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Itabashi, Yukihiro ; Baba, Toshiaki ; Kato, Satoru ; Hakamada, Kenichi
概要:
Forty patients with an average age of 64.6 years （range: 45-83） with early gastric cancer of cT1 （M,SM） underwent a cur
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ative-intended laparoscopy-assisted distal gastrectomy （LADG） where laparoscopic D1+αnodal clearance and extra-abdominal Billroth-I stapled anastomosis were performed. There was no conversionto open gastrectomy. The operation time for the 40 cases ranged 150 - 482 min （median: 285）, while that for thelatest 10 cases reduced to 154-278 min （median: 216）. The length of hospital stay of the patients varied 10-85 days（median: 17）. Postoperative complications encountered were anastomosis-related: 2 anastomotic bleeding and 2anastomotic passage disturbance（ 1 stricture and 1 temporary stenosis） occurred but no dehiscence. Four inaccuratepreoperative diagnoses of tumor invasion depth were revealed by postoperative pathology of the resected specimens.Thereafter the accuracy in the preoperative diagnosis was highly enhanced with implementation of endoscopicultrasound. Recurrence occurred in one patient with pT2（ SS） pN2, who died of pleural carcinomatosis 4 years and 3months after surgery. As the reduced operation time in LADG came closer to that in open distal gastrectomy, we will continuethis procedure for early gastric cancer. For this, the importance of an accurate preoperative diagnosis can’t beoveremphasized.
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| 2.
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Nodagashira, Tatsuya ; Odagiri, Hiroki ; Ikenaga, Shojiro-Kazunori ; Maruyama, Masateru ; Sato, Toshiyuki ; Hakamada, Kenichi
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Tissue-specifi c promoter has been used for cancer-specifi c suicide gene therapy, but its transcriptionalactivity is r
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elatively low. For more effi cient gene therapy of HER2-expressing tumor, a double adenovirus infectionsystem was established, in which a ‘regulator’ vector carried Cre gene under the control of HER2 promoter and ‘target’vectors carried target genes activated by Cre. We constructed a Cre recombinase expression vector, AxHER2Cre, forthe ‘regulator’ vector. By the combination of this vector and AxCALNLZ, β-D-galactosidase was induced in 90% and70% of MKN7 and MDA-MB-453, HER2‒overexpressing cell lines, but only about 20% and 10% of MKN28 and MCF7,low HER2-expressing cell lines. By the quantifi cation analysis, the β-galactosidase activities induced by this systemwere comparable to those by the combination of AxCANCre and AxCALNLZ. These results indicated that Cre/loxP system under the regulation of HER2 promoter could induce effi cient gene expression, maintaining the HER2-expression specifi city. Breast cancer with HER2 overexpression is treated with trastuzumab. However, refractoryor resitance of HER2 positive breast cancer against trastuzumab becomes a severe clinical problem, recently. Thissystem seemed to be another therapeutic option.
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Sashinami, Hiroshi ; Hu, Dong-Liang ; Li, Sheng-Jun ; Mitsui, Toshihito ; Hakamada, Kenichi ; Ishiguro, Yoh ; Fukuda, Shinsaku ; Nakane, Akio
概要:
We investigated the eff ect of p60 that is one of virulence factors of Listeria monocytogenes on host immune response in
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vitro and in vivo. C57BL/6 mice immunized with p60 showed antigen-specifi c T-helper I type immune response. Mouse macrophage RAW264.7 cells produced tumor necrosis factor alpha （TNF-α）, interleukin-12 and interferon beta （IFN-β） in response to stimulation with recombinant p60. Administration of p60 prior to a sublethal infection with L. monocytogenes enhanced innate host resistance in naïve mice. TNF-α and IFN-β production from RAW264.7 cells and bone marrow-derived macrophages were Toll-like receptor 4 （TLR4）-dependent. The enhanced clearance of L. monocytogenes by p60 administration was not shown in C3H/HeJ mice. Our fi ndings demonstrated that p60 enhances host resistance against L. monocytngenes infection through both activation and attenuation of host innate immune response in the TLR4-dependent manner.
