Yukio Mikami

University of Freiburg, Freiburg, Baden-Württemberg, Germany

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Publications (24)51.52 Total impact

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    ABSTRACT: The role of polymorphonuclear neutrophil granulocytes (PMNs) and the PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on gut barrier dysfunction in rat SAP. SAP was induced by the injection of 5% sodium taurocholate, and anti-rat PMN serum or BB-94 were administered 48 h and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four hours after the induction of acute pancreatitis, the gut barrier dysfunction and the incidence of bacterial translocation (BT) and PMN transmigration were investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive oxygen species were evaluated by spin trap assay. The mucosal injury and the infiltration of PMNs into the gut tissue of rats with SAP were significantly increased in comparison with rats treated with anti-rat PMN serum or BB-94. The levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were significantly higher than those of the rats treated with anti-rat PMN serum or BB-94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in SAP. The incidence of BT in SAP was prevented by the depletion of PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in both BT and PMN transmigration in rat SAP.
    Surgery 03/2009; 145(2):147-56. DOI:10.1016/j.surg.2008.08.036 · 3.38 Impact Factor
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    ABSTRACT: Patients with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas are likely to have a better prognosis than those with conventional pancreatic ductal adenocarcinoma. Recently there have been some reports on extrapancreatic malignant neoplasms (EPM) occurring in patients with IPMN. The purpose of this study was to discover the characteristic features of IPMN with EPM compared with IPMN without EPM. 61 patients with IPMN who underwent surgery at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. Results: The 61 patients with IPMN in this study comprised 25 with intraductal papillary-mucinous adenomas (IPMA) and 36 with intraductal papillary-mucinous carcinomas (IPMC) including 6 with invasive carcinomas. Synchronous and metachronous EPM were observed in 15 out of the 61 patients (24.6%). Three of these patients, including 2 with IPMA and 1 with invasive carcinoma associated with IPMC, died of the EPM. None of the features, including sex, age, smoking, family history, macroscopic types (main duct type or branch duct type), histological types (gastric, intestinal, pancreatobiliary or oncocytic), and aberrant expression of molecules including CDKN2A, TP53, SMAD4 and DUSP6, except for the histological diagnoses were associated with the occurrence of EPM, i.e., the EPM occurred more often in patients with IPMA (10 out of 25) than in those with IPMC (5 out of 36) in our series (p = 0.0199 by the chi(2) test, p = 0.0330 by Fisher's exact probability test, p = 0.0422 by Yates' correction). Patients with IPMA were more likely to have EPM than those with IPMC. Patients with IPMA are usually expected to have a fair prognosis but EPM could be fatal in some of them, so it must be noted during follow-up.
    Pancreatology 10/2008; 8(6):577-82. DOI:10.1159/000159844 · 2.84 Impact Factor
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    ABSTRACT: It is known that prophylaxis with imipenem reduces the risk of infection accompanying severe acute pancreatitis. In this study,we modified a rat experimental model of severe acute pancreatitis for antibiotic evaluation, and the effect of biapenem was compared with that of imipenem to determine the usefulness of biapenem. Severe acute pancreatitis was induced by 5% sodium taurocholate. Antibiotics were subcutaneously administered at 3 and 6 hours and evaluated at 12 hours after the pancreatitis induction. For pharmacokinetic evaluation, antibiotics were subcutaneously administered at 3 hours after the pancreatitis induction. From 3 hours after the induction, bacteria were detected from the pancreas. The total bacterial count increased in a time-dependent manner for 12 hours. Biapenem administration reduced the total bacterial count in the pancreas, as observed in imipenem administration. The plasma concentration of biapenem was almost equivalent to that of imipenem; however, the pancreatic penetration of biapenem was approximately twice that of imipenem in this model. Biapenem was suggested to be effective in prophylactic treatment of infectious complications as much as imipenem because of its superior penetration to the pancreas in severe acute pancreatitis.
    Pancreas 04/2008; 36(2):125-32. DOI:10.1097/MPA.0b013e3181568ed7 · 2.96 Impact Factor
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    ABSTRACT: This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation. In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan's islet transplantation registry. Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines. Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.
    Journal of Hepato-Biliary-Pancreatic Surgery 02/2008; 15(5):488-92. DOI:10.1007/s00534-007-1309-3 · 1.60 Impact Factor
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    ABSTRACT: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas encompasses a spectrum of neoplasms with both morphological and immunohistochemical variations of mucin glycoproteins. Recently, a consensus nomenclature and criteria were histologically defined for classifying these variants of IPMNs into gastric, intestinal, pancreatobiliary, and oncocytic types. The purpose of this study was to determine associations between the histological types and clinicopathological features in patients with IPMN. Sixty-one patients with IPMN operated upon at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. Our series included 27 gastric-, 29 intestinal-, 4 pancreatobiliary-, and 1 oncocytic-type IPMNs. Statistically, the types of IPMN were significantly associated with the histological diagnoses, macroscopic types, and survival of the patients. Characteristically, the gastric-type IPMNs were likely to be diagnosed as benign, to be confined to branch ducts, and to have fair prognoses. On the other hand, the intestinal-type IPMNs were likely to be diagnosed as malignant, occupy the main duct, and have poor prognoses. Because of the small number of pancreatobiliary-type IPMNs and only 1 case of oncocytic-type IPMN, we were unable to determine any of their clinicopathological characteristics in our series. Evaluation of the histological types of IPMN may help to predict the clinical course of patients with IPMN and to design improved clinical management for these patients.
    Pancreas 12/2007; 35(4):348-52. DOI:10.1097/mpa.0b013e31806da090 · 2.96 Impact Factor
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    ABSTRACT: This study analyses the results of face-shield blood spatter contamination at six medical facilities to determine exposure risk when facial protection is not used. Blood spatter exposure was evaluated on the basis of overall incidence, location of spatter on face shields, surgical specialty, risk for operating room staff, length of surgery and volume of blood loss. Six hundred face shields were evaluated for blood spatter contamination by visual inspection as well as by staining with leucomalachite green. The face shield was divided into three regions: Orbital (O-region), Paraorbital (P-region) and Mask (M-region). Visual examination detected blood spatter contamination in 50.5% (303/600) of the face shields, whereas leucomalachite green staining detected blood contamination in 66.0% (396/600). Blood contamination was 36.6% (220/600) in the O-region, 37.8% (227/600) in the P-region and 57.0% (342/600) in the M-region. Among operating room staff, the incidence of blood spatter was greatest among lead surgeons at 83.5% (167/200), followed by the first assistant at 68.5% (137/200) and the scrub nurse at 46.0% (92/200). By specialty, cardiovascular surgery was at highest risk with an incidence of 75.3% (113/150) followed by neurosurgery at 69.3% (104/150), gastrointestinal at 60.0% (90/150) and orthopaedic surgery at 60.0% (90/150).
    Journal of Hospital Infection 10/2007; 67(1):56-61. DOI:10.1016/j.jhin.2007.05.020 · 2.54 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Pancreas 06/2007; 35(1):89. DOI:10.1097/01.mpa.0000278688.48189.f4 · 2.96 Impact Factor
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    ABSTRACT: A 72-year-old woman, who had undergone pylorus-preserving pancreatoduodenectomy 3 years before for cancer of Vater's papilla associated with a branch-type intraductal papillary-mucinous adenoma (IPMA), developed dilatation of the main duct and a nodular lesion in the remnant pancreas. Total pancreatectomy was performed, which revealed that the lesion was intraductal papillary-mucinous adenocarcinoma (IPMC) with minimal invasion, suggesting the metachronous multicentric occurrence of this intraductal papillary-mucinous neoplasm (IPMN). Because there were no malignant cells at the pancreaticojejunostomy, and because the histological appearance of the main-duct IPMC was different from that of the IPMA in the primary specimen, the main-duct IPMC was thought to be of different origin from the IPMA. These findings suggest that careful surveillance of the gastrointestinal tract and careful follow up are necessary for IPMN, because an IPMN could be associated with other gastrointestinal tract malignancies.
    Journal of Hepato-Biliary-Pancreatic Surgery 02/2007; 14(5):522-5. DOI:10.1007/s00534-006-1199-9 · 1.60 Impact Factor
  • S. Egawa · N. Sakata · Y. Mikami · F. Motoi · T. Abe · S. Fukuyama · M. Unno ·

    Pancreas 11/2006; 33(4). DOI:10.1097/00006676-200611000-00076 · 2.96 Impact Factor

  • Pancreas 11/2006; 33(4). DOI:10.1097/00006676-200611000-00194 · 2.96 Impact Factor
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    ABSTRACT: The aim of this study was to identify genes that are differentially expressed in the early period after pancreatic cold ischemia/reperfusion (I/R) injury. Grafts of isogeneic rat pancreaticoduodenal transplantation were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-hour CIT; UW, 18-hour CIT; and physiologic saline solution, 6-hour CIT. Animals that did not receive transplants served as controls. At 2-hour reperfusion, grafts were removed and pancreatic RNA was isolated, pooled, and hybridized to Affymetrix RG-U34A arrays. Quantitative reverse-transcription polymerase chain reaction was used to confirm the results of microarray technology. A total of 49 genes were consistently upregulated (more than threefold) in all three groups of transplant recipient animals. Prominent genes include transcription factors; cytoskeletal factors; heat-shock proteins (e.g. Hsp27, Hsp90); molecules involved in inflammation (e.g. PAPIII), immunology, signal transduction, and translation; and genes that have not been associated with I/R injury so far (e.g. Best5). Messenger RNA levels of some genes were exclusively downregulated in response to the different conditions applied to the pancreatic grafts: Cybb, Reg3a, Per2, BMAL1, MAP, and Isl2. These results provide new insight in I/R-induced gene expression after experimental pancreas transplantation. The reported upregulation of heat shock proteins, Best5, and PAPIII may play a pathologic role in pancreatic cold I/R injury and could therefore provide a promising perspective for further investigations.
    Transplantation 06/2006; 81(10):1428-34. DOI:10.1097/01.tp.0000208619.71264.40 · 3.83 Impact Factor
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    ABSTRACT: It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock. Cannabinoid means a mind-active material in cannabis (marijuana). Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock. The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis. Male Wistar rats were injected with caerulein intravenously to induce mild edematous pancreatitis or injected with 5% sodium taurocholate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. The animals in the latter group were also injected with a CB1 receptor antagonist, AM251, or vehicle solution to see if the inhibition of endocannabinoids improves their survival. Plasma anandamide level was measured by the liquid chromatography/tandem mass spectrometry method. In both models of acute pancreatitis, the plasma anandamide levels were increased, and the levels were significantly higher in rats with severe necrotizing pancreatitis than those in rats with mild edematous pancreatitis. The mean arterial pressure and survival rate were significantly improved by the treatment with AM251, despite that the local inflammatory changes in the pancreas and various parameters (white blood cells, hematocrit, serum amylase, and serum interleukin-6) were similar. This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.
    The Tohoku Journal of Experimental Medicine 11/2005; 207(2):99-107. DOI:10.1620/tjem.207.99 · 1.35 Impact Factor
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    ABSTRACT: Whereas mucinous cystadenomas of the pancreas are considered premalignant, serous cystadenomas are believed to remain benign. We present a case of an 80-year-old woman with a primary tumor of the pancreas that was histologically classified as serous cystadenocarcinoma. Because preoperatively available criteria that determine malignancy in serous lesions are lacking, observation is the preferred option in serous cystadenomas. Operating every serous lesion is not justified. Reviewing all reports of serous cystadenocarcinomas that have been published to date, we are providing recommendations for the management of this rare entity.
    Pancreas 09/2005; 31(2):182-7. DOI:10.1097/01.mpa.0000167001.89018.3c · 2.96 Impact Factor
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    ABSTRACT: The rat experimental model of continuous regional arterial infusion of protease inhibitor (CRAI) on acute pancreatitis has yet to be established. Therefore, the aims of this study were (1) to establish the rat experimental model of CRAI and (2) to evaluate the effects of nafamostat on rat severe acute pancreatitis via different routes of administration. The rat internal jugular vein or the celiac artery was infused with nafamostat, and the concentration of nafamostat in the lung and pancreas was measured. After the induction of severe acute pancreatitis, rats received intravenous or regional intraarterial infusion of nafamostat and then concentrations of trypsinogen activated peptide (TAP) and serum interleukin (IL-6), and histologic sections of the pancreas were examined and the 96-hour survival rate was evaluated. CRAI rats had higher concentrations of nafamostat in the pancreas than those infused intravenously. However, CRAI rats had lower concentrations of nafamostat in the lung that those infused intravenously. CRAI significantly reduced the levels of TAP and pancreatic necrosis. Moreover, the levels of serum IL-6 and the mortality rate were significantly reduced after CRAI compared with the intravenous infusion of nafamostat. The effectiveness of the rat experimental model of CRAI on acute pancreatitis was clearly demonstrated. The concentration of nafamostat in the lung and pancreas and the effects of nafamostat differ according to the route of administration.
    Pancreas 05/2005; 30(3):248-53. DOI:10.1097/01.mpa.0000153328.54569.28 · 2.96 Impact Factor
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    Y Mikami · K Takeda · N Omura · H Abe · S Fukuyama · F Motoi · S Egawa · M Sunamura · S Matsuno ·
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    ABSTRACT: Acute pancreatitis is an autodigestive disease, of which protease inhibition has been the focus of experimental and clinical research. Different from Europe and the United States, protease inhibitors are often applied in the treatment of acute pancreatitis in Japan. However, in clinical settings, the effect of protease inhibitors on acute pancreatitis is still controversial. Continuous Regional Arterial Infusion (CRAI) of protease inhibitors and antibiotics therapy were developed in Japan and it has been demonstrated that CRAI therapy has beneficial effects on severe acute necrotizing pancreatitis. In the Japanese clinical guidelines for the treatment of acute pancreatitis, published in 2003, CRAI therapy is still classified as a special therapy. However, a Randomized Controlled Trial for CRAI therapy has started and CRAI therapy is expected to become a new standard therapy for severe acute pancreatitis. CRAI therapy is aimed at preventing the progression of pancreatic inflammation and pancreatic infection. CRAI therapy can decrease the mortality rate and the frequency of pancreatic infection in severe acute pancreatitis, but it should be started as soon as possible after the onset of acute pancreatitis.
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    ABSTRACT: The angiographic appearance of acute necrotizing pancreatitis (ANP) demonstrates ischemic change with vasospasm in and around the pancreas. We investigated the role of vasospasm in pancreatic ischemia and necrosis in the early phase of human ANP. The relationship between the angiographic abnormalities and the perfusion status of the pancreas documented by contrast-enhanced computed tomography (CE-CT) was examined in 102 patients with ANP who were admitted during the early phase of the disease. Ischemic change with vasospasm on angiography of the intrapancreatic and extrapancreatic arteries was observed and corresponded with the poorly perfused area of the pancreas detected by CE-CT done at admission. Resultant pancreatic necrosis was confirmed on follow-up CE-CT examination consistent with the location where angiography demonstrated ischemic change with vasospasm. Severe ischemic change on angiography was primarily observed in patients in whom more than 50% of the pancreas was poorly perfused. The extent of the ischemic change was correlated with the extent of the poorly perfused area of the pancreas and the mortality rate. These results suggest that vasospasm is involved in the development of pancreatic ischemia and necrosis in the early phase of ANP.
    Pancreas 02/2005; 30(1):40-9. · 2.96 Impact Factor
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    ABSTRACT: Acute pancreatitis is a protean disease capable of wide clinical variation, ranging from mild discomfort to severe organ failure. Moreover, the inflammatory process may remain localized in the pancreas, spread to regional tissues, or even involve remote organ systems. This variability in presentation and clinical course has plagued the study and management of acute pancreatitis since its original clinical description. However, precise comprehension about the pathological physiology is required for better treatment. We described about the clinical classification and pathological physiology in the general in this
    Nippon rinsho. Japanese journal of clinical medicine 12/2004; 62(11):1973-6.
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    ABSTRACT: Macrophages are considered to play an essential role in the events leading to systemic inflammatory response. Some are known to reside in the peritoneal cavity but there are no reports defining the participation of peritoneal macrophages (PMs) in the progression of acute pancreatitis. To clarify the role of PMs in the progression of acute pancreatitis. Acute pancreatitis was induced in rats from which macrophages other than PMs were greatly depleted, and in rats greatly depleted of macrophages including PMs. Macrophages were depleted by the injection of liposome encapsulated dichloromethylene bisphosphonate. After the induction of acute pancreatitis, local pancreatic inflammation, intraperitoneal inflammation and lung injury were compared between the 2 groups. Local pancreatic inflammation did not differ between the 2 groups. However, intraperitoneal inflammation was clearly improved by the depletion of PMs. Serum cytokine level and lung injury were also improved by the depletion of PMs. Peritoneal macrophages extend inflammation from the pancreas to the peritoneal cavity and subsequently induce lung injury in acute pancreatitis. Peritoneal macrophages play an essential role in the systemic inflammatory response and the progression of acute pancreatitis in the rat.
    Pancreas 11/2003; 27(3):253-60. DOI:10.1097/00006676-200310000-00011 · 2.96 Impact Factor
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    ABSTRACT: The purpose of this study was to clarify the still poorly understood dynamics of peritoneal inflammatory cells (PICs) in acute pancreatitis. Acute pancreatitis of 3 different degrees of severity was induced in male Wistar rats. Peritoneal lavage was performed at 1, 6, 12, and 24 hours after the induction, and the fluids collected were analyzed for the number and subpopulation of PICs. The levels of apoptosis and necrosis, cytokines, and bacterial infection were also investigated. The number of PICs was increased in mild and moderate pancreatitis, and the infiltration of inflammatory cells had occurred. In severe pancreatitis, the number of PICs increased until 6 hours after the induction, but thereafter the number decreased. Infiltration of neutrophils occurred 6 hours after the induction, but it was not sustained thereafter and infiltration of peritoneal macrophages did not occur. Cytokines in the lavage fluid increased in all 3 models during the first 6 hours after the induction. Subsequently, cytokines were reduced in mild and moderate pancreatitis but significantly increased in severe pancreatitis. The level of bacterial infection increased according to the severity. The relationship between the PIC dynamics and cytokine levels in severe pancreatitis is very different from that observed in mild or moderate pancreatitis.
    Surgery 08/2002; 132(1):86-92. DOI:10.1067/msy.2002.125171 · 3.38 Impact Factor
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    ABSTRACT: We report a case of severe acute pancreatitis in a 9-year-old boy. In 1998, the patient had pneumonia and received antibiotics for 2 weeks. One day after discharge, he suffered severe abdominal pain, and high serum amylase and hypoperfusion of the whole pancreas were observed. We undertook continuous infusion of protease inhibitor and antibiotics from the celiac artery in intensive care and he recovered. Seven weeks after initial onset, however, he suffered a high fever. Abdominal computed tomography (CT) showed a low-density area around the pancreatic body to the splenic hilum. Fine-needle aspiration confirmed bacterial infection by methicillin-resistant S. aureus (MRSA), for which we conducted debridement and open retroperitoneal abscess drainage. Case reports of severe acute pancreatitis in a child are few. Continuous arterial infusion of protease inhibitor and antibiotics appear to be effective for children and adults. The abscess was drained retroperitoneally for the retroperitoneal abscess.
    Nippon Shokaki Geka Gakkai zasshi 01/2002; 35(6):641-644. DOI:10.5833/jjgs.35.641

Publication Stats

380 Citations
51.52 Total Impact Points


  • 2009
    • University of Freiburg
      • Institute of Psychology
      Freiburg, Baden-Württemberg, Germany
  • 2006-2008
    • Tohoku University
      • • Division of Surgery
      • • Department of Gastroenterological Surgery
      Sendai, Kagoshima, Japan