Akiyoshi Kasuga

Kyorin University, Edo, Tokyo, Japan

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Publications (28)83.76 Total impact

  • No preview · Article · Sep 2015

  • No preview · Article · Sep 2015
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    ABSTRACT: Background Trametinib is an inhibitor of MEK1/MEK2 activation and kinase activity. In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results. Methods In part 1, 13 patients with advanced solid tumors were enrolled into 3 dose cohorts, receiving trametinib once daily at a dose of 1.0, 2.0, or 3.0 mg. In part 2, 5 patients with pancreatic cancer received trametinib (2.0 mg once daily) in combination with gemcitabine (1000 mg/m(2)). Results In part 1, a dose-limiting toxicity was observed in a patient in the 2.0-mg dose cohort, but the maximum tolerated dose was not reached at doses up to 3.0 mg daily. The best overall response was a PR in 1 patient, and 6 patients had SD. In part 2, the combination of trametinib and gemcitabine was tolerated for a short period of time. However, serious interstitial lung disease (ILD) was observed in 3 of 5 patients 4 weeks or more after the start of the treatment, including 1 fatal case. Three patients achieved a PR, and 2 patients had SD. The most common adverse event was rash (85 % in part 1 and 100 % in part 2). Conclusions Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.).
    No preview · Article · Aug 2015 · Investigational New Drugs
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    ABSTRACT: The purpose of this study was to assess the efficacy and safety of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) in patients with gemcitabine (GEM)-refractory pancreatic cancer (PC) and to explore independent variables associated with survival. We retrospectively reviewed consecutive patients with GEM-refractory PC who received FGS at our institution from March 2009 to December 2013. GEM was administered by fixed dose rate intravenous infusion of 1,200 mg/m(2) as a 120-min infusion on day 1, and S-1 was administered orally twice a day at a dose of 40 mg/m(2) on days 1-7. Cycles were repeated every 14 days. Sixty-one patients with GEM-refractory PC received FGS. Sixteen patients received FGS as third-line treatment. Twenty-nine patients (48 %) had a history of S-1 administration. The objective response rate was 13 %, and the disease control rate was 49 %. The median progression-free survival time was 2.7 months, and the median overall survival time was 6.0 months. Major Grade 3 or 4 adverse events included neutropenia (15 %), diarrhea (3 %), anorexia (2 %), and fatigue (2 %). A high inflammation-based prognostic score (modified Glasgow prognostic score (mGPS), which incorporates C-reactive protein and albumin), a performance status >0, and serum carbohydrate antigen 19-9 level >2,000 IU/ml were independently associated with a poor outcome. FGS might be effective and well tolerated as salvage chemotherapy in a practical setting. The inflammation-based prognostic score is a simple and reliable indicator of survival in the setting of salvage chemotherapy.
    No preview · Article · Dec 2014 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n=85), stomach (n=70), small bowel (n=6), colorectum (n=31), hepato-biliary system (n=31), and pancreas (n=31). Median overall survival (OS) was esophagus (13.4), stomach (13.3), small bowel (29.7), colorectum (7.6), hepato-biliary system (7.9), and pancreas (8.5) months. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n=160/46), the response rate was 50%/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs. HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35–0.97) and baseline serum lactate dehydrogenase (LDH) levels (not elevated vs. elevated; HR 0.65, 95% CI 0.46–0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48–1.33; p=0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated LDH levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176.This article is protected by copyright. All rights reserved.
    Preview · Article · Jun 2014 · Cancer Science

