ICAM-1 expression but did not express E-selectin and VCAM-1. These results suggest that the elevated serum levels of adhesion molecules in HCC patients are mainly attributable to the associated liver inflammation, although some ICAM-1 is shed into the circulation by tumor cells.

e14560 Background: UGT1A1*6 as well as UGT1A1*28 polymorphisms is associated with decreased glucuronidation of SN-38, the active metabolite of irinotecan (CPT-11). Although the maximum tolerated dose (MTD) and the recommended dose (RD) in Hetero was determined 150 mg/m2 (approval dose in Japan), those of Homo were unknown. Methods: Pts received prior chemotherapies except for CPT-11 for metastatic gastrointestinal cancer were enrolled. UGT1A1 polymorphisms were categorized into Wild(*1/*1), Hetero(*1/*28, *1/*6), and Homo(*28/*28, *6/*6, *28/*6). CPT-11 was administered biweekly. Starting doses were 150 mg/m2 in Wild, 100 mg/m2 in Hetero, and 75 mg/m2 in Homo. DLT was defined as grade 4 hematological, or grade 3 non-hematological toxicity. MTD closest to dose-limiting toxicity (DLT) appearance of 30% was guided by the continual reassessment method in the cohort of Hetero and Homo. DLT and pharmacokinetic (PK) sampling was evaluated during the 1st cycle. Results: Eighty-two pts were enrolled from November 2006 to November 2008 (Wild, Hetero, Homo: 41, 20, and 21, respectively). The dose level reached at 150 mg/m2 in Homo. At 150 mg/m2, DLT was observed in six pts of Homo (grade 4 neutropenia, grade 3 diarrhea: 6 and 1, respectively). The probability of DLTs were 22.2% at 125 mg/m2, and 37.4% at 150 mg/m2. The MTD was determined 150 mg/m2 in pts with Homo group. However, the incidences of grade 3/4 neutropenia at 150 mg/m2 during the 1st cycle were 9.8% (4/41), 18.8% (3/16), and 62.5% (10/16) in Wild, Hetero, and Homo, respectively. And the second administration was delayed 7 days or more in most pts in Homo (63% at 150 mg/m2). In one pt of Homo for *28/*28 died of septic shock during the 2nd cycle. SN-38 AUC (0–24h, ng*hr/mL, median) was 239 in Wild, 237 in Hetero, and 410 in Homo. Pts with Homo showed the different trend of PK/PD compared to those with Wild and Hetero. Conclusions: The MTD was 150 mg/m2 in pts with Homo group and the most frequent DLT was grade 4 neutropenia. However, our findings suggest that 150 mg/m2 q2w is difficult to recommend and the initial dosage and administration should be considered carefully for pts with Homo. [Table: see text]

14502 Background: UGT1A1*28 and *6 polymorphisms are reported to be associated with decreased glucuronidation of SN-38, the active metabolite of irinotecan (CPT-11). In 2005, the FDA revised the pa...

