Xanthogranulomatous inflammation is a chronic inflammatory reaction microscopically characterized by aggregation of foamy histiocytes, fibrous tissue, and infiltration of various inflammatory cells. In contrast to xanthogranulomatous inflammation in the gallbladder or kidney, xanthogranulomatous pancreatitis is rare. We herein present a case of xanthogranulomatous pancreatitis in a patient who underwent distal pancreatectomy with splenectomy under preoperative suspicion of a pancreatic pseudocyst or pancreatic tumor. A 77-year-old woman with a 1 month history of epigastric pain, anorexia, and general fatigue was admitted to our hospital. Contrast-enhanced computed tomography revealed a cystic mass with ill-defined margins at the pancreatic tail together with a splenic abscess. Contrast-enhanced endoscopic ultrasound detected a hyperechoic cystic lesion at the tail of the pancreas with heterogeneous internal echogenicity, and part of the intra-cystic content was enhanced by the contrast agent. Endoscopic retrograde cholangiopancreatography showed a cystic lesion at the tail of the pancreas that continued into the main pancreatic duct, and the main pancreatic duct was slightly narrowed downstream of the cystic lesion. Pancreatic juice cytology revealed suspicious cells, leading to the possibility of intraductal papillary mucinous carcinoma. Distal pancreatectomy with splenectomy was performed, and the histopathological diagnosis was xanthogranulomatous pancreatitis with no malignant findings.

Spindle and giant cell type undifferentiated carcinoma of the extrahepatic bile duct is an uncommon malignancy. We report a case involving the common bile duct in a 72-year-old male with jaundice who was admitted to our hospital. Diagnostic imaging, including abdominal computed tomography and magnetic resonance imaging, revealed a mass in the distal common bile duct, accompanied by dilatation of both intra- and extrahepatic bile ducts and regional lymph node enlargement. Endoscopic retrograde cholangiography demonstrated stenosis in the distal common bile duct, with a biopsy confirming adenocarcinoma. The patient underwent endoscopic retrograde biliary drainage followed by a subtotal stomach-preserving pancreaticoduodenectomy with regional lymphadenectomy. Microscopic examination revealed that the tumor predominantly comprised spindle and giant atypical cells within the stroma. Immunohistochemical analysis showed the tumor cells expressing cytokeratins and mesenchymal markers, confirming the diagnosis of spindle and giant cell type undifferentiated carcinoma of the common bile duct. Ki-67 labeling index was observed to be above 80%. Postoperatively, intra-abdominal lymph node recurrence was noted at two months, and multiple liver metastases were identified at three months. The patient died seven months post-surgery. The literature pertaining to this rare disease is reviewed and discussed.

症例は71歳の男性で，発熱を主訴に来院した．造影CTで肝内胆管の拡張と動脈相での肝実質の不均一な濃染像を認め，胆管炎の診断となり入院・加療を開始した．ERCPでは左肝管の胆管狭窄を認め，狭窄部の胆管擦過細胞診では疑陽性であった．胆管炎を繰り返すことや肝内胆管癌が否定できないことから，拡大左葉切除術を施行した．病理組織診断では悪性所見は認めず，hepatic peribiliary cysts（以下，HPBCと略記）の診断であった．HPBCは比較的大きいグリソン鞘に見られる多発小囊胞であり，基本的には無症状だが，圧排により胆管の閉塞を来し閉塞性黄疸や胆管炎を繰り返すことがある．また，肝内胆管狭窄と末梢胆管の拡張像が肝内胆管癌による胆管拡張像と類似しており，慎重な鑑別診断を要する．今回，胆管炎の制御を要し，胆管癌も否定できず肝左葉切除を行った症例を経験したため報告する．

症例は60歳代男性．左上葉肺癌（pT2aN0M0）術後の補助化学療法としてUFTを8カ月間服用した．術後12カ月後のPET-CTでは異常所見を認めなかったが，術後31カ月後のPET-CTにて門脈臍部に接する肝外側区域にFDGの高度集積像（SUV max = 6.57）を認めた．EOB-MRIにて，同部位に造影早期相でリング状の造影効果を認め，肝細胞相では6 mm大の低信号域を認めた．肺癌の肝転移の可能性が否定出来ないため，腹腔鏡下肝左葉切除術を施行した．術後経過は良好で，術後8日目に退院となった．病理組織学的検査にて標本内に腫瘍性病変を認めず，術前の画像評価で指摘された領域に一致して炎症細胞浸潤を伴う限局性の胆管周囲線維化を認めた．本症例ではPET-CTにてFDGが高度に集積し，転移性肝腫瘍との鑑別が困難であった．