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| 4.
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Hasebe, Tatsuya ; Umeda, Takashi ; Danjo, Kazuma ; Takahashi, Ippei ; Matsuzaka, Masashi ; Kudo, Junko ; Sematoo, Mariko ; Saito, Yuriko ; Hisada, Takayoshi ; Benno, Yoshimi ; Nakaji, Shigeyuki ; Hakamada, Kenichi
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Background and aim: The aim of this study is to investigate the relationship between methane production and gut microbio
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ta in a general population. Methods: Total of 697 subjects（58±13 years, 261 men and 436 women）have participated in this study. Their breath methane and hydrogen concentration were measured after an overnight fasting using gas chromatography,and their gut bacterial component was analyzed using T-RFLP（Terminal restriction fragment length polymorphism）method. All gut microbiota were divided into 28 operational taxonomic units（OTUs）according to its predominant bacterial groups. The breath methane concentration of above 10ppm and breath hydrogen concentration of above20ppm were considered positive. Subjects were divided into four groups;（1）Both negative: both methane and hydrogen were negative（2）CH₄only: only methane was positive（3）H₂only: only hydrogen was positive（4）Both positive: both hydrogen and methane were positive Results: OTU317（Prevotella）was significantly higher in CH₄only than both negative and H₂only. And OTU940（Clostridium subcluster XIVa and Enterobacteriales）was significantly lower in CH₄only than both negative and H₂only.Conclusions: OTU317 and OTU940 might affect the bacterial metabolism of methanogens.
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Morohashi, Hajime ; Murata, Akihiko ; Koyama, Motoi ; Sakamoto, Yoshiyuki ; Tsutsumi, shinji ; Yonaiyama, Shinnosuke ; Ogasawara, Hiroshi ; Yoshikawa, Toru ; Muroya, Takahiro ; Nakai, Makoto ; Ishido, Keinosuke ; Wajima, Naoki ; Hakamada, Kenichi
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Introduction: The employment of laparoscopic resection for the treatment of colorectal cancer has beenexpanding rapidly.
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However, its indication is still on debate. We have been actively employing laparoscope-assisted colectomy （LAC） for patients with early colorectal cancer. Here we retrospectively review the 71 cases of early colorectal cancer treated with LAC and analyzed the initial institutional surgical outcome.Results: LAC was indicated as an additional surgical resection after endoscopic treatment in 27 cases, while it was employed as a definitive non-endoscopic treatment in 44 cases. Mean operative time was 163 min, and mean blood loss was 57 ml. Complications were encountered in 8 cases（ 11.3%）. Advanced lesions invading to the muscularis propria or the serosa were more included in the group initially treated with LAC alone（ p=0.04）. The reasons for additional LAC were the depth of submucosal invasion >1000 μm in 15 cases and lymphatic or microvascular invasion in 5 cases. Lymph node metastases were detected pathologically in 9 patients, in which one suffered relapse after surgery.Conclusion: Implementation of LAC for early colorectal cancer seems an acceptable strategy in terms of bothradicality and less invasiveness. Cooperation between endoscopists and laparoscopic surgeons is important to apply LAC appropriately for colorectal cancer.
