2021/10/20 更新

写真a

イチカワ ヒロシ
市川 寛
ICHIKAWA Hiroshi
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 生体機能調節医学専攻 機能再建医学 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2014年3月   新潟大学 )

  • 学士(医学) ( 2004年3月   新潟大学 )

研究分野

  • ライフサイエンス / 消化器外科学

経歴(researchmap)

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 機能再建医学   助教

    2016年2月 - 現在

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  • 新潟大学   医歯学総合病院 消化器外科   助教

    2015年4月 - 2016年1月

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  • 新潟大学   医歯学総合病院 腫瘍センター   特任助教

    2013年9月 - 2015年3月

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  • 国立がん研究センター研究所   創薬プロテオーム研究分野   リサーチレジデント

    2012年4月 - 2013年3月

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  • 国立がん研究センター研究所   創薬プロテオーム研究分野

    2011年4月 - 2012年3月

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経歴

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 機能再建医学   助教

    2016年2月 - 現在

  • 新潟大学   医歯学総合病院 消化器外科   助教

    2015年4月 - 2016年1月

  • 新潟大学   医歯学総合病院 腫瘍センター   特任助教

    2013年9月 - 2015年3月

 

論文

  • Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer. 国際誌

    Kizuki Yuza, Masayuki Nagahashi, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakajima, Yoshifumi Shimada, Takashi Ishikawa, Jun Sakata, Shiho Takeuchi, Shujiro Okuda, Yasunobu Matsuda, Manabu Abe, Kenji Sakimura, Kazuaki Takabe, Toshifumi Wakai

    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract   25 ( 9 )   2231 - 2241   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations. METHODS: An in vitro study was performed to investigate the biological role of ACVR2A via CRISPR/Cas9-mediated ACVR2A knockout MKN74 human gastric cancer cells. One hundred twenty-four patients with gastric cancer were retrospectively analyzed, and relations between MSI status, ACVR2A mutations, and clinicopathological factors were evaluated. RESULTS: ACVR2A knockout cells showed less aggressive tumor biology than mock-transfected cells, displaying reduced proliferation, migration, and invasion (P < 0.05). MSI mutations were found in 10% (13/124) of gastric cancer patients, and ACVR2A mutations were found in 8.1% (10/124) of patients. All ACVR2A mutations were accompanied by MSI. The 5-year overall survival rates of ACVR2A wild-type patients and ACVR2A-mutated patients were 57% and 90%, respectively (P = 0.048). Multivariate analysis revealed that older age (P = 0.015), distant metastasis (P < 0.001), and ACVR2A wild-type status (P = 0.040) were independent prognostic factors for overall survival. CONCLUSIONS: Our study demonstrated that gastric cancer patients with ACVR2A mutation have a significantly better prognosis than those without. Dysfunction of ACVR2A in MKN74 human gastric cancer cells caused less aggressive tumor biology, indicating the importance of ACVR2A in the progression of MSI-H tumors.

    DOI: 10.1007/s11605-020-04889-9

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  • Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer. 国際誌

    Takuya Ando, Jun Sakata, Tatsuya Nomura, Kabuto Takano, Kazuyasu Takizawa, Kohei Miura, Yuki Hirose, Takashi Kobayashi, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Masayuki Nagahashi, Shin-Ichi Kosugi, Toshifumi Wakai

    Langenbeck's archives of surgery   406 ( 5 )   1521 - 1532   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS: Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS: Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION: The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

    DOI: 10.1007/s00423-021-02165-1

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  • Accuracy of the endoscopic evaluation of esophageal involvement in esophagogastric junction cancer. 国際誌

    Takeshi Sakai, Hiroshi Ichikawa, Takaaki Hanyu, Kenji Usui, Yosuke Kano, Yusuke Muneoka, Takashi Ishikawa, Yoshifumi Shimada, Jun Sakata, Toshifumi Wakai

    Annals of medicine and surgery (2012)   68   102590 - 102590   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Esophageal involvement length (EIL) is a promising indicator of metastasis or recurrence in mediastinal lymph nodes (MLNs) in adenocarcinoma of the esophagogastric junction (EGJ). This study aimed to elucidate the accuracy of the preoperative endoscopic evaluations of EIL and its clinical significance in this disease. Materials and methods: In total, 75 patients with Siewert type II (N = 53) or III (N = 22) adenocarcinoma of the EGJ, who underwent surgical resection without preoperative therapy between 1995 and 2016 were enrolled. We retrospectively examined the accuracy of the preoperative endoscopic evaluations of EIL (preoperative EIL), compared to the pathologically evaluated EIL. Finally, we investigated the association between preoperative EIL and metastasis or recurrence in MLNs. Results: The accuracy of the preoperative EIL within a 1-cm interval was only 53.3%. Among patients with discordance between the pre- and postoperative evaluations, 68.6 % had the underestimation in the preoperative EIL. pN1-3 (OR = 5.85, 95% CI: 1.03-33.17) and undifferentiated histologic type (OR = 2.52, 95% CI: 0.89-7.14) were potential risk factors for the discordance. Regarding metastasis or recurrence in MLNs, preoperative EIL of 2-3 cm (OR = 10.41, 95% CI: 1.35-80.11) and >3 cm (OR = 8.33, 95% CI: 1.09-63.96) were independent predictors. Conclusion: Although the accuracy of the endoscopic evaluations of EIL is insufficient with many underestimations, EIL should be assessed in preoperative staging because of significant predictive power for metastasis or recurrence in MLNs.

    DOI: 10.1016/j.amsu.2021.102590

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  • Histopathological characteristics and artificial intelligence for predicting tumor mutational burden-high colorectal cancer.

    Yoshifumi Shimada, Shujiro Okuda, Yu Watanabe, Yosuke Tajima, Masayuki Nagahashi, Hiroshi Ichikawa, Masato Nakano, Jun Sakata, Yasumasa Takii, Takashi Kawasaki, Kei-Ichi Homma, Tomohiro Kamori, Eiji Oki, Yiwei Ling, Shiho Takeuchi, Toshifumi Wakai

    Journal of gastroenterology   56 ( 6 )   547 - 559   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Tumor mutational burden-high (TMB-H), which is detected with gene panel testing, is a promising biomarker for immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC). However, in clinical practice, not every patient is tested for TMB-H using gene panel testing. We aimed to identify the histopathological characteristics of TMB-H CRC for efficient selection of patients who should undergo gene panel testing. Moreover, we attempted to develop a convolutional neural network (CNN)-based algorithm to predict TMB-H CRC directly from hematoxylin and eosin (H&E) slides. METHODS: We used two CRC cohorts tested for TMB-H, and whole-slide H&E digital images were obtained from the cohorts. The Japanese CRC (JP-CRC) cohort (N = 201) was evaluated to detect the histopathological characteristics of TMB-H using H&E slides. The JP-CRC cohort and The Cancer Genome Atlas (TCGA) CRC cohort (N = 77) were used to develop a CNN-based TMB-H prediction model from the H&E digital images. RESULTS: Tumor-infiltrating lymphocytes (TILs) were significantly associated with TMB-H CRC (P < 0.001). The area under the curve (AUC) for predicting TMB-H CRC was 0.910. We developed a CNN-based TMB-H prediction model. Validation tests were conducted 10 times using randomly selected slides, and the average AUC for predicting TMB-H slides was 0.934. CONCLUSIONS: TILs, a histopathological characteristic detected with H&E slides, are associated with TMB-H CRC. Our CNN-based model has the potential to predict TMB-H CRC directly from H&E slides, thereby reducing the burden on pathologists. These approaches will provide clinicians with important information about the applications of ICIs at low cost.

    DOI: 10.1007/s00535-021-01789-w

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  • Outcome of radical surgery for gallbladder carcinoma according to TNM stage: implications for adjuvant therapeutic strategies. 国際誌

    Kizuki Yuza, Jun Sakata, Yuki Hirose, Kohei Miura, Takuya Ando, Tomohiro Katada, Kazuyasu Takizawa, Takashi Kobayashi, Hiroshi Ichikawa, Yoshifumi Shimada, Masayuki Nagahashi, Toshifumi Wakai

    Langenbeck's archives of surgery   406 ( 3 )   801 - 811   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Outcomes following surgery for advanced gallbladder carcinoma remain unsatisfactory. This study aimed to determine the surgical outcome and effectiveness of adjuvant chemotherapy according to TNM stage in patients with gallbladder carcinoma. METHODS: A total of 200 patients undergoing surgery for gallbladder carcinoma were enrolled. Clinicopathological data were evaluated and surgical outcomes were compared between patients with and without adjuvant chemotherapy according to TNM stage. RESULTS: The 5-year overall survival (OS) after resection for patients with stage I (n = 27), IIA (n = 18), IIB (n = 28), IIIA (n = 25), IIIB (n = 43), IVA (n = 7), and IVB (n = 52) disease was 90.8%, 94.4%, 73.6%, 33.7%, 57.7%, 14.3%, and 11.8%, respectively (p < 0.001). R0 resection was performed in all patients with stage I or II disease, in 89.7% of those with stage III disease, and 69.5% of those with stage IV disease. For patients with stage III disease, adjuvant chemotherapy was associated with improved OS (5-year OS, 60.9% vs. 41.1%; p = 0.028) and was an independent prognostic factor (hazard ratio, 2.045; p = 0.039). For patients with stage IV disease, adjuvant chemotherapy appeared to affect OS (5-year OS, 25.1% vs. 5.3%; p = 0.041); R0 resection (hazard ratio, 1.882; p = 0.040) was the only independent prognostic factor. CONCLUSION: TNM stage clearly predicts survival after resection of gallbladder carcinoma. R0 resection with adjuvant chemotherapy is recommended for long-term survival in the multimodal management of patients with stage III or IV gallbladder carcinoma.

    DOI: 10.1007/s00423-020-02068-7

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  • NQO1 as a Marker of Chemosensitivity and Prognosis for Colorectal Liver Metastasis. 国際誌

    Yuki Hirose, Jun Sakata, Takashi Kobayashi, Kohei Miura, Kizuki Yuza, Mae Nakano, Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Hitoshi Kameyama, Toshifumi Wakai

    Anticancer research   41 ( 3 )   1563 - 1570   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIM: This study aimed to evaluate how NAD(P)H: quinone oxidoreductase-1 (NQO1) affects survival after hepatectomy in patients with colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A retrospective analysis was conducted of 88 consecutive patients who underwent hepatectomy for CRLM. Of the 88 patients, preoperative chemotherapy was administered to 30 patients. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody. RESULTS: NQO1-positive expression in tumor cells of CRLM was associated with worse overall survival (p=0.026) and was an independent adverse prognostic factor in multivariate analysis (hazard ratio=5.296, p=0.007). Among 30 patients who received preoperative chemotherapy, patients with loss of NQO1 expression in non-neoplastic epithelial cells of the bile ducts (NQO1 polymorphism: n=19) showed significantly better response to preoperative chemotherapy for CRLM (p=0.004). CONCLUSION: NQO1-positive expression in tumor cells of CRLM may be an adverse prognostic factor after hepatectomy for CRLM.

    DOI: 10.21873/anticanres.14916

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  • Oncological outcomes of surgery for recurrent biliary tract cancer: who are the best candidates? 国際誌

    Jun Sakata, Tatsuya Nomura, Takashi Aono, Chie Kitami, Naoyuki Yokoyama, Masahiro Minagawa, Kazuyasu Takizawa, Kohei Miura, Yuki Hirose, Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Takashi Kobayashi, Toshifumi Wakai

    HPB : the official journal of the International Hepato Pancreato Biliary Association   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease. METHODS: A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%). RESULTS: In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p < 0.001). Surgery was an independently prognostic factor (p < 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%). CONCLUSION: Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.