Purpose: The treatment strategy for acute cholecystitis (AC) is based on clinical guidelines such as the Tokyo Guidelines 2018, and early surgery is recommended. However, we sometimes encounter patients with AC who are high risk for early emergency surgery. Materials and Methods: From November 2013 to October 2018, 201 patients with AC underwent emergency surgeries at our hospital. These patients were divided into groups based on the time from AC onset to surgery and age: (1) early cholecystectomy within 72 hours of AC onset ( n =159) and delayed cholecystectomy over 72 hours after AC onset ( n =42); and (2) extremely elderly patients over 85 years old ( n =23) and patients less than 85 years old ( n =178). Clinical outcomes were compared for each of these groups. Result: In patients with early cholecystectomy, the rate of laparoscopic cholecystectomy (Lap C) was significantly higher (82.4% vs. 57.1%, P =0.0005), intraoperative blood loss was significantly lower (92.9 vs. 185.1 ml, P <0.0001), the postoperative complication rate was significantly lower (6.3% vs. 16.7%, P =0.03), and the postoperative hospital stay was significantly shorter (7.4 vs. 8.5 days, P =0.029). Extremely elderly patients had significantly higher intraoperative blood loss (166.1 vs. 105.2 ml, P =0.04) and a significantly longer postoperative hospital stay (14.2 vs. 6.8 days; P =0.0001) compared to patients less than 85 years old, but there were no differences in the rates of Lap C (65.2% vs. 78.7%, P =0.15) and postoperative complications (13.0% vs. 7.9%, P =0.40). Conclusion: Patients with AC who underwent surgery at more than 72 hours after onset and extremely elderly patients over 85 years old had increased intraoperative blood loss and a prolonged postoperative hospital stay. Therefore, careful perioperative management may be required in these high risk patients with AC.

INTRODUCTION AND IMPORTANCE:Although variations from the standard anatomy of the extrahepatic bile ducts are common, duplication of the cystic duct draining a single gallbladder is an extremely rare variant. We herein describe the first report of gallbladder cancer spreading into the aberrant cystic duct.CASE PRESENTATION:A 60-year-old female presented with upper abdominal pain, and she was diagnosed with gallbladder cancer. Intraoperatively, she was found to have a duplicated cystic duct draining a single gallbladder, and her cancer had spread into the aberrant cystic duct entering the anterior right hepatic duct. Right hepatectomy with extrahepatic bile duct resection was performed to achieve R0 resection.CLINICAL DISCUSSION:In the English literature, 28 cases of duplicated cystic duct draining a single gallbladder have been reported. However, no cases of gallbladder cancer have been described in these previous reports.CONCLUSION:We report the first case of gallbladder cancer spreading into the aberrant cystic duct. To perform an oncologically adequate operation, exact assessment of the biliary tree is essential not only preoperatively but also intraoperatively.

BACKGROUND Distal pancreatic cancers may be unresectable at the time of diagnosis because these cancers are asymptomatic and readily infiltrate neighboring organs. Radical resection of a pancreatic tail cancer with colonic perforation is rare. We describe successful resection of a locally advanced pancreatic tail cancer with colonic perforation using a multidisciplinary approach. CASE REPORT A 66-year-old man presented to our hospital with a chief concern of high fever. Abdominal computed tomography revealed a pancreatic tail tumor infiltrating the neighboring organs and causing colonic obstruction with perforation, which resulted in an intra-abdominal abscess. Colonoscopy revealed obstruction of the descending colon by extramural invasion. Laboratory tests showed high tumor marker concentrations (carcinoembryonic antigen, 11.6 ng/dL; pancreatic cancer-associated antigen-2, >1600 U/mL). We clinically diagnosed locally advanced pancreatic tail cancer with an intra-abdominal abscess caused by colonic perforation. First, we performed transverse colostomy and percutaneous drainage. We then started neoadjuvant chemotherapy with FOLFIRINOX for tumor shrinkage and prevention of distant metastases. The therapeutic effect was a partial response, and no distant metastases was found. We therefore performed radical surgery comprising distal pancreatectomy with partial resection of neighboring organs. Although pathological examination revealed a pancreatic tail tubular adenocarcinoma with direct invasion of the neighboring organs, R0 resection was achieved. The patient was discharged with no perioperative complications. Tegafur/gimeracil/oteracil potassium were administered as adjuvant chemotherapy. The patient remained recurrence-free for 19 months after surgery. CONCLUSIONS We achieved successful en bloc resection of a locally advanced distal pancreatic cancer with colonic perforation by using a multidisciplinary approach.

