Researchers Database

tamada kiichi

    InternalMedicineGastroenterology Professor
Last Updated :2022/11/26

Researcher Information

J-Global ID

Research Interests

  • 消化器内科   Gastroenterology   

Research Areas

  • Life sciences / Gastroenterology

Academic & Professional Experience

  • 2007/04 - Today  Jichi Medical University内科学消化器内科部門准教授
  • 2002/12 - 2007/04  Jichi Medical University内科学消化器内科部門助教授


  • 1976/04 - 1982/03  Jichi Medical University  School of Medicine  医学科

Association Memberships


Published Papers

  • Shigeki Matsubara, Chihiro Kamozawa, Kiichi Tamada
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 (2) 617 - 617 1341-8076 2013/02 [Refereed][Not invited]
  • Susumu Hijioka, Kazuo Hara, Nobumasa Mizuno, Hiroshi Imaoka, Takeshi Ogura, Shin Haba, Mohamed A. Mekky, Vikram Bhatia, Waki Hosoda, Yasushi Yatabe, Yasuhiro Shimizu, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Kiichi Tamada, Kenji Yamao
    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 19 (6) 650 - 655 1868-6974 2012/11 [Refereed][Not invited]
    Background Obtaining histological evidence of gallbladder carcinoma (GBC) is difficult due to its extraductal nature, and pathological confirmation remains challenging. We compared the diagnostic value and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with endoscopic retrograde cholangiography (ERC) in patients with suspected GBC. Patients Eighty-three patients with GBC were evaluated. Prior to definitive management, pathological evidence of GBC was obtained through either ERC cytopathologic sampling (n = 33), EUS-FNA (n = 24) or both (n = 26). Results Among the 83 patients, 59 (71.0%) with biliary obstruction were sampled using ERC with 47.4% (28/59) sensitivity. In 19 of the remaining 31 cases, EUS-FNA sampling had 100% diagnostic sensitivity. Likewise, 50 (60.2%) of the 83 patients with suspected GBC underwent EUS-FNA of regional lymph nodes or the gallbladder (GB) mass itself with 94.8% sensitivity. The overall diagnostic sensitivity rates of ERC and EUS-FNA were 47.4 and 96%, respectively (P < 0.001). Post-procedural complications were seen in 6.7% of the ERC group (4/59, all were mild pancreatitis), and in none of the EUS-FNA group (P = 0.10). Conclusions Gallbladder carcinoma sampling using ERC and EUS-FNA should be incorporated into the diagnostic workup of GB lesions as complementary tools, and EUS-FNA should be applied in the setting of failed or not indicated ERC.
  • Hisashi Hatanaka, Hironori Yamamoto, Tomonori Yano, Jun Ushio, Takeshi Tomiyama, Shin-ichi Wada, Hirotsugu Sakamoto, Masahiro Okada, Kiichi Tamada, Kentaro Sugano
    DIGESTIVE ENDOSCOPY 24 (6) 479 - 479 0915-5635 2012/11 [Refereed][Not invited]
  • Chishio Noguchi, Kiichi Tamada, Shinichi Wada, Akira Ohashi, Hisashi Hatanaka, Jun Ushio, Katsuyuki Nakazawa, Norikatsu Numao, Kentaro Sugano
    DIGESTIVE ENDOSCOPY 24 (3) 195 - 196 0915-5635 2012/05 [Refereed][Not invited]
  • Shigeki Matsubara, Tomoyuki Kuwata, Chihiro Kamozawa, Yuki Sakamoto, Mitsuaki Suzuki, Kiichi Tamada
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 38 (2) 446 - 448 1341-8076 2012/02 [Refereed][Not invited]
    Jaundice in hyperemesis gravidarum may cause physicians to suspect several underlying diseases. Jaundice appeared in a woman with hyperemesis gravidarum and an ultrasound revealed biliary sludge. Hydration concomitantly ameliorated the symptoms, jaundice and the biliary sludge. Another woman with hyperemesis gravidarum showed elevated aminotransferases, with biliary sludge also being present. Hydration ameliorated the symptoms and liver dysfunction, and reduced the total bilirubin level. Biliary sludge appeared, but was ameliorated according to the symptoms of hyperemesis gravidarum.
  • Hiroyuki Isayama, Ichiro Yasuda, Shomei Ryozawa, Hiroyuki Maguchi, Yoshinori Igarashi, Yutaka Matsuyama, Akio Katanuma, Osamu Hasebe, Atsushi Irisawa, Takao Itoi, Hidekazu Mukai, Yoshifumi Arisaka, Kazumu Okushima, Koji Uno, Mitsuhiro Kida, Kiichi Tamada
    DIGESTIVE ENDOSCOPY 23 (4) 310 - 315 0915-5635 2011/10 [Refereed][Not invited]
    Background: No study has compared covered metallic stents with Tannenbaum stents. We evaluated the efficacy of the DoubleLayer stent (DLS) and Covered Wallstent (CWS) in patients with pancreatic head cancer (PHC). Patients & Methods: This was a multicenter, prospective randomized study. Between October 2005 and December 2007, we enrolled 113 patients (58 DLS, 55 CWS) with unresectable PHC with distal biliary obstructions and observed them for at least 6 months. Results: No significant difference in patient survival was found between groups, with a median survival of 231 and 248 days in the DLS and CWS groups, respectively. The cumulative stent patency was significantly higher (P = 0.0072) in the CWS group. The respective mean and median stent patency was 202 and 133 days in the DLS group and 285 and 419 days in the CWS group. The incidence of DLS occlusion (53.5%) was significantly higher than that of CWS (23.6%; P = 0.0019). The respective causes of occlusion were tumor overgrowth (0, 1), ingrowth (0, 2), sludge (24, 2), food impaction (3, 5), kinking bile duct (2, 0), and other (2, 3). Other complications were cholecystitis (0, 4), pancreatitis (0, 1), migration (1, 5), liver abscess (2, 0), and other (1, 2). No significant difference in the incidence of complications between groups was observed. Conclusion: CWS had significantly longer patency than DLS for the management of PHC with obstructive jaundice. The incidence of complications other than stent occlusion was higher in CWS, but this difference did not reach significance.
  • Tamada K, Ushio J, Sugano K
    World journal of clinical oncology 5 2 203 - 216 2011/05 [Refereed][Not invited]
  • Susumu Hijioka, Mohamed A. Mekky, Vikram Bhatia, Akira Sawaki, Nobumasa Mizuno, Kazuo Hara, Waki Hosoda, Yasuhiro Shimizu, Kiichi Tamada, Yasumasa Niwa, Kenji Yamao
    GASTROINTESTINAL ENDOSCOPY 72 (3) 622 - 627 0016-5107 2010/09 [Refereed][Not invited]
    Background: EUS-guided FNA (EUS-FNA) is a useful modality for sampling various targets, but its applicability to gallbladder (GB) mass lesions is limited. Objective: To determine the usefulness of EUS-FNA for diagnosing GB mass lesions. Design: Single-center, retrospective, case-series study. Setting: Tertiary-care referral center. Patients: This study involved 15 consecutive patients who underwent EUS-FNA of GB mass lesions. We punctured GB masses in patients with suspected xanthogranulomatous cholecystitis to distinguish them from malignancy, and in patients with unresectable GB carcinoma for pathological confirmation. The final diagnosis was based on surgical histopathological results or follow-up outcome. Interventions: EUS-FNA. Main Outcome Measurements: Evaluation of EUS-FNA sampling adequacy rate and diagnostic yield. Results: Xanthogranulomatous cholecystitis was suspected in 6 of the 15 patients. EUS-FNA revealed foam cells (n = 3), inflammatory cells (n = 1, proven by cholecystectomy), and GB carcinoma (n = 1), and the amount of the aspirate was insufficient in one case (xanthogranulomatous cholecystitis was later proven by extended hepatectomy). The mean follow-up period of the patients with xanthogranulomatous cholecystitis was 1177 days. Adenocarcinoma was confirmed by EUS-FNA in 8 of the 9 patients with suspected unresectable GB carcinoma, and the FNA was inconclusive in one. All 10 patients with GB carcinoma underwent chemotherapy. The overall sampling adequacy was 86.6%. The accuracy of EUS-FNA for detecting malignancy and for the final diagnosis was 93.3% (95% CI, 62.4%-99.9%) and 80% (95% CI, 54%-93.7%), respectively. Limitations: A small patient cohort and a retrospective design with potential selection bias. Conclusions: Malignant GB mass lesions can be safely and accurately differentiated by EUS-FNA. Thus, patients with xanthogranulomatous cholecystitis can avoid undue extensive surgery.