    DOI: 10.1016/j.hpb.2021.01.007

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  • Profiling of host genetic alterations and intra-tumor microbiomes in colorectal cancer. 国際誌

    Shujiro Okuda, Yoshifumi Shimada, Yosuke Tajima, Kizuki Yuza, Yuki Hirose, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Yiwei Ling, Nobuaki Miura, Mika Sugai, Yu Watanabe, Shiho Takeuchi, Toshifumi Wakai

    Computational and structural biotechnology journal   19   3330 - 3338   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Some bacteria are symbiotic in tumor tissues, and metabolites of several bacterial species have been found to cause DNA damage. However, to date, the association between bacteria and host genetic alterations in colorectal cancer (CRC) has not been fully investigated. We evaluated the association between the intra-tumor microbiome and host genetic alterations in 29 Japanese CRC patients. The tumor and non-tumor tissues were extracted from the patients, and 16S rRNA genes were sequenced for each sample. We identified enriched bacteria in tumor and non-tumor tissues. Some bacteria, such as Fusobacterium, which is already known to be enriched in CRC, were found to be enriched in tumor tissues. Interestingly, Bacteroides, which is also known to be enriched in CRC, was enriched in non-tumor tissues. Furthermore, it was shown that certain bacteria that often coexist within tumor tissue were enriched in the presence of a mutated gene or signal pathway with mutated genes in the host cells. Fusobacterium was associated with many mutated genes, as well as cell cycle-related pathways including mutated genes. In addition, the patients with a high abundance of Campylobacter were suggested to be associated with mutational signature 3 indicating failure of double-strand DNA break repairs. These results suggest that CRC development may be partly caused by DNA damage caused by substances released by bacterial infection. Taken together, the identification of distinct gut microbiome patterns and their host specific genetic alterations might facilitate targeted interventions, such as modulation of the microbiome in addition to anticancer agents or immunotherapy.

    DOI: 10.1016/j.csbj.2021.05.049

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  • [Long-Term Survival after Surgery with Postoperative Chemotherapy for Perihilar Cholangiocarcinoma with Residual Invasive Carcinoma at Ductal Resection Margins-A Case Report].

    Tomo Oiwa, Kohei Miura, Jun Sakata, Kizuki Yuza, Koji Toge, Yuki Hirose, Kazuyasu Takizawa, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakano, Masayuki Nagahashi, Yoshifumi Shimada, Takashi Ishikawa, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 13 )   1899 - 1901   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 64-year-old man with liver dysfunction was given a diagnosis of perihilar cholangiocarcinoma(Bismuth type Ⅳ). The tumor was predominantly right-sided and invaded to the bifurcation of the right and left portal veins. After confirming sufficient liver functional reserve and future liver remnant, the patient underwent extended right hepatectomy, extrahepatic bile duct resection, and portal vein resection and reconstruction. Intraoperative examination of frozen sections revealed the presence of residual invasive carcinoma on both the hepatic and duodenal sides of the ductal resection margins. However, we did not perform pancreaticoduodenectomy or additional resection of the margin-positive proximal bile duct considering the curability and invasiveness of these procedures. He received postoperative chemotherapy with biweekly gemcitabine plus cisplatin for 1 year, followed by gemcitabine monotherapy for 1 year, and S-1 monotherapy has been performed since then. He remains alive and well with no evidence of disease 63 months after surgery.

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  • [A Case of Umbilical Metastasis from Pancreatic Cancer after Surgery].

    Kazuyasu Takizawa, Jun Sakata, Hiroki Nagaro, Kizuki Yuza, Koji Toge, Yuki Hirose, Hirosuke Ishikawa, Natsuru Sudo, Kohei Miura, Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Takashi Kobayashi, Takashi Ishikawa, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 13 )   2409 - 2411   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    The patient was a 63-year-old woman with diagnosis of pancreatic cancer. Abdominal CT showed pancreatic head tumor and paraaortic lymph node metastasis. We performed chemotherapy with nab-paclitaxel plus gemcitabine. After 5 courses of chemotherapy, the tumor reduced in size. Pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1 was performed. Fourteen months after surgery, umbilical metastasis(Sister Mary Joseph's nodule: SMJN)was found in the umbilicus near the abdominal incisional hernia. There was no evidence of metastasis except in the umbilicus, we performed the umbilical tumor resection and abdominal incisional hernia repair. Pathological diagnosis was pancreatic cancer metastasis. Although following chemotherapy, multiple skin metastases was found in the lower abdomen 3 months after umbilical resection. We performed skin metastases resection to relieve pain and symptoms of bleeding. But she died 29 months after the initial therapy(7 months after umbilical resection).

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  • [A Case of a"Watch and Wait Therapy"Approach after Preoperative Chemoradiotherapy for Rectal Cancer Accompanied by Severe Emphysema].

    Yasuo Obata, Yoshifumi Shimada, Atsushi Ohta, Akio Matsumoto, Kana Tanaka, Hidehito Oyanagi, Mae Nakano, Masato Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Kazuyasu Takizawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 13 )   1960 - 1962   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 72-year-old man was referred to our hospital for treatment for rectal cancer. Digital rectal examination and colonoscopy revealed a 4 cm tumor located at the anterior rectal wall 5 cm away from the anal verge, and pathological examination confirmed that the tumor was adenocarcinoma. A computed tomography scan detected neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage Ⅱa rectal cancer. The preoperative general examination revealed bradyarrhythmia and severe emphysema, and he was considered to be high risk for general anesthesia. After placement of a pacemaker, preoperative capecitabine-based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. The digital rectal examination and imaging evaluation 4 weeks after preoperative CRT revealed that the tumor disappeared, and pathological examination showed no malignant findings. Considering the risks of general anesthesia, the"watch and wait therapy"approach was adopted with sufficient informed consent. At present, 15 months after preoperative CRT, no evidence of regrowth or distant metastasis has been detected under rigorous follow- up evaluations.

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  • [Amelanotic Malignant Melanoma of the Esophagogastric Junction-A Case Report].

    Ryota Magara, Yosuke Kano, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Yusuke Muneoka, Kohei Miura, Kazuyasu Takizawa, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Kaori Takamura, Hajime Umezu, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 13 )   2083 - 2085   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 73-year-old man presented with anemia, and gastroscopy showed a nonpigmented tumor in the esophagogastric junction. The result of the tumor biopsy initially suspected poorly differentiated adenocarcinoma. However, additional immunohistochemical examination revealed malignant melanoma. The final diagnosis was amelanotic malignant melanoma of the esophagogastric junction with adrenal and spinal metastasis. Although immunotherapy was performed, the patient died 132 days after diagnosis.

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  • A giant pelvic solitary fibrous tumor with Doege-Potter syndrome successfully treated with transcatheter arterial embolization followed by surgical resection: a case report. 国際誌

    Kizuki Yuza, Jun Sakata, Hiroki Nagaro, Takuya Ando, Yuki Hirose, Kohei Miura, Kazuyasu Takizawa, Takashi Kobayashi, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Masayuki Nagahashi, Shin-Ichi Kosugi, Toshifumi Wakai

    Surgical case reports   6 ( 1 )   299 - 299   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Solitary fibrous tumor (SFT), a mesenchymal fibroblastic tumor with a hypervascular nature, rarely develops in the pelvis. Resection of a giant SFT occupying the pelvic cavity poses an increased risk of developing massive hemorrhage during resection, although surgical resection is the most effective treatment method for this tumor to achieve a potential cure. SFT rarely develops with Doege-Potter syndrome, which is known as a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) secondary to SFT that secretes insulin-like growth factor-II (IGF-II). We present a case of a giant pelvic SFT with Doege-Potter syndrome, which was successfully treated with transcatheter arterial embolization (TAE) followed by surgical resection. CASE PRESENTATION: A 46-year-old woman presented with a disorder of consciousness due to refractory hypoglycemia. Images of the pelvis showed a giant and heterogeneously hypervascular mass displacing and compressing the rectum. Endocrinological evaluation revealed low serum levels of insulin and C-peptide consistent with NICTH. Angiography identified both the inferior mesenteric artery and the bilateral internal iliac artery as the main feeders of the tumor. To avoid intraoperative massive bleeding, super-selective TAE was performed for the tumor 2 days prior to surgery. Hypoglycemia disappeared after TAE. The tumor was resected completely, with no massive hemorrhage during resection. Histologically, it was diagnosed as IGF-II-secreting SFT. Partial necrosis of the rectum in the specimen was observed due to TAE. The patient was followed up for 2 years and no evidence of disease has been reported. CONCLUSIONS: Preoperative angiography followed by TAE is an exceedingly helpful method to reduce intraoperative hemorrhage when planning to resect SFT occupying the pelvic cavity. Complications related to ischemia should be kept in mind after TAE, which needs to be planned within 1 or 2 days before surgery. TAE for tumors may be an option in addition to medical and surgical treatment for persistent hypoglycemia in Doege-Potter syndrome.

    DOI: 10.1186/s40792-020-01076-5

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  • Clinical Utility of ypTNM Stage Grouping in the 8th Edition of the American Joint Committee on Cancer TNM Staging System for Esophageal Squamous Cell Carcinoma. 査読 国際誌

    Natsuru Sudo, Hiroshi Ichikawa, Yusuke Muneoka, Takaaki Hanyu, Yosuke Kano, Takashi Ishikawa, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Takeo Bamba, Satoru Nakagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Annals of surgical oncology   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. OBJECTIVE: This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. RESULTS: Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. CONCLUSIONS: ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

    DOI: 10.1245/s10434-020-09181-3

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  • ASO Author Reflections: ypTNM Stage Grouping in the 8th Edition of the AJCC Cancer Staging Manual Refines the Prognostic Prediction for Patients with Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy. 査読 国際誌

    Natsuru Sudo, Hiroshi Ichikawa, Yusuke Muneoka, Takaaki Hanyu, Yosuke Kano, Takashi Ishikawa, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Takeo Bamba, Satoru Nakagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Annals of surgical oncology   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1245/s10434-020-09184-0

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  • [A Case of High-Frequency Microsatellite Instability in Colorectal Cancer with MSH2 Mutation Detected Using Gene Panel Testing with a Next-Generation Sequencer]. 査読

    Yoshifumi Shimada, Hitoshi Kameyama, Mae Nakano, Chie Toshikawa, Kazuki Moro, Junko Tsuchida, Michiru Arabiki, Akio Matsumoto, Kana Tanaka, Kaoru Abe, Hidehito Oyanagi, Yosuke Tajima, Masato Nakano, Yuki Hirose, Yosuke Kano, Hiroshi Ichikawa, Takaaki Hanyu, Kazuyasu Takizawa, Masayuki Nagahashi, Jun Sakata, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   47 ( 7 )   1113 - 1115   2020年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.

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  • RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer. 査読 国際誌

    Akio Matsumoto, Yoshifumi Shimada, Mae Nakano, Hidehito Oyanagi, Yosuke Tajima, Masato Nakano, Hitoshi Kameyama, Yuki Hirose, Hiroshi Ichikawa, Masayuki Nagahashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Yiwei Ling, Shujiro Okuda, Toshifumi Wakai

    Oncology reports   43 ( 6 )   1853 - 1862   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutant-type were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., right-sided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/frameshift mutation compared with left-sided RNF43 mutant-type. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.

    DOI: 10.3892/or.2020.7561

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  • Primary lung squamous cell carcinoma and its association with gastric metastasis: A case report and literature review. 査読 国際誌

    Mariko Nemoto, Pankaj Prasoon, Hiroshi Ichikawa, Takaaki Hanyu, Yosuke Kano, Yusuke Muneoka, Kenji Usui, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Ishikawa, Masanori Tsuchida, Toshifumi Wakai

    Thoracic cancer   11 ( 6 )   1708 - 1711   2020年6月

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    記述言語:英語  

    Nearly 50% of primary lung carcinoma patients present with distant metastasis at their first visit. However, gastrointestinal tract (GIT) metastasis is an infrequent impediment. Herein, we report a case of progressive dysphagia and epigastralgia as an initial manifestation of recurrence as gastric metastasis of primary lung squamous cell carcinoma (SCC) after curative surgery. A 64-year-old man was diagnosed with primary lung SCC of the right lower lobe, and underwent thoracoscopic lower lobectomy. One year after lobectomy, computed tomography (CT) scan showed a gastric fundal mass located in the gastric cardia which measured 5 cm. Endoscopic biopsies and histopathology subsequently confirmed that tumor was SCC. The patient then underwent proximal gastrectomy with resection of the diaphragmatic crus. Following surgery, histopathological examination revealed gastric metastasis from primary lung SCC. KEY POINTS: Gastric metastasis of primary lung carcinoma is one of the rarest phenomena. Gastrointestinal symptoms should raise suspicion of the presence of advanced metastatic disease with poor prognosis.

    DOI: 10.1111/1759-7714.13410

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  • XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary. 査読 国際誌

    Ryo Tamura, Kosuke Yoshihara, Hirofumi Nakaoka, Nozomi Yachida, Manako Yamaguchi, Kazuaki Suda, Tatsuya Ishiguro, Koji Nishino, Hiroshi Ichikawa, Keiichi Homma, Akira Kikuchi, Yutaka Ueda, Yuji Takei, Hiroyuki Fujiwara, Teiichi Motoyama, Shujiro Okuda, Toshifumi Wakai, Ituro Inoue, Takayuki Enomoto

    Oncogene   39 ( 17 )   3541 - 3554   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.

