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Dive into the research topics where Hiroshi Hisatsune is active.

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Featured researches published by Hiroshi Hisatsune.


Transplantation | 2003

Endoscopic management of biliary strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation

Hiroshi Hisatsune; Shujiro Yazumi; Hiroto Egawa; Masanori Asada; Kazunori Hasegawa; Yuzo Kodama; Kazuichi Okazaki; Kyo Itoh; Hiroshi Takakuwa; Koichi Tanaka; Tsutomu Chiba

Background. The aims of this study were to characterize the features of the biliary strictures that occur after duct-to-duct biliary reconstruction during right-lobe living-donor liver transplantation (LDLT) and to evaluate the feasibility of correcting such stricture endoscopically by inserting an “inside stent,” that is, a short internal stent, above the sphincter of Oddi. Methods. Biliary stricture occurred in 26 (35.6%) of 73 consecutive patients who underwent right-lobe LDLT with duct-to-duct biliary reconstruction from July 1999 through October 2001 and survived for more than 3 months. Of the 26 patients who had biliary stricture, 22 were referred for endoscopic retrograde cholangiography (ERC) and 4 for percutaneous cholangiography. Results. ERC disclosed biliary stricture in 19 (86.4%) of the 22 patients who underwent the procedure. One patient had an unbranched stricture, 16 had a fork-shaped stricture, 1 had a trident-shaped stricture, and 1 had a stricture with more than three branches. Fourteen (73.7%) of the patients with strictures were treated endoscopically by inserting inside stents ranging from 7 F to 12 F in size, three underwent a Roux-en-Y hepaticojejunostomy to repair their stricture, and two were closely observed as outpatients. Of the 14 patients who were treated with the inside-stent, only 1 had acute cholangitis immediately after the procedure and underwent a Roux-en-Y hepaticojejunostomy. The other 13 patients who were treated with the inside stent have not required surgical repair for as long as an average of 586 days. Conclusion. Endoscopic placement of an inside stent is useful for treating biliary strictures in patients who have undergone right-lobe LDLT with duct-to-duct reconstruction.


Gut | 2005

Possible role of REG Iα protein in ulcerative colitis and colitic cancer

Akira Sekikawa; Hirokazu Fukui; Shigehiko Fujii; Apichart Nanakin; Naoki Kanda; Yoshito Uenoyama; Tateo Sawabu; Hiroshi Hisatsune; Toshihiro Kusaka; Satoru Ueno; Hiroshi Nakase; Hiroshi Seno; Takahiro Fujimori; Tsutomu Chiba

Background and aims: Although regenerating gene (REG) Iα protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Iα gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Iα gene expression and whether REG Iα protein has a trophic and/or an antiapoptotic effect on colon cancer cells. Methods: Expression of REG Iα mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Iα promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Iα protein on growth and H2O2 induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. Results: REG Iα protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Iα mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Iα promoter activity was enhanced by stimulation with interferon γ or interleukin 6. REG Iα protein promoted cell growth and conferred resistance to H2O2 induced apoptosis in LoVo cells. REG Iα protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. Conclusions: The REG Iα gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.


Digestion | 2004

Expression of Reg Iα Protein in Human Gastric Cancers

Hirokazu Fukui; Shigehiko Fujii; Jun Takeda; Takahisa Kayahara; Akira Sekikawa; Apichart Nanakin; Katsumasa Suzuki; Hiroshi Hisatsune; Hiroshi Seno; Mitsutaka Sawada; Takahiro Fujimori; Tsutomu Chiba

Background/Aims: Although regeneratinggene(Reg) Iα protein has a trophic effect on gastric epithelial cells, it is unclear whether Reg Iα protein and its receptor are involved in gastric carcinogenesis. Therefore, we investigated the Reg Iα protein expression in human gastric cancers and assessed its relationship to clinicopathological factors. Methods: Sixty-one gastric cancer specimens were examined, using immunohistochemistry, for Reg Iα protein, p53, and proliferating cell nuclear antigen. The expression of both Reg Iα and Reg receptor mRNA was examined in seven human gastric cancer cell lines (MKN1, MKN28, MKN45, MKN74, KATOIII, GCIY, and AGS) by reverse transcription-polymerase chain reaction and Northern blot analysis. Results: Twenty-three (37.7%) of the 61 gastric cancer tissues samples were positive for Reg Iα protein. The Reg Iα expression was significantly related to the presence of lymphatic invasion but not to tumor size, tumor stage, Lauren’s classification, presence of venous invasion, lymph node metastases, or p53 overexpression. Gastric cancers positive for Reg Iα protein showed a significantly higher proliferating cell nuclear antigen labeling index than negative ones. The expression of both Reg Iα and Reg receptor mRNA was detected in all seven gastric cancer cell lines. Conclusion: Reg Iα protein may play a role in the development of gastric cancers.