  • Hisashi Hatanaka, Mamiko Tsukui, Shuji Takada, Kentaro Kurashina, Young Lim Choi, Manabu Soda, Yoshihiro Yamashita, Hidenori Haruta, Toru Hamada, Toshihide Ueno, Kiichi Tamada, Yoshinori Hosoya, Naohiro Sata, Yoshikazu Yasuda, Hideo Nagai, Kentaro Sugano, Hiroyuki Mano
    CANCER SCIENCE 101 (1) 54 - 59 1347-9032 2010/01 [Refereed][Not invited]
    Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. (Cancer Sci 2009).
  • Hisashi Hatanaka, Shuji Takada, Mamiko Tsukui, Young Lim Choi, Kentaro Kurashina, Manabu Soda, Yoshihiro Yamashita, Hidenori Haruta, Toru Hamada, Kiichi Tamada, Yoshinori Hosoya, Naohiro Sata, Hideo Nagai, Yoshikazu Yasuda, Kentaro Sugano, Hiroyuki Mano
    CANCER SCIENCE 101 (1) 60 - 64 1347-9032 2010/01 [Refereed][Not invited]
    To identify novel cancer-promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non-cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ. (Cancer Sci 2009).
  • Hirotsugu Sakamoto, Hiroyuki Mutoh, Kenichi Ido, Shin Satoh, Machio Kumagai, Hiroko Hayakawa, Kiichi Tamada, Kentaro Sugano
    HUMAN PATHOLOGY 40 (12) 1762 - 1767 0046-8177 2009/12 [Refereed][Not invited]
    We reported previously that intestinal metaplasia in the gallbladder is strongly associated with expression of caudal-related homeobox transcription factor Cdx2. It has been documented that occult pancreatobiliary reflux, even in the absence of pancreaticobiliary maljunction, is associated with elevated risk of biliary malignancy. We ascertained the correlation between intestinal metaplasia in the gallbladder and occult pancreatobiliary reflux. In 196 patients with a normal pancreaticobiliary ductal arrangement who had undergone laparoscopic cholecystectomy, we performed intraoperative cholangiography and measured amylase levels in bile sampled from the gallbladder. The cutoff value for high cystic amylase was defined as a biliary amylase level higher than the normal upper limit of serum amylase (215 IU/L). We also retrospectively reviewed the cholecystectomized tissue specimens to investigate the presence of intestinal metaplasia and expression of Cdx2. Then, we explored the relationship between intestinal metaplasia in the gallbladder and occult choledocho-pancreatic reflux. Intestinal metaplasia was found in 16.8% (33/196) of the gallbladders. The prevalence of choledochopancreatic reflux revealed by intraoperative cholangiography was not significantly different between cases with intestinal metaplasia (5/33, 15.2%) and those without (25/163, 15.3%; P = .81). However, in cases with intestinal metaplasia, the rate of high cystic amylase (13/33, 39.4%) was significantly higher compared with cases without intestinal metaplasia (26/163, 16.0%, P = .005). In conclusion, intestinal metaplasia in the gallbladder is significantly correlated with high amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement. (C) 2009 Published by Elsevier Inc.
  • Hiromi Fukushima, Hironori Yamamoto, Hidetoshi Nakano, Katsuyuki Nakazawa, Keijiro Sunada, Shinichi Wada, Kiichi Tamada, Kentaro Sugano
    GASTROINTESTINAL ENDOSCOPY 70 (3) 592 - 595 0016-5107 2009/09 [Refereed][Not invited]
    Adenomas of the major duodenal papilla have the potential to undergo malignant transformation. Although surgical resection has historically been the standard treatment for ampullary neoplasms, endoscopic resection (ampullectomy) of these lesions is increasingly being performed as a less-invasive alternative to surgery.(1-3) Complete histologic assessment of the resected specimen is desired to ensure curability with endoscopic therapy, because lesions may harbor focal invasive cancer missed on biopsy. However, en bloc resection that provides a complete tissue sample for pathologic evaluation is difficult for lesions larger than 2 cm With use of endoscopic snare ampullectomy(4,5) Endoscopic submucosal dissection (ESD) is a recently developed technique that enables reliable en bloc resection of early stage GI neoplasms.(6) ESD for ampullary neoplasm has not yet been reported. We describe our experience with successful ESD for a large ampullary adenoma with focal carcinoma.
  • Akira Ohashi, Kiichi Tamada, Shinichi Wada, Hisashi Hatanaka, Takeshi Tomiyama, Shigeo Tano, Katsuyuki Nakazawa, Kentaro Sugano
    DIGESTIVE ENDOSCOPY 21 (2) 73 - 77 0915-5635 2009/04 [Refereed][Not invited]
    Little is known about the long-term results of endoscopic papillary balloon dilation (EPBD) for bile duct stones. Between 1995 and 2000, 204 patients with bile duct stones successfully underwent EPBD and stone removal. Complete stone clearance was confirmed using balloon cholangiography and intraductal ultrasonography (IDUS). Long-term outcomes of EPBD were investigated retrospectively in the year 2007, and risk factors for stone recurrence were multivariately analyzed. Long-term information was available in 182 cases (89.2%), with a mean overall follow-up duration of 9.3 years. Late biliary complications occurred in 22 patients (12.1%), stone recurrence in 13 (7.1%), cholangitis in 10 (5.5%), cholecystitis in four, and gallstone pancreatitis in one. In 11 of 13 patients (84.6%), stone recurrence developed within 3 years after EPBD. All recurrent stones were bilirubinate. Multivariate analysis identified three risk factors for stone recurrence: dilated bile duct (> 15 mm), previous cholecystectomy, and no confirmation of clean duct using IDUS. Approximately 7% of patients develop stone recurrence after EPBD; however, retreatment with endoscopic retrograde cholangiopancreatography is effective. Careful follow up is necessary in patients with dilated bile duct or previous cholecystectomy. IDUS is useful for reducing stone recurrence after EPBD.
  • Satoshi Shinozaki, Hirohide Ohnishi, Kouji Hama, Hiroto Kita, Hironori Yamamoto, Hiroyuki Osawa, Kiichi Satu, Kiichi Tamada, Hirosato Mashima, Kentaro Sugano
    JOURNAL OF CELLULAR PHYSIOLOGY 216 (1) 38 - 46 0021-9541 2008/07 [Refereed][Not invited]
