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Background Plexiform schwannoma is one of the least common variants of schwannoma, accounting for only 5% of all schwannoma cases. It generally occurs in the skin and subcutaneous tissues and is uncommon in deep soft tissue or viscera. We present an extremely rare case of plexiform schwannoma arising from the peripancreatic plexus. Case presentation A 29-year-old man presented with hyperglycemia detected during a medical checkup. He was diagnosed with type 1 diabetes based on the clinical findings and laboratory tests. During the diagnostic process for diabetes, a 2.5 cm mass was incidentally detected in the pancreas by abdominal ultrasound. Contrast-enhanced computed tomography revealed a mass that was gradually enhanced at the body and tail of the pancreas. Magnetic resonance imaging revealed low signal intensity of the mass on T1-weighted images and high signal intensity on T2-weighted and diffusion-weighted images. Magnetic resonance cholangiopancreatography showed no abnormal findings in the main pancreatic duct. Endoscopic ultrasonography (EUS) showed a lobulated, low-echoic mass with a clear boundary. EUS-guided fine needle biopsy was performed, and spindle-shaped cells that were diffusely immunopositive for S-100 and negative for c-kit and desmin were detected, resulting in a diagnosis of a neurogenic tumor arising from the pancreas or the peripancreatic nerve plexus. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. Although the tumor was connected to the splenic plexus, the splenic artery could be divided along its adventitial plane. Macroscopic findings of the excised tumor consisted of multiple yellowish-white nodules, and its histopathological features were consistent with plexiform schwannoma. There was no pancreatic tissue on the dorsal surface of the tumor, which suggested that the tumor arose from the peripancreatic nerve plexus. Conclusions The findings documented herein can aid in the differential diagnosis of peripancreatic schwannoma and in planning appropriate treatment.

Background Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

Background Postpancreatectomy hemorrhage (PPH) is a life-threatening complication of pancreatic surgery. The shift from surgical to radiological intervention was recently reported in retrospective cohort studies, but it has remained controversial as to which emergent intervention provides optimal management. Methods All 553 patients who underwent standard pancreatic resection at Kobe University Hospital between January 2003 and December 2013 were included. Patient data and complication data were identified from a prospective database. Results The overall incidence of PPH was 6% (35 of 553 patients). Ten patients underwent endoscopic intervention or observation monitoring, or suffered hemorrhagic sudden death. Among the remaining 25 PPH patients, primary surgical intervention was successful in the 6 hemodynamically unstable PPH patients. Primary radiological intervention could successfully stop the bleeding in 15 of the 17 patients with late-PPH. Nine patients who had bleeding from the hepatic artery after pancreaticoduodenectomy were rescued by endovascular embolization of the artery-trunk. The in-hospital mortality of PPH was 20% (7 of 35). Four of the 5 PPH patients who died following any intervention eventually died due to the other complications associated with prolonged pancreatic fistula. Conclusions The leading treatment has been radiological intervention. Endovascular embolization of the hepatic artery-trunk can be securely performed only if blood flow to the liver by an alternate route is confirmed. To reduce mortality of PPH patients, it is necessary to prevent other complications associated with pancreatic fistula following hemostasis. Proactive surgical intervention such as abscess drainage or remnant pancreatectomy is a key consideration.

Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection.Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines.ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%).There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