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Wajima, Naoki ; Morohashi, Hajime ; Watanabe, Nobukazu ; Nakai, Makoto ; Miyamoto, Keiichi ; Kawasaki, Hitoshi ; Yonaiyama, Shinnosuke ; Ogasawara, Hiroshi ; Yoshikawa, Toru ; Muroya, Takahiro ; Yakoshi, Yuta ; Ishido, Keinosuke ; Sakamoto, Yoshiyuki ; Koyama, Motoi ; Murata, Akihiko ; Ohishi, Susumu ; Tateoka, Hiroshi ; Hakamada, Kenichi
概要:
INTRODUCTION: Pylorus-preserving gastrectomy （PPG）, which had been developed in 1960s, has been reappraised for years an
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d now accepted as a type of function-preserving compared with those of laparoscopy- ssisted distal gastrectomy （LADG）, which does not preserve the pylorus and involves resection of the suprapyloric lymph nodes.METHODS: Ninety six patients diagnosed as having gastric cancer of cT1N0 underwent either LADG （n=66） or LAPPG （n=30）. The patient demographics and the early surgical outcomes were evaluated retrospectively. The quality of lymph node dissection in LAPPG was also assessed pathologically.RESULTS: Among 96 patients preoperatively diagnosed as cT1, pT1 was 88 cases and pT2 in 8, 91.7 % of diagnostic accuracy. There were no differences in patient demographics, operative time, blood loss, the number of dissected lymph nodes, postoperative morbidity and length of hospitalization. Pathologically, the number of dissected lymph nodes at No. 3, 4, 6 were equal between the two groups. Among our LADG cases, 35（ 53%） were lesions confined to the mucosa with a distance between the pylorus and the anal margin of the tumor <4 cm.CONCLUSIONS: Our initial experience suggests that LAPPG can be performed with acceptable quality of lymph node dissection and early surgical outcome. Because LAPPG was thought to be applied for about a half of our LADG cases according to the new guideline, LAPPG is expected to be indicated for more cases with early gastric cancer as a function-preserving limited surgery.
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| 7.
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Narumi, Shunji ; Murakami, Reiichi ; Hatakeyama, Shingo ; Fujita, Tadashi ; Koie, Takuya ; Yoneyama, Takahiro ; Kudo, Shigemasa ; Kamimura, Noritaka ; Mori, Kazuyuki ; Shimada, Michiko ; Nakamura, Norio ; Umehara, Minoru ; Saito, Hisao ; Okumura, Ken ; Hakamada, Kenichi ; Ohyama, Chikara
概要:
Introduction Kidney transplantation has been widely accepted as a definitive therapy for patients with renal failure. Th
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e Hirosaki Kidney Transplant Unit was organized in June 2006 in conjunction with the Departments of Urology, Cardiology, Respiratory Medicine and Nephrology, and Gastrointestinal Surgery, from the Hirosaki University School of Medicine. Herein, we introduce our current results and discuss our future strategies. Patients and Methods From June 2006 to December 2011, 36 kidney transplants were performed with 31 living donors and 5 deceased donors. Immunosuppression therapy included an inductor treatment of anti-CD25 antibody andtriple therapy with calcineurin inhibitor, mycophenolate mofetil, and steroids. Results Recipients included 25 males and 11 females. The patients’ average age was 41.8 years. Nine living–pairs were ABO incompatible. Deceased donors were performed at Oyokyo Hospital. Median follow-up period was 27.6 months. Acute cellular rejection occurred in 8.3% of patients. Positive antigenemia for cytomegalovirus happened in 16.7% of patients, but none developed invasive diseases. All recipients are currently surviving. Graft survival rates at 1, 3, and 5 years are 100%, 94.7%, and 94.7%, respectively. Conclusion Successful kidney transplantations have been performed by a multidisciplinary unit at Hirosaki University. Our next step is a promotion to increase organ donation.
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| 8.
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Shibutani, Koichi ; Tsushima, Fumiyasu ; Kakehata, Shinya ; Miura, Hiroyuki ; Ono, Shuichi ; Seino, Hiroko ; Kakuta, Akihisa ; Tokuda, Toshihide ; Toyoki, Yoshikazu ; Hakamada, Kenichi ; Takai, Yoshihiro
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Purpose: To evaluate the clinical efficacy and safety of preoperative percutaneous transhepatic portal vein embolization
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（PVE） with an ipsilateral approach, using microfibrillar collagen（MFC） as an embolic material for carcinomas of the biliary tract and liver metastases of colorectal carcinoma. Materials and methods: PVE using MFC was performed in 35 consecutive patients（ 29 men and 6 women; mean age 64 years, range 44–81 years） with small estimated future liver remnants （FLRs） after planned major hepatectomy. Patient malignancies included bile duct carcinoma（ n = 20）, gallbladder carcinoma（ n = 5）, and metastases of colorectal carcinoma （n = 8）. In one patient preoperatively diagnosed with gallbladder carcinoma, the pathological diagnosis of xanthogranulomatous cholecystitis was confirmed after resection. PVE was performed with ultrasound guidance （ipsilateral approach, 35; contralateral approach, 1）. Total liver volume （TLV） and FLR changes, hypertrophy ratio before and after PVE, and procedure-related complications were analyzed retrospectively. Results: PVE was successful in all patients. There were no major procedure-related complications. Mean absolute FLR volume increased significantly（ p < 0.001） from 434 to 524 cm3, as did the standardized FLR to TLV ratio（ p < 0.001）, from a mean of 37.9% to 46.1%. The mean ratio of standardized FLR increase was 8.2%. The hypertrophy ratio was 23%. In the group receiving selective embolization in a centripetal direction, the increase in FLR/TLV ratio was 9.5%, while the hypertrophy ratio was 27%. Neither puncture-related complications nor deterioration of liver function were observed. Conclusion: MFC was a safe and effective embolic material for preoperative PVE in patients with hepatobiliary malignancies, resulting in sufficient hypertrophy of FLRs.
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| 9.
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Kubo, Norihito ; Narumi, Shunji ; Hakamada, Kenichi ; Nakane, Akio
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Stem cell therapy is one of the remarkable treatments for fatal diseases. Mesenchymal stem cells （MSCs） are adult stem c
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ells and detected in various tissues such as bone marrow, umbilical cord blood and adipose tissue. MSCs have some abilities to differentiate into multi-lineage mature cells, modify immune responses and play a role for tissue repairing. The purpose of the present study was to investigate the effect of adipose tissuederived mesenchymal stem cells（ ASCs） against fulminant hepatitis, a life threatening liver injury due to massive destruction of hepatocytes. BALB/c mice were sacrificed and adipose tissues were harvested. ASCs were purified from the tissues and confirmed by characterization of cell surface markers and induction of differentiation into multi-lineage mature cells. Concanavalin A （ConA）, a protein of jackbean, can induce fulminant hepatitis for mice. BALB/c mice were administered lethal or sublethal dose of ConA intravenously and treated by ASCs, phosphate buffered saline（ PBS） or splenocytes （SPLCs）. The survival rates, liver enzymes, cytokines, histopathological changes and localization of ASCs were investigated. ASCs could increase the survival rates, inhibit elevation of liver enzymes and cytokines, and attenuate necroses of hepatocytes compared to PBS or SPLCs. Fluorescent stained ASCs were detected in inflammatory liver, but not in normal liver. These findings suggest that ASCs have an ability to improve or attenuate fulminant hepatitis.
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| 10.
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Miura, Takuya ; Kimura, Norihisa ; Yamada, Toshiyuki ; Shimizu, Takeshi ; Nanashima, Naoki ; Yamana, Daisuke ; Hakamada, Kenichi ; Tsuchida, Shigeki
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Background/Aims: To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between
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such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model.Methods: Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested on 0, 1, 3, and 7 days for microarray analysis, the quantitative real-time polymerase chain reaction （RT-PCR）, Western blotting and immunohistochemistry to examine the expression of multidrug resistance protein 4 （Mrp4）, bile salt export pump（ Bsep） and sodium-dependent taurocholate cotransporting polypeptide（ Ntcp）.Results: Persistently elevated serum bile acids were observed on days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased on day 3. Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. Bsep, an export pump localized to the canalicular membrane, was unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, Ntcp was localized in the cytoplasm on days 3 and 7 and was hardly detected in the basolateral membrane.Conclusions: These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seemed to be responsible for the high blood bile acids levels after massive hepatectomy.
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