    Indian hedgehog (Ihh) is a member of hedgehog peptides family that exerts diverse effects on multiple cellular functions. Since Ihh expression is elevated in the pancreas of chronic pancreatitis patients, Ihh has been assumed to participate in the chronic pancreatic injury, especially in pancreatic fibrosis. However, its function in pancreatic fibrosis is still unknown. We thus examined Ihh effects on rat activated pancreatic stellate cells (PSCs) that play a central role in pancreatic fibrosis. Activated PSCs express both patched-I and smoothened that are essential components of hedgehog receptor system. Ihh did not alter the PSC expression of collagen-I or alpha-smooth muscle actin, a parameter of PSC transformation, or did not change PSC proliferation. However, Ihh enhanced PSC migration in both chemotactic and chemokinetic manners. Furthermore, Inn increased the amount of membrane-type I matrix metalloproteinase (MTI-MMP) and altered its localization on the plasma membrane, which plays a stimulatory role in cellular migration. In addition, tissue inhibitor of metalloproteinase-2 (TIMP-2) attenuated lhh-stimulated PSC migration. Since most hedgehog intracellular signals are mediated by Gli-I transcription factor, we investigated its contribution to lhh-enhancement of PSC migration. Ihh induced Gli-I nuclear accumulation in PSCs, indicating that Ihh stimulates Gli-I-dependent signaling pathway in PSCs. Unexpectedly, however, adenovirus-mediated Gli-I overexpression blocked the Inn enhancement of both MTI-MMP localization on the plasma membrane and PSC migration. Furthermore, reduction of Gli-I expression with RNA interference augmented lhh-stimulated PSC migration. These data indicate that lhh promotes PSC migration by enhancing MTI-MMP localization on the plasma membrane but is negatively regulated by Gli-I.
  • Masashi Izumiya, Kiichi Tamada, Takeshi Tomiyama, Kazunobu Hanatsuka, Akira Ohashi, Kentaro Sugano
    JOURNAL OF MAGNETIC RESONANCE IMAGING 26 (4) 1097 - 1100 1053-1807 2007/10 [Refereed][Not invited]
    We present the case of a 79-year-old female with acute cholangitis and cholangitis who presented with right up-per quadrant pain. Thin-collimation MR cholangiogram showed a filling defect measuring 1 cm, which was less prominent on single-slab images. Endoscopy showed dynamic ballooning and collapsing of the ampulla of Vater, and a cholangiogram showed characteristic bulding at the distal common bile duct, which led to the diagnosis of choledochocele. It is important to differentiate choledochocele as a cause of filling defect of the lower common bile duct on the MP cholangiogram.
  • Hiroyoshi Aoki, Hirohide Ohnishi, Kouji Hama, Satoshi Shinozaki, Hiroto Kita, Hiroyuki Osawa, Hironori Yamamoto, Kiichi Sato, Kiichi Tamada, Kentaro Sugano
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 292 (1) C259 - C268 0363-6143 2007/01 [Refereed][Not invited]
    Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines. Am J Physiol Cell Physiol 292: C259-C268, 2007. First published July 12, 2006; doi:10.1152/ajpcell.00030.2006.-Cyclooxygenase-2 (COX-2) mediates various inflammatory responses and is expressed in pancreatic tissue from patients with chronic pancreatitis. To examine the role of COX-2 in chronic pancreatitis, we investigated its participation in regulating functions of pancreatic stellate cells (PSCs), using isolated rat PSCs. COX-2 was expressed in culture-activated PSCs but not in freshly isolated quiescent PSCs. TGF-beta 1, IL-beta, and IL-6 enhanced COX-2 expression in activated PSCs, concomitantly increasing the expression of alpha-smooth muscle actin (alpha-SMA), a parameter of PSC activation. The COX-2 inhibitor NS-398 blocked culture activation of freshly isolated quiescent PSCs. NS-398 also inhibited the enhancement of alpha-SMA expression by TGF-beta 1, IL-1 beta, and IL-6 in activated PSCs. These data indicate that COX-2 is required for the initiation and promotion of PSC activation. We further investigated the mechanism by which cytokines enhance COX-2 expression in PSCs. Adenovirus-mediated expression of dominant negative Smad2/3 inhibited the increase in expression of COX-2, alpha-SMA, and collagen-1 mediated by TGF-beta 1 in activated PSCs. Moreover, dominant negative Smad2/3 expression attenuated the expression of COX-2 and alpha-SMA enhanced by IL-1 beta and IL-6. Anti-TGF-beta neutralizing antibody also attenuated the increase in COX- 2 and alpha-SMA expression caused by IL-1 beta and IL-6. IL-6 as well as IL-1 beta enhanced TGF-beta 1 secretion from PSCs. These data indicate that Smad2/3-dependent pathway plays a central role in COX-2 induction by TGF-beta 1, IL-1 beta , and IL-6. Furthermore, IL-1 beta and IL- 6 promote PSC activation by enhancing COX- 2 expression indirectly through Smad2/3-dependent pathway by increasing TGF-beta 1 secretion from PSCs.
  • Hiroyoshi Aoki, Hirohide Ohnishi, Kouji Hama, Satoshi Shinozaki, Hiroto Kita, Hironori Yamamoto, Hiroyuki Osawa, Kiichi Sato, Kiichi Tamada, Kentaro Sugano
    JOURNAL OF CELLULAR BIOCHEMISTRY 99 (1) 221 - 228 0730-2312 2006/09 [Refereed][Not invited]
    Interleukin (IL)-6 is a proinflammatory cytokine assumed to participate in pancreatic fibrosis by activating pancreatic stellate cells (PSCs). Autocrine TGF-beta(1) is to central in PSC functional regulation. In this study, we examined IL-6 secretion from culture-activated rat PSCs and its regulatory mechanism. Activated PSCs express and secrete IL-6. When anti-TGF-beta(1) neutralizing antibody was added in the culture medium, IL-6 secretion from activated PSCs was inhibited, whereas exogenous TGF-beta(1) added in the culture medium enhanced IL-6 expression and secretion by PSCs in a dose dependent manner. Infection of PSCs with an adenovirus expressing dominant-negative Smad2/3 attenuated basal and TGF-beta(1)-stimulated IL-6 expression and secretion of PSCs. We also demonstrated the reciprocal effect of PSCs-secreted IL-6 on autocrine TGF-beta(1). Anti-IL-6 neutralizing antibody inhibited TGF-beta(1) secretion from PSCs. Preincubation of cells with 10 nM PD98059, an extracellular signal-regulated kinase (ERK)-dependent pathway inhibitor, attenuated IL-6-enhanced TGF-beta(1) expression and secretion of PSCs. In addition, IL-6 activated ERK in PSCs. These data indicate the existence of autocrine loop between IL-6 and TGF-beta(1) through ERK- and Smad2/3-dependent pathways in activated PSCs.
  • H Aoki, H Ohnishi, K Hama, T Ishijima, Y Satoh, K Hanatsuka, A Ohashi, S Wada, T Miyata, H Kita, H Yamamoto, H Osawa, K Sato, K Tamada, H Yasuda, H Mashima, K Sugano
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 290 (4) C1100 - C1108 0363-6143 2006/04 [Refereed][Not invited]