The therapeutic strategy for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) has remained unestablished because the preoperative prognostic factors have not been determined. One hundred eighty-four consecutive PDAC patients who underwent upfront surgery with a curative resection between January 2000 and June 2013 at Kobe University Hospital were retrospectively studied. The PDAC patients were stratified into resectable (R)-PDAC (n = 147) and BR-PDAC patients (n = 37). We evaluated the independent prognostic significance of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) in the BR-PDAC patients. BR-PDAC patient survival was significantly worse than R-PDAC patient survival (median survival time: 22.1 months vs. 24.3 months; 5-year survival rate 6 vs. 21 %; P = 0.042). The median survival in BR-PDAC patients with a preoperative NLR of >3 (n = 12) was 10.2 months, while that in patients with preoperative NLR of ≤3 (n = 25) was 24.9 months (P = 0.002). Moreover, the median survival in BR-PDAC patients with a preoperative PLR of >225 (n = 8) was 10.2 months, while that in patients with a preoperative PLR of ≤225 (n = 29) was 24.7 months (P = 0.003). Preoperative NLR >3 (HR = 2.980, 95 % CI 1.251–6.920; P = 0.015) and PLR >225 (HR = 3.050, 95 % CI 1.169–7.468; P = 0.024) were independent prognostic factors in BR-PDAC patients. Higher preoperative NLR and PLR can be independent predictive risk factors in BR-PDAC patients following curative resection.

Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year-old male with severe type 1 diabetes with chronic renal failure who received simultaneous PKT from a female donor. Diarrhea developed on postoperative day (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin rashes appeared with pain and itching on his trunk and extremities on POD 40. As pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD because skin biopsies revealed the XX chromosome signal in a fluorescence in situ hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5 days. Although every symptom was temporarily improved, on POD 156, the patient expired from the septic pneumonia without any effects of antibiotics. Clinician should be aware that PKT has the potential to induce aGVHD.

Background and Objectives Pylorus-preserving pancreatoduodenectomy (PPPD) has been associated with a high incidence of delayed gastric emptying (DGE). There are few studies comparing DGE associated with PPPD and subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Moreover, differences between the procedures with respect to long-term results have not been reported. A prospective randomized study was conducted to compare perioperative complications and long-term nutritional status with PPPD and SSPPD. Methods One hundred patients with periampullary lesions were randomized to receive either PPPD (n = 50) or SSPPD (n = 50). All patients were followed up for 3 years after surgery or to the time of recurrence to evaluate nutritional status for the study. The effects of the procedure, age, and malignancy on changes in nutritional indicators were estimated with linear mixed models. This study was registered at UMIN Clinical Trials Registry (UMIN 000012337). Results The incidence of DGE assessed by the International Study Group of Pancreatic Surgery was 20% with PPPD and 12% with SSPPD (P = 0.414). There were no significant differences between the two procedures on postoperative serum albumin levels, serum total cholesterol levels, and body mass index during the 3-year follow-up period. Conclusions SSPPD is equally effective in DGE occurrence rate and long-term nutritional status comparing to PPPD. J. Surg. Oncol 2014; 109:690–696. © 2014 Wiley Periodicals, Inc.

Background & Aims There are no accurate and reliable tools for diagnosis of early stage pancreatic ductal adenocarcinoma (PDA) or small metastatic lesions. It is also a challenge to differentiate PDA from focal mass-forming pancreatitis (FMP). There is controversy regarding the efficacy of 18-fluorodeoxyglucose positron-emission tomography (FDG-PET) in the diagnosis of PDA. We investigated whether FDG-PET provides information that, combined with data from other imaging techniques, can aid in decision making for patients with suspected PDA. Methods We performed a retrospective analysis of data collected from 232 consecutive patients with suspected PDA at Kobe University Hospital from January 2006 through June 2012. All patients underwent a diagnostic imaging protocol that included multidetector row computed tomography, superparamagnetic iron oxide–enhanced magnetic resonance imaging, and FDG-PET. Based on endoscopic ultrasonography, fine-needle aspiration biopsy, or endoscopic retrograde cholangiopancreatography analyses, 218 patients had PDA (89 underwent resection and 129 did not) and 14 patients had FMP (8 had focal mass-forming chronic pancreatitis and 6 had focal mass-forming autoimmune pancreatitis). Results FDG-PET detected 50% of stages 0 and I, 91.9% of stage II, 100% of stage III, and 96.8% of stage IV tumors. Detection was affected significantly by tumor size ( P = .024) and T stage ( P = .023) in resected tumors. Multidetector row computed tomography detected significantly more liver metastases than FDG-PET. Few para-aortic lymph node or peritoneal metastases were detected by FDG-PET. FDG-PET correctly identified 11 of the 14 patients with FMP (5 of 8 with focal mass-forming chronic pancreatitis and 6 of 6 with focal mass-forming autoimmune pancreatitis). Conclusions FDG-PET is not effective in detecting early stage PDA and small metastases, or in differentiating PDA from FMP. Combining FDG-PET with current diagnostic techniques for PDA did not provide any decisive information, therefore it should not be included in this analysis.