Laboratory Investigation | 2007

Expression of the REG IV gene in ulcerative colitis

Apichart Nanakin; Hirokazu Fukui; Shigehiko Fujii; Akira Sekikawa; Naoki Kanda; Hiroshi Hisatsune; Hiroshi Seno; Yoshitaka Konda; Takahiro Fujimori; Tsutomu Chiba

The regenerating gene (REG) IV gene was isolated from a cDNA library of ulcerative colitis (UC) tissues. However, its role in the pathophysiology of UC and subsequent development of colitic cancer is still unclear. We investigated the expression of the REG IV gene in UC and colitic cancer tissues and examined whether cytokines or growth factors are responsible for REG IV gene expression and whether REG IV gene induction affects cell growth and apoptosis in colon cancer cells. The expressions of REG IV and growth factor genes in UC tissues were analyzed by real time reverse transcription-polymerase chain reaction. The effects of cytokines and growth factors on REG IV gene expression were examined in SW403 cells by Northern blot analysis. The effects of REG IV gene induction on cell growth and H2O2-induced apoptosis were examined in DLD-1 cells by MTT and TUNEL assays, respectively. REG IV mRNA was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG IV mRNA expression was correlated with that of basic fibroblast growth factor (bFGF) as well as hepatocyte growth factor (HGF) mRNA expression in UC tissues. The REG IV gene expression in SW403 colon cancer cells was enhanced by stimulation with transforming growth factor-α, epidermal growth factor, bFGF, and HGF. REG IV gene induction promoted cell growth and conferred resistance to H2O2-induced apoptosis in DLD-1 cells. The REG IV gene is inducible by growth factors and may function as a growth promoting and/or an antiapoptotic factor in the pathophysiology of UC.


Digestive Endoscopy | 2016

Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double‐blinded, placebo‐controlled multicenter trial

Hiroyuki Tamaki; Hiroshi Nakase; Satoko Inoue; Chiharu Kawanami; Toshinao Itani; Masaya Ohana; Toshihiro Kusaka; Suguru Uose; Hiroshi Hisatsune; Masahide Tojo; Teruyo Noda; Souichi Arasawa; Masako Izuta; Atsushi Kubo; Chikara Ogawa; Toshihiro Matsunaka; Mitsushige Shibatouge

We conducted a randomized, double‐blinded, placebo‐controlled trial to investigate the efficacy of Bifidobacterium longum 536 (BB536) supplementation for induction of remission in Japanese patients with active ulcerative colitis (UC).


Cancer Science | 2007

Restoration of RUNX3 enhances transforming growth factor-β-dependent p21 expression in a biliary tract cancer cell line

Kazunori Hasegawa; Shujiro Yazumi; Manabu Wada; Toshiharu Sakurai; Masaya Kida; Junichi Yamauchi; Hiroshi Hisatsune; Shinsuke Tada; Hiroshi Ida; Nakase Y; Sakakura C; Akeo Hagiwara; Tsutomu Chiba

RUNX3 is a candidate tumor suppressor gene localized in 1p36, a region commonly inactivated by deletion and methylation in various human tumors. To elucidate the role of RUNX3 in transforming growth factor (TGF)‐β signaling in biliary tract cancer, we transfected Mz‐ChA‐2 cells, which do not express RUNX3 but have intact TGF‐β type II receptor and SMAD4 genes, with the RUNX3 expression plasmid pcDNA3.1/RUNX3 or with the vector pcDNA3.1 as a control. Four Mz‐ChA‐2/RUNX3 clones and one control clone were obtained. Although TGF‐β1 only slightly inhibited growth of the control cells, growth inhibition and TGF‐β‐dependent G1 arrest were significantly enhanced in the RUNX3‐transfected clones. None of the clones, however, exhibited apoptosis. The slightly increased TGF‐β1‐induced p21 expression in the control clone was strongly enhanced in the RUNX3‐transfected clones, and was accompanied by augmented decreases in the expression of cyclins D1 and E. When RUNX3 small interfering RNA was added, TGF‐β‐dependent induction of p21 was reduced in the RUNX3‐transfected clones. Xenografts of the clones in nude mice demonstrated that tumorigenicity was significantly decreased in the RUNX3‐transfected clones in inverse proportion to the expression levels of RUNX3. Based on these results, RUNX3 is involved in TGF‐β‐induced expression of p21 and the resulting induction of TGF‐β‐dependent G1 arrest. (Cancer Sci 2007; 98: 838–843)


Clinical Gastroenterology and Hepatology | 2003

Endoscopic management of postoperative biliary complications in donors for living donor liver transplantation

Kazunori Hasegawa; Shujiro Yazumi; Hiroto Egawa; Hiroyuki Tamaki; Masanori Asada; Yuzo Kodama; Hiroshi Hisatsune; Kazuichi Okazaki; Koichi Tanaka; Tsutomu Chiba