    Pancreatic stellate cells ( PSCs) are activated during pancreatitis and promote pancreatic fibrosis by producing and secreting ECMs such as collagen and fibronectin. IL-1 beta has been assumed to participate in pancreatic fibrosis by activating PSCs. Activated PSCs secrete various cytokines that regulate PSC function. In this study, we have examined IL-1 beta secretion from culture-activated PSCs as well as its regulatory mechanism. RT-PCR and ELISA have demonstrated that PSCs express IL-1 beta mRNA and secrete IL-1 beta peptide. Inhibition of TGF-beta(1) activity secreted from PSCs by TGF-beta(1)-neutralizing antibody attenuated IL-1 beta secretion from PSCs. Exogenous TGF-beta(1) increased IL-1 beta expression and secretion by PSCs in a dose-dependent manner. Adenovirus-mediated expression of dominant-negative ( dn) Smad2/3 expression reduced both basal and TGF-beta(1)-stimulated IL-1 beta expression and secretion by PSCs. Coexpression of Smad3 with dnSmad2/3 restored IL-1 beta expression and secretion by PSCs, which were attenuated by dnSmad2/3 expression. In contrast, coexpression of Smad2 with dnSmad2/3 did not alter them. Furthermore, inhibition of IL-1 beta activity secreted from PSCs by IL-1 beta-neutralizing antibody attenuated TGF-beta(1) secretion from PSCs. Exogenous IL-1 beta enhanced TGF-beta(1) expression and secretion by PSCs. IL-1 beta activated ERK, and PD-98059, a MEK1 inhibitor, blocked IL-1 beta enhancement of TGF-beta(1) expression and secretion by PSCs. We propose that an autocrine loop exists between TGF-beta(1) and IL-1 beta in activated PSCs through Smad3- and ERK-dependent pathways.
  • K Hama, H Ohnishi, H Aoki, H Kita, H Yamamoto, H Osawa, K Sato, K Tamada, H Mashima, H Yasuda, K Sugano
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 340 (3) 742 - 750 0006-291X 2006/02 [Refereed][Not invited]
    Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-beta(1) inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-beta(1)-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-beta(1)-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results Suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-beta(1)-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway. (c) 2005 Elsevier Inc. All rights reserved.
  • Kiichi Tamada, Kentaro Sugano
    Japanese Journal of Gastroenterology 102 (7) 866 - 872 0446-6586 2005/07 [Refereed][Not invited]
  • M Ishikawa, K Yoshida, Y Yamashita, J Ota, S Takada, H Kisanuki, K Koinuma, YL Choi, R Kaneda, T Iwao, K Tamada, K Sugano, H Mano
    CANCER SCIENCE 96 (7) 387 - 393 1347-9032 2005/07 [Refereed][Not invited]
    Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies, mainly because of the lack of sensitive detection methods. Although gene expression profiling by DNA microarray analysis is a promising tool for the development of such detection systems, a simple comparison of pancreatic tissues may yield misleading data that reflect only differences in cellular composition. To directly compare PDC cells with normal pancreatic ductal cells, we purified MUC1-positive epithelial cells from the pancreatic juices of 25 individuals with a normal pancreas and 24 patients with PDC. The gene expression profiles of these 49 specimens were determined with DNA microarrays containing > 44000 probe sets. Application of both Welch's analysis of variance and effect size-based selection to the expression data resulted in the identification of 21 probe sets corresponding to 20 genes whose expression was highly associated with clinical diagnosis. Furthermore, correspondence analysis and 3-D projection with these probe sets resulted in separation of the transcriptomes of pancreatic ductal cells into distinct but overlapping spaces corresponding to the two clinical classes. To establish an accurate transcriptome-based diagnosis system for PDC, we applied supervised class prediction algorithms to our large data set. With the expression profiles of only five predictor genes, the weighted vote method diagnosed the class of samples with an accuracy of 81.6%. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC.
  • K Tamada, XP Wang, FC Brunicardi
    WORLD JOURNAL OF SURGERY 29 (3) 325 - 333 0364-2313 2005/03 [Refereed][Not invited]
    During the last decade significant advances in gene therapy have made it possible to treat various pancreatic disorders in both animal models and in humans. For example, insulin gene delivery to non-beta-cell tissues has been shown to reverse hyperglycemia in diabetic mice, and islet transplantation, based on in vitro differentiation of beta cells and concomitant gene targeting to prevent host autoimmune responses, has become more feasible. Additionally, introduction of the glucokinase regulatory protein and protein kinase C-zeta have been shown to improve glucose tolerance in non-insulin-dependent diabetes mellitus animal models. Pancreatic cancer studies utilize several DNA-based strategies for tumor treatment including introduction of tumor suppressor genes, suppression of oncogenes, suicide gene/prodrug therapy, and restricted replication-competent virus therapy. Tumor-specific targeting is an important part of suicide gene therapy, and tumor-specific promoters are used for cell-specific targeting. Tumor-specific suicide gene therapy directed by the rat insulin promoter has been used to eliminate insulinoma tumors in a mouse model. This review compiles a compendium of information related to the treatment of pancreatic disorders using gene therapy.
  • H Mutoh, K Satoh, H Kita, H Sakamoto, H Hayakawa, H Yamamoto, N Isoda, K Tamada, K Ido, K Sugano
    INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY 49 (7) 867 - 871 0214-6282 2005 [Refereed][Not invited]
    Many transcription factors are involved in the molecular control of intestinal epithelial cell differentiation. We report in this study that the transcription factor Cdx2 functions to define absorptive enterocytes during intestinal epithelial differentiation. Cdx2 is expressed in the villi of the normal small intestine. Intestinal metaplasia, which expresses Cdx2, occurs as a pathological condition in gastric mucosa. We have previously established Cdx2transgenic mice expressing Cdx2 exclusively in the gastric epithelium. In this study using Cdx2 transgenic mice, we show that Cdx2 plays a key role in the differentiation of intestinal absorptive enterocytes. The gastric mucosa of Cdx2 transgenic mice was morphologically completely changed into intestinal metaplastic mucosa. Absorptive enterocytes had microvilli which were observed by electron microscope. The intestinal metaplastic mucosa of Cdx2 transgenic mice expressed sucrase and peptide transporter PepT1. Disaccharidase and leucine aminopeptidase activities were observed in the intestinal metaplastic mucosa. Glucose and amino acids were absorbed from Cdx2 transgenic mouse stomach with intestinal metaplasia. Finally we generated mice whose intestine was extensively excised. Cdx2 transgenic mice with intestinal metaplasia survived even after extensive intestinal excision. We successfully demonstrated that Cdx2 induced not only morphological but also functional absorptive enterocytes in the intestinal metaplastic mucosa in vivo. Our results suggest that Cdx2 is necessary and sufficient by itself to specify the development of intestinal absorptive enterocytes, whereas other factors which are expressed in the small intestine are not always necessary for the differentiation of functional absorptive enterocytes.
  • H Mutoh, S Sakurai, K Satoh, K Tamada, H Kita, H Osawa, T Tomiyama, Y Sato, H Yamamoto, N Isoda, T Yoshida, K Ido, K Sugano