  • No preview · Article · Oct 2013 · Journal of Geriatric Oncology
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    ABSTRACT: To clarify the effectiveness and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of pancreatic cancer (PC). Patients who were diagnosed with unresectable, locally advanced or metastatic PC between February 2006 and September 2011 were selected for this retrospective study. FNA biopsy for pancreatic tumors had been performed percutaneously under extracorporeal ultrasound guidance until October 2009; then, beginning in November 2009, EUS-FNA has been performed. We reviewed the complete medical records of all patients who met the selection criteria for the following data: sex, age, location and size of the targeted tumor, histological and/or cytological findings, details of puncture procedures, time from day of puncture until day of definitive diagnosis, and details of severe adverse events. Of the 121 patients who met the selection criteria, 46 had a percutaneous biopsy (Group A) and 75 had an EUS-FNA biopsy (Group B). Adequate cytological specimens were obtained in 42 Group A patients (91.3%) and all 75 Group B patients (P = 0.0192), and histological specimens were obtained in 41 Group A patients (89.1%) and 65 Group B patients (86.7%). Diagnosis of malignancy by cytology was positive in 33 Group A patients (78.6%) and 72 Group B patients (94.6%) (P = 0.0079). Malignancy by both cytology and pathology was found in 43 Group A (93.5%) and 73 Group B (97.3%) patients. The mean period from the puncture until the cytological diagnosis in Group B was 1.7 d, which was significantly shorter than that in Group A (4.1 d) (P < 0.0001). Severe adverse events were experienced in two Group A patients (4.3%) and in one Group B patient (1.3%). EUS-FNA, as well as percutaneous needle aspiration, is an effective modality to obtain cytopathological confirmation in patients with advanced PC.
    Full-text · Article · Apr 2013 · World Journal of Gastroenterology
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    ABSTRACT: Background This study aims to evaluate the safety and efficacy of simultaneous endoscopic submucosal dissection (ESD) for synchronous double early gastric cancers. Methods We retrospectively evaluated 832 single gastric cancers from 789 patients treated by single ESD (single group) and 124 synchronous double cancers from 62 patients treated by simultaneous ESD (simultaneous group). Results The overall rate of en bloc resection and curative resection was comparable between the two groups. Procedure time was significantly longer in the simultaneous group than in the single group (131.0 ± 66.5 and 94.8 ± 64.1 min, respectively, P < 0.001). White blood cell count on the day after ESD was significantly higher in the simultaneous group (9310 ± 2774/μl) than in the single group (8633 ± 2341/μl) (P = 0.032). Length of fasting period after ESD was 1.1 ± 0.5 days in the single group and 1.4 ± 1.1 days in the simultaneous group (P = 0.082). Complications were more frequent in the simultaneous group than in the single group (11.3 vs. 5.4 %, respectively), but the difference was not significant (P = 0.082). Complication rate per one lesion did not differ between the two groups (5.6 vs. 5.4 %, respectively, P = 0.914). Multivariate analysis showed procedure time longer than 150 min was independently predictive for complications of simultaneous ESD (P < 0.042, odds ratio = 6.094). Large tumors, upper portion location and tumors not in the standard guideline criteria were significantly associated with long procedure time. Conclusions Simultaneous ESD for synchronous early gastric cancer can be a feasible and safe option, and it can reduce hospital stay. These results need to be validated by further studies.
    No preview · Article · Nov 2012 · Gastric Cancer
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    ABSTRACT: Objective: To clarify the prognostic factors for patients with obstructive jaundice due to advanced colorectal and gastric cancers who had undergone percutaneous transhepatic biliary drainage. Methods: Baseline variables and clinical outcomes were evaluated for 92 consecutive patients treated with percutaneous transhepatic biliary drainage. Results: Of the 92 patients, 32 (35%) had colorectal cancer and the remaining 60 (65%) had gastric cancer. Percutaneous transhepatic biliary drainage was successfully achieved in 74 (80%) patients, and 39 of them could receive subsequent chemotherapy. The median survival after percutaneous transhepatic biliary drainage was 273 days in the 39 patients who had undergone successful percutaneous transhepatic biliary drainage and subsequent chemotherapy, 65 days in 35 patients who had undergone successful percutaneous transhepatic biliary drainage but who had not received subsequent chemotherapy and 34 days in the remaining 18 patients who had undergone unsuccessful percutaneous transhepatic biliary drainage (P < 0.001). Multiple liver metastases and hepatic hilar bile duct stricture were independently associated with unsuccessful percutaneous transhepatic biliary drainage. Poor performance status, multiple liver metastases, presence of ascites, multiple prior chemotherapy administrations, undifferentiated type histology and high serum CA19-9 level were independently associated with a poor prognosis. A prognostic index calculated based on the number of these six factors was used to classify the patients into a good-risk group (index ≤2) (n = 56) and a poor-risk group (index ≥3) (n = 36). The median survival time and 2-month survival rate for the two groups were 163 and 44 days, respectively, and 85.7 and 33.3%, respectively (P < 0.001). Conclusions: As regards the introduction of percutaneous transhepatic biliary drainage in patients with obstructive jaundice due to colorectal and gastric cancers, careful patient selection might be necessary. A prognostic model seems to be useful for making decisions as to whether percutaneous transhepatic biliary drainage is indicated for particular patients.
    Preview · Article · Oct 2012 · Japanese Journal of Clinical Oncology