A 69-year-old man who had undergone endoscopic sphincterotomy and cholecystectomy for choledocholithiasis and cholelithiasis 17 years earlier visited his private doctor with a complaint of upper abdominal pain and elevated liver enzymes. ERCP revealed an irregular stenosis of 1 cm in diameter in the lower bile duct. Repeat biopsies were obtained from the stenosed area of the bile duct, but malignant cells could not be confirmed histologically. However, malignant biliary stenosis was strongly suspected, based on imaging studies. Therefore, we performed subtotal stomach-preserving pancreaticoduodenectomy with lymph node dissection. The resected specimen had formed a thickened wall in the intrapancreatic lower bile duct macroscopically, and histopathological findings revealed thickened fibrous tissue with prominent proliferation of nerve fibers without malignancy. The tumor cells were S-100- and neurofilament-positive, immunohistochemically. The final pathological diagnosis was a neuroma of the intrapancreatic bile duct. Neuromas located in the intrapancreatic bile duct are very rare and these tumors are difficult to diagnose and treat.

虫垂神経内分泌腫瘍について，膵・消化管神経内分泌腫瘍診療ガイドライン（第2版）では腫瘍径が2cm以上もしくはリスク因子あり（脈管侵襲あり，G2以上，虫垂間膜への浸潤ありのずれか）の症例において回盲部切除術が推奨されている．しかし，小児に限った症例での検討は少なく一定の見解が無い．

Introduction: Serous Cystic Neoplasm (SCN) are relatively rare pancreatic tumors. Close observation is usually recommended. However, surgical resection should be considered with suspicious malignant tumor, and/or with symptom. Method: From October 1994 to October 2018, 12 patients underwent the surgical resection in our institute. We evaluated clinicopathological findings and surgical indications, retrospectively. Result: 1) Patients and tumor characteristics: The mean age was 58.5 years old(34-83y.o), 3 were male, and 9 cases were female. The tumor locations were head of pancreas in 2, body and tail in each 5 cases. The median tumor size was 3.9 cm(1.0-8.0cm) in a diameter. 2) Symptom: Nine cases were asymptomatic, and 3 cases were symptomatic. Asymptomatic cases were all found incidentally. In symptomatic cases, 2 patients had liver dysfunction and one had acid reflex caused by the tumor compression toward the common bile duct, and the stomach. 3) Surgical indications: Surgical indication was the suspicious malignant in 9 cases and 3 cases with symptom, located in head in 2 cases, and in tail in 1 case. In one case, he was diagnosed 16 years ago, tumor gradually increased, finally come down with the liver dysfunction. 4) Surgical procedure: Distal pancreatectomy was performed in 9 cases, and conventional pancreaticoduodenectomy, duodenum preserving pancreatic head resection, segmental pancreatectomy in each 1 case. 5) Histopathological findings: Patients were pathologically diagnosed as macrocystic type in 7, microcystic type in 4 cases, and solid type in 1 case. There was no mixed type in macroscopic. In all cases, final diagnosis was serous cystadenoma and no findings on malignancy. 6) Prognosis: All cases survive with no recurrence (postoperative 2 month-24 years). Conclusion: Surgical indications regarding tumor size and growth rate were still unclear and not established. However, the aggressive surgical resection should be considered in symptomatic patients and rapid tumor growth.