    CANCER RESEARCH 64 (21) 7740 - 7747 0008-5472 2004/11 [Refereed][Not invited]
    In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc(Min) mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.
  • H Osawa, H Kita, K Satoh, H Ohnishi, Y Kaneko, H Mutoh, K Tamada, K Ido, K Sugano
    AMERICAN JOURNAL OF SURGICAL PATHOLOGY 28 (9) 1253 - 1254 0147-5185 2004/09 [Refereed][Not invited]
  • H Ohnishi, T Miyata, H Yasuda, Y Satoh, K Hanatsuka, H Kita, A Ohashi, K Tamada, N Makita, T Iiri, N Ueda, H Mashima, K Sugano
    JOURNAL OF BIOLOGICAL CHEMISTRY 279 (10) 8873 - 8878 0021-9258 2004/03 [Refereed][Not invited]
    Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor-beta(1) (TGF-beta(1)) regulates PSC activation and proliferation in an autocrine manner. The intracellular signaling pathways of the regulation were examined in this study. Immunoprecipitation and immunocytochemistry revealed that Smad2, Smad3, and Smad4 were functionally expressed in PSCs. Adenovirus-mediated expression of Smad2, Smad3, or dominant-negative Smad2/3 did not alter TGF-beta(1) mRNA expression level or the amount of autocrine TGF-beta(1) peptide. However, expression of dominant-negative Smad2/3 inhibited PSC activation and enhanced their proliferation. Co-expression of Smad2 with dominant-negative Smad2/3 restored PSC activation inhibited by dominant-negative Smad2/3 expression without changing their proliferation. By contrast, co-expression of Smad3 with dominant- negative Smad2/3 attenuated PSC proliferation enhanced by dominant- negative Smad2/3 expression without altering their activation. Exogenous TGF-beta(1) increased TGFbeta(1) mRNA expression in PSCs. However, PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MEK1), inhibited ERK activation by TGF-beta(1), and consequently attenuated TGF-beta(1) enhancement of its own mRNA expression in PSCs. We propose that TGF-beta(1) differentially regulates PSC activation, proliferation, and TGF-beta(1) mRNA expression through Smad2-, Smad3-, and ERK-dependent pathways, respectively.
  • K Hama, H Ohnishi, H Yasuda, N Ueda, H Mashima, Y Satoh, K Hanatsuka, H Kita, A Ohashi, K Tamada, K Sugano
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 315 (4) 905 - 911 0006-291X 2004/03 [Refereed][Not invited]
    Although angiotensin II (Ang II) is known to participate in pancreatic fibrosis, little is known as to the mechanism by which Ang II promotes pancreatic fibrosis. To elucidate the mechanism, we examined the action of Ang II on the proliferation of rat pancreatic stellate cells (PSCs) that play central roles in pancreatic fibrosis. Immunocytochemistry and Western blotting demonstrated that both Ang II type 1 and type 2 receptors were expressed in PSCs. [H-3]Thymidine incorporation assay revealed that Ang II enhanced DNA synthesis in PSCs, which was blocked by Ang II type 1 receptor antagonist losartan. Western blotting using anti-phospho-epidermal growth factor (EGF) receptor and anti-phospho-extracellular signal regulated kinase (ERK) antibodies showed that Ang II-activated EGF receptor and ERK. Both EGF receptor kinase inhibitor AG1478 and MEK1 inhibitor PD98059 attenuated ERK activation and DNA synthesis enhanced by Ang II. These results indicate that Ang II stimulates PSC proliferation through EGF receptor transactivation-ERK activation pathway. (C) 2004 Elsevier Inc. All rights reserved.
  • S Wada, K Tamada, T Tomiyama, H Yamamoto, K Nakazawa, K Sugano
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 18 (10) 1215 - 1218 0815-9319 2003/10 [Refereed][Not invited]
  • S Wada, T Yano, K Tamada, T Tomiyama, S Tano, K Ido, K Sugano
    GASTROINTESTINAL ENDOSCOPY 58 (3) 464 - 466 0016-5107 2003/09 [Refereed][Not invited]
  • Arai W, Hosoya Y, Hyodo M, Yokoyama T, Saito S, Kurasina K, Aoki T, Yasuda Y, Nagai H, Tamada K
    Gan to kagaku ryoho. Cancer & chemotherapy 9 29 (9) 1651 - 1655 0385-0684 2002/09 [Refereed][Not invited]
    We report 3 cases in which palliation was achieved with every-other-day administration of TS-1 for recurrent or non-curative advanced gastric carcinoma that had resulted in obstructive jaundice. Two patients had received MTX-5-FU chemotherapy as first-line therapy and showed progressive disease, presenting with obstructive jaundice 6-24 months later. One of them experienced obstructive jaundice 2 months after surgery. After lowering serum bilirubin via per-cutaneous transhepatic biliary drainage (PTBD), TS-1 was given not in full dose but every other day based upon Shirasaka's theory, as well as for fear of further liver damage. Palliation in terms of long NC and/or decreased serum CEA level persisted for 4-14 months without severe liver dysfunction. Other side effects of the drug were negligible. Shirasaka's theory stresses the difference in proliferation cycles between cancer cells and normal tissue cells (GI tract, bone marrow, etc.); therefore, with every-other-day administration of chemotherapeutic agents, the cytotoxic effects against tumors would be augmented while the adverse reactions in normal cells could be reduced. The present experience seems to support the theoretical and clinical feasibility of every-other-day TS-1 administration for unresectable gastric cancer.
  • K Utsunomiya, K Tamada, T Tomiyama, S Wada, A Ohashi, K Ido, K Sugano
    SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 12 (3) 184 - 186 1530-4515 2002/06 [Refereed][Not invited]
    When we remove bile duct stones in endoscopic retrograde cholangiopancreatography, we sometimes encounter the complication of basket impaction. In most cases, bile duct stones can be crushed with a mechanical lithotriptor. An endotriptor also is commonly used to resolve the problem of basket impaction. An endotriptor is more powerful than a mechanical lithotriptor in crushing stones. We report a case of basket impaction that was not resolved by means of an endotriptor. When abdominal radiography shows apparent calcified bile duct stone, it should be cautioned that the stone is sometimes too hard to be crushed, even with use of the endotriptor as well as a mechanical lithotriptor.
  • T Higashizawa, K Tamada, T Tomiyama, S Wada, A Ohashi, Y Satoh, Y Gotoh, T Miyata, K Ido, K Sugano
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 17 (3) 332 - 336 0815-9319 2002/03 [Refereed][Not invited]
    Background: The introduction of a guidewire through bile duct strictures may facilitate transpapillary bile duct biopsy and subsequent biliary drainage. Methods: Endoscopic bile duct biopsy was attempted in 61 patients with bile duct strictures. After the introduction of a guidewire into the bile duct, biopsy forceps were inserted via the papilla. Both devices were inserted through the working channel (3.2 mm in diameter) of a conventional duodenoscope. After the procedure, an endoscopic naso-biliary drainage catheter was advanced along the guidewire. The success rate of inserting the biopsy forceps, the sensitivity of the biopsy, and the success rate of endoscopic biliary drainage after the biopsy were analyzed prospectively. Results: The final diagnosis was malignant strictures in 50 patients and benign strictures in 11. The success rate of inserting biopsy forceps without performing endoscopic papillary balloon dilation was 85%. The sensitivity of the biopsy for primary bile duct cancer (83%) was significantly higher (P < 0.05) than that of pancreatic cancer (47%). All patients had successful endoscopic biliary drainage after the procedure. Conclusion: A previously placed guidewire facilitates insertion of biopsy forceps and endoscopic biliary drainage. The histological diagnosis of cancer is more likely with bile duct cancer than with pancreatic cancer. (C) 2002 Blackwell Science Asia Pty Ltd.
