Details of a Researcher - TAKADA Kouichi

Papers - TAKADA Kouichi

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大須賀崇裕, 宮西浩嗣, 田中信悟, 中村元, 坂本拡基, 大沼啓之, 村瀬和幸, 高田弘一, 小船雅義, 加藤淳二, 永山稔, 木村康利, 竹政伊知朗, 辻脇光洋, 長谷川匡

肝臓 ( (一社)日本肝臓学会 ) 60 ( 8 ) 294 - 301 2019.08

症例は56歳男性。B型肝硬変とアルコール性肝障害で当科通院中。2017年7月のEOB-MRIにて肝S4に多血性腫瘍を認められ入院。採血検査では、肝硬変による肝トランスアミナーゼ上昇、血小板減少を認めたが、腫瘍マーカーは陰性であった。EOB-MRIでは、腫瘍は10mm大で早期相で不均一な高信号、肝細胞相で低信号、拡散強調画像で高信号を呈した。肝細胞癌(HCC)Stage1と診断し、腹腔鏡下肝部分切除術を施行した。術後16ヵ月経過し再発は認めていない。病理学的に腫瘍は高分化型HCC、中分化型HCC、HCCと肝内胆管癌の移行部、高-中分化型肝内胆管癌の4領域で構成される混合型肝癌であった。本症例は小型の段階で、HCCの一部が胆管細胞癌へ脱分化又は形質転換した非常に初期の混合型肝癌と考えられた。(著者抄録)

Spindle cell rhabdomyosarcoma in a lumbar vertebra with FUS-TFCP2 fusion

Yohei Tagami, Shintaro Sugita, Terufumi Kubo, Noriyuki Iesato, Makoto Emori, Kohichi Takada, Mitsuhiro Tsujiwaki, Keiko Segawa, Taro Sugawara, Tomoki Kikuchi, Tadashi Hasegawa

Pathology - Research and Practice ( Elsevier BV ) 215 ( 8 ) 152399 - 152399 2019.08 [Refereed] [International journal]

A 70-year-old woman developed severe buttock pain that progressed to a walking disturbance. Radiographs and computed tomography scans revealed an osteolytic lesion with osteosclerosis extending from the body to the arch of the fifth lumbar vertebra. Magnetic resonance imaging showed multinodular masses in the fifth lumbar vertebral body extending into the spinous processes and right transverse process. The masses were hypointense to isointense on T1-weighted images and hypointense to hyperintense on T2-weighted images. Histologic examination of biopsy specimens showed destruction of the trabecula of the vertebral bone by a fascicular and solid proliferation of spindle tumor cells and scattered rhabdomyoblasts, in a fibrotic background. The tumor cells were immunoreactive for keratins, vimentin, desmin, MyoD1, myogenin, and anaplastic lymphoma kinase. Fluorescence in situ hybridization detected split signals for FUS and TFCP2 in 80% and 64% of the tumor cells, respectively, suggesting FUS-TFCP2 fusion. Reverse transcription-polymerase chain reaction revealed a FUS-TFCP2 fusion. The final diagnosis was spindle cell rhabdomyosarcoma of a lumbar vertebra with a FUS-TFCP2 fusion. A spindle cell rhabdomyosarcoma with a FUS-TFCP2 fusion in a vertebral bone is rare and should be differentiated from metastatic carcinoma, particularly in the elderly.

DOI PubMed

Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis Type 1 That Was Successfully Treated with Regorafenib

Akihito Fujimi, Yasuhiro Nagamachi, Naofumi Yamauchi, Fumito Tamura, Tomohiro Kimura, Naoya Miyajima, Hidetoshi Inomata, Takuji Nishisato, Makoto Yoshida, Kohichi Takada, Ko Kobayashi, Junji Kato

Internal Medicine ( Japanese Society of Internal Medicine ) 58 ( 13 ) 1865 - 1870 2019.07 [Refereed]

DOI

Successful Treatment of Hepatocellular Carcinoma with Transcatheter Arterial Chemoembolization followed by Radical Liver Transplantation in a Patient with Severe Liver Damage

Hajime Nakamura, Yutaka Kawano, Koji Miyanishi, Kazuma Ishikawa, Tomohiro Kubo, Shingo Tanaka, Kohichi Takada, Masayoshi Kobune, Kohei Harada, Norio Kawamura, Tsuyoshi Shimamura, Hiromi Kanno-Okada, Junji Kato

Case Reports in Oncology ( S. Karger AG ) 12 ( 1 ) 289 - 296 2019.04 [Refereed]

Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage.

