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Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal-retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

Brain masking of MRI images separates brain from surrounding tissue and its accuracy is important for further imaging analyses. We implemented a new brain masking technique based on multi-atlas brain segmentation (MABS) and compared MABS to masks generated using FreeSurfer (FS; version 5.3), Brain Extraction Tool (BET), and Brainwash, using manually defined masks (MM) as the gold standard. We further determined the effect of different masking techniques on cortical and subcortical volumes generated by FreeSurfer. METHODS Images were acquired on a 3-Tesla MR Echospeed system General Electric scanner on five control and five schizophrenia subjects matched on age, sex, and IQ. Automated masks were generated from MABS, FS, BET, and Brainwash, and compared to MM using these metrics: a) volume difference from MM; b) Dice coefficients; and c) intraclass correlation coefficients. RESULTS Mean volume difference between MM and MABS masks was significantly less than the difference between MM and FS or BET masks. Dice coefficient between MM and MABS was significantly higher than Dice coefficients between MM and FS, BET, or Brainwash. For subcortical and left cortical regions, MABS volumes were closer to MM volumes than were BET or FS volumes. For right cortical regions, MABS volumes were closer to MM volumes than were BET volumes. CONCLUSIONS Brain masks generated using FreeSurfer, BET, and Brainwash are rapidly obtained, but are less accurate than manually defined masks. Masks generated using MABS, in contrast, resemble more closely the gold standard of manual masking, thereby offering a rapid and viable alternative.

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.

The international staging system (ISS) is the most commonly used risk-stratification system for patients with multiple myeloma (MM) and is determined by serum albumin and β2-microglobulin levels. In the two determinants, β2-microglobulin levels are frequently observed to be elevated in patients with myeloma, particularly in those with renal impairment. In comparison with patients with intact immunoglobulin myeloma, patients with LC myeloma do not necessarily show decreased levels of serum albumin. The clinical impact of ISS in patients with LCMM, in particular the distinction between ISS I and II, may be complicated due to non-decreased levels of serum albumin in both stages. Accordingly, we have attempted to assess clinical relevance of the ISS in patients with LC myeloma. The clinical data of 1899 patients with MM diagnosed between January 2001 and December 2012 were collected from 38 affiliated hospitals of the Japanese Society of Myeloma. Significant difference was not found between stage I (n = 72) and stage II (n = 92) in LC myeloma patients (n = 307). The mean serum albumin concentration of patients with LC myeloma was within the reference range but higher than that of patients with IgG + IgA myeloma (n = 1501), which complicates the distinction between ISS stage I and II myeloma. Patients with LC myeloma had low frequencies of t(4; 14) and high frequency of elevated lactate dehydrogenase, and despite a relevant amount of missing data in our registry (R-ISS stage I; n = 11, stage II; n = 32, and stage III: n = 18), the information included in the R-ISS scoring system seems to be more accurate than ISS to obtain a reliable risk stratification approach in non-ISS stage III LC myeloma patients.

Background Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand. Patients and Methods The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of ≥65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP. Results A total of 836 patients with a median age of 74 years (range, 65–96 years) were analyzed. In the SoLT-J cohort (n = 555), age >75 years, serum albumin level Conclusion The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP.

Background and Aim: For large colorectal tumors, the en bloc resection rate achieved by endoscopic mucosal resection (EMR) is insufficient, and this leads to a high rate of local recurrence. As endoscopic submucosal dissection (ESD) has been reported to achieve a higher rate of en bloc resection and a lower rate of local recurrence in the short-term, it is expected to overcome the limitations of EMR. We conducted a matched case-control study between ESD and EMR to clarify the effectiveness of ESD for colorectal tumors. Methods: Between April 2005 and February 2009, a total of 28 colorectal tumors in 28 patients were resected by ESD and were followed up by colonoscopy at least once. As a control group, 56 EMR cases from our prospectively completed database were matched. En bloc resection, complication and recurrence rates were compared between the two groups. Results: The mean sizes of the lesions were 27.1 mm in the ESD group and 25.0 mm in the EMR group. The en bloc resection rate was significantly higher in the ESD group (92.9% vs 37.5% with ESD vs EMR), and the rate of perforation was also significantly higher (10.7% vs 0%). All cases of perforation were managed conservatively. No recur- rence was observed in the ESD group, whereas local recurrences were detected in 12 EMR cases (21.4%). Eleven of the 12 recurrences (91.7%) were managed endoscopically, and one required surgical resection. Conclusions: Endoscopic submucosal dissection is a promising technique for the treat- ment of colorectal tumors, giving an excellent outcome in comparison with EMR.