Introduction Pancreatogenic diabetes after pancreatectomy is of growing importance due to the increasing life expectancy of pancreatectomized patients. Although reduction of pancreatic volume is thought to affect glucose metabolism, a consistent relationship has yet to be determined. This study aimed to investigate functional consequences of distal pancreatectomy (DP) in preoperatively non-diabetic patients. Methods This study included 61 non-diabetic patients who underwent DP. Clinical data were obtained, and the percent resected volume (PRV) of each pancreas was determined via multi-detector row computed tomography volumetry. Results During the follow-up period (median 26 months), 22 patients (36 %) developed new-onset diabetes within a median onset time of 8 months (range 0.5–42 months) postoperatively. The remaining 39 patients also showed impaired glucose metabolism. Multivariate analysis identified preoperative hemoglobin A1c ≥ 5.7 % (odds ratio 15.6, p = 0.001) and PRV > 44 % (odds ratio 11.3, p = 0.004) as independent risk factors for new-onset diabetes. Conclusions Key determinants of postoperative glycemic control include preoperative functional reserve of the endocrine pancreas and the volume reduction of pancreatic parenchyma. Our findings enable reliable preoperative evaluation of the risk of postoperative diabetes and appropriate postoperative surveillance, which is helpful for early intervention in high risk patients.

症例は51歳女性．検診の腹部USで膵腫瘤を指摘され紹介となった．EUSでは膵頭体部移行部に内部に嚢胞成分を有する10mmの低エコー腫瘤を認め，ダイナミックCTでは腫瘤は指摘できず5mmの嚢胞のみを認めた．ERPでは膵管像に異常はなく膵液細胞診はclass IIIであった．IDUSでは10mmの腫瘤内に5mmの嚢胞を認めた．以上より術前診断は確定できず，膵内分泌腫瘍，Solid-pseudopapillary neoplasm，浸潤性膵管癌（膵癌）などの疑診にて膵中央切除を行った．術中迅速病理検査は膵癌であったため，亜全胃温存膵頭十二指腸切除術に術式を変更した．病理診断は中分化型管状腺癌でpTS1（15mm）pT1 pN0 cM0 fStage Iであり，嚢胞部分は拡張した腫瘍腺管であった．嚢胞を伴う小膵癌の診断は困難であるが，常に念頭に置き診療にあたることが重要と考えられた．

臓器保存法は歴史的に主に腎移植の領域で研究，開発が進められ，灌流保存法（hypothermic pulsatile perfusion）が提唱され，臓器保存液による単純浸漬保存法（simple cold storage）がそれに続いた．膵保存では灌流保存法は臨床応用に至らず，1980年代に開発されたUniversity of Wisconsin solution（UW液）による単純浸漬保存法は長期膵保存を可能とし，現在でも標準的保存法である．いくつかの新規保存液が開発され臨床応用されているが，現時点でUW液を凌駕するエビデンスはない．本学で開発されたPerfluorochemical（PFC）と臓器保存液を用いた二層法膵保存は，PFCにより保存中の臓器に酸素を供給できるという特性を有する．二層法は主に膵島移植において2000年以降北米を中心に臨床応用され，優れた成績を示した．近年，従来のUW液の代わりにM-Kyoto液を用いた二層法や膵管内注入保存法などによりさらに優れた成績が報告されている． マージナルドナーや心停止ドナーからの膵臓移植，1ドナー1レシピエントでの膵島移植の実現など，今後も臓保存法が果たす役割は大きく，さらなる研究，発展が望まれる．