BACKGROUND & AIMS Biliary leakage and stricture are serious complications that occur in donors whose liver is resected for living donor transplantation. We assessed the usefulness of endoscopic nasobiliary drainage and endoscopic biliary stenting, respectively, in repairing biliary leakage and stricture. METHODS Between July 1999 and December 2001, a total of 276 donors underwent liver resection (left side, 118; right side, 158) for living donor transplantation at Kyoto University Hospital. Seven (2.5%) donors developed biliary leakage, which required endoscopic nasobiliary drainage; 3 of these donors also had biliary stricture. RESULTS All 7 patients who developed biliary leakage were the right-lobe donors. Endoscopic retrograde cholangiography identified the site of the biliary leakage in all 7 of the donors. In 6 of these donors, the biliary leakage resolved within an average of 15 days after an endoscopic nasobiliary drainage tube was placed. In the seventh donor, the biliary leakage resolved after percutaneous transhepatic biliary drainage was performed. Three patients developed biliary stricture that required endoscopic biliary stenting. The angles between common hepatic duct and the left hepatic duct were more acute in patients with stricture than in those without stricture (62 degrees vs. 119 degrees). CONCLUSIONS Biliary complications requiring endoscopic treatment developed exclusively in donors for right-lobe living donor transplantation. Endoscopic retrograde cholangiography is a favorable modality for diagnosing and treating postoperative biliary complications in donors for living donor liver transplantation.


Vaccine | 2001

Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: A new method for vaccination

Hiroshi Nakase; Kazuichi Okazaki; Yasuhiko Tabata; Kazushige Uchida; Suguru Uose; Masaya Ohana; Toshiki Nishi; Tomohiro Watanabe; Minoru Matsuura; Hiroshi Hisatsune; Kazuyoshi Matsumura; Toshiyuki Itoh; Chiharu Kawanami; Tsutomu Chiba

The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.


Gastrointestinal Endoscopy | 2000

7160 Usefulness of endoscopic treatment for persistent biliary leak due to hepatectomy.

Hiroshi Hisatsune; Yuzou Kodama; Kazunori Matsumura; Suguru Uose; Shujirou Yazumi; Yasuhisa Hosotani; Masaya Oohana; Masahide Tojou; Kazuichi Okazaki; Tsutomu Chiba

[Aim] Biliary leak is one of the major causes of morbidity after hepatectomy. To resolve this problem, we evaluated the efficacy of endoscopic treatment for biliary leak after hepatectomy using technique of endoscopic retrograde cholangiopancreatography (ERCP). [Subjects and Methods] From 1996 to 1999, eight patients (6 men and 2 women, mean age 48 years old) were diagnosed as having biliary leak after hepatectomy in Kyoto University Hospital. Original disease were hepatocellular carcinoma in 6 cases, traumatic liver injury in one case, donor for living related liver transplantation in one case. Five patients received right lobectomy, 2 left lobectomy and one segmentectomy. [Results] The biliary tract was clearly visualized on ERCP images in all patients. The leaking point was well defined with accuracy at the level of the hepatic duct in 7 patients and common bile duct in one. Seven of 8 patients had strictures of the biliary tract.We performed endoscopic treatment in all 8 patients [a combination of endoscopic sphincterotomy (EST) and placement of nasobiliary drainage (NBD) in 6 patients, and NBD placement alone in 2]. Successful drainage was achieved in all the patients without any complications. The biliary leak ceased after drainage in all the patients (mean duration of drainage, 18 days). However, one patient resulted in the recurrence of a bile leak after the removal of NBD, and subsequently received percutaneous transhepatic biliary drainage. This patient was discharged after 90 days. [Conclusion] Endoscopic management is very useful in not only accurate diagnosis but also treatment for biliary leak. Therefore, this procedure should be attempted as a first line of therapy for bile leak occurred after hepatectomy.


Gastroenterology | 1998

Gastroesophageal reflux diseases: The relationship between the hospital anxiety and depression scale and its severity

Hiroshi Hisatsune; Shigeto Mizuno; Tadashi Itoh; Takanobu Hayakumo; Kunihiko Kimoto; Keiichi Kawai

[Aim] Gastroesophageal reflux diseases(GERD) is a clinical entity in which refluxing gastric contents produce symptoms, and impairs the quality of life. Patients with GERD tend to be have impaired feeling of well-being and functional status, yet the impact of GERD on quality of life including emotional functioning has not carefully studied. We examined whether GERD and its severity were related to anxiety and depression as assessed by the hospital anxiety and depression (HAD) scale. [Methods] We studied 97 patients who visited our department with reflux symptom. Inclusion criteria was primary symptom of heartburn without other organic diseases. A control group compromised 106 patients referred to our department without symptom. All patients completed self report HAD questionnaires and GERD symptom questionnaires including the grading of GERD symptom. GERD patients were asked whether their daily activities were interrupted because of GERD symptom, and were asked to rate their overall health related quality of life as excellent, good, or poor. [Results] The GERD patients gave higher HAD scores than the normal group(anxiety score: mean 5.44 vs. 3.59, depression score: mean 5.30 vs. 3.69, p < 0.01). The severer the GERD symptom was, the higher HAD score tended to be(mean anxiety score: excellent 3.59, good 6.97, poor 6.22, mean depression score: excellent 4.23, good 5.71, poor 7.66). There was a significant correlation between HAD score and GERD severity(anxiety: r=0.328, p < 0.01, depression: r=0.320, p < 0.01). [Conclusion] This study confirms that anxiety and depression scores are higher in patients with GERD symptom than in controls. The severity of GERD symptom has close relationship to the mental health. This research was made possible by grant from Astra Japan.

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Hiroto Egawa

California Pacific Medical Center

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