    DOI: 10.1038/s41388-020-1237-0

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  • Long-Term Trends in Respiratory Function After Esophagectomy for Esophageal Cancer. 査読

    Otani T, Ichikawa H, Hanyu T, Ishikawa T, Kano Y, Kanda T, Kosugi SI, Wakai T

    The Journal of surgical research   245   168 - 178   2020年1月

  • Genetic profiling for diffuse type and genomically stable subtypes in gastric cancer. 国際誌

    Yiwei Ling, Yu Watanabe, Mayuki Nagahashi, Yoshifumi Shimada, Hiroshi Ichikawa, Toshifumi Wakai, Shujiro Okuda

    Computational and structural biotechnology journal   18   3301 - 3308   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gastric cancer is one of the most common and clinically important diseases worldwide. The traditional Laeuren classification divides gastric cancer into two histopathological subtypes: diffuse and intestinal. Recent cancer genomics research has led to the development of a new classification based on molecular characteristics. The newly defined genomically stable (GS) subtype shares many cases with the histopathologically diffuse type. In this study, we performed genetic profiling of recurrently and significantly mutated genes in diffuse type and GS subtype tumors. We observed significantly different genetic characteristics, although the two subtypes overlapped in many cases. In addition, based on the profiles of the significantly mutated genes, we identified molecular functions and mutational signatures characteristic of each subtype. These results will advance the clinical application of the diffuse type and GS subtype gastric cancer in precision medicine for treating gastric cancer.

    DOI: 10.1016/j.csbj.2020.10.021

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  • [A Case of Pathological Complete Response with Neoadjuvant Chemotherapy for Advanced Rectal Cancer]. 査読

    Shukichi Okada, Hitoshi Kameyama, Kaoru Abe, Kana Tanaka, Hidehito Oyanagi, Mae Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Kazuyasu Takizawa, Masato Nakano, Masayuki Nagahashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2057 - 2059   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 62-year-old man was admitted with complaints of bloody stool. Colonoscopy revealed a 5 cm diameter type 2 tumor in the lower rectum close to the anal canal. Tumor biopsy indicated a well-differentiated tubular adenocarcinoma. Computed tomography revealed locally advanced rectal cancer with mesorectal lymph node metastases(cT3N1P0M0, Stage Ⅲa, JSCCR 8th). The patient was treated with neoadjuvant chemotherapy(NAC)after transverse colostomy as an anus-preserving procedure. For the NAC, 12 courses of capecitabine plus oxaliplatin(CapeOX)and bevacizumab(BV)were administered. Colonoscopy after NAC revealed that the main tumor had considerably shrunk. No malignant tissues were found on biopsy. However, rectal wall thickness remained unchanged. Therefore, response evaluation for chemotherapy indicated partial response. Intersphincteric resection(ISR)with diverting loop ileostomy was performed as an anus-preserving surgical procedure. No remnant tumor in the rectum or lymph node metastases were found upon the pathological examination of resected specimens. Ileostomy closure was performed at 6 months post-ISR. At 12 months post-ISR, the patient was well and showed no signs of recurrence. This case demonstrated that NAC with CapeOX and BV can be a promising option for treating locally advanced lower rectal cancer and preserving the anus.

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  • [A Case of Esophageal Cancer Achieving a Pathological Complete Response after Preoperative Docetaxel, Cisplatin, and 5-Fluorouracil Therapy]. 査読

    Daisuke Motegi, Hiroshi Ichikawa, Yosuke Kano, Takaaki Hanyu, Takashi Ishikawa, Kenji Usui, Takeshi Sakai, Yuki Hirose, Kohei Miura, Masayuki Nagahashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2192 - 2194   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 66-year-old man with middle thoracic esophageal squamous cell carcinoma with supraclavicular lymph node metastasis visited our hospital. He underwent 3 courses of preoperative chemotherapy with docetaxel, cisplatin, and 5-FU(DCF)with a clinically-determined partial response. Minimally-invasive esophagectomy with 3-fieldlymphad enectomy was subsequently performed. Histopathologic examination revealedno viable tumor cells in the resectedesophagus andsupraclavicular lymph node. DCF is a promising preoperative chemotherapy regimen for locally advanced esophageal cancer because of its higher complete response rate comparedto that for cisplatin plus 5-FU.

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  • [Digestive Surgery Intervention for Gynecological Malignant Tumor]. 査読

    Hitoshi Kameyama, Yoshifumi Shimada, Kaoru Abe, Hidehito Oyanagi, Mae Nakano, Masato Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Kazuyasu Takizawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Nobumichi Nishikawa, Takayuki Enomoto, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2176 - 2178   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    AIM: This study aimed to determine surgical outcomes in patients with gynecological cancers for whom surgery was performed by gynecologists and digestive surgeons. METHODS: Seventy-three patients who underwent surgery for a gynecological malignant tumor from January 2010 to December 2014 were included in this retrospective study. Data on the definitive diagnosis, operative procedures, postoperative complications, stoma settings, length of hospital stay, and prognosis was collected for each patient. RESULTS: The median age of this female-only cohort was 60 years. Emergency surgery was performed in 8(11.0%)patients. Ovarian cancer was diagnosed in 56(76.7%)patients, and among these patients, the clinical disease Stage was Ⅰ, Ⅱ, Ⅲ, and Ⅳ in 4, 4, 20, and 11 patients, respectively. Moreover, 17 patients had recurrent ovarian cancer. Intestinal resection with anastomosis was performed in 25(34.2%)patients. Stoma formation was performed in 22 (30.1%)patients, however no patient underwent stoma closure surgery in the current study. The median operative time was 252 minutes, and the median blood loss was 1,190 mL. Regarding postoperative complications, ileus, pelvic abscess, and anastomotic leakage developed in 6(8.2%), 4(5.5%), and 2(2.7%)patients, respectively. The postoperative median survival time in patients with ovarian cancer was 1,399 days. CONCLUSION: These results suggest that tumor debulking, including intestinal tract resection, may contribute to the prolonged prognosis of gynecological tumors, although stoma closure is difficult to perform.

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  • [A Case of Long-Term Survival in a Patient with Advanced Rectal Cancer and Paraaortic and Lateral Lymph Node Metastases]. 査読

    Yumiko Yamashita, Hitoshi Kameyama, Kaoru Abe, Kana Tanaka, Hidehito Oyanagi, Mae Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Kazuyasu Takizawa, Masato Nakano, Masayuki Nagahashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2033 - 2035   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 65-year-old woman was referred for further examination following positive results on a fecal occult blood test. Colonoscopy revealed type 0-Ⅱa cancer, with a lesion measuring 2 cm in diameter in the rectosigmoid colon, and type 5 cancer, with a lesion measuring 6 cm in diameter in the upper rectum. Computed tomography(CT)and positron emission tomography (PET)-CT revealed mesorectal lymph node metastases. Therefore, she was diagnosed with rectosigmoid colon cancer(Stage Ⅰ)and upper rectal cancer(Stage Ⅲa). However, PET-CT also revealed slight fluorodeoxyglucose uptake in the paraaortic and lateral lymph node lesions; hence, the possibility ofmetastasis could not be ruled out. Given that chemotherapy was restricted due to renal dysfunction, low anterior resection was performed as the first choice. Analysis of intraoperative frozen sections showed paraaortic and lateral lymph node metastases; thus, we performed lymph node dissection of these lesions. Pathological examination ofthe resected lymph nodes revealed that 21 of 37 lesions were cancer metastases. S-1 was administered as adjuvant chemotherapy for 5 months. Mediastinal lymph node metastases was suspected on chest CT 5 months and 3 years post-surgery; thus, panitumumab was administrated. These lymph nodes decreased in size immediately. Six years after the first surgery, the patient was well without any signs of recurrence.

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  • [A Case of Peritoneal Metastases after Radiofrequency Ablation for Liver Metastasis from a Pancreatic Neuroendocrine Tumor]. 査読

    Hiroki Nagaro, Yuki Hirose, Tomohiro Katada, Jun Sakata, Takashi Kobayashi, Kazuyasu Takizawa, Kohei Miura, Koji Toge, Takuya Ando, Kizuki Yuza, Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Hitoshi Kameyama, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2015 - 2017   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 77-year-old woman presented with peritoneal metastases from a pancreatic neuroendocrine tumor(p-NET). At the age of 56 years, she underwent distal pancreatectomy for p-NET, which was pathologically diagnosed as G2. She underwent right hemihepatectomy for liver metastasis(S6)from the p-NET 10 years post-pancreatectomy. Eight years post-hepatectomy, radiofrequency ablation(RFA)was attempted for liver metastasis(S4)from the p-NET. However, RFA was not completed because of hematoma development along the needle tract of RFA. She underwent partial hepatectomy for this lesion 6 months post-RFA. Two years post-RFA, localized peritoneal metastases on the right diaphragm were detected. She underwent en bloc tumor resection with partial resection of the diaphragm. She remains alive and well with no evidence of disease 2 years post-resection of the peritoneal metastases from the p-NET.

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  • [A Case of Esophageal Primary Malignant Melanoma That Developed During the Follow-Up of Esophageal Melanocytosis]. 査読

    Daisuke Yamai, Hiroshi Ichikawa, Yosuke Kano, Takaaki Hanyu, Takashi Ishikawa, Kenji Usui, Mariko Nemoto, Yuki Hirose, Kohei Miura, Masayuki Nagahashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2012 - 2014   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 78-year-old woman was endoscopically followed up for benign melanocytosis in the middle thoracic esophagus that was detected 3 years prior. She presented with chest tightness, and an endoscopic examination revealed a protruding tumor at the melanotic lesion. She was histologically diagnosedwith an esophageal primary malignant melanoma. Computedtomography showedno metastatic lesions. She underwent minimally invasive esophagectomy with 2-fieldlymphad enectomy. Immunotherapy with nivolumab is ongoing for liver metastasis, which developed1 year and6 months after esophagectomy. Careful follow-up for esophageal melanocytosis is important for early diagnosis of esophageal primary malignant melanoma.

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  • [A Case of Long-Term Survival after Resection for Metachronous Liver and Lung Metastases of Rectal Cancer Associated with Familial Adenomatous Polyposis]. 査読

    Michiru Arabiki, Hitoshi Kameyama, Kaoru Abe, Kana Tanaka, Hidehito Oyanagi, Yosuke Tajima, Mae Nakano, Masato Nakano, Yoshifumi Shimada, Hiroshi Ichikawa, Kazuyasu Takizawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 13 )   2228 - 2230   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 37-year-old man was admitted to our hospital for the treatment of familial adenomatous polyposis and rectal carcinoma. He underwent total colectomy with ileoanal anastomosis(pT3N1M0, pStage Ⅲa)followed by adjuvant therapy with S-1. Three months after primary surgery, CT and MRIrevealed liver metastases(S5, S6). Laparoscopic partial hepatectomy was performed. Two years after primary surgery, new liver metastases(S2, S8)were found and we performed open partial hepatectomy and administered mFOLFOX6. Three years and 5 months after primary surgery, right lung metastases(S6, S9) were detected and the patient underwent a thoracoscopic-assisted right lung wedge resection. Repeated resection of metastases might have contributed to the long-survival in our case.