  • K Tamada, N Kanai, N Ueno, M Ichiyama, T Tomiyama, S Wada, A Oohashi, T Nishizono, S Tano, T Aizawa, K Ido, K Kimura
    ENDOSCOPY 29 (8) 721 - 725 0013-726X 1997/10 [Refereed][Not invited]
    Background and Study Aims: We investigated whether intraductal ultrasonography (IDUS) could distinguish between stage T1 and T2 bile duct cancer. Materials and Methods: In-vitro study. Resected bile duct specimens (n = 8) were immersed in a water tank and were pierced with straight pins to clarify the normal layer structure. Ultrasonosgraphic images (20MHz) of the positions of pin echoes were compared to the positions of pin holes as seen on histologic analysis of the specimens. In-vivo study. A thin-caliber high-frequency (6Fr, 20MHz) ultrasonic probe was inserted into the bile duct via a transhepatic route or a transpapillary route in 26 patients with bile duct cancer who underwent surgical resection. Results: In-vitro study. The inner hypoechoic layer on the IDUS image corresponded not only to the fibromuscular layer but also to a part of fibrous layer of the perimuscular loose connective tissue on histologic analysis, especially in the cases with moderate to severe bile duct wall fibrosis. The outer hyperechoic layer corresponded to the subserosal fat tissue. In-vivo study. In four of six patients with tumor limited to the inside hypoechoic layer on IDUS images, the histologic findings showed tumor invasion to the fibrous layer of the perimuscular loose connective tissue. Due to this limitation, accuracy of IDUS in T-staging was only 20/26 (77%). Conclusions: IDUS cannot reliably distinguish bile duct cancer in stage T1 from that in stage Ti.
  • K Ido, K Tamada, K Kimura, A Oohashi, N Ueno, C Kawamoto
    JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES-PART A 7 (3) 151 - 156 1092-6429 1997/06 [Refereed][Not invited]
    We clarified the significance of endoscopic balloon sphincteroplasty (EBS) in the therapeutic treatment of biliary tract stones in the present era of laparoscopic cholecystectomy (LC). Patients with cholecysto-choledocholithiasis (n = 33) were treated by EBS. After endoscopic retrograde cholangiography (ERC), a balloon catheter (8 mm in diameter and 3 cm in width) was inserted into the bile duct using a guidewire, and positioned at the sphincter of Oddi. After inflating the balloon catheter, bile duct stones were removed by mechanical lithotripsy, a basket catheter, or a balloon catheter. In all patients, bile duct stones were removed by EBS without endoscopic sphincterotomy. No complication occurred except for 2 cases of mild pancreatitis, which was resolved within 48 hours. Twenty-four patients underwent LC before or after EBS. The remaining 9 patients did not undergo LC due to a poor-risk status for general anesthesia. None of them, however, experienced cholecystitis or colicky attacks after EBS. The combination of EBS and LC is an excellent method for treating cholecysto-choledocholithiasis.
  • Diagnosis of extrahepatic bile duct stones using intraductal ultrasonography: a case series.
    Ueno N, Nishizono T, Tamada K, Ichiyama M, Tomiyama T, Wada S, Tano S, Aizawa T, Miyata T, Kimura K
    Endoscopy 356 - 360 1997 [Refereed][Not invited]
  • K Tamada, K Ido, N Ueno, M Ichiyama, T Tomiyama, T Nishizono, S Wada, S Tano, T Aizawa, K Kimura
    GASTROINTESTINAL ENDOSCOPY 44 (3) 249 - 256 0016-5107 1996/09 [Refereed][Not invited]
    Background: We evaluated the course and variations of the hepatic artery in bile duct cancer using intraductal ultrasonography (IDUS). Methods: IDUS was used to demonstrate the course of the hepatic artery preoperatively in 20 patients with extrahepatic bile duct cancer, and the image was compared with angiographic and surgical findings. Results: IDUS was able to assess tumor invasion to the main branch of the right hepatic artery in all cases. However, it demonstrated only three cases in the left hepatic artery and four cases in the proper hepatic artery. When the hepatic artery indicated re-entry or bifurcation on the IDUS image, the proximal portion of re-entry or bifurcation was established as the proper hepatic artery, but when it showed neither re-entry nor bifurcation it was established as the right hepatic artery. Conclusions: IDUS demonstrated the main branch of the right hepatic artery in all cases, but was not useful for demonstration of the left and proper hepatic arteries. Correct assessment of re-entry and bifurcation was essential on IDUS images for making the distinction between the right hepatic artery and the proper hepatic artery.
  • K Ido, C Kawamoto, K Tamada, T Suzuki, Y Taniguchi, N Isoda, K Kimura
    ENDOSCOPY 28 (7) 638 - 638 0013-726X 1996/09 [Refereed][Not invited]
  • K Tamada, N Ueno, M Ichiyama, T Tomiyama, T Nishizono, S Wada, A Oohashi, S Tano, T Aizawa, K Ido, K Kimura
    ENDOSCOPY 28 (6) 492 - 496 0013-726X 1996/08 [Refereed][Not invited]
    Background and Study Aims: This study was performed to clarify the diagnostic accuracy of intraductal ultrasonography (IDUS) in assessing pancreatic parenchymal invasion by bile duct cancer, Patients and Methods: Preoperative assessment of pancreatic parenchymal invasion was carried out by IDUS via a percutaneous tract or a transpapillary route in 18 patients with extrahepatic bile duct cancer, Various probes with diameters of 1.4, 2.0, 2.4, 2.6 and 3.2 mm, and frequencies of 7.5, 15, 20 and 30 MHz were used, All patients underwent angiography and endoscopic ultrasonography (EUS), In the first six cases, IDUS and EUS images were analyzed retrospectively without knowledge of the operative outcome or the results of other imaging tests, In the subsequent 12 cases, the IDUS und EUS images were prospectively reviewed prior to surgery. The diagnostic accuracy of IDUS was compared with angiography and EUS by means of a histopathological examination of the resected specimens. Results: The accuracy of IDUS, EUS, and angiography in assessing pancreatic parenchymal invasion was 100%, 78% and 61%, respectively, However, IDUS could not assess pancreatic capsular invasion. The accuracy of IDUS in assessing horizontal tumor extension to the intrapancreatic bile duct and to the hepatic side was 83% and 72%, respectively. Conclusions: IDUS proved useful for assessing the extension of cancer invasion to the pancreatic parenchyma, but not to the pancreatic capsule or mucosal surface.