  • No preview · Conference Paper · Oct 2012

  • No preview · Article · Oct 2012 · Gan to kagaku ryoho. Cancer & chemotherapy

  • No preview · Conference Paper · Oct 2012
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    ABSTRACT: The aim of this study was to elucidate characteristics of gastric lesions that are initially diagnosed as low-grade adenomas and to establish appropriate treatment. We retrospectively reviewed 231 lesions initially diagnosed as gastric adenomas. All forceps biopsy samples were histologically diagnosed as category 3 low-grade adenomas according to the revised Vienna Classification. All patients underwent endoscopic resection with endoscopic findings and post-resection diagnoses evaluated subsequently. Sixty-three lesions were initially diagnosed as depressed adenomas, and 168 lesions were diagnosed as protruding adenomas. The depressed lesions were significantly smaller (11.6 ± 5.0 mm) than the protruding lesions (17.0 ± 10.8 mm) (P < 0.001). Diagnoses reclassified to category 4 mucosal high-grade neoplasia (i.e. high-grade adenoma, adenocarcinoma in adenoma and adenocarcinoma) were more frequent among depressed lesions (52.4%) than among protruding lesions (31.0%) (P = 0.004). Multivariate analysis of all 231 lesions showed that lesion size larger than 20 mm (P < 0.001) and depressed appearance (including central depression) (P < 0.001) were significant independent factors suggesting cancer. For the 168 protruding lesions, lesion size larger than 20 mm (P < 0.001) and central depression (P < 0.001) were significant independent factors suggesting cancer. For the 63 depressed lesions, lesion size larger than 15 mm (P = 0.016) and a moth-eaten appearance (P = 0.017) were significant independent factors in the pre-treatment diagnosis of cancer. Adenocarcinoma lesions were often found in depressed lesions and protruding lesions with central depression. Endoscopic resection for total biopsy is recommended, even if forceps biopsy indicates low-grade adenoma, as pre-treatment biopsy may be inadequate for an accurate histological diagnosis.
    No preview · Article · Sep 2012 · Digestive Endoscopy