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  • Palliative interventions for patients with incurable locally advanced or metastatic thoracic esophageal carcinoma. 査読

    Kakuta T, Kosugi SI, Ichikawa H, Hanyu T, Ishikawa T, Kanda T, Wakai T

    Esophagus : official journal of the Japan Esophageal Society   16 ( 3 )   278 - 284   2019年7月

  • SMAD4 alteration associates with invasive-front pathological markers and poor prognosis in colorectal cancer. 査読

    Oyanagi H, Shimada Y, Nagahashi M, Ichikawa H, Tajima Y, Abe K, Nakano M, Kameyama H, Takii Y, Kawasaki T, Homma KI, Ling Y, Okuda S, Takabe K, Wakai T

    Histopathology   74 ( 6 )   873 - 882   2019年5月

  • Hyperbilirubinemia predicts the infectious complications after esophagectomy for esophageal cancer. 査読

    Muneoka Y, Ichikawa H, Kosugi SI, Hanyu T, Ishikawa T, Kano Y, Shimada Y, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Akazawa K, Wakai T

    Annals of medicine and surgery (2012)   39   16 - 21   2019年3月

  • [Surgical Resection after Transarterial Chemoembolization for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus-Report of a Long-Term Survivor]. 査読

    Sakata J, Kobayashi T, Takizawa K, Miura K, Katada T, Hirose Y, Toge K, Ando T, Soma D, Yuza K, Ichikawa H, Nagahashi M, Shimada Y, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   46 ( 2 )   297 - 299   2019年2月

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  • BRAF V600E and SRC mutations as molecular markers for predicting prognosis and conversion surgery in Stage IV colorectal cancer. 査読

    Shimada Y, Muneoka Y, Nagahashi M, Ichikawa H, Tajima Y, Hirose Y, Ando T, Nakano M, Sakata J, Kameyama H, Takii Y, Ling Y, Okuda S, Takabe K, Wakai T

    Scientific reports   9 ( 1 )   2466   2019年2月

  • Phospho-Sphingosine Kinase 1 Expression in Lymphatic Spread of Esophageal Squamous Cell Carcinoma 査読

    Nemoto M, Ichikawa H, Nagahashi M, Hanyu T, Ishikawa T, Kano Y, Muneoka Y, Wakai T

    Journal of Surgical Research   234   123 - 131   2019年2月

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    記述言語:英語  

    DOI: 10.1016/j.jss.2018.09.012

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  • Left colic artery aneurysm rupture after stent placement for abdominal aortic aneurysm associated with neurofibromatosis type 1. 査読

    Moro K, Kameyama H, Abe K, Tsuchida J, Tajima Y, Ichikawa H, Nakano M, Ikarashi M, Nagahashi M, Shimada Y, Kato K, Okamoto T, Umezu H, Gabriel E, Tsuchida M, Wakai T

    Surgical case reports   5 ( 1 )   12   2019年1月

  • Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma 査読

    Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida

    Scientific Reports   8 ( 1 )   1005   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

    DOI: 10.1038/s41598-017-18560-y

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  • [A Case of Long-Term Survival after Reoperation for Neck Lymph Node Metastasis Occurring Seven Years after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma]. 査読

    Ando T, Takizawa K, Yuza K, Soma D, Toge K, Hirose Y, Katada T, Miura K, Sakata J, Kobayashi T, Ichikawa H, Nagahashi M, Shimada Y, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   2312 - 2314   2018年12月

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  • [Surgical Resection for Peritoneal Metastasis in Hepatocellular Carcinoma-A Report of Three Cases]. 査読

    Nakano T, Sakata J, Ando T, Yuza K, Soma D, Hirose Y, Katada T, Miura K, Takizawa K, Kobayashi T, Ichikawa H, Nagahashi M, Shimada Y, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   1949 - 1951   2018年12月

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  • [Chemoresistance in Microsatellite Instability-High Gastric Cancer-A Case Report]. 査読

    Otani T, Ichikawa H, Hanyu T, Ishikawa T, Sakai T, Nemoto M, Muneoka Y, Usui K, Sudo N, Kano Y, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   1895 - 1897   2018年12月

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  • [Pancreaticoduodenectomy for Recurrent Retroperitoneal Liposarcoma]. 査読

    Ishikawa H, Sakata J, Ando T, Soma D, Yuza K, Toge K, Hirose Y, Katada T, Miura K, Takizawa K, Kobayashi T, Ichikawa H, Nagahashi M, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   1845 - 1847   2018年12月

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  • [A Case of Resistance to Systemic Therapy in Hypermutation of Colorectal Cancer]. 査読

    Tanaka K, Shimada Y, Tajima Y, Yamada S, Hotta S, Nakano M, Nakano M, Kameyama H, Miura K, Ichikawa H, Nagahashi M, Nogami H, Maruyama S, Takii Y, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   2476 - 2478   2018年12月

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  • [A Case of Long-Term Survival in a Patient with Ascending Colon Cancer and Synchronous Multiple Liver Metastases after Multimodality Therapy Including Multiple Hepatectomy]. 査読

    Hotta S, Kameyama H, Shimada Y, Yamada S, Tanaka K, Tajima Y, Nakano M, Ichikawa H, Hanyu T, Takizawa K, Nakano M, Nagahashi M, Sakata J, Kobayashi T, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 13 )   2464 - 2466   2018年12月

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  • Clinical Significance of BRAF Non-V600E Mutations in Colorectal Cancer: A Retrospective Study of Two Institutions. 査読

    Shimada Y, Tajima Y, Nagahashi M, Ichikawa H, Oyanagi H, Okuda S, Takabe K, Wakai T

    The Journal of surgical research   232   72 - 81   2018年12月

  • Next generation sequencing-based gene panel tests for the management of solid tumors. 査読

    Nagahashi M, Shimada Y, Ichikawa H, Kameyama H, Takabe K, Okuda S, Wakai T

    Cancer science   2018年10月

  • Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma. 査読

    Nagahashi M, Sato S, Yuza K, Shimada Y, Ichikawa H, Watanabe S, Takada K, Okamoto T, Okuda S, Lyle S, Takabe K, Tsuchida M, Wakai T

    The Journal of surgical research   230   181 - 185   2018年10月

  • Unusual lymph node metastasis from cancer of the thoracic esophagus. 査読

    Kosugi SI, Ichikawa H, Sato Y, Sunami E, Hirano K, Matsuzawa T, Takahashi M

    Journal of surgical case reports   2018 ( 8 )   rjy214   2018年8月

  • Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis. 査読

    Hirose Y, Nagahashi M, Katsuta E, Yuza K, Miura K, Sakata J, Kobayashi T, Ichikawa H, Shimada Y, Kameyama H, McDonald KA, Takabe K, Wakai T

    Scientific reports   8 ( 1 )   10814   2018年7月

  • Pathogenic Germline BRCA1/2 Mutations and Familial Predisposition to Gastric Cancer 査読

    Ichikawa H, Wakai T, Nagahashi M, Shimada Y, Hanyu T, Kano Y, Muneoka Y, Ishikawa T, Takizawa K, Tajima Y, Sakata J, Kobayashi T, Kameyama H, Yabusaki H, Nakagawa S, Sato N, Kawasaki T, Homma K, Okuda S, Lyle S, Takabe K

    JCO Precision Oncology   ( 2 )   1 - 8   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1200/PO.18.00097

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  • Genomic characterization of colitis-associated colorectal cancer. 査読

    Kameyama H, Nagahashi M, Shimada Y, Tajima Y, Ichikawa H, Nakano M, Sakata J, Kobayashi T, Narayanan S, Takabe K, Wakai T

    World journal of surgical oncology   16 ( 1 )   121   2018年7月

  • Actionable Gene Alterations in an Asian Population With Triple-Negative Breast Cancer 査読

    Nagahashi M, Ling Y, Hayashida T, Kitagawa Y, Futamura M, Yoshida K, Kuwayama T, Nakamura S, Toshikawa C, Yamauchi H, Yamauchi T, Kaneko K, Kanbayashi C, Sato N, Miyoshi Y, Tsuchida J, Nakajima M, Shimada Y, Ichikawa H, Lyle S, Takabe K, Okuda S, Wakai T

    JCO Precision Oncology   ( 2 )   1 - 13   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1200/PO.17.00211

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  • Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung 査読

    Tatsuro Okamoto, Kazuki Takada, Seijiro Sato, Gouji Toyokawa, Tetsuzo Tagawa, Fumihiro Shoji, Ryota Nakanishi, Eiji Oki, Terumoto Koike, Masayuki Nagahashi, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kouhei Akazawa, Stephen Lyle, Kazuaki Takabe, Shujiro Okuda, Kenji Sugio, Toshifumi Wakai, Masanori Tsuchida, Yoshihiko Maehara

    Annals of Surgical Oncology   25 ( 6 )   1564 - 1571   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer New York LLC  

    Background: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. Methods: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. Results: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B
    35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB
    p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). Conclusions: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

    DOI: 10.1245/s10434-018-6401-1

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  • Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type and lymphatic invasion in human gastric cancer 査読

    Takaaki Hanyu, Masayuki Nagahashi, Hiroshi Ichikawa, Takashi Ishikawa, Takashi Kobayashi, Toshifumi Wakai

    Surgery (United States)   163 ( 6 )   1301 - 1306   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Mosby Inc.  

    Background: Sphingosine-1-phosphate, a pleiotropic bioactive lipid mediator, is an important player in cancer progression. Previous studies suggested that sphingosine-1-phosphate produced by sphingosine kinase 1, which is activated by phosphorylation, plays important roles in the progression of disease and metastasis. The association between phospho-sphingosine-1-phosphate produced by sphingosine kinase 1 and clinical parameters in human gastric cancer have not been fully investigated to date. Methods: We created phospho-sphingosine-1-phosphate produced by sphingosine kinase expression profiles by immunohistochemistry for 136 patients who underwent operative intervention for gastric cancer in 2007–2009. Phospho-sphingosine-1-phosphate produced by sphingosine kinase expression and compared clinicopathologic factors by univariate and multivariate analyses. Results: The univariate analysis revealed that phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was correlated significantly with depth of tumor invasion, lymph node metastasis, distant metastasis, histologic type, and lymphatic invasion. The multivariate analysis revealed that the diffuse type (odds ratio 2.210
    95% confidence interval, 1.045–4.671, P =.038) and the presence of lymphatic invasion (odds ratio 3.697
    95% confidence interval, 1.161–8.483, P =.002) were associated independently with phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in patients with gastric cancer. The 5-year rate of disease-specific survival was 79.3% in patients with phospho-sphingosine-1-phosphate produced by sphingosine kinasephospho-sphingosine-1-phosphate produced by sphingosine kinase-positive expression and 98.3% in those with phospho-sphingosine-1-phosphate produced by sphingosine kinase-negative expression (P =.002). In multivariate analysis, however, high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression was not an independent prognostic factor for disease-specific survival (hazard ratio 5.540
    95% confidence interval, 0.717–42.81, P =.100). Conclusion: We provide the first evidence that diffuse histologic type and lymphatic invasion were independently associated with high phospho-sphingosine-1-phosphate produced by sphingosine kinase expression in gastric cancer patients, indicating a role of sphingosine-1-phosphate in disease progression among patients with gastric cancer. (Surgery 2017
    160:XXX-XXX.)

    DOI: 10.1016/j.surg.2017.11.024

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  • Carcinoma in the Remnant Stomach During Long-Term Follow-up After Distal Gastrectomy for Gastric Cancer: Analysis of Cumulative Incidence and Associated Risk Factors 査読

    Takaaki Hanyu, Atsuhiro Wakai, Takashi Ishikawa, Hiroshi Ichikawa, Hitoshi Kameyama, Toshifumi Wakai

    World Journal of Surgery   42 ( 3 )   782 - 787   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer New York LLC  

    Background: The number of patients with remnant gastric cancer following resection of gastric cancer may increase. The aims of this study were to investigate the development of remnant gastric cancer after distal gastrectomy for gastric cancer and to examine its cumulative incidence, clinicopathological characteristics, and risk factors. Methods: We examined 437 patients with relapse-free survival for 5 years or more after distal gastrectomy with Billroth I reconstruction for gastric cancer performed between 1985 and 2005. Results: A total of 17 patients suffered from remnant gastric cancer. The cumulative incidence was 3.7% at 10 years and 5.4% at 20 years. The median time until development of remnant gastric cancer was 79 months (range 30–209 months). The presence of synchronous multiple gastric cancers was a significant independent risk factor for remnant gastric cancer (hazard ratio 4.036
    95% confidence interval 1.478–11.02
    P = 0.006). Of the 17 patients, the 13 whose remnant gastric cancer was detected via regular endoscopy showed better prognoses than the patients detected by other means (P &lt
     0.001). Conclusion: The cumulative incidence of remnant gastric cancer was 5.4% at 20 years. In particular, patients who had multiple gastric cancers at initial gastrectomy were at higher risk for remnant gastric cancer. Therefore, long-term endoscopic surveillance is important.