    ENDOSCOPY 27 (8) 579 - 583 0013-726X 1995/10 [Refereed][Not invited]
    Background and Study Aims: This study was performed to clarify the diagnostic accuracy of intraductal ultrasonography (IDUS) in assessing hepatic artery invasion by bile duct cancer. Patients and Methods: Preoperative assessment of hepatic artery invasion was performed by IDUS via a percutaneous tract or the transpapillary route in a total of 22 patients with extrahepatic bile duct cancer. The probes used had a diameter of 1.4, 2.0, 2.4, 2.6, and 3.2 mm, and frequencies of 7.5, 15, 20, and 30 MHz. In the first six cases, IDUS images were analyzed retrospectively with no knowledge of the operative results or of the other imaging tests. In the following 16 cases, the IDUS images were prospectively reviewed prior to surgery without knowledge of the angiographic findings. The diagnostic accuracy of IDUS was compared with angiography in all cases, with the histopathological results in 20 resected cases, and with the intraoperative findings in two cases with only surgical exploration. Results: IDUS was able to demonstrate the right hepatic artery in all cases, and its accuracy in diagnosing right hepatic invasion was 100%. However, IDUS was able to visualize the proper hepatic artery in only four cases (18%), and the left hepatic artery in only three cases (14%), respectively. IDUS could not visualize the area outside of the hepatoduodenal ligament, because of its low penetration depth. Conclusions: IDUS proved useful for assessing the extension of bile duct cancer invasion into the right hepatic artery. However, IDUS did not sufficiently demonstrate the proper hepatic artery and the left hepatic artery for diagnosing vascular involvement.
    ENDOSCOPY 27 (8) 573 - 578 0013-726X 1995/10 [Refereed][Not invited]
    Background and Study Aims: We recently reported on the contribution of intraductal ultrasonography (IDUS) to the regional staging of bile duct cancer, and we present here the first detailed study of the value of IDUS in assessing the portal vein invasion by bile duct cancer. Patients and Methods: Preoperative assessment of portal vein invasion was performed by IDUS via a percutaneous tract or via transpapillary route in 18 patients with extrahepatic bile duct cancer, Various probes, with diameters of 1,4, 2.0, 2.4, 2.6, and 3.2 mm, and frequencies of 7.5, 15, 20, and 30 MHz, were used. All patients additionally underwent endoscopic ultrasonography (EUS) and angiography. In the first six cases, the IDUS and EUS images were analyzed retrospectively without the knowledge of operative results or the other imaging tests. In the remaning 12 cases, IDUS and EUS images were prospectively reviewed prior to surgery, without knowledge of the angiographic findings. The gold standard for the results of IDUS, EUS and angiography was the histopathological findings in 17 resected tumors, and the intraoperative findings in one patient who did not undergo resective surgery. Results: IDUS was able to demonstrate the portal vein in all cases. Its accuracy in diagnosing portal vein invasion was 100% for all locations. EUS was useful in assessing portal vein invasion at the middle and distal bile duct (the accuracy was 91%), but was not useful in assessing invasion at the proximal bile duct (the accuracy was 57%). Conclusions: IDUS proved useful for assessing the extension of cancer invasion into the portal vein, even in proximal bile duct tumors.
  • Preoperative staging of extrahepatic bile duct cancer using intraductal ultrasonography(IDUS).
    Tamada K, Ido K, Ueno N, Ichiyama M, Tomiyama T, Kimura K
    Am J Gastroenterol 90 239 - 246 1995 [Refereed][Not invited]
  • Noda T, Ido K, Ueno N, Tamada K, Ichiyama M, Tomiyama T, Nisizono T, Tano S, Aizawa T, Kimura K
    Ultrasound Int 1 141 - 147 1995 [Refereed][Not invited]
    AMERICAN JOURNAL OF GASTROENTEROLOGY 89 (11) 2066 - 2069 0002-9270 1994/11 [Refereed][Not invited]
    We report a case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice. A 49-yr-old male was admitted with the complaints of fever and jaundice. Laboratory findings included high biliary tract enzyme values and normal serum amylase value. Ultrasonography and computed tomographic scan demonstrated a cyst, 4 cm in diameter, in the pancreas head. Cholangiography revealed a long, tapered obstruction of the common bile duct which was apparently compressed by the cyst. Although the jaundice improved after percutaneous transhepatic biliary drainage, fever continued, and the cyst was aspirated. Bacteriological examination of the contents revealed infection. The symptoms disappeared rapidly and the cyst decreased in size soon after aspiration. The stenosis of the common bile duct showed improvement for several weeks but then regressed. In a patient with secondary pancreatic infection or obstructive jaundice following pancreatic disease, distinguishing the condition is an important aspect of accurate diagnosis and therapy.
    AMERICAN JOURNAL OF GASTROENTEROLOGY 89 (10) 1893 - 1895 0002-9270 1994/10 [Refereed][Not invited]
    A 55-yr-old female was hospitalized with epigastric pain. Conventional ultrasonography revealed marked dilation of the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography showed fusiform dilation of the CBD. The common channel of the pancreatic duct and choledochus was 20 mm long. A diagnosis of congenital choledochal dilation accompanied by anomalous arrangement of the pancreaticobiliary ductal system (AAPBDS) was made. Intraductal ultrasonography (IDUS) was performed. IDUS demonstrated the union of the pancreatic duct and choledochus within the pancreatic parenchyma. This meant that the union existed outside the duodenal wall, confirming the diagnosis of AAPBDS. Although endoscopic retrograde cholangiopancreatography alone could show the maljunction in this case, simultaneous IDUS will be useful in making an accurate diagnosis of AAPBDS.
    ENDOSCOPY 23 (2) 79 - 82 0013-726X 1991/03 [Refereed][Not invited]
    Nasobiliary double contrast radiography and nasobiliary cytological diagnosis via nasobiliary catheter were performed in 30 patients with biliary diseases to assess the diagnostic usefulness and limitations of the procedures. The results showed that the contour and fine mucosal pattern of the extrahepatic bile duct could be demonstrated adequately (88%) by nasobiliary double contrast radiography. In contrast, the intrahepatic bile duct could not be fully demonstrated (56%) by nasobiliary double contrast radiography because of its anatomical structure. On the other hand the fine reticular pattern of the mucosa was defined in each section of the gallbladder by nasobiliary double contrast radiography. This procedure is thus a valuable method for detection of mucosal lesions of the extrahepatic bile duct and gallbladder, especially carcinoma. The cell collection rate was not as high (59%) using conventional nasobiliary cytological diagnosis. Brush cytology via a nasobiliary catheter was shown to be a useful adjunct to other diagnostic procedures.