  • No preview · Article · Jul 2012 · Digestive Endoscopy
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    ABSTRACT: Background and Aim: A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis. Methods: We investigated a total of 229 patients with rectal carcinoids. The relationship between each clinicopathological variable and the presence of lymph node metastasis was evaluated. Results: Tumor size (larger than 10 mm), presence of central depression, depth of tumor invasion, lymphatic invasion, and venous invasion were significantly associated with the incidence of lymph node metastasis (P < 0.001). Multivariate analysis revealed that tumor size (odds ratio: 63.3, P < 0.001) and venous invasion (odds ratio: 40.9, P < 0.001) were independently predictive of lymph node metastasis. In 204 patients with small (no larger than 10 mm) tumors, 10 patients had lymph node metastasis. All 10 tumors had low proliferation values indicated by mitosis and Ki-67 index. Multivariate analysis for the 204 patients revealed that only venous invasion was independently associated with metastasis (odds ratio: 40.1, P < 0.001). Five-year disease free survival rates of the total patients with metastasis and without metastasis were 81.1% and 95.5%, respectively (P < 0.001, log-rank test). Conclusions: Venous invasion as well as tumor size and lymphatic invasion indicates high malignant potential to metastasize to lymph node and would provide useful information in considering the addition of radical surgery. Postoperative pathological examinations of specimens obtained by local resection are very important to avoid underestimation.
    No preview · Article · Jun 2012 · Journal of Gastroenterology and Hepatology
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    ABSTRACT: The purpose of chemotherapy in patients with advanced solid cancers, including biliary tract cancer, is generally to improve the survival and quality of life of the patients. Also, adjuvant chemotherapy is expected to increase the curability of surgery in patients scheduled to undergo surgery. Most patients with unresectable biliary tract cancer develop obstructive jaundice, and biliary drainage is needed before any of the aforementioned treatments. Once jaundice is resolved by stenting of the bile duct or bilio-intestinal bypass, cholangitis often develops, leading to rapid deterioration of the patient's general condition. Therefore, the beneficial effect of chemotherapy in such patients remains controversial. A few randomized controlled trials have demonstrated the survival benefit of chemotherapy as compared with supportive care. In one of these trials, improvement of the quality of life was also confirmed. Recently, since the survival benefit of combined gemcitabine plus cisplatin therapy over gemcitabine alone has been demonstrated in randomized controlled clinical trials, this combined regimen has been recognized as a standard therapy for unresectable biliary tract cancer. A second-line regimen is now expected to be established for patients with gemcitabine-refractory biliary tract cancer, although the significance of second-line therapy remains unclear. One of the next issues in relation to chemotherapy for biliary tract cancer is the development of molecular-targeted agents; however, few large clinical trials of such agents have been conducted for biliary tract cancer. Various issues in chemotherapy for biliary tract cancer remain to be investigated, and global cooperation is necessary to conduct large clinical trials.
    No preview · Article · Mar 2012 · Journal of Hepato-Biliary-Pancreatic Sciences
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    ABSTRACT: Miriplatin is a platinum complex developed to treat hepatocellular carcinoma (HCC) through administration into the hepatic artery as a sustained-release formulation suspended in lipiodol. A single-institute pilot study was conducted to investigate the antitumor efficacy of miriplatin infusion therapy for small and multiple HCCs. Small HCCs sized 2 cm or less, judged to be inadequate for curative treatment, were indicated for transcatheter arterial miriplatin infusion therapy. We prospectively investigated the course of patients treated with miriplatin between March 2010 and September 2010. Efficacy was evaluated by computed tomography at 4-8 weeks and the overall evaluation was carried out more than 3 months after treatment. The study included 14 patients, of whom 13 were evaluable for efficacy. Of the 13 patients, one (8%) showed a complete response and three (23%) showed a partial response, with an overall response rate of 31%. Grade 3/4 hematological toxicity including thrombocytopenia was not seen. Increases to grade 3/4 in aspartate aminotransferase and alanine aminotransferase were observed for nonhematological toxicity. Irreversible deleterious changes in hepatic function were not seen. Miriplatin infusion therapy showed safe and moderate effects on small HCCs. However, transarterial chemoembolization as a standard therapy cannot be replaced. We await the results of an ongoing study of transarterial chemoembolization with miriplatin.