4093 Background: The results of phase I portion of the treatment with the oral S-1 (a new oral fluoropyrimidine) plus oral leucovorin (LV) in patients (pts) with untreated metastatic colorectal cancer (mCRC) was reported at ESMO 2006. Dose limiting toxicities (DLTs) were grade 3 stomatitis/pharyngitis, nausea, diarrhea, ileus and exanthema. The recommended doses (RDs) for this phase II portion were determined to be S-1 40 mg/m2 and LV 25 mg/body orally given twice daily on days 1 to 14 of a 28-day cycle. The PK profiles of S-1 plus LV were similar to those of S-1 monotherapy and UFT plus LV, respectively. The main purpose of this phase II portion is to evaluate the efficacy and safety of S-1 plus LV at RD level in pts with untreated mCRC. Methods: Pts were eligible as follows; unresectable mCRC with no prior chemotherapy or receiving adjuvant chemotherapy completed at least 6 months before, histologically proven adenocarcinoma, PS(ECOG) 0–2, age 20 to 75, measurable lesions, adequate organ function and written informed consent. The pts received 40 mg/m2 of S-1 plus 25 mg/body of LV twice daily as RD in this phase II portion. The primary endpoint was the objective response rates (RRs), and secondary endpoints were time to progression (TTP) and toxicities. Results: Between Sep 2004 and Jun 2006, 56 pts of 65 enrolled pts received the treatment at RD level. The objective RRs were 55% (36 of 65) for all pts and 55% (31 of 56) for pts at RD. Disease control rates (DCRs) were 86% (56 of 65) for all pts and 86% (48 of 56) for pts at RD. Median TTP was 5.5 months for pts at RD, with a median follow-up of 5.5 months. The median survival time is under observation. During the 6 months from starting the treatment, the most common grade 3/4 toxicities at RD were as follows: diarrhea, 23%; stomatitis, 20%; anorexia, 18%; and neutropenia 13%. Conclusions: A combination of S-1 plus oral LV is an effective, well tolerated, and convenient regimen in pts with untreated mCRC, without the addition of either oxaliplatin or irinotecan. The updated results of the objective RRs, DCRs, TTP reviewed extramurally, and detailed safety profile will be presented at the meeting. This trial was supported by Taiho pharmaceutical co., Ltd., Tokyo, Japan. No significant financial relationships to disclose.

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

3693 Background: The oral fluoropyrimidine X (Xeloda) is highly active and well tolerated in pts with MCRC. In a phase II Japanese study (ASCO 2002, abstract 2322), a 4-weekly regimen of X (828 mg/...

4071 Background: Fluoropyrimidine (F) derivatives have remained the mainstay of treatment for advanced gastric cancer (AGC). Irinotecan (CPT-11) is active as a single agent against AGC. Preclinical evidence indicates that mitomycin C ( MMC) acts synergistically with CPT-11. The objective of the present study was to evaluate the efficacy and toxicity of a combined CPT-11 and MMC regimen in patients (pts) with AGC that in resistant to F-based regimens. Methods: Eligibility criteria included histologically proven AGC, disease progression during F-based regimens or disease recurrence within 6 months of the completion of F-based adjuvant treatment, an age of 75 years or younger, PS 0 to 2, measurable disease, adequate organ functions, and written informed consent. Each course of chemotherapy consisted of 5 mg/m2 of MMC by bolus injection and 150 mg/m2 of CPT-11 by 90-minute infusion. Courses were repeated every 2 weeks. The total dose of MMC was limited to 50mg/m2. Results: Between April 2002 and July 2003, 45...

In 144 cases of hepatocellular carcinoma (HCC), 166 cases of cirrhosis without HCC and 142 cases of chronic hepatitis, we examined HBsAg, anti-HBs and anti-HBc in sera and compared the following factors between hepatitis B virus marker-negative and -positive patients: age, sex, alcohol consumption, family clustering of liver diseases, and histories of blood transfusion and post-transfusion hepatitis. Results of this study demonstrated several distinct differences in clinical backgrounds between non-B (negative for HBsAg, anti-HBs and anti-HBc) and B (positive for HBsAg) patients with HCC. Non-B patients were significantly older, had a lower frequency of familial tendencies for liver diseases, and more frequently had cancers other than HCC in their families. Some of these differences were also observed between non-B and B patients with cirrhosis and chronic hepatitis. Among patients with chronic hepatitis, the non-B patients had received blood transfusion or had post-transfusion hepatitis more frequently than the B patients. However, this difference was not apparent in patients with liver cirrhosis or HCC, suggesting that progression of non-A, non-B post-transfusion hepatitis to cirrhosis and HCC may not be as frequent as progression to chronic hepatitis.

A typical case of hairy cell leukemia, very rare in Japan, is described. The biological characteristics of the disease and histological features of liver and spleen are also reported. Treatment with alpha-interferon and splenectomy was successfully performed, and the patient is now in good health.