Primary mediastinal liposarcoma was observed in a 73-year-old man. Because of tight adhesions to adjacent tissues, neither complete resection nor surgical debulking of the tumor was possible. A T-tube was inserted into the patient's trachea for severe dyspnea, and he was treated with radiotherapy and an oral peroxisome proliferator-activated receptor-gamma agonist. The patient died 6 years after the initial diagnosis. Autopsy revealed liposarcoma composed of 3 subtypes in the primary tumor: well-differentiated, dedifferentiated, and round cell components. Round cell and dedifferentiated liposarcomas were predominantly observed in the metastatic nodules.

Gefitinib, the epidermal growth factor receptor tyrosine kinase inhibitor, is effective for patients with non-small cell lung cancer. However, a serious adverse effect, interstitial lung disease (ILD), has been reported. The re-administration of gefitinib might be considered when there is no other choice of treatment and a therapeutic effect can be expected; however, there is no published data on the safety of restarting gefitinib after its discontinuation in cases suspected of having gefitinib-induced ILD. We report a case with recurrent gefitinib-induced ILD, which suggests that re-administration of gefitinib should be considered cautiously in patients who have previously developed gefitinib-induced ILD.

Background: Accurate staging of mediastinal and hilar lymph nodes is a critical factor determining operability in patients with non-small cell lung cancer (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer (FDG-PET) has recently been reported to be more effective in detecting tumor involvement in mediastinal and hilar lymph nodes than computed tomography (CT). Objective: In this study, we analyzed the accuracy of FDG-PET in mediastinal and hilar lymph node staging in patients with NSCLC and the factors associated with false-positive or false-negative FDG-PET findings in mediastinal and hilar lymph node staging. Methods: Fifty-four patients with NSCLC who underwent preoperative analysis including chest CT and whole-body FDG-PET were evaluated retrospectively. Using FDG-PET, lesions were considered to be positive if a definite, localized area of higher uptake, excluding physiologic uptake, than in surrounding normal tissue was present. On CT findings, lymph nodes were considered to be positive if they were >10 mm in short-axis diameter, except subcarinal lymph nodes (#7), which were considered to be positive if they were >15 mm in short-axis diameter. All patients underwent surgical resection of primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our institute. Resected lymph nodes were histologically examined for the existence of tumor cells. Results: A total of 306 lymph nodes were resected and used for analysis. The sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55, 96, 55 and 96%, respectively. When pre-operative nodal staging was compared with post-operative histopathological staging, 44 patients (81%) were correctly staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39 patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary complications, including interstitial pneumonitis (n = 2), previous pulmonary tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were also undetectable by CT. Conclusion: FDG-PET is superior to CT in mediastinal and hilar lymph node staging of patients with NSCLC. However, care should be taken in lymph node staging for patients who have other pulmonary complications, including interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.