Introduction: Generally the outcome of synchronous CRLM (S-CRLM) is regarded as the poorer prognosis than that of metachronous CRLM (M-CRLM), however it still remains unknown in the detailed prognosis of M-CRLM. Method: From September 2008 to December 2018, 64 M-CRLM patients underwent the total 73 hepatectomies in our institute. We evaluated the relevant clinicopathological variables, including patient and tumor characteristics in M-CRLM group, and compared survival data between M-CRLM (n=64) and S-CRLM (n=53) groups. Moreover we compared the survival data according to various parameters and statuses such as the recurrent pattern and timing after the primary tumor resection of colorectal cancer in M-CRLM group. Result: 1) Patients and tumor characteristics: The mean age of study patients was 71.1 years (46–93, 34 men and 30 women) and the repeated liver resection was performed in 7 cases. Primary tumor location was right-sided type in 14, left-sided type in 50 cases. Median time of the diagnosis of M-CRLM after primary tumor resection was 12 months (3-114). The mean tumor number of multiple recurrent cases was 3 (2-15), the median maximum tumor diameter was 2.2cm (0.6-11).2) Over all survival (OS) in subgroups: The OS of M-CRLM was similar to that of S-CRLM (5-year M:77.8% vs S:63.3%; p=0.08). The OS of early recurrent M-CRLM within 6 months after the primary tumor resection (n=24) was significantly poorer than that of delayed recurrent cases (n=40) (5- year early: 56.1% vs delayed: 85.1%; p=0.037). OS of bilobular recurrent cases (n=14) had the significant poorer prognosis than unilobular recurrent cases (n=50) (5- year 50% vs 81% p=0.038). Conclusion: Although the prognosis of M-CRLM was similar to that of S-CRLM, early recurrent M-CRLM within 6 months after the primary tumor resection and bilobular multiple CRLM were very poor prognosis.

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia–reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-β (TGF-β) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-β expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-β mRNA upregulation.

症例は86歳の男性で3回の下血後の腹痛を主訴に受診．腹部所見および血液検査所見は軽症であったが，腹部造影CT検査でS状結腸壁の著明な浮腫性肥厚と結腸間膜内にfree airを認めた．S状結腸穿通および腹膜炎と診断し，緊急開腹手術を施行した．腹腔内には混濁した血性腹水を少量認めたが便臭はなく，S状結腸から直腸Rsにかけて虚血性変化を認めた．病変は腸間膜側に限局しており，穿通に伴う壊死と診断した．一期的吻合はリスクが高いと判断し，Hartmann手術を施行した．術後経過良好で人工肛門の自己管理を修練し，術後25日目に退院となった．特発性大腸穿孔は糞便性の腹膜炎から敗血症，多臓器不全に移行する危険性のある疾患である．大腸の構造・生理学上，S状結腸の結腸間膜付着部反対側に好発するため，腸間膜側の穿通症例は極めて稀である．今回，われわれは特発性S状結腸穿通の1例を経験したので，若干の文献的考察を加えて報告する．

Background/Aim: Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. Materials and Methods: Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4°C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. Results: Data are presented as mean ± SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 ± 5.3, 63.2 ± 17.3, 25.6 ± 3.9, and 82.8 ± 27.3 U/l) and lactate dehydrogenase levels (289.4 ± 41.2, 2,139.4 ± 542.7, 577.2 ± 117.2, and 2,429 ± 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 ± 0.3, 2.7 ± 1, 1.0 ± 0, and 3.9 ± 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 ± 1, 21.2 ± 3.1, 16.1 ± 1, and 23.2 ± 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 ± 0.17, 1.8 ± 0.2, 2.7 ± 0.2, and 2.6 ± 0.1 μmol/l). Bile production levels showed no statistical significance (23.2 ± 3.8, 27.3 ± 1.8, 43.5 ± 18, and 31 ± 2.5 μl/45 min). Conclusion: Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts.