症例は61歳の男性で，膵頭部癌に対して膵頭十二指腸切除術（Pancreatoduodenectomy；以下，PDと略記）を施行した．術後10日目に膵空腸吻合部ドレーンから大量出血を認め，出血性ショックとなった．血管造影検査で上腸間膜動脈（Superior mesenteric artery；以下，SMAと略記）根部に径1 cmの仮性動脈瘤を認め，同部からの出血と判明した．仮性動脈瘤がSMA根部にあったため，Interventional radiology（以下，IVRと略記）による止血は不可能と判断し，緊急手術を施行した．手術は残膵全摘，SMA縫合閉鎖，左大伏在静脈による右総腸骨動脈-SMAバイパス術を施行した．術後CTではSMA本幹からの血流はなく，腸管血流はグラフト経由で供給されていた．PD術後の仮性動脈瘤大量出血に対しIVR施行困難例では躊躇なく積極的な外科手術を考慮すべきと考えられた．

Bile acid has an important role in protecting immune systems related to gut-associated lymphoid tissue. This study was designed to evaluate the effects of internal biliary drainage after a pancreaticoduodenectomy (PD) on postoperative nutrition and complications in a randomized study.The authors compared the morbidity, mortality, and postoperative nutritional status of 46 patients who had a hepaticojejunostomy (HJ) with a stented external biliary drainage (group E) or with a non-stented internal biliary drainage (group I) after a PD.Systemic infection was recognized in four patients in group E, while no patients in group I. Transthyretin at postoperative 28 days in group I was 15.6 +/- 6.2, higher than that in group E. Retinol-binding protein at postoperative 28 days in group I was 2.6 +/- 1.0 and also higher than that in group E.HJ with no-stented internal biliary drainage was not associated with systemic infections and mortality, but showed the possibility of improving nutritional status.

重症急性膵炎モデルとしてラット胆汁酸膵管内注入モデルなどが頻用されるが，in vivoのモデルだけでは分子機構の解析や再構成実験として限界がある．我々は重症急性膵炎の臓器障害におけるアポトーシスの関与と分子機構を解明するため，ラットDCA（デオキシコール酸）膵炎の腹水（pancreatitis-associated ascitic fluid；PAAF）を培養細胞（肝細胞，腎尿細管細胞，腸管上皮細胞）に添加するin vitroの実験系を確立している．最近では，in vivoにおいて腸管粘膜上皮のアポトーシスが加速し，アポトーシスを抑制することにより腸管粘膜上皮が保護され, bacterial translocationが減少することを明らかにした．実際，PAAFをT84細胞（ヒト腸管上皮）に添加するとアポトーシスが増強し，電気抵抗が減弱（透過性が亢進）していることが確認できた．PAAFを用いた実験系は，重症急性膵炎に特異的な臓器障害機構や感染成立機構の解明に有用である．

69歳，女性．黄疸を主訴に近医受診し肝門部胆管癌と診断され，精査加療目的にて当科紹介入院となったが，肝転移を認めたため手術適応外と判断し，gemcitabine（GEM）を投与開始し外来継続投与を行った．投与開始後148日目に下肢脱力感を訴え，両側下肢近位筋の軽度筋力低下を認めたが，血液検査で異常なく経過観察となった．しかし，両下肢疼痛・筋力低下が進み，投与開始後162日目に両下肢疼痛・近位筋筋力低下，発熱，乏尿を主訴に当院救急外来受診となった．血液検査で炎症反応，筋原性逸脱酵素の上昇を認め，急性腎不全の所見で入院となったが，安静，輸液にてcreatine kinase（CK）は低下を示し，利尿を得た．疼痛，筋力低下は徐々に改善し入院後13日目からリハビリテーションを開始し，症状発現後約2カ月で症状消失した．原因精査の結果，GEMによる横紋筋融解症が最も強く推測された．