Survival outcomes of patients with multiple myeloma (MM) vary considerably depending on the presence or absence of disease-related risk factors [i.e., advanced ISS (International Staging System) stage, CAs (cytogenetic abnormalities), etc.], patient-related risk factors, and/or treatment-related risk factors. ISS, developed in 2006 by the IMWG (International Myeloma Working Group), has been considered an important disease-related baseline prognostication model and has been used in routine clinical practice worldwide. However, it is solely determined by the serum biochemistry data without taking account of CAs which are currently identified as the most powerful prognostic indicator for MM. Recently, a Revised ISS (R-ISS) scoring system which is accounting the presence or absence of serum LDH abnormality as well as CAs such as t(4;14), t(14;16), or del(17p) in addition to the ISS stage has been proposed (Oliva S, et al. EHA 2014, #S1289). In the present study, we applied the R-ISS to the Japanese MM patients diagnosed between 2001 and 2012 and compared the clinical relevance of the R-ISS with that of the original ISS in the era of novel agents and autologous stem cell transplantation (ASCT). Clinical data of 3,270 patients were collected from 38 centers; however, ISS and R-ISS were only applicable to 2,998 and 788 patients, respectively. Patient characteristics including age, gender, type of M protein, Durie and Salmon stage, ISS stage, and chromosomal abnormalities were not significantly different between the patients to which ISS and R-ISS were applied. In the 788 patients evaluable for the R-ISS analysis, distribution of the patients according to the ISS stages I, II, and III were 31.4%, 35.8%, and 32.8%, respectively, whereas that of the R-ISS stages were 22.2%, 67.6%, and 10.2%, respectively. Median overall survival (OS) for the ISS stages I, II, and III were 100.7, 65.2, and 50.9 months, respectively, and that of R-ISS stages I, II, and III were 152.8, 62.4, and 40.5 months, respectively. Accordingly, the difference of survival time between the stages seemed more distinct in R-ISS compared with the performance of the original ISS. According to the analysis by the ISS, there were no significant difference in the median OS between the patients whether initially treated with novel agents or with conventional chemotherapy (stage I, 91.2 vs 84.6 months, p=0.054; stage II, 64.1 vs 62.5 months, p=0.18; and stage III, 41.2 vs 37.2 months, p=0.24). In contrast, the analysis by the R-ISS disclosed a beneficial effect of novel therapy than with conventional chemotherapy, particularly in patients with stage I disease (stage I, not reached vs 87.6 months, p=0.018; stage II, 78.8 vs 61.7 months, p=0.075; and stage III, 37.5 vs 45.3 months, p=0.87). As for ASCT, both ISS and R-ISS stages showed a significant difference in the median OS between the patients treated with ASCT and those without ASCT (ISS stages: stage I, 101.3 vs 78.8 months, p=0.40; stage II, 83.8 vs 52.4 months, p=0.0002; stage III, 67.5 vs 31.7 months, p=0.0004; and R-ISS stages: stage I, not reached vs 90.7 months, p=0.21; stage II, 74.2 vs 56.5 months, p Disclosures Sunami: Takeda pharmaceutical Compani Limited: Research Funding; ONO PHAMACEUTICAL CO.,LTD: Research Funding.

Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) are more likely to face severe adverse events and/or insufficient dose intensity when treated with R-CHOP. The International Prognostic Index (IPI) predicts treatment outcome of patients with DLBCL, but risk stratification for such patients remains uncertain. Thus, we developed a new decision making model, which serves as a guide to the optimal personalized therapy for elderly DLBCL. Patients and methods This is a multicenter, retrospective study conducted by Society of Lymphoma Treatment in Japan (SoLT-J). Clinical features and treatment records of patients aged ≥ 65-years old, who had been diagnosed with de novo DLBCL and given at least one cycle of R-CHOP between 2001and 2012, were collected and analyzed for their prognostic significance after receiving approval from each institutional review board. Charlson Comorbidity Index (CCI) (Charlson et al, 1987) was used to access the co-existing medical status. Relative dose intensity (RDI) (i.e. the percentage of actual dose administered per protocol specified dose) for the average of cyclophosphamide and doxorubicin, adjusted by the effect of radiation therapy, was calculated for all patients. Results A total of 633 patients with a median 75-years old (range 65-96) treated with a median 6 cycles of R-CHOP (range 1-8) was analyzed. Ninety-six (15%) patients received planned or additional radiation therapy. R-CHOP therapy was discontinued in 129 (20%) patients because of treatment related toxicities, of which 30 (5%) patients died. The advanced age, hypoalbuminemia, and high score of CCI were identified as independent prognostic factors by the backward stepwise analysis for survival. The multivariate Cox regression analysis revealed that age > 75-years, serum albumin concentration < 3.7 g/dl, and CCI score ≥ 3 were significantly associated with worse overall survival (OS), progression free survival (PFS), and treatment related mortality (TRM), independently of IPI score ≥ 3 (Table 1). Regarding the index consisting of these three new risk factors, 135, 270, 184 and 44 patients were scored 0, 1, 2, and 3 point(s), respectively. The elevation of this score was significantly associated with lower average RDI (72% vs 63% vs 48% vs 41%, P < .0001) and more frequent unanticipated discontinuance of the treatment (10% vs 16% vs 31% vs 34%, P < .0001). Accompanied by IPI score ≥ 3, this index discriminated five risk groups with 3-year OS of 88%, 79%, 59%, 38%, and 6% (P < .0001), respectively (Figure 1). Conclusion The combination of age, serum albumin concentration, and comorbidities predicts adherence to R-CHOP-and outcome, as well as the IPI-in elderly patients with DLBCL. This prognostic model may help physicians to decide the intensity of the treatment, and needs to be validated further. Table 1. Multivariate analysis for overall survival, progression free survival, and treatment related mortality. OS PFS TRM Prognostic Factor HR P HR P HR P Age > 75-years 2.16 Disclosures Miura: CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; Meiji Seika Pharma: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene K.K.: Honoraria; Astellas Pharma Inc.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria. Miyake:CHUGAI PHAMACEUTICAL CO., LTD: Honoraria. Masaki:Celgene K.K: Honoraria; TAIHO Phamaceutical Co., Ltd: Research Funding; Asahi Kasei Pharma Corporation: Research Funding; ONO PHAMACEUTICAL CO., LTD: Research Funding; SHIONOGI & CO., LTD: Research Funding; Sumitomo Dainippon pharma Co., Ltd: Research Funding; TEIJIN PHARMA LIMITED: Research Funding; Kyowa Hakko Kirin Company, Limited: Honoraria, Research Funding; Takeda pharmaceutical Compani Limited: Honoraria, Research Funding; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria, Research Funding; Astellas pharma Inc: Research Funding; Eisai Co., Ltd: Honoraria, Research Funding. Sakai:Kyowa Hakko Kirin Company, Limited: Research Funding; Bayer Yakuhin,Ltd: Honoraria; Bristol-Myers Company: Honoraria; FUJIFILM RI Pharma Co., Ltd: Honoraria; Eisai Co., Ltd: Honoraria, Research Funding; SHIONOGI & CO., LTD: Honoraria; Sumitomo Dainippon pharma Co., Ltd: Honoraria; YakuLt Honsya Co., Ltd: Honoraria, Research Funding; Takeda pharmaceutical Compani Limited: Honoraria, Research Funding; Celgene K.K: Honoraria; TAIHO Phamaceutical Co., Ltd: Honoraria, Research Funding; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria, Research Funding. Sunami:Takeda pharmaceutical Compani Limited: Research Funding; ONO PHAMACEUTICAL CO., LTD: Research Funding. Aoyama:Mochida Pharmaceutical Co., Ltd: Honoraria; Kyowa Hakko Kirin Company, Limited: Honoraria; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria. Hatta:CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; Celgene K.K.: Honoraria. Kanno:Nippon Kayaku Co., Ltd: Research Funding; TAIHO Phamaceutical Co., Ltd: Research Funding; Merck Serono Japan: Honoraria; FUJIFILM RI Pharma Co., Ltd: Honoraria; Mochida Pharmaceutical Co., Ltd: Honoraria; Kyowa Hakko Kirin Company, Limited: Honoraria; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria.