    DOI: 10.1007/s00268-017-4227-9

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  • Management of rectal gastrointestinal stromal tumor 査読

    Hitoshi Kameyama, Tatsuo Kanda, Yosuke Tajima, Yoshifumi Shimada, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Toshifumi Wakai

    Translational Gastroenterology and Hepatology   2018   8   2018年2月

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    記述言語:英語   出版者・発行元:AME Publishing Company  

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. However, rectal GIST is rare, the incident rate of it is approximately 5% of all GISTs. Rectal GIST symptoms generally include bleeding and/or pain and occasionally, urinary symptoms. Immunohistochemical evaluation finds that most rectal GIST tumors are CD117 (KIT) positive, and are sometimes CD34, platelet-derived growth factor receptor alpha (PDGFRA), smooth muscle actin, S-100, or vimentin positive. The National Institutes of Health (NIH) classifies rectal GIST as very-low risk, low risk, intermediate risk, or high risk, and the frequencies have been estimated as 0-23.8% for very-low risk, 0-45% for low risk, 0-34% for intermediate risk, and 21-100% for high risk tumors. The first-line treatment for localized GIST is curative resection, but is difficult in rectal GIST because of anatomical characteristics such as the deep, narrow pelvis and proximity to the sphincter muscle or other organs. Several studies noted the efficacy of the minimally invasive surgery, such as trans-anal, trans-sacral, trans-vaginal resection, or laparoscopic resection. The appropriate surgical procedure should be selected depending on the case. Imatinib mesylate (IM) is indicated as first-line treatment of metastatic or unresectable GIST, and clinical outcomes are correlated with KIT mutation genotype. However, the KIT mutation genotypes in rectal GIST are not well known. In this review, as in other GISTs, a large proportion (59-100%) of rectal GISTs carry exon 11 mutations. Although curative resection is indicated for localized rectal GIST, a high rate of local recurrence is a problem. Multimodal therapy including perioperative IM may improve postoperative outcomes, contributing to anus-preserving surgery. Moreover, KIT mutation analysis before IM treatment is important. This review summarizes current treatment strategies for rectal GIST.

    DOI: 10.21037/tgh.2018.01.08

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  • Formalin-fixed paraffin-embedded sample conditions for deep next generation sequencing 査読

    Masayuki Nagahashi, Yoshifumi Shimada, Hiroshi Ichikawa, Satoru Nakagawa, Nobuaki Sato, Koji Kaneko, Keiichi Homma, Takashi Kawasaki, Keisuke Kodama, Stephen Lyle, Kazuaki Takabe, Toshifumi Wakai

    JOURNAL OF SURGICAL RESEARCH   220   125 - 132   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Introduction: Precision medicine is only possible in oncology practice if targetable genes in fragmented DNA, such as DNA from formalin-fixed paraffin-embedded (FFPE) samples, can be sequenced using next generation sequencing (NGS). The aim of this study was to examine the quality and quantity of DNA from FFPE cancerous tissue samples from surgically resected and biopsy specimens.
    Methods: DNA was extracted from unstained FFPE tissue sections prepared from surgically resected specimens of breast, colorectal and gastric cancer, and biopsy specimens of breast cancer. A total quantity of DNA &gt;= 60 ng from a sample was considered adequate for NGS. The DNA quality was assessed by Q-ratios, with a Q-ratio &gt;0.1 considered sufficient for NGS.
    Results: The Q-ratio for DNA from FFPE tissue processed with neutral-buffered formalin was significantly better than that processed with unbuffered formalin. All Q-ratios for DNA from breast, colorectal and gastric cancer samples indicated DNA levels sufficient for NGS. DNA extracted from gastric cancer FFPE samples prepared within the last 7 years is suitable for NGS analysis, whereas those older than 7 years may not be suitable. Our data suggested that adequate amounts of DNA can be extracted from FFPE samples, not only of surgically resected tissue but also of biopsy specimens.
    Conclusions: The type of formalin used for fixation and the time since FFPE sample preparation affect DNA quality. Sufficient amounts of DNA can be extracted from FFPE samples of both surgically resected and biopsy tissue, thus expanding the potential diagnostic uses of NGS in a clinical setting. (C) 2017 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.jss.2017.06.077

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  • [A Case of Ascending Colon Cancer with Synchronous Liver Metastases and Peritoneal Dissemination]. 査読

    Mito M, Kameyama H, Shimada Y, Yamada S, Hotta S, Hirose Y, Yagi R, Tajima Y, Nakano M, Okamura T, Nakano M, Ichikawa H, Nagahashi M, Sakata J, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1126 - 1128   2017年11月

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  • [Two Cases of Colorectal Cancer with SRC Amplification]. 査読

    Oyanagi H, Shimada Y, Yagi R, Tajima Y, Ichikawa H, Nakano M, Nakano M, Nagahashi M, Sakata J, Kameyama H, Kobayashi T, Nogami H, Maruyama S, Takii Y, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1757 - 1759   2017年11月

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  • [Mixed Type Liposarcoma with Intra-Abdominal Bleeding - Report of a Case]. 査読

    Miura Y, Sakata J, Ando T, Soma D, Yuza K, Hirose Y, Ishikawa H, Miura K, Takizawa K, Kobayashi T, Ichikawa H, Nagahashi M, Shimada Y, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1155 - 1157   2017年11月

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  • [A Case of Hepatocellular Carcinoma with Lymph Node Metastasis Successfully Treated by Multidisciplinary Treatment]. 査読

    Soma D, Sakata J, Ando T, Yuza K, Ishikawa H, Ohashi T, Takizawa K, Takano K, Kobayashi T, Ichikawa H, Hanyu T, Nagahashi M, Shimada Y, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1565 - 1567   2017年11月

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  • [Quality of Life of Patients after Colorectal Cancer Surgery as Assessed Using EQ-5D-5L Scores]. 査読

    Kameyama H, Shimada Y, Yagi R, Yamada S, Hotta S, Tajima Y, Nakano M, Okamura T, Nakano M, Ichikawa H, Hanyu T, Nagahashi M, Sakata J, Kobayashi T, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   44 ( 12 )   1083 - 1085   2017年11月

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  • Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer 査読

    Yoshifumi Shimada, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yusuke Muneoka, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Tetsu Hayashida, Hiromasa Takaishi, Yuko Kitagawa, Eiji Oki, Tsuyoshi Konishi, Fumio Ishida, Shin-ei Kudo, Jennifer E. Ring, Alexei Protopopov, Stephen Lyle, Yiwei Ling, Shujiro Okuda, Takashi Ishikawa, Kohei Akazawa, Kazuaki Takabe, Toshifumi Wakai

    ONCOTARGET   8 ( 55 )   93567 - 93579   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.
    Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as "all wild-type", while remaining patients were defined as "mutant-type".
    Results: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared with "all wild-type" LCRC (P = 0.004).
    Conclusions: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

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  • Cardiac tamponade communicating with a posterior mediastinal chylocele after esophagectomy. 査読

    Kosugi SI, Hashimoto T, Sato Y, Hirano K, Sunami E, Matsuzawa T, Takahashi M, Ichikawa H

    Journal of surgical case reports   2017 ( 10 )   rjx216   2017年10月

  • Intravenous Carnitine Administration in Addition to Parenteral Nutrition With Lipid Emulsion May Decrease the Inflammatory Reaction in Postoperative Surgical Patients. 査読

    Koyama Y, Moro K, Nakano M, Miura K, Nagahashi M, Kosugi SI, Tsuchida J, Ikarashi M, Nakajima M, Ichikawa H, Hanyu T, Shimada Y, Sakata J, Kameyama H, Kobayashi T, Wakai T

    Journal of clinical medicine research   9 ( 10 )   831 - 837   2017年10月

  • Actionable gene-based classification toward precision medicine in gastric cancer 査読

    Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Takaaki Hanyu, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Jun Sakata, Hiroshi Yabusaki, Satoru Nakagawa, Nobuaki Sato, Yuki Hirata, Yuko Kitagawa, Toshiyuki Tanahashi, Kazuhiro Yoshida, Ryota Nakanishi, Eiji Oki, Dana Vuzman, Stephen Lyle, Kazuaki Takabe, Yiwei Ling, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai

    GENOME MEDICINE   9 ( 1 )   93   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed.& para;& para;Methods: A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tum or tissues were obtained from surgical or biopsy specimens and were subjected, to DMA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired, with US Food and Drug Administration-approved targeted therapies, and the evaluation o f Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status.& para;& para;Results: Comprehensive genomic sequencing detected at least one alteration o f 435 cancer-related genes in 194 GCs (93.7%) and o f 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomicaliy stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated. phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six dusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM duster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC. with a remarkable response to anti-HER2 therapy in the ERBB2 duster.& para;& para;Conclusions: This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.

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  • Benign esophageal schwannoma: a brief overview and our experience with this rare tumor. 査読 国際誌

    Kazuki Moro, Masayuki Nagahashi, Kotaro Hirashima, Shin-Ichi Kosugi, Takaaki Hanyu, Hiroshi Ichikawa, Takashi Ishikawa, Gen Watanabe, Emmanuel Gabriel, Tsutomu Kawaguchi, Kazuaki Takabe, Toshifumi Wakai

    Surgical case reports   3 ( 1 )   97 - 97   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Benign esophageal tumors are uncommon, comprising approximately 2% of esophageal tumors. Esophageal schwannomas constitute an even rarer entity, with few cases reported in the literature. CASE PRESENTATION: We present a 66-year-old male who was referred for dysphagia. A computed tomography scan showed a well-demarcated, enhancing, and homogenous esophageal tumor measuring 50 mm. The tumor was hypermetabolic on positron emission tomography, and an endoscopic ultrasound-guided fine needle aspiration demonstrated the presence of benign spindle cells. We performed an uncomplicated, simple, tumor enucleation through a cervical approach. Histology revealed spindle-shaped cells in a fasciculated, disarrayed pattern. Immunohistochemistry demonstrated positive staining for S-100 protein and negative staining for KIT, CD34, desmin, and α-smooth muscle actin. These findings were consistent with a benign esophageal schwannoma. CONCLUSIONS: We report our experience with esophageal schwannoma, a rare but benign diagnosis of the esophagus.

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  • Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer 査読

    Yoshifumi Shimada, Ryoma Yagi, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Yo Sato, Takeaki Matsuzawa, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Takashi Kawasaki, Kei-ichi Homma, Hiroshi Izutsu, Keisuke Kodama, Jennifer E. Ring, Alexei Protopopov, Stephen Lyle, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai

    HUMAN PATHOLOGY   66   1 - 9   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 MC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P &lt; .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment. (C) 2017 The Authors. Published by Elsevier Inc.

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  • Appropriate extent of lymphadenectomy for squamous cell carcinoma of the esophagogastric junction 査読

    Shin-ichi Kosugi, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   44   339 - 343   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Aim: To investigate the appropriate extent of lymphadenectomy for squamous cell carcinoma (SCC) of the esophagogastric junction (ECJ).
    Methods: We retrospectively reviewed the cases of 52 patients with SCC of the ECJ who underwent extended mediastinal lymphadenectomy. We assessed potential risk factors for lymph node metastasis (LNM) in the upper/middle mediastinum by conducting univariate and multivariate analyses, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value. Survival rates were calculated using the Kaplan-Meier method, and the therapeutic value index of each nodal basin dissection was calculated by multiplying the frequency of metastasis at the basin and the 5-year overall survival rate of patients with metastasis at that basin.
    Results: Twenty patients (38%) had mediastinal LNM; 13 (25%) had metastasis in the upper/middle mediastinum, and 13 (25%) had metastasis in the lower mediastinum. Tumor length (P = 0.03) and pathological nodal status (P = 0.01) were independent risk factors for upper/middle mediastinal LNM. The optimal ROC cutoff value of tumor length was 54 mm. The 5-year overall survival rate of the patients with LNM in the upper/middle mediastinum was 46%. The therapeutic value index of upper/middle mediastinal lymphadenectomy was 11.6, which was inferior to that of perigastric lymphadenectomy at 17.3, but superior to that of lower mediastinal lymphadenectomy at 5.8.
    Conclusion: An upper/middle mediastinal lymphadenectomy may be required for patients with tumors that are &gt;= 54 mm long, and in those with suspected LNM. (C) 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • Clinical significance of NQO1 expression in KRAS wild-type colorectal cancer 査読

    Hitoshi Kameyama, Yuki Hirose, Yasunobu Matsuda, Masayuki Nagahashi, Hiroshi Ichikawa, You Sato, Saki Yamada, Shinnosuke Hotta, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   10 ( 5 )   5841 - 5849   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    NAD(P)H: quinone oxidoreductase-1 (NQO1) protects cells against redox cycling and oxidative stress; however, in cancer cells, NQO1 confers resistance against anticancer agents. The aim of this study was to evaluate the association between NQO1 expression and prognosis in patients with advanced (locally advanced or metastatic/recurrent) colorectal cancer (CRC). A retrospective analysis of 47 patients [28 male and 19 female; median age: 62 years (range, 17-78)] with advanced CRC was conducted. Immunohistochemical examination of tumor tissue specimens was performed using monoclonal anti-NQO1 antibody. The association of NQO1 expression with patient characteristics, chemotherapeutic response, and clinical prognosis was assessed. Therapeutic efficacy (complete response, partial response, stable disease, and progressive disease) was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. We compared the therapeutic efficacy in KRAS wild and mutant CRC because epidermal growth factor receptor (EGFR)-signaling pathway plays a pivotal role in CRC. Of the 47 patients, 31 (66.0%) had KRAS wild CRC and 16 (34.0%) had KRAS mutant CRC. Moreover, 37 (78.7%) had NQO1-positive tumors and 10 (21.3%) had NQO1-negative tumors. Among the patients with KRAS wild CRC, NQO1-negative patients showed significantly better disease control rate (complete response + partial response + stable disease) than NQO1-positive patients (P = 0.028). Moreover, NQO1-negative patients had longer progression-free survival and overall survival than NQO1-positive patients (P = 0.041 and P = 0.043, respectively). NQO1 expression in the tumor may be a predictor of therapeutic efficacy and prognosis in patients with KRAS wild advanced CRC.