DOI

miR-7977 inhibits the Hippo-YAP signaling pathway in bone marrow mesenchymal stromal cells.

Masahiro Yoshida, Hiroto Horiguchi, Shohei Kikuchi, Satoshi Iyama, Hiroshi Ikeda, Akari Goto, Yutaka Kawano, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Junji Kato, Masayoshi Kobune

PloS one ( Public Library of Science (PLoS) ) 14 ( 3 ) e0213220 - e0213220 2019 [Refereed] [International journal]

We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known. In this study, we performed transduction of a miR-7977 mimic into MSCs, compared transcriptomes between control-transduced (n = 3) and miR-7977-transduced MSCs (n = 3), and conducted pathway analysis. The array data revealed that the expression of 0.05% of genes was reduced 2-fold and the expression of 0.01% of genes was increased 2-fold. Interestingly, approximately half of these genes possessed a miR-7977 target site, while the other genes did not, suggesting that miR-7977 regulates the gene expression level directly and indirectly. Gene set enrichment analysis showed that the gene sets of Yes-associated protein 1 (YAP1) _up were significantly enriched (p<0.001, q<0.25), suggesting that miR-7977 modulates the Hippo-YAP signaling pathway. Visualization of pathway and network showed that miR-7977 significantly reduced the expression of Hippo core kinase, STK4. miR-7977 inactivated the Hippo-YAP signaling pathway as proven by GFP-tagged YAP nuclear trans localization and TEAD reporter assay. The miR-7977-transduced MSC cell line, HTS-5, showed elevated saturation density and enhanced entry into the cell cycle. These results suggest that miR-7977 is a critical factor that regulates the Hippo-YAP signaling pathway in BM-MSCs and may be involved in the upregulation of leukemia-supporting stroma growth.

DOI PubMed

A case of small combined hepatocellular-cholangiocellular carcinoma

Takahiro Osuga, Koji Miyanishi, Shingo Tanaka, Hajime Nakamura, Hiroki Sakamoto, Hiroyuki Onuma, Kazuyuki Murase, Koichi Takada, Masayoshi Kobune, Junji Kato, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Mitsuhiro Tsujiwaki, Tadashi Hasegawa

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 60 ( 8 ) 294 - 301 2019

A 56-year-old man who had been visiting our hospital for type B cirrhosis since 1988 was admitted for the treatment of hepatic tumor that was detected using an EOB-MRI study in July 2017. Blood test showed elevated aminotransferase and thrombocytopenia due to liver cirrhosis however, tumor markers were negative. In CT during angiography, CTAP showed low absorption, and CTHA showed heterogeneously high absorption. We diagnosed the tumor as hepatocellular carcinoma, followed by a laparoscopic partial resection of the liver. In 16 months after surgery, there was no recurrence. As per the pathological findings, the tumor consisted of (1) well-differentiated hepatocellular carcinoma component, (2) moderately-differentiated hepatocellular carcinoma component, (3) transitional portion between hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and (4) intrahepatic cholangiocarcinoma component. Thus, the tumor was diagnosed as classical type combined hepatocellular-cholangiocellular carcinoma as per the WHO classification. It was suggested that dedifferentia-tion and transformation occurred in the untreated small hepatocellular carcinoma.

DOI

Trastuzumab-Based Combination Chemotherapy in Patients with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

Yohei Arihara, Kazuyuki Murase, Kohichi Takada, Naotaka Hayasaka, Shogo Miura, Koji Miyanishi, Masayoshi Kobune, Makoto Kurose, Yukinori Akiyama, Shintaro Sugita, Junji Kato

Case Reports in Oncology ( S. Karger AG ) 11 ( 3 ) 835 - 841 2018.12 [Refereed] [International journal]

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

DOI PubMed

Denosumab prevents bone loss in newly diagnosed malignant lymphoma patients undergoing corticosteroid-containing chemotherapy: A prospective, non-randomized study

Ayumi Tatekoshi, Tsutomu Sato, Satoshi Iyama, Kohichi Takada, Kazuyuki Murase, Masahiro Yoshida, Soushi Ibata, Akari Hashimoto, Yusuke Kamihara, Hiroto Horiguchi, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Sapporo Medical journal ( Sapporo Medical University ) 87 ( 1-6 ) 35 - 47 2018.12