    No preview · Article · Feb 2012 · European journal of gastroenterology & hepatology
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    ABSTRACT: Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC. Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes. The rates of en bloc and curative resection were 99.0% (102/103) and 82.5% (85/103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6%) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19-92 months) and 36.0 months (range 9-92 months), the 3-and 5-year overall mortality rates were 1.9% and 3.9%, respectively, and the 3-and 5-year overall disease-free survival rates were both 96.7%. Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes.
    No preview · Article · Feb 2012 · Endoscopy
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    ABSTRACT:   The diagnostic use of magnification endoscopy with narrow-band imaging (ME-NBI) to assess histopathologically undifferentiated-type early gastric cancers (UD-type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME-NBI images and histopathological findings in UD-type EGCs.   We analyzed 78 consecutive cases of UD-type EGCs ≤ 20 mm in diameter that underwent ME-NBI ≤ 2 weeks prior to resection. The ME-NBI images were compared with histopathological findings following either endoscopic submucosal dissection (ESD) or surgery. Applying the comparative results, we prospectively evaluated the success of identifying the lateral extent of UD-type EGCs resected by ESD in additional consecutive cases.   Lesions with preserved but irregular surface microstructures (S-type based on ME-NBI) showed mucosal atrophy and corresponded histologically to the non-whole-layer type of intramucosal cancer (24/24, 100%). Lesions with an irregular microvasculature type (V-type, for example, corkscrew pattern) or mixed type upon ME-NBI corresponded histopathologically to the non-whole-layer type of intramucosal cancer (15/54, 27.8%), the whole-layer type of intramucosal cancer (27/54, 50.0%) or submucosal (sm) invasion cancer (12/54, 22.2%). Applying these comparative results, we used ME-NBI to successfully predict the lateral extent of cancer, which corresponded to the histopathological lateral extent in all 18 additional consecutive UD-type EGCs resected by ESD.   ME-NBI images of UD-type EGCs were very closely related to the histopathological findings. Thus, ME-NBI can be useful in the pretreatment assessment of the histopathological patterns of cancer development and the lateral extent of such lesions.
    No preview · Article · Mar 2011 · Journal of Gastroenterology and Hepatology
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    ABSTRACT: Endoscopic ultrasonography (EUS) has become a reliable method for predicting the invasion depth of early gastric cancer (EGC). This study evaluated the accuracy of EUS in identifying lesions meeting expanded-indication criteria for endoscopic submucosal dissection (ESD) and analyzed clinicopathologic factors influencing the diagnostic accuracy of EUS in assessing tumor invasion depth. This study investigated 542 EGCs of 515 patients who underwent EUS pretreatment. The pretreatment EUS-determined diagnosis was compared with the final histopathologic evaluation of resected specimens, and the impact of various clinicopathologic parameters on diagnostic accuracy was analyzed. The diagnostic accuracy of EUS in identifying lesions meeting expanded-indication criteria for ESD was 87.8% (259/295) for differentiated adenocarcinoma (D-type) 30 mm in diameter or smaller, 43.5% (10/23) for D-type tumor larger than 30 mm in diameter, and 75% (42/56) for undifferentiated adenocarcinoma (UD-type) 20 mm in diameter or smaller. Using multivariate analysis, the diagnostic accuracy of EUS in predicting tumor invasion depth was determined to be decreased significantly by ulcerous change and large tumor size (diameter, ≥30 mm). For patients with EGC, D-type lesions 30 mm in diameter or smaller and UD-type lesions 20 mm in diameter or smaller can be diagnosed with high accuracy by EUS, but larger D-type lesions (diameter, >30 mm) should be considered carefully in terms of EUS-based treatment decisions. Findings of ulceration and large tumors are associated with incorrect diagnosis of tumor invasion depth by EUS.
    No preview · Article · Mar 2011 · Surgical Endoscopy

Publication Stats

246 Citations
83.76 Total Impact Points


  • 2012-2015
    • Kyorin University
      Edo, Tokyo, Japan
  • 2011-2012
    • Japanese Foundation for Cancer Research
      • Department of Urology
      Edo, Tōkyō, Japan
  • 2010
    • Funabashi Municipal Medical Center
      Hunabasi, Chiba, Japan
  • 2008
    • Chiba University
      • Department of Gastroenterology
      Tiba, Chiba, Japan
    • Chiba University Hospital
      Tiba, Chiba, Japan