Defects in human leukocyte antigen (HLA) class I expression may allow tumor cells to escape immune recognition. T cell infiltration is associated with a good prognosis in many cancers. However, the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM) has not been fully analyzed. In the present study, we investigated the immune profiles and conducted outcome analyses of MPM patients. HLA class I expression and TILs (CD4(+), CD8(+), and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. The expression of HLA class I was positive in all patients. There was no case that showed negative HLA class I expression. The density of CD4(+) and CD8(+) TILs were strongly correlated (R = 0.76, p0.001). A high density of CD8(+) TILs was a significantly better prognostic factor for the survival of patients with extrapleural pneumonectomy (p0.05). Multivariate analysis revealed that a high density of CD8(+) TILs is an independent prognostic factor for patients who underwent extrapleural pneumonectomy. The presence of intratumoral CD8(+) T cells was correlated with an improved clinical outcome, raising the possibility that CD8(+) T cells might play a pivotal role in the antitumor immune response against MPMs. Thus, the stimulation of CD8(+) lymphocytes might be an efficacious immunotherapy for MPM patients.

Combination chemotherapy comprising amrubicin and vinorelbine as a second-line therapy for advanced non-small cell lung cancer (NSCLC) has not been fully evaluated. To determine the maximum tolerated dose (MTD) and recommended dose (RD), the present phase I study examined patients with advanced NSCLC.The subjects were nine patients with histologically confirmed advanced NSCLC, Eastern Cooperative Oncology Group performance status 0-1, prior platinum-based first-line chemotherapy, and measurable or evaluable lesions. Treatment consisted of five dose levels, with amrubicin 35-45 mg/m2 administered as a 5-min intravenous infusion on days 1-3 and vinorelbine 15-25 mg/m2 given as a 1-h intravenous infusion on days 1 and 8, every 3 weeks.All patients had received carboplatin and paclitaxel as first-line therapy. Dose-limiting toxicity (DLT) was seen in two of six patients (febrile neutropenia and deep vein thrombosis ) at level 1, allowing us to conduct level 2. At level 2, all three patients experienced DLT (leucopeniaor =4 days in one patient; febrile neutropenia in three patients; and infection in two patients), and this level was determined as the MTD. Subsequently, level 1 (amrubicin 35 mg/m2 and vinorelbine 15 mg/m2) was defined as the RD. Responses in the nine patients included a partial response in one patient and stable disease in four patients.As second-line therapy, the RD of the combination of amrubicin and vinorelbine is 35 mg/m2 and 15 mg/m2, respectively. Further study should proceed to clarify the efficacy of this regimen.