Background: Malignant lymphoma patients have a high risk of bone mineral density (BMD) loss caused by corticosteroid-containing chemotherapy. Bisphosphonates have been used to prevent bone loss: however, little is known about effects of denosumab, a fully humanized monoclonal antibody inhibiting osteoclast-mediated bone resorption. Methods: This clinical trial was conducted in newly diagnosed lymphoma patients undergoing corticosteroidcontaining chemotherapy. BMD was evaluated at baseline, and patients with a lumbar spine T-score of < -1 were subcutaneously administered once with 60 mg of denosumab ("Denosumab" group). Patients with a T-score > -1 were allocated to the "No treatment" group. BMD was reevaluated at 24 weeks after enrollment. Bone turnover markers (BTMs) were collected at 0,2, and 24 weeks. Results: Forty-three patients were enrolled (19 in the "Denosumab" group and 24 in the "No treatment" group). Patients in the "No treatment" group had decreased T-scores for the lumbar spine or femoral neck (P < 0.0001 or P = 0.0029, respectively) at 24 weeks after enrollment, whereas both T-scores were stable in the "Denosumab" group. Of the 18 patients in the "Denosumab" group, 12 had a T-score change from baseline (AT-score) of > 0, whereas the remaining six patients had a AT-score < 0. These six patients had severely low T-scores at enrollment. Osteoclastic BTMs were strongly suppressed during the 24 weeks in the "Denosumab" group. The probability of major osteoporotic fracture or hip fracture in the "No treatment?' group increased during the 24 weeks (P = 0.0195 or P = 0.0289, respectively), whereas pretreatment with denosumab prevented increased risks of both types of fractures. Conclusions: Our data suggests that BMD screening at diagnosis of lymphoma should be considered so that the bone health of lymphoma survivors can be improved with denosumab.

DOI

An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

Free radical biology & medicine 129 88 - 96 2018.12 [Refereed] [International journal]

BACKGROUND & AIMS: The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC). METHODS: Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n = 38 HCC and 55 controls). The effects of modifying the intronic variants were determined by luciferase assays. MUTYH-null mice were used to examine the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis. RESULTS: Significant associations were found for a single intron SNP (rs3219487) in the MUTYH gene. The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (OR = 9.27, 95% CI = 2.39 -32.1, P = 0.0005). MUTYH mRNA levels in both peripheral mononuclear cells were significantly lower in G/A or A/A genotyped subjects (P = 0.0157 and 0.0108, respectively). We found that -2000 in the MUTYH promoter region is involved in enhanced expression of MUTYH by insertion of a major allele sequence of rs3219487. Liver tumors were observed in MUTYH-null mice after 12 months´ high iron diet, but no tumors developed when dietary anti-oxidant (N-Acetyl-L-cysteine) was also provided. CONCLUSIONS: CHC patients with the rs3219487 adenine allele had a significantly increased risk of developing HCC. MUTYH-null mice with iron-associated oxidative stress were susceptible to development of liver tumors unless prevented by dietary anti-oxidants.

DOI PubMed

低用量IL2はBCL2の発現を誘導することでCD4制御性T細胞のアポトーシスを抑制する(Low-close interleukin-2 induces BCL2 expression and resistance to apoptosis in CD4 regulatory T Cells)

松野鉄平, 村瀬和幸, 高田弘一, 河野豊, 平川昌宏, 宮西浩嗣, 小船雅義, 加藤淳二

札幌医学雑誌 ( 札幌医科大学 ) 87 ( 1-6 ) 49 - 61 2018.12 [Refereed]

制御性T細胞(Treg)は自己免疫寛容や恒常性の維持に重要な役割を果たしている。インターロイキン2(IL-2)はTregの増加、活動、生存に非常に重要である。既報では低用量IL-2はTregの増加に選択的に作用し、自己免疫疾患の臨床症状を改善させると報告されている。IL-2がTregの内因性アポトーシスにどのように作用するのかを調べるために、我々はBH3プロファイリングを用い、ミトコンドリアのアポトーシスプライミングを定量的に測定した。BH3ペプチドパターンではTregのプライミングがTconより多く、それがBCL2に依存していることを示した。実際に、TregではTconよりもBCL2の発現が低かった。IL-2の作用を調べるために、TregとTconに分け、異なった用量のIL-2で培養した。Tregでは低用量のIL-2(10 IU/ml)でプライミングは低下しBCL2発現は増加したが、Tconではプライミングの低下とBCL2発現の増加には高用量のIL-2(>100 IU/ml)が必要であった。また、低用量IL-2はTregにおいてのみアポトーシスへの感受性を減らすことがアポトーシスアッセイによって判明した。ABT-199というBCL2選択的阻害剤はTregとTcon両者のプライミングとアポトーシスを増加させる。IL2はTregにおいてのみこのABT-199の効果を打ち消した。このことからTregにおけるIL2による内因性アポトーシスの阻害がBCL2に依存していることが判明した。(著者抄録)