In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. Immunosuppressive acidic protein (IAP) is an immunosuppressive factor to be present in serum and ascites of cancer patients, and it is used as a tumor marker and an index of immune status of cancer hosts.We measured serum IAP levels in 42 patients with SAP (Japanese severity score [JSS]or = 2) on admission and analyzed the relationships with disease severity, pancreatic necrosis, blood biochemical parameters on admission, and clinical outcome (infection and death).Serum IAP level increased 791 +/- 285 microg/mL (range, 159-1430 microg/mL) on admission and recognized abnormal high level (normal range,500 microg/mL) in 37 patients (88.1%). Serum IAP level was significantly lower in patients of stages 3 and 4 (JSSor = 9) (678 +/- 187 microg/mL) than that in patients of stage 2 (2or = JSSor = 8) (848 +/- 311 microg/mL). It was also significantly lower in patients whose Ranson score was 5 or higher (674 +/- 287 microg/mL) than that in patients whose Ranson score was 4 or less (910 +/- 287 microg/mL). Moreover, it was significantly lower in patients with pancreatic necrosis (693 +/- 194 microg/mL) than that in patients without pancreatic necrosis (922 +/- 336 microg/mL). Among the blood biochemical parameters on admission, serum IAP was significantly negatively correlated with hematocrit, serum lipase, and serum interferon gamma and was significantly positively correlated with serum total protein. Serum IAP levels in patients of stage 2 reached higher peak at 7 days after admission and decreased more rapidly than those in patients of stages 3 and 4.Serum IAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis. These results suggest that serum IAP levels may be related to systemic inflammatory response and reflect the immunoresponsiveness in patients with SAP.

Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP.We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C.The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN.SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.

In severe acute pancreatitis, multiple organ dysfunction syndrome and infectious complications are contributors to high mortality. Interleukin (IL)-15 is a novel cytokine that shares many biologic properties with IL-2. Serum IL-15 levels have not yet been determined in SAP.Serum IL-15 concentrations were measured in 54 patients with severe acute pancreatitis on admission. The relationships with severity, organ dysfunction, infection, and prognosis were analyzed. Utility of IL-15 for the prediction of clinical outcome was evaluated by receiver operator characteristic (ROC) curve analysis.Serum IL-15 levels were increased significantly in severe acute pancreatitis (5.8 +/- 0.5 pg/mL), and they were correlated with Ranson, APACHE II, and Japanese severity score. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors (P05 each). Incidences of organ dysfunction in patients whose IL-15 levels were less than 3.0, 3.0-5.3, and greater than or equal to 5.3 pg/mL, were 8%, 31%, and 89%, respectively (P.001). Usefulness of IL-15 for the prediction of organ dysfunction was superior to CRP, IL-6, and IL-8, and it was similar to Ranson, APACHE II, and Japanese severity score. Incidences of infection in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 7%, 25%, and 50%, respectively (P.05). Mortality rates in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 11%, 25%, and 80%, respectively (P.001). Usefulness of IL-15 for the prediction of death was superior to CRP, IL-6, and IL-8.Serum IL-15 level is a useful predictor of the complications (especially organ dysfunction) and mortality in severe acute pancreatitis.

In severe acute pancreatitis (SAP), infectious complications are the main contributors to high mortality. Since 1995, we have performed continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI) and enteral nutrition (EN) as prevention therapies against infection. When infected pancreatic necrosis was proven, surgical intervention was adapted. The aim of this study was to investigate the clinical outcome of these treatments. We examined the relationship between the historical change of treatment strategy and clinical outcome. We divided 84 patients with acute necrotizing pancreatitis into two groups, CRAI (−) and CRAI (+), and compared the outcome. We divided 145 patients with SAP into two groups, EN (−) and EN (+), and compared the outcome. We also analyzed the outcome of surgical treatment. In the CRAI (+) group, the incidence of infection, the frequency of surgery, and the mortality rate were lower than those in CRAI (−) group: 34% versus 51%, 27% versus 63% (P < 0.05), and 37% versus 54%, respectively. In the EN (+) group, the frequency of surgery and the mortality rate were lower than those in the EN (−) group: 23% versus 32% and 19% versus 35% (P < 0.05), respectively. These improvement effects were manifest in stage 3 (9 ≤ Japanese Severity Score ≤ 14). Treatment outcome of necrosectomy for infected pancreatic necrosis was still poor. Bleeding and abscess–gut fistula were postoperative life-threatening complications. CRAI and EN may improve the clinical outcome of SAP, reducing infection and averting pancreatic surgery.