  • Yuki ARAI, Kiichi TAMADA, Shinichi WADA, Akira OHASHI, Katsuyuki KAZAWA, Hisashi HATANAKA, Kentaro SUGANO  Jichi Medical University journal  33-  91  -99  2011/03  [Not refereed][Not invited]
    Purpose. To evaluate gallbladder motility on ultrasonography after the ingestion of different forms and quantities of fat.Methods. After a fast, 111 volunteers underwent ultrasonography to measure gallbladder volumes before, 30 min, and 60 min after ingesting Calorie Mate Liquid&reg;, Calorie Mate Jelly&reg;, Terumeal 2.0&reg;, or Terumeal 2.0α&reg;, which are used as nutritional supplements. The Calorie Mate products contain 4.4 g of fat, while the Terumeal products contain 15 g of fat. Most of the fat in these products is composed of long-chain fatty acids except for Terumeal 2.0α&reg;, in which 15% of the fat is composed of medium-chain fatty acids. Gallbladder volume and the ejection fraction were measured using the ellipsoid method.Results. There were significant differences in gallbladder volume before, 30 min, and 60 min after taking Calorie Mate Liquid&reg; and Terumeal 2.0α&reg;, and in gallbladder volume before and 30 min after taking Calorie Mate Jelly&reg; and Terumeal 2.0&reg;. There were significant differences in the 30-min ejection fraction between Calorie Mate Jelly&reg; and Calorie Mate Liquid&reg; and Terumeal 2.0α&reg;, and in the 60-min ejection fraction between Calorie Mate Jelly&reg; and Terumeal 2.0&reg; and Terumeal 2.0α&reg;. There were no other significant differences.Conclusions. Calorie Mate Liquid&reg;, which contains 4.4 g of fat, can be used as an appropriate gallbladder stimulant. Gallbladder contractions were weaker with jellies than with others; thus, jelly meals are not appropriate for evaluating gallbladder contraction. There was no difference in gallbladder contraction between the meal containing a medium-chain fatty acid component of 15% and the other meals.
  • 畑中 恒, 玉田 喜一, 牛尾 純  映像情報medical  43-  (2)  116  -120  2011/02  [Not refereed][Not invited]
  • 玉田 喜一, 和田 伸一, 大橋 明  Gastroenterology  50-  (2)  170  -174  2010/02  [Not refereed][Not invited]
  • TAMADA Kiichi, OHASHI Akira, TOMIYAMA Takeshi  Tando  23-  (2)  229  -234  2009/05  [Not refereed][Not invited]
    Ultrasonography, including color Doppler US is useful in assessing right hepatic artery invasion and portal vein invasion of the superior bile duct carcinoma. On the other hand, endoscopic ultrasonography via the transduolenal scanning has some limitations in staging superior bile duct carcinoma compared to it of inferior bile duct carcinoma. Intraductal ultrasonography produces high-quality cross-sectional images of the bile duct without blind area, and is useful in assessing tumor depth infiltration, hepatic parenchymal invasion, portal vein invasion, and right hepatic artery invasion of superior bile duct carcinoma. However, it has limitations in assessing lymph nodes metastases. The assessment of longitudinal cancer extension along the bile duct is a promising aspect of this area. Transpapillary IDUS prior to biliary drainage is essential to prevent inflammatory changes that may result from mechanical irritation by a biliary drainage catheter.
  • 新井 由季, 玉田 喜一, 松原 茂樹  周産期医学  38-  (12)  1565  -1569  2008/12  [Not refereed][Not invited]
  • 中澤 克行, 玉田 喜一, 菅野 健太郎  Pharmavision  11-  (10)  2  -8  2007/10  [Not refereed][Not invited]
  • TAMADA Kiichi, TOMIYAMA Takeshi, OHASHI Akira, IDO Kenichi  胆道 = Journal of Japan Biliary Association  20-  (5)  619  -627  2006/12  [Not refereed][Not invited]
  • ARAI Yuki, TAMADA Kichi, SATOH Yukihiro, WADA Shinichi, TANO Shigeo, HANATSUKA Kazunobu, OHASHI Akira, SUGANO Kentarou  Nippon Shokakibyo Gakkai Zasshi  102-  (11)  1412  -1416  2005/11  [Not refereed][Not invited]
    We usually use yolks to assess gallbladder motility by ultrasonography. In this study, we evaluated liquid type CalorieMate® as a simple oral stimulus instead of yolks. The volunteers (n=27) underwent ultrasonography before, 30 min after, and 60min after taking liquid type CalorieMate®. Gallbladder volume and the ejection fraction were measured by ellipsoid method. The mean fasting gallbladder volume, 30-min ejection fraction, and 60-min one were 13.5 ml, 53%, and 62%, respectively. These results were similar to the previous reports by yolks. If the fasting volume is lower than 4 ml, they should take re-examination after longer fast to reduce the influence of the dinner the day before the exam. In conclusion, liquid type CalorieMate® is useful stimulus to assess gallbladder motility.
  • TAMADA Kiichi, SUGANO Kentaro  Nippon Shokakibyo Gakkai Zasshi  102-  (7)  866  -872  2005/07  [Not refereed][Not invited]
    胆管癌の早期診断には胆管拡張例にmagnetic resonance cholangiopancreatographyを施行し,内視鏡的逆行性膵胆道造影時にintraductal ultrasonographyと胆管生検を行う.進展度診断にはmultidetector row-CTとintraductal ultrasonographyが有用である.胆管癌の治療には多くのオプションがあり,入院早期から内科医と外科医が十分に連絡をとり,診断を進める事が大切である.保存的治療では,メタリックステントが有用である.ステント内への腫瘍増殖を防ぐために腫瘍の局所制御を十分行う必要がある.ステント閉塞時の対処も大切である.
  • TAMADA Kiichi, SUGANO Kentaro  日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy  46-  (12)  2525  -2531  2004/12  [Not refereed][Not invited]
  • MIYATA T, TOMIYAMA T, TAMADA K, NISHIZONO T, TANO S, WADA S, AIZAWA T, MIYATA T, UENO N, KIMURA K  Journal of medical ultrasonics = 超音波医学  24-  (3)  364  -364  1997/03  [Not refereed][Not invited]
  • Kiichi Tamada, Norio Ueno, Masahiko Ichiyama, Hideichi Seki, Takashi Kanou, Masami Fukuda, Takeshi Tomiyama, Takashi Nishizono, Toshiyasu Iwao, Ken Kimura  Nippon Shokakibyo Gakkai Zasshi  91-  (4)  863  -874  1994  [Not refereed][Not invited]
    Intraductal ultrasonography (IDUS) were performed in patients with extrahepatic bile duct cancer and compared to other diagnostic modalities and to resected specimens. Endoscopic ultrasonography (EUS) is a non-invasive diagnostic method useful for screening patients with bile duct cancers and determining whether they are resectable or not. While, EUS was not useful for the differential diagnosis of advanced and early tumors, and less useful in case of bile duct tumors located at the hilus hepatis. IDUS proved useful without blind spot even in case of bile duct cancers at the hilus hepatis. IDUS was especially useful for the differential diagnosis of advanced and early tumors. IDUS is the very accurate diagnostic modality which make up for EUS and essential to determine the appropriate operation plan. © 1994, The Japanese Society of Gastroenterology. All rights reserved.
  • Ichiyama Masahiko  Nippon Shokakibyo Gakkai Zasshi  91-  (6)  1994  [Not refereed][Not invited]

Research Grants & Projects

  • 胆管癌の診断と治療
  • Diagnosis and treatment of bile durt cancer

Media Coverage

  • 象牙海岸共和国内視鏡指導
    Date : 1992/12

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