Guest Editor Gabriele Schackert, Dresden The abstracts are available online, free of charge, under http://www.karger.com/Article/FullText/445224 Published online: April 20, 2016 www.karger.com/esr DOI: 10.1159/000445224 Basel • Freiburg • Paris • London • New York • Chennai • New Delhi • Bangkok • Beijing • Shanghai • Tokyo • Kuala Lumpur • Singapore • Sydney 35 Eur Surg Res 2016;57:34–80 DOI: 10.1159/000445224 Abstracts: 133rd Congress of the German Society of Surgery (DGCH) www.karger.com/esr © 2016 S. Karger AG, Basels: 133rd Congress of the German Society of Surgery (DGCH) www.karger.com/esr © 2016 S. Karger AG, Basel 1 Role of ENTPD2 in Liver Regeneration and Liver Fibrosis L. Feldbruegge1, S. Mitsuhashi1, E. Csizmadia1, M. Schmelzle2, S. Robson1 1Beth Israel Deaconess Medical Center, Boston, USA 2Charité, Berlin, Germany Background: Ecto-nucleoside triphosphate diphosphohydrolases (ENTPD) comprise a family of cell surface located transmembrane proteins that regulate purinergic signaling by catalyzing extracellular nucleotides, such as ATP and ADP. The prototype ENTPD1/CD39 is expressed on endothelium and sinusoidal immune cells, and is a regulator of liver regeneration. The closely related enzyme ENTPD2 is expressed on portal fibroblasts and perivascular cells. In vitro co-incubation studies show that this enzyme on fibroblasts regulates proliferation of cholangiocytes. Its role in liver function in vivo however, has not yet been determined. Herein, we examine pathophysiological functions of ENTPD2 in liver regeneration and liver fibrosis using a newly generated ENTPD2 deficient mouse line. Materials and Methods: Global ENTPD2 knockout mice and matched wild type mice were subjected to 2/3 hepatectomy as a model for liver regeneration, and to 6 weeks of carbon tetrachloride (CCl4) treatment to induce liver fibrosis. Outcomes were compared by studying serum liver function tests, liver histology and immunohistochemistry. Collagen content of liver tissue was determined biochemically by measuring relative hydroxyproline content. Results: ENTPD2 null mice develop normally on the C57BL6 background and do not show abnormalities in liver morphology at baseline. After partial hepatectomy, hepatic ENTPD2 mRNA expression in wild type mice decreased in the first 24 hours and then significantly increased to 3 times basal level at day 5. Serum ALT and other parameters of liver injury as well as the rate of hepatocellular proliferation were comparable in both groups, and there was no relevant difference in liver mass regeneration. However, when fibrosis was induced by CCl4 treatment, mice deficient for ENTPD2 showed significantly more collagen deposition as measured by hydroxyproline content. Histological analysis confirmed more severe fibrosis in the knockout mice while there was no significant difference in liver function tests. Conclusion: ENTPD2 null mice show no major hepatic developmental abnormalities and appear to maintain normal liver regeneration responses when subjected to the acute injury of partial hepatectomy in otherwise healthy livers. In the setting of chronic hepatocellular injury by CCl4 ingestion however, ENTPD2 deficient mice show significantly more fibrosis. As this ecto-enzyme is expressed by myofibroblastic cells surrounding bile ductules within portal triads, and deletion promotes fibrogenesis, we propose that ATP scavenging by ENTPD2 might represent a novel therapeutic target in fibrotic liver disease. 2 Platelets Promote CD133+BMSC Adhesion to Murine Micro and Hepatic Sinusoidal Endothelium Independent of ADP Stimulation Under Flow Condition J. Kirchner1, C. Duhme1, N. Lehwald1, K. Wieferich1, M. Schmelzle2, N.H. Stoecklein1, A. Krieg1, W.T. Knoefel1, J. Schulte am Esch1 1Universitätsklinikum der Heinrich Heine Universität Düsseldorf, Düsseldorf, 2Chirurgische Kliniken der Charité am Campus Virchow-Klinikum, Berlin, Germany Background: We previously demonstrated the therapeutic potential of hematopoetic CD133+ bone marrow stem cells (CD133+BMSC) to promote clinical liver regeneration and the potential of platelets for CD133+BMSC homing along human micro endothelium under shear stress. In this study, we have established a murine model to gain the option of investigation of null and overexpressing cells for homing relevant factors. Furthermore, we evaluated a putative adhesion promoting effect of platelets for CD133+BMSC-homing along hepatic sinusoidal vasculature. Materials and Methods: Commercially available mouse primary dermal micro vasculature endothelial cells (dMECC57BL/6) and mouse hepatic sinusoidal endothelial cells (mSEC) were cultured in capillaries in a live cell imaging system (Bioflux). Primary CD133+BMSC were purified from bone marrow flushed from murine tibiae and femori utilizing FACsorting. dMEC or mSEC were co-cultured under shear stress with CD133+BMSC and platelet rich plasma (PRP) or platelet poor plasma (PPP) as control prepared from murine BMSC donors. To test the effect