Objectives Bacterial translocation (BT) plays an important role in systemic complications in severe acute pancreatitis (SAP). We recently demonstrated that accelerated apoptosis of intestinal mucosa might have a role in BT. Effects of vascular endothelial growth factor (VEGF) on intestinal epithelial cell apoptosis and BT were investigated in SAP. Methods Severe acute pancreatitis was induced by retrograde injection of sodium deoxycholate into the biliopancreatic duct in rats. Recombinant rat VEGF (2 microg) was injected, and SAP was immediately induced. Eight hours after the induction, serum amylase/lipase levels and apoptosis of ileal mucosa were evaluated. After 18 hours, the villous height of ileum was examined. After 22 hours, hematocrit, pancreatic water content, BT to the mesenteric lymph nodes, plasma plasminogen activator inhibitor 1 levels, and microvessel density in the small intestine were investigated. Results Amylase/lipase levels were significantly elevated in SAP, but VEGF did not affect them. Apoptosis of ileal mucosa was accelerated in SAP, and VEGF significantly reduced the apoptosis. Villous height was significantly decreased in SAP, and VEGF significantly improved it. Vascular endothelial growth factor did not affect the hematocrit or pancreatic water content. Bacterial translocation occurred in the SAP group, and VEGF significantly prevented that. Plasminogen activator inhibitor 1 levels were significantly elevated in SAP, and VEGF significantly improved the elevation. Microvessel counts were significantly reduced in SAP, and VEGF significantly increased them. Conclusion These results suggest that VEGF inhibits intestinal epithelial cell apoptosis and subsequent BT in SAP.

Background and aim Endotoxin/bacterial translocation (E/BT) plays an important role in systemic complications in severe acute pancreatitis (SAP). The breakdown of intestinal integrity is considered to be implicated in E/BT. We recently demonstrated that accelerated apoptosis of intestinal mucosa may have a part in E/BT. On the other hand, caspase is believed to play a central role in apoptosis. The aim of this study was to investigate the efficacy of caspase inhibitor on intestinal integrity and E/BT in SAP. Methods SAP was induced by retrograde injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. At the same time, polycaspase inhibitor (Z-VAD-fmk) was administered intraperitoneally. Caspase activation in the intestine was evaluated by immunohistochemical staining and Western blotting. Apoptosis of intestinal mucosa was detected by TdT-mediated dUTP-biotin nick end labeling staining and DNA fragmentation enzyme-linked immunosolvent assay. Intestinal permeability was assayed ex vivo by measuring the leaked amount of FITC-dextran. Blood endotoxin level, bacterial culture of the ascites and mesenteric lymph nodes, and 24-h mortality rate were evaluated. Results Immunoreactivities for activated caspase-10, -9, and -3 were increased 2 h after induction of SAP. Apoptosis and permeability of ileum were significantly increased 6 h after induction of SAP. Caspase inhibitor significantly improved the increasing apoptosis and permeability. It did not prevent the bacterial translocation but improved the disorder of intestinal mucosa and elevation of blood endotoxin 18 h after induction of SAP. Moreover, caspase treatment significantly improved the 24-h mortality rate. Z-VAD-fmk indeed inhibited the caspase-3 activation in intestinal mucosa of SAP. Conclusions These results suggest that caspase activation has a key role in the accelerated apoptosis of intestinal epithelial cells in SAP and that breakdown of intestinal mucosa via accelerated apoptosis causes the increase in intestinal permeability following endotoxin translocation in SAP.