Introduction A significant progress in the management of multiple myeloma (MM) has been made in recent years by the introduction of novel treatment modalities including high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) and novel drugs such as proteasome inhibitors and immunomodulatory drugs (IMiDs). Nevertheless, MM is still an incurable disease with various complications, and it is not clear whether these approaches contribute to the improvement of patient outcomes in routine practice. Previously, the Japanese Society of Myeloma surveyed the clinical features of 1383 patients with MM diagnosed and treated between January 1990 and December 2000. In the present study, we conducted a multicenter retrospective study to evaluate the treatment outcome and prognostic factors in the era of novel agents in Japan involving 2593 new patients diagnosed and treated after December 2000. Patients and Methods We analyzed 2593 patients with symptomatic MM newly diagnosed in the period between January 2001 and December 2012 at the affiliated hospitals of the Japanese Society of Myeloma. This study was conducted in accordance with the institutional guidelines with approval of the local institutional review board. There were 1342 males and 1251 females. The median age was 66 (range 26-96) years; 21% were older than 75 years. The type of monoclonal immunoglobulin was IgG in 1547 patients, IgA in 488, light chain only in 399, IgD in 72, and others in 87, respectively. Performance status (PS) of 0, 1, ≥2, and unknown were 340, 657, 756, and 840 patients, respectively. Durie & Salmon stage was as follows: 8.4% had Stage I, 25.5% Stage II, and 66.1% Stage III, respectively. As for the International Staging System (ISS) stages, 28.0% had stage I, 38.0% stage II, and 34.0% stage III, respectively. Cytogenetic abnormalities were detected in 24.9% of the patients. Initial therapy was composed of conventional chemotherapy in 45.6%, novel agents such as bortezomib-based or IMiDs-based regimens in 20.6%, conventional chemotherapy + ASCT in 20.4%, and novel agents (mainly bortezomib) + ASCT in 12.8% of the patients, respectively. Results The median overall survival (OS) was 63.8 and 62.5 months in the 2001-2005 cohort and in the 2006-2012 cohort, respectively, which was significantly improved compared with our previous results of 38.9 months in the 1990-2000 cohort. The median OS tended to be shorter according to the patient age (97.3, 79.7, 56.9, and 44.6 months in the patients aged Conclusion In comparison with our previous survey, the current study confirmed the recent improvement of the treatment outcome and the impact of both novel agents and ASCT as initial therapy on the outcome. The use of novel agents as salvage therapy could have also provided additional survival benefit. However, the prognosis of elderly patients remains unaltered, and alternative approaches are needed to improve the outcome of elderly patients with MM. Disclosures No relevant conflicts of interest to declare.

Objective: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. Methods: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m 2 and escalated in 10 mg/m 2 increments. Results: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m 2 ) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m 2 . Nine of 21 (42.9%) patients demonstrated a therapeutic response. Conclusion: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m 2 of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was

We report a case of a 71-year-old man who presented with cerebellar dysfunction. He was diagnosed as having squamous cell carcinoma of the lung (T2N3M0, Stage IIIB). No anti-onconeural antibodies were found in his serum. Cerebral spinal fluid (CSF) examination showed mild mononuclear pleocytosis alone. Magnetic resonance imaging (MRI) of the brain and spinal cord revealed no abnormalities. At autopsy, there was complete disappearance of Purkinje cells with reactive astrocytosis. These findings are compatible with paraneoplastic cerebellar degeneration (PCD). To our knowledge, no case of PCD has been reported previously in patients with squamous cell carcinoma of the lung.

A total of 411 patients (median age 64) consisting of 203 in Group A and 208 in Group B were enrolled. Before treatment, early HNSCC were detected 2(1%) in Group A, and 7(3%) in Group B. Mean observation period of all patients was 1165 days (range: 180-3768), (Group A:1273, Group B: 1060, p 0.001). Metachronous HNSCC was detected 6 lesions in 5 patients (2%) in group A and 16 lesions in 12 (6%) in Group B (p 0.13), however, most of lesions in Group B were early stage (clinical stage I or II: 4 (67%) in A, 15 (94%) in B, p 0.16). In Group B, all HNSCC except for a case of stage IV were diagnosed with NBI endoscopy during follow up examination, and 12 (76%) of them treated with ER. After treatment for HNSCC, 2 of 5 patients (40%) in Group A and none in group B lost laryngeal function (p 0.07). Furthermore, 5 of 203 patients (2%) in Group A and one of 208 (0.5%) in Group B were dead with HNSCC (p 0.11). Conclusions: After the commencement of screening for HN region using NBI endoscopy, detection of early HNSCC was increased and events related to metachronous advanced HNSCC in patients with ESCC were decreased compared with before commencement, however the difference did not reach statistically significant.