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  • Genomic landscape of colorectal cancer in Japan: clinical implications of comprehensive genomic sequencing for precision medicine 査読

    Masayuki Nagahashi, Toshifumi Wakai, Yoshifumi Shimada, Hiroshi Ichikawa, Hitoshi Kameyama, Takashi Kobayashi, Jun Sakata, Ryoma Yagi, Nobuaki Sato, Yuko Kitagawa, Hiroyuki Uetake, Kazuhiro Yoshida, Eiji Oki, Shin-ei Kudo, Hiroshi Izutsu, Keisuke Kodama, Mitsutaka Nakada, Julie Tse, Meaghan Russell, Joerg Heyer, Winslow Powers, Ruobai Sun, Jennifer E. Ring, Kazuaki Takabe, Alexei Protopopov, Yiwei Ling, Shujiro Okuda, Stephen Lyle

    GENOME MEDICINE   8 ( 1 )   136   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Comprehensive genomic sequencing (CGS) has the potential to revolutionize precision medicine for cancer patients across the globe. However, to date large-scale genomic sequencing of cancer patients has been limited to Western populations. In order to understand possible ethnic and geographic differences and to explore the broader application of CGS to other populations, we sequenced a panel of 415 important cancer genes to characterize clinically actionable genomic driver events in 201 Japanese patients with colorectal cancer (CRC).
    Methods: Using next-generation sequencing methods, we examined all exons of 415 known cancer genes in Japanese CRC patients (n = 201) and evaluated for concordance among independent data obtained from US patients with CRC (n = 108) and from The Cancer Genome Atlas-CRC whole exome sequencing (WES) database (n = 224). Mutation data from non-hypermutated Japanese CRC patients were extracted and clustered by gene mutation patterns. Two different sets of genes from the 415-gene panel were used for clustering: 61 genes with frequent alteration in CRC and 26 genes that are clinically actionable in CRC.
    Results: The 415-gene panel is able to identify all of the critical mutations in tumor samples as well as WES, including identifying hypermutated tumors. Although the overall mutation spectrum of the Japanese patients is similar to that of the Western population, we found significant differences in the frequencies of mutations in ERBB2 and BRAF. We show that the 415-gene panel identifies a number of clinically actionable mutations in KRAS, NRAS, and BRAF that are not detected by hot-spot testing. We also discovered that 26% of cases have mutations in genes involved in DNA double strand break repair pathway. Unsupervised clustering revealed that a panel of 26 genes can be used to classify the patients into eight different categories, each of which can optimally be treated with a particular combination therapy.
    Conclusions: Use of a panel of 415 genes can reliably identify all of the critical mutations in CRC patients and this information of CGS can be used to determine the most optimal treatment for patients of all ethnicities.

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  • Surgical and long-term outcomes following oesophagectomy in oesophageal cancer patients with comorbidity 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Takaaki Hanyu, Yusuke Muneoka, Takahiro Otani, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   36 ( Pt A )   212 - 218   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Introduction: The elucidation of the clinical impact of comorbidities is important to optimize the treatment and follow-up strategy in oesophageal cancer. We aimed to clarify the surgical and long-term outcomes following oesophagectomy in oesophageal cancer patients with comorbidity.
    Methods: A total of 658 consecutive patients who underwent oesophagectomy for oesophageal cancer between 1985 and 2008 at our institution were enrolled. Based on the criteria of comorbidity as we defined it, we retrospectively reviewed and compared the surgical outcomes and survival between the comorbid (n= 251) and non-comorbid group (n=407).
    Results: Postoperative morbidity and mortality were not significantly different between the two groups. The 5-year overall survival rate of the comorbid group was significantly lower (39.3% vs. 45.2%, adjusted HR = 1.31, 95% CI: 1.07-1.62) but the 5-year disease-specific survival rate was not significantly different between the comorbid and non-comorbid groups (53.9% vs. 53.1%, adjusted HR = 1.11, 95% CI: 0.86 -1.42). The 5-year incidence rate of death from other diseases in the comorbid group was significantly higher than that in the non-comorbid group (26.7% vs. 14.8%, P &lt; 0.01). The leading cause of death from other diseases was pneumonia.
    Conclusions: Oesophagectomy in oesophageal cancer patients with comorbidity can be safely performed. However, the overall survival after oesophagectomy in these patients was unfavorable because of the high incidence of death from other diseases, especially pneumonia. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • Low fat-containing elemental formula is effective for postoperative recovery and potentially useful for preventing chyle leak during postoperative early enteral nutrition after esophagectomy 査読

    Kazuki Moro, Yu Koyama, Shin-ichi Kosugi, Takashi Ishikawa, Hiroshi Ichikawa, Takaaki Hanyu, Kohei Miura, Masayuki Nagahashi, Masato Nakajima, Kumiko Tatsuda, Junko Tsuchida, Chie Toshikawa, Mayuko Ikarashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    CLINICAL NUTRITION   35 ( 6 )   1423 - 1428   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHURCHILL LIVINGSTONE  

    Background and aims: Transthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery.
    Methods: A total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak.
    Results: Patients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P &lt; 0.01). Duration of respirator use and length of ICU stay were also significantly shorter, and TPN was used significantly less in Group LF compared to Group F (P &lt; 0.05). Postoperative chyle leak was observed in six patients in total (8.1%); five patients in Group F and one patient in Group LF, although there was no significant difference in frequency of chyle leak per patient between Group LF and Group F.
    Conclusions: Early EN using low-fat elemental formula after esophagectomy with three-field lymphadenectomy was safe and valid for postoperative recovery and potentially useful in preventing chyle leak. (C) 2016 The Authors. Published by Elsevier Ltd.

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  • [New Classification for Advanced Colorectal Cancer Using CancerPlex®Genomic Tests]. 査読

    Kameyama H, Shimada Y, Ichikawa H, Nagahashi M, Sakata J, Kobayashi T, Nogami H, Maruyama S, Takii Y, Okuda S, Ling Y, Izutsu H, Kodama K, Nakada M, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 11 )   1361 - 1365   2016年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery 査読

    Yusuke Muneoka, Kohei Akazawa, Takashi Ishikawa, Hiroshi Ichikawa, Atsushi Nashimoto, Hiroshi Yabusaki, Norio Tanaka, Shin-ichi Kosugi, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   35   153 - 159   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5-year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer.
    Materials and methods: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation.
    Results: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P &lt; 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5-year RFS.
    Conclusion: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • [A Case of Metastatic Colon Cancer Dramatically Affected by Anti-EGFR Antibody Therapy]. 査読

    Yagi R, Shimada Y, Miura K, Tajima Y, Okamura T, Nakano M, Ichikawa H, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Wakai T, Nogami H, Maruyama S, Takii Y

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   1800 - 1802   2016年11月

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  • [A Case of Advanced Gastric Cancer with Portosystemic Shunt Successfully Treated with Percutaneous Transvenous Coil Embolization]. 査読

    Usui K, Hanyu T, Ichikawa H, Ishikawa T, Muneoka Y, Sato Y, Kano Y, Otani T, Hishiki M, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Kosugi S, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   1917 - 1919   2016年11月

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  • [A Case of Metastatic Colorectal Cancer with HER2 Overexpression/Amplification]. 査読

    Matsumoto A, Shimada Y, Yagi R, Miura K, Tajima Y, Okamura T, Nakano M, Kameyama H, Nogami H, Maruyama S, Takii Y, Ichikawa H, Sakata J, Kobayashi T, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2307 - 2309   2016年11月

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  • [A Case of Simultaneous Multiple Gastric Cancers Showing Differences of Response after Neoadjuvant Chemotherapy with Docetaxel, CDDP, and S-1]. 査読

    Sakai T, Ichikawa H, Ishikawa T, Kosugi S, Hanyu T, Usui K, Muneoka Y, Otani T, Hishiki M, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2377 - 2379   2016年11月

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  • [A Case of Advanced Gastric Cancer Resected for Rebleeding after Palliative Radiotherapy for Hemostasis]. 査読

    Muneoka Y, Ichikawa H, Ishikawa T, Hanyu T, Sato Y, Kano Y, Usui K, Otani T, Hishiki M, Miura K, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Kosugi S, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   1936 - 1938   2016年11月

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  • [A Systematic Analysis of Oncogene and Tumor Suppressor Genes for Panitumumab-Resistant Rectal Cancer with Wild RAS Gene - A Case Report]. 査読

    Tajima Y, Shimada Y, Yagi R, Okamura T, Nakano M, Kameyama H, Nogami H, Maruyama S, Takii Y, Miura K, Ichikawa H, Nagahashi M, Sakata J, Kobayashi T, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2280 - 2282   2016年11月

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  • Mutation burden and microsatellite instability in colorectal cancer in Japan and US 査読

    Nagahashi Masayuki, Wakai Toshifumi, Shimada Yoshifumi, Ichikawa Hiroshi, Kameyama Hitoshi, Kobayashi Takashi, Nakajima Masato, Muneoka Yusuke, Akazawa Kohei, Moro Kazuki, Tsuchida Junko, Soma Daiki, Yuza Kizuki, Ando Takuya, Izutsu Hiroshi, Tse Julie, Okuda Shujiro, Takabe Kazuaki, Protopopov Alexei, Lyle Stephen

    JOURNAL OF CLINICAL ONCOLOGY   34 ( 15 )   2016年5月

  • Risk Factors and Clinical Outcomes of Recurrent Laryngeal Nerve Paralysis After Esophagectomy for Thoracic Esophageal Carcinoma 査読

    Yu Sato, Shin-ichi Kosugi, Naotaka Aizawa, Takashi Ishikawa, Yosuke Kano, Hiroshi Ichikawa, Takaaki Hanyu, Kotaro Hirashima, Takeo Bamba, Toshifumi Wakai

    WORLD JOURNAL OF SURGERY   40 ( 1 )   129 - 136   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The objectives of this study were to assess the incidence of recurrent laryngeal nerve paralysis (RLNP) using laryngoscopy after esophagectomy for thoracic esophageal carcinoma and to clarify the risk factors influencing postoperative RLNP.
    A total of 299 patients who underwent laryngoscopic examination after esophagectomy were retrospectively reviewed. Patients who were found to have postoperative RLNP were followed up every 1-3 months, with a median follow-up period of 3 months. Recovery from paralysis was also evaluated on the basis of each affected nerve. Multivariate analyses using logistic regression were used to identify independent risk factors for RLNP. Cumulative recovery rate was calculated using Kaplan-Meier method.
    A total of 178 (59.5 %) patients were diagnosed with RLNP by first laryngoscopy [bilateral in 59 (33.1 %) patients, right in 15 (8.4 %), and left in 104 (58.4 %)]. In 206 patients who underwent transthoracic and thoracoscopic esophagectomy, independent risk factors for RLNP were lymph node dissection along the right RLN (odds ratio [OR] 3.01, 95 % confidence interval [CI] 1.06-8.54, P = 0.04) and cervical anastomosis (OR 5.94, 95 % CI 1.78-19.80, P &lt; 0.01). Cumulative recovery rate from RLNP was 61.7 % at 12 months after esophagectomy with 91 nerves eventually recovering from paralysis. Median recovery time was 6 months.
    RLNP developed in 60 % of patients after esophagectomy and may be associated with lymphadenectomy around the right RLN and cervical esophageal mobilization. Although 62 % of affected nerves recovered within 12 months, great attention should be given when performing these procedures.

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  • Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma 査読

    Jun Sakata, Toshifumi Wakai, Yasunobu Matsuda, Taku Ohashi, Yuki Hirose, Hiroshi Ichikawa, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Yu Koyama, Kouhei Akazawa, Yoichi Ajioka

    ANNALS OF SURGICAL ONCOLOGY   23 ( 1 )   225 - 234   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma.
    A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model.
    Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or a parts per thousand yen2; P = 0.005) and the LNR (0, 0-5, or &gt; 5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes.
    The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

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  • Histologic determination of primary site of perihilar cholangiocarcinoma based on microscopi'c tumor invasion of the vasculo-biliary sheaths 査読

    Yuki Hirose, Jun Sakata, Makoto Inoue, Zhengkun Zhang, Taku Ohashi, Kohei Miura, Kazuyasu Takizawa, Hiroshi Ichikawa, Masayuki Nagahashi, Takashi Kobayashi, Shin-ichi Kosugi, Hitoshi Kameyanna, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   9 ( 2 )   627 - 638   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    This study aimed to histologically characterize microscopic tumor invasion of the vasculo-biliary sheaths in perihilar cholangiocarcinoma so as to determine the primary tumor site and to clarify clinicopathologic differences according to the primary site. A retrospective analysis was conducted of 52 patients who underwent resection for perihilar cholangiocarcinoma involving both the hepatic hilus and the liver, verified histologically. Histologic features of the vasculo-biliary sheath invasion were evaluated by double staining with hematoxylin-eosin to assess general morphology and Victoria Blue to detect the elastic fibers of the vasculo-biliary sheaths. The perihilar cholangiocarcinomas were classified into extrahepatic-type (34 patients), featuring an extrahepatic component involving the liver, and intrahepatic-type (18 patients), featuring an intrahepatic component involving the hepatic hilus. Hemihepatectomy with extrahepatic bile duct resection was the most common surgical procedure. Tumor size (p = 0.002), pN classification (p = 0.005), and pM classification (p = 0.023) were significant independent prognostic factors. The primary site was not significantly associated with survival after resection (p = 0.214), as patients with extrahepatictype tumors had a cumulative 5-year survival rate of 32%, compared with 28% for patients with intrahepatic-type tumors. Double staining with hematoxylin-eosin and Victoria Blue permits histologic discrimination between tumors of extrahepatic and intrahepatic origin, and thereby determination of the primary tumor site in clinical cases of perihilar cholangiocarcinoma. Combining extrahepatic-type and intrahepatic-type tumors under the term perihilar cholangiocarcinoma is valid clinically, as these tumors show comparable surgical outcomes with similar clinical management.

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  • Prognostic significance of NQO1 expression in esophageal squamous cell carcinoma after preoperative chemotherapy with cisplatin and 5-fluorouracil followed by curative esophagectomy 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Yuki Hirose, Yasunobu Matsuda, Takashi Ishikawa, Takaaki Hanyu, Kenji Usui, Yusuke Muneoka, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   9 ( 7 )   7393 - 7401   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    NAD(P) H:quinone oxidoreductase-1 (NQO1) confers resistance to anticancer agents, particularly to oxidative stress inducers such as cisplatin or 5-fluorouracil in malignant tumors. Here we evaluated the association between NQO1 expression in esophageal squamous cell carcinoma (ESCC) cells and the patients' responses to preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), and we elucidated the prognostic significance of NQO1 expression in ESCC patients. We retrospectively analyzed the cases of 40 patients who underwent preoperative CF therapy followed by curative esophagectomy with lymphadenectomy. Immunohistochemistry of the surgically resected specimens was conducted using the primary monoclonal antibody against NQO1. Eighteen of the 40 patients (45%) had tumors that showed high NQO1 expression (NQO1-high group). The poorer histological response to preoperative CF therapy was dominant in the NQO1-high group compared to the NQO1-low group (72% and 45%, respectively) but the difference was not significant (P=0.09). The 3-year recurrence-free survival rate after esophagectomy in the NQO1-high group was significantly lower compared to the NQO1-low group (39% vs. 76%; P&lt;0.01). A Cox proportional hazards model revealed that high NQO1 expression was an independent unfavorable prognostic factor (HR=3.53; P=0.02) as was pN3 (HR=14.7; P&lt;0.01). The immunohistochemical evaluation of NQO1 expression has potential to predict the treatment response and prognosis in patients who undergo preoperative CF therapy followed by esophagectomy for ESCC.

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  • [Usefulness of Palliative Gastrojejunal Bypass Surgery]. 査読

    Hashimoto Y, Suzuki S, Nihei K, Ohtaki M, Sakamoto K, Yagi R, Shironomae T, Nagai Y, Mishina T, Kameyama H, Ichikawa H, Tatsuda K, Kobayashi T, Kosugi S, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   1559 - 1560   2015年11月

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  • Severe cellulitis and abdominal wall emphysema following laparoscopic colonic surgery: A case report. 査読

    Tanaka R, Kameyama H, Chida T, Kanda T, Kano Y, Ichikawa H, Hanyu T, Ishikawa T, Kosugi S, Wakai T

    Asian journal of endoscopic surgery   8 ( 2 )   193 - 196   2015年5月

  • Three cases of esophageal carcinoma achieved a pathological complete response after neoadjuvant chemotherapy with cisplatin and 5-fluorouracil 査読

    Hidehito Oyanagi, Hiroshi Ichikawa, Shin-Ichi Kosugi, Takeo Banba, Takaaki Hanyu, Kotaro Hirashima, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   42 ( 4 )   497 - 501   2015年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    We report three cases of esophageal carcinoma all of which achieved a pathological complete response after neoadjuvant chemotherapy (NAC) with cisplatin and 5-fluorouracil (CF). All three patients were men with clinical stage II squamous cell carcinoma of the middle thoracic esophagus. We administered 2 courses of CF treatment as NAC and then performed radical esophagectomy. Pathologic examination revealed no viable tumor cells in the resected esophagus. The patients are currently alive with no evidence of disease.

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  • Prognostic analysis of submucosa-invasive gastric cancer with lymph node metastasis 査読

    Takaald Hanyu, Atsushi Matsuki, Shin-ichi Kosugi, Takashi Ishikawa, Atsushi Nashimoto, Hiroshi Yabusaki, Masaki Aizawa, Hiroshi Ichikawa, Yoshifumi Shimada, Yuki Hirose, Toshifumi Wakai

    SURGERY   157 ( 4 )   716 - 722   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    Background. The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease.
    Methods. We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort.
    Results. The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P &lt; .01), male sex (HR 2.26; 95% CI 1.5- 3.26; P &lt; .01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P &lt; .01) were independent prognostic factors. The 5-year overall survival rates were 92.5 % in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P &lt;.01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73).
    Conclusion. The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

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  • Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis 査読

    Hiroshi Ichikawa, Akihiko Yoshida, Tatsuo Kanda, Shin-ichi Kosugi, Takashi Ishikawa, Takaaki Hanyu, Takahiro Taguchi, Marimu Sakumoto, Hitoshi Katai, Akira Kawai, Toshifumi Wakai, Tadashi Kondo

    CANCER SCIENCE   106 ( 1 )   115 - 124   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of the small intestine (I-GIST) show more aggressive behavior than those of the stomach (S-GIST), and the molecular background of the malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for four cases each of surgically resected I-GIST and S-GIST using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GIST and 23 S-GIST. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly downregulated in I-GIST at both the protein and mRNA levels (P&lt;0.01; fold difference 2.0). Immunohistochemistry of 254 additional cases from multiple clinical facilities showed that PML-negative cases were significantly frequent in the I-GIST group (P&lt;0.001). The 5-year recurrence-free survival rate was significantly lower in the PML-negative than in the PML-positive cases (60.1% vs 91.7%; P&lt;0.001). Multivariate analysis revealed that downregulation of PML was an independent unfavorable prognostic factor (hazard ratio=2.739; P=0.001). Our study indicated that prognostication based on PML expression may have potential for optimizing the treatment strategy for GIST patients. Further validation studies of PML for clinical application, and investigation for the mechanistic significance of PML to clarify the molecular backgrounds of malignancy in GIST are warranted.

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  • Internal hernia after laparoscopic-assisted proximal gastrectomy with jejunal interposition for gastric cancer: a case report. 査読

    Hirashima K, Ishikawa T, Kosugi S, Kano Y, Sato Y, Ichikawa H, Hanyu T, Bamba T, Wakai T

    Surgical case reports   1 ( 1 )   49   2015年

  • Conservative treatment of idiopathic spontaneous pneumoperitoneum in a bedridden patient: a case report. 査読

    Tanaka R, Kameyama H, Nagahashi M, Kanda T, Ichikawa H, Hanyu T, Ishikawa T, Kobayashi T, Sakata J, Kosugi S, Wakai T

    Surgical case reports   1 ( 1 )   69   2015年

  • Intrathoracic esophagojejunostomy using OrVil™ for gastric adenocarcinoma involving the esophagus. 査読

    Yajima K, Kanda T, Kosugi S, Kano Y, Ishikawa T, Ichikawa H, Hanyu T, Wakai T

    World journal of gastrointestinal surgery   6 ( 12 )   235 - 240   2014年12月

  • A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer 査読

    Ryo Tanaka, Hitoshi Kameyama, Mae Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakano, Takashi Ishikawa, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Shin-Ichi Kosugi, Masahiro Minagawa, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2364 - 2366   2014年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, NO, MO, Stage IA) during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

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  • A case of an elderly patient who underwent single-incision laparoscopic surgery for small intestine cancer 査読

    Yoshifumi Hashimoto, Hitoshi Kameyama, Yuki Hirose, Ryoma Yagi, Mae Nakano, You Sato, Tomoki Kido, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakano, Takashi Ishikawa, Yoshifumi Shimada, Takashi Kobayashi, Jun Sakata, Masahiro Minagawa, Shin-Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2442 - 2443   2014年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    An 81-year-old man presented with chief complaints of abdominal pain and vomiting. Intestinal obstruction was found at the time of admission to a local hospital in October 2011. Conservative treatment provided symptomatic relief
    however, he was readmitted with similar symptoms in December 2011. Small-intestinal wall thickening was detected by abdominal and pelvic computed tomography, and he was referred to our hospital. Small-bowel endoscopy revealed an elevated subcircumferential tumor in the jejunum. Biopsy revealed well to moderately differentiated adenocarcinoma diagnosed as jejunal cancer, which caused narrowing of the jejunum. Single-incision laparoscopy-assisted small-bowel resection was performed. The intraoperative findings were a tumor with inflammatory changes in the jejunum and enlarged surrounding lymph nodes. We performed regional lymph node dissection. Histopathological analysis showed moderately differentiated small-intestinal tubular adenocarcinoma and 2 of 5 lymph nodes positive for metastatic cancer cells. After an uneventful postoperative course, he was discharged on day 7. He preferred not to undergo postoperative adjuvant chemotherapy and quickly recovered his activities of daily living postoperatively. He stayed home until he developed abdominal distention resulting from peritoneal recurrence 1 year and 6 months postoperatively and died 1 month later.

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  • Prognostic Significance of Initial Recurrence Site in Hematogenous Recurrence of Esophageal Squamous Cell Carcinoma 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Tatsuo Kanda, Takashi Ishikawa, Kazuhito Yajima, Kohei Akazawa, Tsutomu Suzuki, Toshifumi Wakai

    HEPATO-GASTROENTEROLOGY   61 ( 136 )   2241 - 2246   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Hematogenous recurrences of esophageal squamous cell carcinoma (ESCC) have dismal prognoses, but prognostic heterogeneity exists in this disease. The objectives of this study were to clarify the prognosis in this disease with regard to the initial recurrence site and to define the prognostic factors. Methodology: We retrospectively reviewed the cases of 67 consecutive patients with hematogenous recurrence in major organs after esophagectomy for ESCC of the thoracic esophagus and the esophagogastric junction. We analyzed clinicopathological characteristics, survival probability and potential prognostic factors. Results: Lung, liver, bone, and multiple-organ metastases occurred in 24, 19, 14, and 10 patients, respectively. Twenty-seven patients simultaneously had locoregional recurrence (combined recurrence). Among all 67 patients, the median disease-free interval (DFI) was 9.7 months, and the median survival time after the initial recurrence was 4.9 months. The patients with initial lung metastasis had most favorable prognosis with the median survival time of 9.8 months. A multivariate analysis identified that initial recurrence site, DFI, combined recurrence, and anticancer therapy were independent prognostic factors. Conclusions: The initial recurrence site contributes to the prognostic heterogeneity of patients with hematogenous recurrence of ESCC. The prognostic factors identified in this study are useful to optimize the management of these patients.