Secondary malignant giant cell tumor of bone with histone H3.3 mutation: A case series

Makoto Emori, Satoshi Nagoya, Masato Sugawara, Emi Mizushima, Junya Shimizu, Yasutaka Murahashi, Kazuyuki Murase, Kohichi Takada, Shintaro Sugita, Michiaki Takagi, Tadashi Hasegawa, Toshihiko Yamashita

Journal of Orthopaedic Science ( Elsevier BV ) 26 ( 5 ) 926 - 930 2018.12 [Refereed] [Domestic journal]

DOI PubMed

Halo formations around senile hemangiomas in diffuse plane normolipemic xanthomatosis associated with monoclonal gammopathy.

Tokimasa Hida, Hiroki Takahashi, Kohichi Takada, Hisashi Uhara

JAAD case reports 4 ( 10 ) 1034 - 1036 2018.11 [Refereed] [International journal]

DOI PubMed

High expression of nucleoporin 133 mRNA in bone marrow CD138+ cells is a poor prognostic factor in multiple myeloma

Soushi Ibata, Masayoshi Kobune, Shohei Kikuchi, Masahiro Yoshida, Shogo Miura, Hiroto Horiguchi, Kazuyuki Murase, Satoshi Iyama, Kohichi Takada, Koji Miyanishi, Junji Kato

Oncotarget ( Impact Journals LLC ) 9 ( 38 ) 25127 - 25135 2018.05 [Refereed]

Recent advances in plasma cell biology and molecularly-targeted therapy enable us to employ various types of drugs including immunomodulatory drugs, proteasome inhibitors, and immunotherapy. However, the optimal therapeutic strategies to introduce these drugs for heterogeneous patients with multiple myeloma (MM) have not yet been clarified. In the present study, we attempted to identify a new factor indicating poor prognosis in CD138+ myeloma cells using accumulated Gene Expression Omnibus (GEO) datasets from studies of MM and to assess the relationship between gene expression and survival using MAQC-II Project Myeloma (GSE24080). Five GEO datasets (GSE5900, GSE58133, GSE68871, GSE57317 and GSE16791) which were analyzed by the same microarray platform (GLP570) were combined into one MM database including various types of MM. However, we found that gene expression levels were quite heterogeneous. Hence, we focused on the differentially-expressed genes (DEGs) between newlydiagnosed MM and relapsed/refractory MM and found that the expression levels of more than 20 genes changed two-fold or more. Additionally, pathway analysis indicated that six pathways including Hippo signaling were significantly enriched. Then, we applied all DEGs and genes associated with core enrichment for GSE24080 to evaluate their involvement in disease prognosis. We found that nucleoporin 133 (NUP133) is an independent poor prognostic factor by Cox proportional hazard analysis. These results suggested that high expression of NUP133 could be useful when choosing the appropriate MM therapy and may be a new target of MM therapy.

DOI

Clostridium difficile肝膿瘍の1例

松野鉄平, 田中信悟, 宮西浩嗣, 河野豊, 中村元, 坂本拡基, 早坂尚貴, 石川和真, 村瀬和幸, 高田弘一, 高梨訓博, 勝木伸一, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 59 ( 3 ) 180 - 186 2018.03 [Refereed]

症例は68歳、男性。発熱、心窩部痛を主訴に近医を受診し、肝膿瘍、播種性血管内凝固症候群(DIC)、門脈血栓症と診断され当院へ転院となった。前医にてメロペネムが投与されるも改善傾向を認められなかったが、当院入院時の血液培養検査にてClostridium difficile(C.difficile)が検出され、メトロニダゾール内服を開始したところ速やかに改善した。肝膿瘍および便からもC.difficileが検出され、PCR-rebotypingで全て同一菌株と同定された。血液培養検査でC.difficileが検出されたため早期にメトロニダゾールの投与を開始でき、治癒が得られた肝膿瘍症例を経験した。広域抗菌薬に対する反応が悪い肝膿瘍に対しては、原因菌としてC.difficileも念頭に診断・治療を進めることが必要である。(著者抄録)

A case of cisplatin-refractory advanced pure seminoma showing complete remission after treatment with high-dose carboplatin plus etoposide as fourth-line salvage chemotherapy

Kimihito Tachikawa, Naotaka Nishiyama, Takashi Muranaka, Koichi Takada, Kazuyuki Murase, Tsutomu Kouno, Kato Junji, Naoya Masumori

International Cancer Conference Journal ( Springer Science and Business Media LLC ) 7 ( 1 ) 6 - 10 2018.01 [Refereed]

DOI

Increased Duodenal Iron Absorption through Upregulation of Ferroportin 1 due to the Decrement in Serum Hepcidin in Patients with Chronic Hepatitis C.