of pre-stimulation of platelets for adhesion of CD133+BMSC, murine PRP was pre-stimulated with ADP monitored by aggregometry utilizing the Bohrlight-transmission method. Latter prevented over-stimulation with clot-formation. Results: Murine CD133+BMSC co-infused with PRP demonstrated mean adhesion rates of 144% (±17% StdDev; Abstracts 36 Eur Surg Res 2016;57:34–80 DOI: 10.1159/000445224 Abstracts: 133rd Congress of the German Society of Surgery (DGCH) www.karger.com/esr © 2016 S. Karger AG, Basels: 133rd Congress of the German Society of Surgery (DGCH) www.karger.com/esr © 2016 S. Karger AG, Basel p < 0.005) along dMEC under flow if contrasted to PPP co-incubation. Pre-stimulation of platelets with ADP demonstrated a further increase leading to improved adhesion of CD133+BMSC compared to unstimulated conditions. Analogue to micro endothelium a boost of mean adhesion rates of CD133+BMSC to 131% (±9% StdDev; p < 0.05) was observed subsequent to unstimulated PRP co-infusion along mSEC. Conclusion: Our data indicate platelets to trigger adhesion of CD133+BMSC to murine micro vasculature analogue to men in a stimulation independent manner. Further we demonstrate here for the first time that thrombocytes bear the capacity to promote BMSC-adhesion to hepatic vasculature. These data may add to the understanding of mechanisms by which platelets support hepatic generation and offer novel strategies to increase the efficacy of therapeutic BMSC-application in clinical liver disease. 3 Peptide XIB13 Reduces Capillary Leak in a Rodent Burn Model L. Von der Lohe1, K. Zhuravleva2, H. Lauer2, M. Lehnhardt2, J. Kolbenschlag1, K. Schossleitner3, P. Petzelbauer3, O. Goertz1 1Martin-Luther Krankenhaus, Berlin, 2Bergmannsheil Bochum, Bochum, Germany; 3Medical University Vienna, Wien, Austria Background: Edema due to capillary leak is a generalized and life threatening event in sepsis and major burns for which there is no causal treatment. Local burn wounds are an ideal model to investigate the impact of a new therapeutic agent on edema formation. We aimed to identify peptide sequences of cingulin that can attenuate stress-induced endothelial cytoskeleton disarrangement in vitro and which reduce burninduced edema in vivo. Materials and Methods: Cingulin-derived peptides were screened in high content cell culture assays monitoring actin displacement and endothelial cell/cell contacts. The ears of male hairless mice were inflicted with full thickness burns using a hot air jet. Mice with and without burn injuries were treated with Xib13 or solvent by continuous intraperitoneal application for 3 days. Edema, microcirculation, leukocyteendothelial interactions and angiogenesis – measured as nonperfused area – were investigated over a 12-day period using intravital fluorescence microscopy. Results: Xib13 reduced endothelial stress formation and stabilized endothelial tight junctions in cell-cultures. In the burn model, Xib13 improved angiogenesis compared to controls (non-perfused area on day 12: 5.7 ± 1.5% vs. 12.0 ± 2.1%; p b 0.05). Edema was significantly reduced at all observation points in Xib13-treated animals as compared to controls (day 12: 67.6 ± 2.6% vs. 83.2 ± 6.4%). Furthermore a dose dependent effect could be observed. Conclusion: Xib13 improved angiogenesis, reduced edema formation. Since edema formation is a serious parameter for burn conversion and is associated with survival it could provide a new treatment option for patients with burn injuries. 4 Horizontal Transfer of microRNA by Bone Marrow Derived Microparticles Modulates Inflammation after Experimental Liver Resection M. Schmelzle1, K. Splith2, I. Kämmerer2, C. Hegewald2, L. Feldbrügge3, J. Schulte am Esch4, J. Pratschke1, S. Robson3, S. Kuhn2 1Charité – Universitätsmedizin Berlin, Campus VirchowKlinikum, Berlin, 2Universität Leipzig, Leipzig, Germany; 3Beth Israel Deaconess Medical Center, Harvard University, Boston, USA; 4Universitätsklinikum Düsseldorf, Düsseldorf, Germany Background: Mechanisms involved in the communication between bone marrow stem cells and resident cells in the regenerating liver remain uncertain. We aimed to study implications of horizontal miRNA transfer by bone marrow (BM) derived plasma microparticles (MP) with regard to modulations of vascular inflammation and apoptosis of primary liver cells after partial hepatectomy. Materials and Methods: Partial hepatectomy was performed in C57Bl/6 wild type and Cd39 null mice, with latter being unable to phosphohydrolyze pro-inflammatory extracellular adenosine triphosphate (ATP) to adenosine. MP were isolated from the plasma and cell culture supernatant via two-step ultracentrifugation. Gene and miRNA expression was analyzed using qPCR. For fusion studies, MP were labeled with Cy3-labeled RNA oligonucleotides and stained with the PKH67. Fusion was imaged by FACS and confocal microscopy. Cell viability and apoptosis rate was measured using a commercial apoptosis assay. Results: After partial h

In liver transplantation, prolonged ischemia and/or a relatively small graft (living, split, reduced) are the risk factors for liver dysfunction. Novel measures to enhance liver function with a smaller graft can be a clue for safe partial or living-donor liver transplantation or safe hepatectomy for malignant disease. The therapeutic potential and immunomodulatory effects of mesenchymal stem cells (MSCs) have been reported. In this chapter, recent finding on the positive effect of MSCs for liver transplantation and hepatectomy are discussed. Our rat experiment revealed that introduction of MSCs provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration, which is shown with the pig model as well. In the rat liver transplantation model, portal transfusion of the MSCs ameliorates the injury of the liver graft after prolonged cold preservation and transplantation. Those findings together suggest a potential advantage with partial or living-donor liver transplantation. The most severe complication with cell therapy is embolus formation due to cell aggregation. However, with modification of the solution, we can keep cells in a suspended form for several hours, which secures safe administration of MSCs.

BackgroundLiver transplantation (LT) used to be contraindicated in patients with portal vein thrombosis (PVT). In comparison to deceased donor LT, living donor LT (LDLT) still presents additional difficulties in determining appropriate vein grafts and overcoming small-for-size syndrome. Here, we introduce our LDLT strategies and assess their outcomes in adult patients with pre-existing PVT.MethodsWe performed 282 consecutive adult LDLTs between April 2006 and December 2011. Forty-eight patients (17%) had pre-existing PVT (grade I; 15, II; 20, III; 12, IV; 1).ResultsOur preferred treatments for PVT were thrombectomies/thromboendovenectomies in 30 patients, replaced grafts in seven, jump grafts in seven, renoportal anastomosis in one and no surgical intervention owing to minimal thrombosis in three. Post-transplant portal vein complications occurred in eight of 48 (17%) cases, which were treated by surgery, anticoagulation therapy, and/or interventional radiology. Post-transplant survival rates of patients with preexisting PVT at 1 year and 5 years were comparable to a PVT-free cohort (1 year; 81% vs. 77%, 5 years; 81% vs. 73%).ConclusionsThe excellent survival rates in patients with PVT who underwent LDLT could be attributed to our strategies, which included surgical techniques and timely treatment of postoperative complications.

BACKGROUND:Due to a worldwide shortage of donor organs for liver transplantation, alternative approaches, such as split and living donor liver transplantations, were introduced to increase the donor pool and reduce mortality on liver transplant waiting lists. Numerous details concerning the mechanisms and pathophysiology of liver regeneration, small-for-size syndrome, rejection, and tolerance in partial liver transplantation facilitated the development of various animal models. The high number of preclinical animal studies contributed enormously to our understanding of many clinical aspects of living donor and partial liver transplantations.SUMMARY:Microsurgical rat models of partial orthotopic liver transplantation are well established and widely used. Nevertheless, several issues regarding this procedure are controversial, not clarified, or not yet properly standardized (graft rearterialization, size reduction techniques, etc.). The major aim of this literature review is to give the reader a current overview of rat orthotopic liver transplantation models with a special focus on partial liver transplantation. The aspects of model evolution, microsurgical training, and different technical problems are analyzed and discussed in detail. Our further aim in this paper is to elaborate a detailed publication guide in order to improve the quality of reporting in the field of rat liver transplantation according to the ARRIVE guidelines and the 3R principle. Key Messages: Partial orthotopic liver transplantation in rats is an indispensable, reliable, and cost-efficient model for transplantation research. A certain consensus on different technical issues and a significant improvement in scientific reporting are essential to improve transparency and comparability in this field as well as to foster refinement.