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  • Current status of adjuvant chemotherapy in patients with p-stage II and p-stage III gastric cancer 査読

    Yu Sato, Kazuhito Yajima, Shin-Ichi Kosugi, Yusuke Muneoka, Hiroshi Ichikawa, Takaaki Hanyu, Kaoru Sakamoto, Takashi Ishikawa, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 8 )   961 - 964   2014年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that postoperative chemotherapy using S-1 is a standard treatment in Japan for patients with p-Stage n and p-Stage in gastric cancer. We retrospectively reviewed the effect of adjuvant chemotherapy received by 47 patients with p-Stage II and p-Stage M gastric cancer between January 2007 and June 2012. Our hospital is a local university hospital with a high intensive care unit. S-1 monotherapy was administered to 32 patients (adjuvant S-1 group, 68.1%)
    22 patients (68.8%) among them completed one year of therapy without any modification to the administration schedule. A total of 8 patients (25.0%) experienced grade 3 adverse events, and 9 patients required a dose reduction, a modification of the administration schedule, or termination of the therapy. S-1 was not administrated to 15 patients (no adjuvant S-1 group, 31.9%)
    among these patients, 12 (80.0%) were not administered S-1 because of their advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of S-1 and survival rate were high for patients in the adjuvant S-1 group, which was similar to the results of the ACTS-GC. However, 25 of 47 patients (53.2%) with p-Stage n and p-Stage IE gastric cancer did not improve after sufficient adjuvant therapy
    therefore, it is important to develop new treatment strategies for these patients.

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  • Is early enteral nutrition initiated within 24 hours better for the postoperative course in esophageal cancer surgery? 査読

    Manba N, Koyama Y, Kosugi S, Ishikawa T, Ichikawa H, Minagawa M, Kobayashi T, Wakai T

    Journal of clinical medicine research   6 ( 1 )   53 - 58   2014年2月

  • Amplification of Genomic DNA for Decoy Receptor 3 Predicts Post-Resection Disease Recurrence in Breast Cancer Patients. 査読

    Kanbayashi C, Koyama Y, Ichikawa H, Sakata E, Hasegawa M, Toshikawa C, Manba N, Ikarashi M, Kobayashi T, Minagawa M, Kosugi SI, Wakai T

    World journal of oncology   5 ( 1 )   14 - 23   2014年2月

  • Proteomic and meta-transcriptomic study on lymph node metastasis in gastric cancer 査読

    Hiroshi Ichikawa, Tatsuo Kanda, Shin-ichi Kosugi, Yasuyuki Kawachi, Toshifumi Wakai, Tadashi Kondo

    EuPA Open Proteomics   3   183 - 194   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    To examine the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed protein expression profiling of paired non-tumor, primary tumor, and LNM tissues. Using a label-free proteomic approach, we generated protein expression profiles of 3894 unique proteins and identified 109 differentially expressed proteins. Functional pathway analysis of the differentially expressed proteins showed that members of the beta-3 integrin (ITGB3) pathway were significantly enriched. Aberrations of ITGB3 were reported in various malignancies
    however, ITGB3 in LNM tissues has not been examined to date. Different level of ITGB3 expression was confirmed in 20 gastric cancer cases by Western blotting. We analyzed the mRNA levels of the differentially expressed proteins by using a public mRNA expression database
    38.8% of the proteins examined, including those involved in oxidation and reduction, showed correlation between protein and mRNA levels. Proteins without such correlation included factors related to cell adhesion. Our study suggests a novel role for the integrin pathway in the development of LNM in gastric cancer and indicated possible benefits of observational transcriptomic analysis for proteomic studies. © 2014 The Authors.

    DOI: 10.1016/j.euprot.2014.03.001

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  • Conservative treatment of esophageal perforation related to a peptic ulcer with pyloric stenosis 査読

    Ryo Tanaka, Shin-Ichi Kosugi, Daisuke Sato, Hiroshi Hirukawa, Tetsuya Tada, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Takashi Kobayashi, Toshifumi Wakai

    Clinical Journal of Gastroenterology   7 ( 4 )   295 - 298   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer-Verlag Tokyo  

    We report a case of esophageal perforation (Boerhaave syndrome) caused by vomiting related to a duodenal ulcer with pyloric stenosis. A 45-year-old male presented with left chest pain and dyspnea after forceful vomiting. Chest radiography and computed tomography (CT) revealed a massive left pleural effusion and left tension pneumothorax. Abdominal CT revealed pyloric stenosis with a remarkably dilated stomach. Tube thoracostomy and nasogastric suction were immediately performed and we selected conservative treatment based on the following factors-a stable general condition without sepsis, early diagnosis, and good drainage. Esophagogastroduodenoscopy on hospital day 9 demonstrated a healing ulcer in the lower esophagus and pyloric stenosis. We performed distal gastrectomy as elective surgery for pyloric stenosis due to a duodenal ulcer on hospital day 30. In summary, an esophageal perforation with contamination spreading to the thoracic cavity was successfully treated with conservative treatment. © 2014 Springer.

    DOI: 10.1007/s12328-014-0493-3

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  • Is Early Enteral Nutrition Better for Postoperative Course in Esophageal Cancer Patients? 査読

    Kazuaki Kobayashi, Yu Koyama, Shin-ichi Kosugi, Takashi Ishikawa, Kaoru Sakamoto, Hiroshi Ichikawa, Toshifumi Wakai

    NUTRIENTS   5 ( 9 )   3461 - 3469   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p &lt; 0.05. Group E showed fewer days for the first fecal passage (p &lt; 0.01), lesser dose of postoperative albumin infusion (p &lt; 0.01), less use of TPN (p &lt; 0.01), and shorter duration of SIRS (p &lt; 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation.

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  • Laser microdissection and two-dimensional difference gel electrophoresis reveal the role of a novel macrophage-capping protein in lymph node metastasis in gastric cancer 査読

    Hiroshi Ichikawa, Tatsuo Kanda, Shin-Ichi Kosugi, Yasuyuki Kawachi, Hiroki Sasaki, Toshifumi Wakai, Tadashi Kondo

    Journal of Proteome Research   12 ( 8 )   3780 - 3791   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer. © 2013 American Chemical Society.

    DOI: 10.1021/pr400439m

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  • Laser Microdissection and Two-Dimensional Difference Gel Electrophoresis Reveal the Role of a Novel Macrophage-Capping Protein in Lymph Node Metastasis in Gastric Cancer 査読

    Hiroshi Ichikawa, Tatsuo Kanda, Shin-ichi Kosugi, Yasuyuki Kawachi, Hiroki Sasaki, Toshifumi Wakai, Tadashi Kondo

    JOURNAL OF PROTEOME RESEARCH   12 ( 8 )   3780 - 3791   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer.

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  • The Association between Sentinel Lymph Node Metastasis and Ki-67 Labeling Index. 査読

    Koyama Y, Ichikawa H, Sakata J, Sakata E, Tatsuda K, Hasegawa M, Toshikawa C, Manba N, Ikarashi M, Wakai T

    Adv. Breast Cancer Res   2 ( 3 )   60 - 65   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Two-step laparoscopic surgery for a patient with synchronous double cancer of the colon and stomach accompanied by severe chronic obstructive pulmonary disease. 査読

    Yajima K, Kosugi S, Kano Y, Hanyu T, Ichikawa H, Ishikawa T, Nogami H, Wakai T

    Case reports in surgery   2013   246515   2013年

  • Proteomic-based identification of the APC-binding protein EB1 as a candidate of novel tissue biomarker and therapeutic target for colorectal cancer 査読

    Sugihara Yutaka, Taniguchi Hirokazu, Kushima Ryoji, Tsuda Hitoshi, Kubota Daisuke, Ichikawa Hiroshi, Sakamoto Kano, Nakamura Yukiko, Tomonaga Takeshi, Fujita Shin, Kondo Tadashi

    JOURNAL OF PROTEOMICS   75 ( 17 )   5342 - 5355   2012年9月

  • Clinicopathological Characteristics and Prognosis of Patients With Esophageal Carcinoma Invading Adjacent Structures Found During Esophagectomy 査読

    Shin-Ichi Kosugi, Hiroshi Ichikawa, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Katsuyoshi Hatakeyama

    JOURNAL OF SURGICAL ONCOLOGY   105 ( 8 )   767 - 772   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Objectives: A treatment strategy for patients with esophageal carcinoma invading adjacent structures found during esophagectomy (surgical T4; sT4) has not been established and the role of esophagectomy remains controversial. The aims of this study were to assess the clinicopathological characteristics and to clarify the prognostic factors of patients who underwent esophagectomy for sT4 tumors.
    Methods: A consecutive series of 76 patients who were found to have sT4 tumors was reviewed retrospectively. T4 tumors were divided into two groups according to the invaded structures. Cox's multivariate proportional hazard model was used to identify prognostic factors.
    Results: Complete tumor clearance with combined resection was performed in 12 patients (16%). Overall 1-, 3-, and 5-year survival rates were 40.8%, 9.2%, and 7.9%, respectively. There was no significant relationship between survival and invaded structure type or residual tumor status. Postoperative therapy was selected as an independent prognostic factor.
    Conclusions: The complete resection rate was low and the prognosis of patients with sT4 tumors was poor. Subclassification according to the invaded structures was not a prognostic factor in this study. Postoperative therapy may improve survival in sT4 patients and should be considered irrespective of residual tumor status after esophagectomy. J. Surg. Oncol. 2012;105:767-772. (C) 2012 Wiley Periodicals, Inc.

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  • Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Satoru Nakagawa, Tatsuo Kanda, Masanori Tsuchida, Teruaki Koike, Otsuo Tanaka, Katsuyoshi Hatakeyama

    SURGERY   149 ( 2 )   164 - 170   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    Background. The clinical significance of operative treatment for metachronous pulmonary metastasis from esophageal carcinoma is unclear.
    Methods. We retrospectively reviewed 23 consecutive patients who underwent operative resection for metachronous pulmonary metastasis from esophageal carcinoma from 1991 to 2008. Patient baseline characteristics, survival probability, and prognostic factors were analyzed. The median follow-up period was 31 months for surviving patients.
    Results. There were 19 men and 4 women, with a median age of 66 years at the time of pulmonary resection. The median disease-free interval was 15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a maximum number of 4. The median operative time and blood loss were 94.5 minutes and 18 mL, respectively. The median length of postoperative stay was 12.5 days. The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7 months. Univariate analysis revealed that an extrapulmonary metastasis as the initial recurrence site was an unfavorable prognostic factor (P = .0411). Multivariate analyses, however, did not identify the initial recurrence site as an independent prognostic factor (P =. 0542).
    Conclusion. Operative resection for metachronous pulmonary metastasis from esophageal carcinoma is an acceptable treatment. This study of a limited number of patients may have created a constitutional selection bias. An antecedent extrapulmonary metastasis was found to be an unfavorable prognostic factor. (Surgery 2011;149:164-70.)

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受賞

  • 優秀演題賞

    2021年12月   第74回日本食道学会学術集会   胸部食道扁平上皮癌術前CF療法症例における臨床的リンパ節転移径と予後との関連

    市川 寛, 須藤 翔, 番場 竹生, 加納 陽介, 羽入 隆晃, 茂木 大輔, 宗岡 悠介, 小杉 伸一, 中川 悟, 若井 俊文

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  • 若手奨励賞

    2018年11月   Japan Digestive Disease Week 2018   胃癌における相同組換え修復機構の破綻と予後

    市川 寛

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  • Young scientist travel award

    2012年5月   Asia Oceania Human Proteome Organization  

    市川 寛

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共同研究・競争的資金等の研究

  • NOTCHシグナルを介した食道癌化学療法奏効性の分子機構の解明

    2019年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 

    市川 寛

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    担当区分:研究代表者  資金種別:競争的資金

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  • 食道癌のリンパ行性進展に関与する脂質メディエーター分子機構の解明および臨床的意義

    2016年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    市川 寛

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    担当区分:研究代表者  資金種別:競争的資金

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