Masanori Sato, Koji Miyanishi, Shingo Tanaka, Akira Sakurada, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Masayoshi Kobune, Junji Kato

Canadian journal of gastroenterology & hepatology 2018 2154361 - 2154361 2018 [Refereed] [International journal]

Hepatic iron accumulation is generally increased in the chronic hepatitis C (CHC) liver; however, the precise mechanism of such accumulation remains unclear. We evaluated iron absorption from the gastrointestinal tract of patients with CHC and control participants. We measured the expression of a panel of molecules associated with duodenal iron absorption and serum hepcidin levels to determine the mechanism of iron accumulation in the CHC liver. We enrolled 24 patients with CHC and 9 patients with chronic gastritis without Helicobacter pylori infection or an iron metabolism disorder as control participants. An oral iron absorption test (OIAT) was administered which involved a dosage of 100 mg of sodium ferrous citrate. Serum level of hepcidin-25 was measured by liquid chromatography-tandem mass spectrometry. Ferroportin 1 (FPN) mRNA was measured by RT-PCR and FPN protein was analyzed by western blot. Samples were obtained from duodenum biopsy tissue from each CHC patient and control participant. Caco-2/TC7 cells were incubated in Costar transwells (0.4 μm pores). The OIAT showed significantly greater iron absorption in CHC patients than control participants. Serum hepcidin-25 in the CHC group was significantly lower than in the control group. Compared with control participants, duodenal FPN mRNA expression in CHC patients was significantly upregulated. The FPN mRNA levels and protein levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with hepcidin. Lower serum hepcidin-25 levels might upregulate not only FPN protein expression but also mRNA expression in the duodenum and cause iron accumulation in patients with CHC.

DOI PubMed

ART療法中に多発血栓症を併発した悪性リンパ腫患者の一例

池田博, 吉田正宏, 舘越鮎美, 菊地尚平, 村瀬和幸, 高田弘一, 井山諭, 小船雅義, 村上則子, 宮越郁子, 又村了輔, 國本雄介, 加藤淳二

日本エイズ学会誌 ( (一社)日本エイズ学会 ) 19 ( 4 ) 501 - 501 2017.11

A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer.

Naoki Uemura, Shohei Kikuchi, Yasushi Sato, Hiroyuki Ohnuma, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Hirakawa, Tamotsu Sagawa, Koshi Fujikawa, Yasuo Takahashi, Toshinori Okuda, Shinya Minami, Minoru Takahashi, Tetsuro Okamoto, Kohichi Takada, Koji Miyanisi, Tetsuji Takayama, Junji Kato

Cancer chemotherapy and pharmacology ( Springer Science and Business Media LLC ) 80 ( 4 ) 707 - 713 2017.10 [Refereed] [International journal]

PURPOSE: Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen. METHODS: Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m2 b.i.d) on days 1-14, and docetaxel (50 mg/m2) plus cisplatin (60 mg/m2) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated. RESULTS: Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%). CONCLUSION: Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.

DOI PubMed

[A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing to Nilotinib Use].

Shogo Miura, Kazuyuki Murase, Akira Sakurada, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Atsuko Muranaka, Kazutoshi Tachibana, Junji Kato

Gan to kagaku ryoho. Cancer & chemotherapy 44 ( 6 ) 529 - 531 2017.06 [Refereed] [Domestic journal]

A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.

PubMed

Hepatitis C virus reactivation due to antiemetic steroid therapy during treatment of hepatocellular carcinoma

Yutaka Kawano, Koji Miyanishi, Satoshi Takahashi, Tomohiro Kubo, Kazuma Ishikawa, Shintaro Sugita, Kohichi Takada, Masayoshi Kobune, Tadashi Hasegawa, Junji Kato

JOURNAL OF INFECTION AND CHEMOTHERAPY ( ELSEVIER SCIENCE BV ) 23 ( 5-6 ) 323 - 325 2017.05 [Refereed]

Hepatitis C virus (HCV) reactivation is relatively rare compared with hepatitis B reactivation in patients treated with immunosuppressive or anticancer drugs. Here, we present the first case of genotype 2 HCV reactivation due to antiemetic steroid therapy during chemotherapy for hepatocellular carcinoma (HCC), which was verified by not only increased viral load but also pathological exacerbation of liver injury during HCV reactivation. Further chemotherapy for HCC could be continued without steroid therapy. This present case highlights the awareness of HCV reactivation and the management of complex situation. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI

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