[Background] CD133 is a membrance glycoprotein with five transmembrance loops. Previous reports have suggested that CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal abilities has biological features as a cancer stem cell. In addition, it has been reported that the presence of CD133-positive cells was associated with a significantly poorer prognosis compared with the CD133-negative cells in some solid tumors, including colon cancer, hepatocellular carcinoma and glioma. However, little is known about the relationship between the expression of CD133 and clinical and clinicopathological characteristics in lung cancer. [Aim and Method] We conducted immunohistochemical assessment of 161 surgically resected non-small cell lung cancers (NSCLCs) at Hokkaido University Hospital between 1982 and 1994 to evaluate the correlation between CD133 expression and various features, including clinical and clinicopathological characteristics. [Results] Normal alveoli were used as negative controls and Bowman's capsule basement membrane as positive controls. CD133 expression was significantly correlated with advanced p-Stage (p=0.040). The Kaplan-Meier method demonstrated that NSCLC patients with CD133 expression in tumor cells showed poor prognosis compared to those without CD133 expression in p-Stage II, III and IV (p=0.0098). CD133 expression alone was an independent factor for unfavorable prognostic in those patients (Hazard Ratio=3.157, p=0.015). [Conclusion] CD133 expression was correlated with p-Stage and was an independent factor for unfavorable prognosis in patients with p-Stage II, III and IV NSCLCs. CD133 expression may be a novel prognostic marker for NSCLCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4118. doi:10.1158/1538-7445.AM2011-4118

[Background and Aim] Notch3 is a member of the Notch signaling pathway, which plays an important role in cancer development. We have already demonstrated that Notch3 is over-expressed in approximately 40% of lung cancer tumors and that inhibition of the Notch3 pathway by γ-secretase-inhibitor (GSI) induces apoptosis and suppresses tumor growth in lung cancer. Although a previous report has shown that radiation enhanced Notch1 expression in breast cancer, little is known about the relationship between radiation and Notch pathway. In this study, we attempt to elucidate the combined effect of GSI and radiotherapy in lung cancer. [Results] We used two Notch3-expressing lung cancer cell lines (HCC2429 and H460). In a MTT proliferation assay and clonogenic assay, combination of GSI and radiation suppressed the growth of lung cancer cells and colony formations compared to GSI or radiation alone. We also showed that GSI down-regulates Notch3 expression in a dose dependent manner, and radiation up-regulates Notch expression and downstream Notch target gene, Hey-1. Notch up-regulation by radiation is down-regulated by the combination. Combination of GSI and radiation reduced p-Bcl2, Bcl-XL and p-Erk compared to GSI or radiation alone, whereas no effect on p-Akt level was seen.[Conclusion] Our results suggest that combination of GSI and radiation may be clinical potential strategy in the treatment of patients with lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4137.

Purpose: Defect in human leukocyte antigen (HLA) class I expression may provide tumor cell with a mechanism to escape immune recognition, while T-cell infiltration is associated with good prognosis in many cancers. However, little has been known about the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM). In this study, we investigated the immune profile and conducted outcome analyses in MPM patients. Experimental Design: HLA class I expression and TILs (CD4+, CD8+, and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. Results: The expression of HLA class I was positive in 33 patients (75%) and heterogenous in 11 patients (25%). There was no case that showed negative HLA class I expression. The density of CD4+ and CD8+ TILs were strongly correlated (R = 0.76, p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4784.

Intracranial lipomas are very rare and reports of infantile lipomas are scarce. Nine cases of intracranial lipomas, five in infants and four in adults are described and characteristic findings of the CT are presented. Two of the six cases involved lipomas at the corpus callosum that were associated with frontal dysraphism and cranium bif idum at the midline of frontal region. Five of the nine cases involved lipomas at the quadrigeminal cistern. In one case with an advanced enlargement in circumference of the head in the pen-natal period, a V-P shunt was conducted for obstructive hydrocephalus. Ano-ther case had widely ranging agenesis of the corpus callosum associated with an interhemispheric cyst showing the right sided parietal and occipital lobes through the callosal agenesis. One of the nine cases had a lipoma in the left sylvian fissure and in the adult was in the interpeduncular cistern. Four of the nine cases were associated with agenesis of the corpus callosum. Based on these cases and published reports, the CT features of intracranial lipoma are discussed.

BackgroundGefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments.MethodWe retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response.ResultsThe best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments.ConclusionPatients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders.