論文 - 北郷　実

Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation

Yamada Y., Hoshino K., Fuchimoto Y., Matsubara K., Hibi T., Yagi H., Abe Y., Shinoda M., Kitago M., Obara H., Yagi T., Okajima H., Kaido T., Uemoto S., Suzuki T., Kubota K., Yoshizumi T., Maehara Y., Inomata Y., Kitagawa Y., Egawa H., Kuroda T.

Transplantation Direct （Transplantation Direct）  4 （ 2 ） e342 2018年02月

ISSN  2373-8731

　概要を見る

Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

• Access to Document (DOI)

Successful living donor liver retransplantation for graft failure within 7 days due to acute de novo donor-specific anti-human leukocyte antigen antibody-mediated rejection

Yamada Y., Hoshino K., Mori T., Kawaida M., Abe K., Ishihama H., Shimizu T., Takahashi N., Matsubara K., Hibi T., Abe Y., Yagi H., Shimojima N., Shinoda M., Kitago M., Obara H., Fuchimoto Y., Kameyama K., Kitagawa Y., Kuroda T.

Hepatology Research （Hepatology Research）  48 （ 3 ） E360 - E366 2018年02月

ISSN  13866346

　概要を見る

Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

• Access to Document (DOI)

Predictive factors of late cholangitis in patients undergoing pancreaticoduodenectomy

Ito Y., Abe Y., Kitago M., Itano O., Kitagawa Y.

World Journal of Surgical Oncology （World Journal of Surgical Oncology）  16 （ 1 ） 19 2018年01月

ISSN  1477-7819

　概要を見る

Background: Because the survival rate for patients experiencing late complications after pancreaticoduodenectomy (PD) is increasing, late complications should receive as much attention as early complications do. Methods: Between April 2007 and August 2016, 133 patients underwent PD at our institution. We analyzed their cases to determine the predictors of late cholangitis after PD. Results: Of the 133 patients, 28 (21.1%) were diagnosed with postoperative cholangitis. A multivariate analysis showed that abnormal postoperative values of alkaline phosphatase were independently associated with postoperative cholangitis (odds ratio, 3.81; 95% confidence interval, 1.519-9.553; P=0.004). The optimal cut-off value for postoperative alkaline phosphatase calculated from the receiver operating characteristic curve was 410IU/L (sensitivity, 76.2%; specificity, 67.9%; area under the curve, 0.73). A univariate analysis to identify risk factors showed that pneumobilia was significantly related to a postoperative alkaline phosphatase value ≥410IU/L (P=0.041). Conclusion: This study suggests that an alkaline phosphatase level ≥410IU/L is a predictor of late postoperative cholangitis. In addition, pneumobilia is also related to the postoperative alkaline phosphatase level. Therefore, alkaline phosphatase levels should be carefully monitored in patients with postoperative pneumobilia in the late postoperative course.

• Access to Document (DOI)

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

Endo Y., Kitago M., Miyajima A., Kurihara I., Kameyama K., Shinoda M., Yagi H., Abe Y., Hibi T., Takagi C., Nakano Y., Koizumi W., Itano O., Kitagawa Y.

International Journal of Surgery Case Reports （International Journal of Surgery Case Reports）  44   139 - 142 2018年

ISSN  22102612

　概要を見る

Introduction: von Hippel-Lindau disease (vHL disease) is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A) associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET), and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A) was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15%) pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection is a safe and effective treatment option for bilateral pheochromocytoma and PNET associated with vHL disease.

• Access to Document (DOI)

Tolvaptan for fluid management in living donor liver transplant recipients

Imai S., Shinoda M., Obara H., Kitago M., Hibi T., Abe Y., Yagi H., Matsubara K., Higashi H., Itano O., Kitagawa Y.

Annals of Transplantation （Annals of Transplantation）  23   25 - 33 2018年

ISSN  14259524

　概要を見る

Background: Tolvaptan, an antagonist of the vasopressin V2 receptor is a novel oral diuretic that promotes water excretion selectively. We have used furosemide as a primary diuretic and added human atrial natriuretic peptide (hANP) if necessary for fluid management postoperatively in living-donor liver transplantation (LDLT) recipients. Recently we introduced tolvaptan and used both tolvaptan and furosemide as primary diuretics. Material/Methods: Clinical outcomes were compared between LDLT recipients whose postoperative fluid management was performed before (control group, n=10) and after (tolvaptan group, n=16) introduction of tolvaptan. Results: Preoperative and intraoperative demographic data did not differ significantly between the groups except for the period of post-surgical follow-up and total ischemic time. Urine volume was 1,242±692, 2,240±1307, and 2,268±1262 mL on postoperative day 1, 3, and 7, respectively, in the tolvaptan group. These volumes did not significantly differ from those in control group (1,027±462, 1,788±909, and 2,057±1216 mL on day 1, 3, and 7 postoperatively, respectively). Body weight gain and fluid volume from abdominal drainage tubes postoperatively did not differ significantly between groups. The time from hANP initiation to discontinuation and the time to removal of central vein catheters were significantly reduced in tolvaptan-treated patients. No severe side effects directly related to tolvaptan were observed. The survival rate at month 6 was 90.0% in control patients versus 93.8% in tolvaptan-treated patients. Conclusions: The outcomes of this investigation indicate that tolvaptan in combination with furosemide provides an adequate diuretic for fluid management subsequent to LDLT without causing adverse effects.

• Access to Document (DOI)

Predictive factors of early recurrence in patients with distal cholangiocarcinoma after pancreaticoduodenectomy

Ito Y., Abe Y., Egawa T., Kitago M., Itano O., Kitagawa Y.

Gastroenterology Research and Practice （Gastroenterology Research and Practice）  2018   6431254 2018年

ISSN  16876121

　概要を見る

Aim. To determine the factors associated with early recurrence in patients with distal cholangiocarcinoma after pancreaticoduodenectomy (PD). Patients and Methods. Sixty-one patients with distal cholangiocarcinoma were enrolled. The clinical data and histopathological findings were collected retrospectively. Results. Patients were divided into two groups as follows: 16 patients (26%) with early recurrence and 45 patients (74%) with late recurrence or no recurrence. In a univariate analysis, lymph node metastases (P = 0 0016), lymphatic invasion (P < 0 0001), pancreatic invasion (P = 0 0006), and perineural invasion (P = 0 0004) were significantly different between the two groups. In a multivariate analysis, a higher incidence of lymphatic invasion was the only independent risk factor for early recurrence (odds ratio: 5.772, 95% confidence interval: 1.123-29.682, P = 0 036). Moreover, the disease-free survival and overall survival of patients with a higher incidence of lymphatic invasion were significantly worse compared with those of patients with a lower incidence of lymphatic invasion (P < 0 001). Conclusions. Our study showed that a higher incidence of lymphatic invasion was a significant predictor of early recurrence in patients with distal cholangiocarcinoma. Therefore, lymphatic invasion might be useful in determining the optimal adjuvant therapy in the early postoperative stage for distal cholangiocarcinoma.

• Access to Document (DOI)

Acceleration of wound healing by ultrasound activation of TiO₂ in Escherichia coli-infected wounds in mice.

Osumi K, Matsuda S, Fujimura N, Matsubara K, Kitago M, Itano O, Ogino C, Shimizu N, Obara H, Kitagawa Y

Journal of biomedical materials research. Part B, Applied biomaterials （John Wiley and Sons Inc.）  105 （ 8 ） 2344 - 2351 2017年11月

ISSN  1552-4973

　概要を見る

Surgical site infections continue to be a common complication affecting surgical prognosis. Reactive oxygen species (ROS) are generated by ultrasound-irradiated titanium dioxide (TiO2) (UIT). Although excessive ROS production can cause cell damage, ROS at physiological levels mediate beneficial cellular responses, including angiogenesis. This study investigated whether UIT can promote healing of Escherichia coli-infected wounds. We used TiO2 and ultrasound irradiation using an ultrasonography machine at a frequency of 1.0 MHz and intensity of 0.4 W cm−2. These levels are not bactericidal in vitro
therefore, we could study the effect of UIT on E. coli survival without interference of ultrasound effects. The number of cluster of differentiation 31-positive blood vessels, which are indicative of angiogenesis, was decreased by bacterial infection, and increased at the wound edges in the UIT-treated infected wounds, suggesting upregulation of neovascularization by UIT. Although UIT treatment did not decrease E. coli survival in vivo, it promoted healing of the infected wounds as evidenced by a significant decrease in the wound area in the UIT-treated mice. Our findings demonstrate that UIT promotes wound healing in surgical site infections and suggest beneficial use of the UIT-based approach as a novel therapeutic method to treat infected surgical wounds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2344–2351, 2017.

• Access to Document (DOI)

Clinical predictive factors of long-term survival after curative resection of pancreatic cancer: a retrospective study.

Nakano Y, Kitago M, Shinoda M, Abe Y, Yagi H, Hibi T, Takeuchi A, Aiura K, Itano O, Kitagawa Y

Cancer medicine （Blackwell Publishing Ltd）  6 （ 10 ） 2278 - 2286 2017年10月

ISSN  2045-7634

　概要を見る

Pancreatic ductal adenocarcinoma (PDAC) continues to have the poorest prognosis of all gastrointestinal malignancies, even after the tumor has been completely resected. However, only a proportion of patients achieve 5-year survival after resection. The factors predictive of achieving 5-year survival remain unclear. The aim of this study was to investigate the pre- and postoperative clinicopathological characteristics of PDAC patients with a &gt
5-year survival after curative resection. We retrospectively reviewed patients who underwent pancreatectomy for PDAC between January 1995 and December 2011. Logistic regression analysis was performed to determine the predictive factors for 5-year survival. One hundred and fifty-one patients were enrolled, including 38 patients with 5-year survival (actual 5-year survival rate, 25.2%). The independent preoperative factors predictive of achieving 5-year survival included serum albumin levels (odds ratio [OR]: 5.06, 95.0% confidence interval [CI]: 1.49–17.19
P = 0.009) and neoadjuvant chemoradiotherapy (OR: 3.02, 95.0% CI: 1.00–9.08
P = 0.049). Venous infiltration (OR: 2.99, 95.0% CI: 1.09–8.25
P = 0.034), liver recurrence (OR: 0.17, 95.0% CI: 0.04–0.69
P = 0.013), and perioperative portal vein infusion chemotherapy (OR: 3.06, 95.0% CI: 1.09–8.25
P = 0.028) were found to be independent postoperative predictive factors for achieving 5-year survival. Serum albumin levels could be a biomarker for predicting the prognosis of PDAC patients after curative resection. Liver recurrence and perioperative portal vein infusion chemotherapy were independent postoperative factors, suggesting that perioperative portal vein infusion chemotherapy could be promising for improving the survival rate of PDAC patients after curative resection.

• Access to Document (DOI)

Pancreas Fat and β Cell Mass in Humans With and Without Diabetes: An Analysis in the Japanese Population.

Murakami R, Saisho Y, Watanabe Y, Inaishi J, Tsuchiya T, Kou K, Sato S, Kitago M, Kitagawa Y, Yamada T, Itoh H

The Journal of clinical endocrinology and metabolism 102 （ 9 ） 3251 - 3260 2017年09月

ISSN  0021-972X

　概要を見る

CONTEXT: The mechanisms by which β cell mass is reduced in patients with type 2 diabetes remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce β cell apoptosis, leading to the development of diabetes. OBJECTIVE: The aim of this study was to clarify the effects of intrapancreatic fat on β and α cell mass in humans with and without diabetes. DESIGN AND SUBJECTS: Using our tissue database, pancreas sections of 72 Japanese nondiabetic (NDM) autopsy cases and 50 diabetic and 49 age- and body mass index (BMI)-matched NDM patients who underwent pancreatic surgery were analyzed. In addition to histological grading, intrapancreatic fat area (IPFA) was quantified as fractional intralobular, but not interlobular, fat area to the whole pancreas area. RESULTS: Although IPFA was positively correlated with age and BMI, there was no significant difference in IPFA between cases with and without diabetes. Moreover, no association was found between IPFA and either β or α cell area, or glycated hemoglobin. CONCLUSION: These findings suggest that pancreatic fat deposits have little effect on β cell mass and the development of diabetes in humans.

• Access to Document (DOI)

Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury.

Fujii T, Obara H, Matsubara K, Fujimura N, Yagi H, Hibi T, Abe Y, Kitago M, Shinoda M, Itano O, Tanabe M, Masugi Y, Sakamoto M, Kitagawa Y

The Journal of surgical research 213   207 - 214 2017年06月

ISSN  0022-4804

　概要を見る

BACKGROUND: Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs. MATERIALS AND METHODS: We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann-Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls. CONCLUSIONS: Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.

• Access to Document (DOI)

First successful perinatal management of pregnancy after ABO-incompatible liver transplantation.

Higashi H, Obara H, Miyakoshi K, Shinoda M, Kitago M, Shimojima N, Abe Y, Hibi T, Yagi H, Matsubara K, Yamada Y, Itano O, Hoshino K, Kuroda T, Kitagawa Y

World journal of gastroenterology （Baishideng Publishing Group Co）  23 （ 3 ） 547 - 550 2017年01月

ISSN  1007-9327

　概要を見る

Many papers have reported on pregnancy and delivery after liver transplantation, but there have been no reports on pregnancy after ABO-incompatible liver transplantation. This paper reports the first successful pregnancy and delivery of a newborn after ABO-incompatible liver transplantation for fulminant hepatic failure. The patient was a 39-year-old female. She had an ABO-incompatible liver transplantation, donated from her husband, due to subacute fulminant hepatitis of unknown etiology. She was taking tacrolimus, methylprednisolone, and mizoribine orally for the maintenance of immunosuppression at the time of discharge. She was discharged uneventfully on postoperative day 38 without any rejection episodes. At 1 year and 6 mo after transplantation, she indicated a wish to become pregnant. Therefore, treatment with mycophenolate mofetil was interrupted at that time. After two miscarriages, she finally became pregnant and delivered transvaginally 3 years after the transplantation. All of the pregnancies were conceived naturally. The newborn was female with a birth weight of 3146 g
the Apgar scores were 9 and 10. Delivery was performed smoothly, and the newborn exhibited no malformations. The mother and the newborn were discharged uneventfully. We suggest that pregnancy is possible for recipients after ABO-incompatible liver transplantation.

• Access to Document (DOI)

Mesenchymal Stem Cells Contribute to Hepatic Maturation of Human Induced Pluripotent Stem Cells.

Takagi C, Yagi H, Hieda M, Tajima K, Hibi T, Abe Y, Kitago M, Shinoda M, Itano O, Kitagawa Y

European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes （S. Karger AG）  58 （ 1-2 ） 27 - 39 2017年

ISSN  0014-312X

　概要を見る

Background: Induced pluripotent stem cells (iPSCs) are human somatic cells that have been reprogrammed to a pluripotent state. Several methods have been used to generate hepatocyte-like cells from iPSCs. However, these hepatic cells have limited clinical application because of their immature function compared to primary hepatocytes. Mesenchymal stem cells (MSCs) have been reported to inhibit apoptosis of hepatic cells and to improve hepatic regeneration in acute liver injury. Therefore, we expected that MSCs had the potential to positively contribute to the maturation of hepatic cells. Here we demonstrate the effect of MSCs on the maturation of hepatoblasts derived from human iPSCs. Methods: MSCs were isolated from human bone marrow and cultured to 70-80% confluence. MSC-conditioned medium (MSC-CM) was collected 48 h after culture in hepatic maturation medium. Human iPSC-derived hepatoblasts were then cultured for 6 days with MSC-CM. Hepatic functions were analyzed and compared to those from cells cultured in general maturation medium. Results: Cells in both groups had a cuboidal morphology typical of hepatocytes. The proportion of Oct4-positive cells was decreased and those of albumin- and alpha-fetoprotein-positive cells were increased in the MSC-CM group. Albumin secretion and urea synthesis as well as cytochrome P450 (CYP) 3A4 activity were enhanced in the MSC-CM group. The gene expressions of some CYP enzymes were upregulated as demonstrated by RT-PCR. Conclusion: Secreted molecules from human MSCs could enhance the hepatic function of human iPSC-derived hepatocyte-like cells. Although more technological innovations are needed, MSC-CM will be useful as a novel efficient strategy for clinically relevant hepatic cell maturation.

• Access to Document (DOI)

Postoperative Delirium in Patients after Pancreaticoduodenectomy.

Ito Y, Abe Y, Handa K, Shibutani S, Egawa T, Nagashima A, Kitago M, Itano O, Kitagawa Y

Digestive surgery 34 （ 1 ） 78 - 85 2017年

ISSN  0253-4886

• Access to Document (DOI)

Increased Incidence of Thrombotic Microangiopathy After ABO-Incompatible Living Donor Liver Transplantation.

Kishida N, Shinoda M, Itano O, Obara H, Kitago M, Hibi T, Yagi H, Abe Y, Matsubara K, Odaira M, Tanabe M, Shimazu M, Kitagawa Y

Annals of transplantation （Medical Science International）  21   755 - 764 2016年12月

ISSN  1425-9524

　概要を見る

Background: Thrombotic microangiopathy (TMA) is a severe life-threatening complication associated with solid organ trans-plantation. We retrospectively investigated the incidence, risk factors, and appropriate treatment of TMA following adult living donor liver transplantation (LDLT). Material/Methods: The subjects were 129 adult patients who underwent LDLT in our department from 1997 to 2014. Patients with TMA were identified retrospectively based on diagnostic criteria. We calculated the incidence of TMA and performed a risk factor analysis for TMA occurrence. We also assessed our past treatments for TMA and sought to identify the most appropriate form of treatment. Results: Thirteen patients were identified as having TMA. The incidence of TMA in the study cohort was 10.1% but was especially high (37.9%) among ABO-incompatible cases. A univariate analysis revealed that ABO incompatibility, usage of tacrolimus, usage of rituximab, and cold ischemic time ≥50 minutes are risk factors for occurrence of TMA (p&lt
0.10). Multivariate analysis demonstrated that ABO incompatibility was the only independent risk factor for TMA (p=0.009). Initiation of treatment on the day of TMA diagnosis was associated with better survival. Conclusions: ABO incompatibility is an independent risk factor for TMA following adult LDLT. Our results suggest that early initiation of treatment is crucial for improving the outcomes.

• Access to Document (DOI)

Two cases of pancreatic ductal adenocarcinoma with intrapancreatic metastasis.

Fujita Y, Kitago M, Masugi Y, Itano O, Shinoda M, Abe Y, Hibi T, Yagi H, Fujii-Nishimura Y, Sakamoto M, Kitagawa Y

World journal of gastroenterology （Baishideng Publishing Group Co）  22 （ 41 ） 9222 - 9228 2016年11月

ISSN  1007-9327

　概要を見る

There are no standardized diagnostic criteria for intrapancreatic metastasis of pancreatic ductal adenocarcinoma (PDAC). Here, we report two cases of patients with PDAC who were pathologically diagnosed as harboring intrapancreatic metastasis. In both cases, the main lesions were located in the pancreatic body, and no other lesion was detected preoperatively. The patients were diagnosed with pancreatic body cancers and distal pancreatectomy was performed. Pathological findings revealed microscopic cancer nests, which had connections to neither the main lesion nor the premalignant lesion in the pancreatic tail parenchyma. In both cases, the histological type of the daughter lesion was quite similar to that of the main lesion. Hence, we diagnosed the daughter lesions as metastatic foci in the pancreas. Although intrapancreatic metastasis of PDAC has been regarded as a poor prognostic factor, few reports of intrapancreatic metastasis are available. This article reports two such cases and provides a review of the literature.

• Access to Document (DOI)

Simeprevir/pegylated interferon/ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation.

Shinoda M, Ebinuma H, Itano O, Yamagishi Y, Obara H, Kitago M, Nakamoto N, Hibi T, Yagi H, Abe Y, Matsubara K, Chu PS, Wakayama Y, Taniki N, Yamaguchi A, Amemiya R, Miyake R, Mizota T, Kanai T, Kitagawa Y

Hepatology research : the official journal of the Japan Society of Hepatology （WILEY-BLACKWELL）  46 （ 11 ） 1118 - 1128 2016年10月

査読有り,  ISSN  1386-6346

　概要を見る

AimSimeprevir (SMV) is a protease inhibitor which demonstrates good tolerability and high antiviral response in patients with hepatitis C. The clinical outcomes of triple therapy using simeprevir, pegylated interferon and ribavirin (SMV/PEG IFN/RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT) have not been well reported. In this study, we assessed the outcomes of patients with recurrent hepatitis C (genotype 1) after LDLT who received triple therapy at our hospital.
MethodsSMV/PEG IFN/RBV was administrated for 12weeks (triple therapy), followed by another 12weeks or extended period of PEG IFN/RBV (dual therapy). Virological response, interaction with calcineurin inhibitors and adverse events were retrospectively analyzed.
ResultsTen patients with recurrent hepatitis C after LDLT completed 12weeks of triple therapy. Nine patients achieved rapid or early virological response, and one patient was a non-responder. The nine responders received subsequent dual therapy, and the duration of dual therapy was extended (24 to 36weeks) in five cases. Although one patient was in relapse 8weeks after completing the standard duration (12weeks) of dual therapy, eight patients achieved sustained virological response for 12weeks (SVR12). The SVR12 rate was 80%. Trough levels of calcineurin inhibitor did not show marked changes after introduction of SMV in all cases. There were no major adverse events associated with SMV.
ConclusionSMV treatment may be a safe and effective option for recurrent hepatitis C after LDLT.

• Access to Document (DOI)

Endocrine pancreas engineered using porcine islets and partial pancreatic scaffolds.

Katsuki Y, Yagi H, Okitsu T, Kitago M, Tajima K, Kadota Y, Hibi T, Abe Y, Shinoda M, Itano O, Takeuchi S, Kitagawa Y

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] （Elsevier B.V.）  16 （ 5 ） 922 - 30 2016年09月

ISSN  1424-3903

　概要を見る

Objectives Because therapeutic options for severe diabetes are currently limited, there is a continuing need for new therapeutic strategies, especially in the field of regenerative medicine. Collaborative efforts across the fields of tissue engineering technology and islet biology may be able to create functionally engineered islets capable of restoring endocrine function in patients with insulin-dependent diabetes. Methods This engineered scaffold was seeded with isolated primary porcine islets via the pancreatic duct using a multi-step infusion technique. Endocrine function of perfusion-cultured islets in the native scaffold was analyzed by immunohistochemical staining of insulin and glucagon as well as by the insulin stimulation test. Results The pancreas in this large animal could be uniformly decellularized by perfusion with trypsin and TritonX-100 via the pancreatic duct, as shown by positive staining of extracellular matrix (ECM) components. These scaffolds derived from porcine pancreas were able to maintain the cellular integrity of islets that had repopulated the parenchymal space, which is fundamental for the restoration of endocrine function. Insulin release up to four days after islet infusion was maintained. Conclusions This scaffold from a large animal maintained islet survival and function in the short-term, retaining the cells as a solid organ in the parenchymal space after infusion through the pancreatic duct. These results suggest that this scaffold is suitable for further fabrication of fully functional bioengineered endocrine pancreases when implanted in vivo. Therefore, it may represent a key improvement in the field of beta-cell replacement therapy. Nonetheless, the facilitation of longer-term islet survival and studies of implantation in vivo is required for successful clinical translation.

• Access to Document (DOI)

Effects of Obesity and Diabetes on α- and β-Cell Mass in Surgically Resected Human Pancreas.

Inaishi J, Saisho Y, Sato S, Kou K, Murakami R, Watanabe Y, Kitago M, Kitagawa Y, Yamada T, Itoh H

The Journal of clinical endocrinology and metabolism 101 （ 7 ） 2874 - 82 2016年07月

ISSN  0021-972X

　概要を見る

CONTEXT: The ethnic difference in β-cell regenerative capacity in response to obesity may be attributable to different phenotypes of type 2 diabetes among ethnicities. OBJECTIVE: This study aimed to clarify the effects of diabetes and obesity on β- (BCM) and α-cell mass (ACM) in the Japanese population. DESIGN, SETTING, AND PARTICIPANTS: We obtained the pancreases of 99 individuals who underwent pancreatic surgery and whose resected pancreas sample contained adequate normal pancreas for histological analysis. Questionnaires on a family history of diabetes and history of obesity were conducted in 59 patients. Pancreatic sections were stained for insulin or glucagon, and fractional β- and α-cell area were measured. Islet size and density as well as β-cell turnover were also quantified. RESULTS: In patients with diabetes, BCM was decreased by 46% compared with age- and body mass index-matched nondiabetic patients (1.48% ± 1.08% vs 0.80% ± 0.54%, P < .001), whereas there was no difference in ACM between the groups. There was no effect of obesity or history of obesity on BCM and ACM irrespective of the presence or absence of diabetes. There was a negative correlation between BCM, but not ACM, and glycated hemoglobin before and after pancreatic surgery. In addition, reduced BCM was observed in patients with pancreatic cancer compared with those with other pancreatic tumors. CONCLUSIONS: These findings suggest that the increase in BCM in the face of insulin resistance is extremely limited in the Japanese, and BCM rather than ACM has a major role in regulating blood glucose level in humans.

• Access to Document (DOI)

Development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high-fat, choline-deficient diet and intraperitoneal injection of diethylnitrosamine.

Kishida N, Matsuda S, Itano O, Shinoda M, Kitago M, Yagi H, Abe Y, Hibi T, Masugi Y, Aiura K, Sakamoto M, Kitagawa Y

BMC gastroenterology （Springer Science and Business Media LLC）  16 （ 1 ） 61 2016年06月

• Access to Document (DOI)

Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma.

Itano O, Oshima G, Minagawa T, Shinoda M, Kitago M, Abe Y, Hibi T, Yagi H, Ikoma N, Aiko S, Kawaida M, Masugi Y, Kameyama K, Sakamoto M, Kitagawa Y

Surgical endoscopy （Springer New York LLC）  29 （ 12 ） 3600 - 7 2015年12月

ISSN  0930-2794

　概要を見る

&lt;p&gt;Background: This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach.&lt;/p&gt;&lt;p&gt;Methods: We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion.&lt;/p&gt;&lt;p&gt;Results: None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309

• Access to Document (DOI)