OBJECTIVE The aim of this study was to reappraise the clinical role of total pancreatectomy with curative intent in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS In 2001 to 2011 database from 7 institutions in Japan, 45 (3.1%) of 1451 patients with PDAC underwent total pancreatectomy (TP group), and 885 patients underwent pancreaticoduodenectomy (PD group). A matched-pairs group consisted of 45 patients matched for age, sex, year, resectability status, and neoadjuvant therapy (matched-PD group). Clinicopathological data, overall survival, and disease-free survival were compared between groups. RESULTS Clinical features of the TP group revealed higher-stage disease, greater surgical stress, a higher frequency of lymph node metastasis, and a lower adjuvant chemotherapy completion rate compared with the PD group (P < 0.05). Overall survival and disease-free survival in the TP group were significantly worse than those in the PD group (P < 0.05). Multivariate analysis revealed resectability status, neoadjuvant therapy, blood transfusion, lymph node metastasis, and adjuvant therapy to be significant prognostic factors. No differences in mortality and morbidity rates were observed between the 2 groups. A matched-pairs analysis revealed similar surgical outcomes and overall survival. CONCLUSIONS The surgical outcome of total pancreatectomy for patients with PDAC is acceptable. When margin-negative resection is expected, total pancreatectomy should not be abandoned in the modern era.

The aim of this study was to evaluate the validity of preoperative resectability status, as defined by the National Comprehensive Cancer Network (NCCN), from the viewpoint of overall survival.A total of consecutive 704 patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with upfront surgery at seven Japanese hospitals between 2001 and 2012 were evaluated retrospectively. According to the NCCN definition of preoperative resectability status, tumors were divided into resectable tumors without vascular contact (R group), resectable tumors with portal or superior mesenteric vein (PV/SMV) contact of ≦180° (R-PV group), borderline resectable(BR) tumors with PV/SMV contact of180° (BR-PV group), and BR tumors with arterial contact (BR-A group). The relationship between the NCCN definition of preoperative resectability status and overall survival was analyzed.Of the 704 patients, 389, 114, 145, and 56 were classified into the R group, the R-PV group, the BR-PV group, and the BR-A group, respectively. Overall survival of the BR-PV and BR-A groups was significantly worse than that of the R group and R-PV groups (P0.05), although there was no significant difference in overall survival between the R group and the R-PV group (P = 0.310). Multivariate analysis revealed that PV/SMV contact of180° (P = 0.008) and arterial contact (P0.001) were independent prognostic factors of overall survival.From the viewpoint of overall survival, the NCCN definition of preoperative resectability status was valid.

Multiple organ failure because of systemic inflammatory response in the early phase and sepsis in the late phase is the main contributor to high mortality in severe acute pancreatitis (SAP). High-mobility group box chromosomal protein 1 (HMGB1) was recently identified as a potent proinflammatory mediator and increases in various pathological conditions such as sepsis. The aim of this study was to investigate contributions of HMGB1 in SAP.We measured serum HMGB1 concentrations by an enzyme-linked immunosorbent assay in 45 patients with SAP at the time of admission. Furthermore, relationship between their serum HMGB1 levels and clinical factors was analyzed.The mean value of serum HMGB1 levels was significantly higher in patients with SAP (5.4 +/- 1.3 ng/mL) than that in healthy volunteers (1.7 +/- 0.3 ng/mL). Serum HMGB1 levels were significantly positively correlated with the Japanese severity score and Glasgow score. Serum HMGB1 levels were significantly positively correlated with lactate dehydrogenase, C-reactive protein, and total bilirubin. The HMGB1 levels were higher in patients with organ dysfunction and infection during the clinical course. The HMGB1 levels in nonsurvivors were higher than those in survivors. Serum HMGB1 levels gradually declined after the admission.Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity. These results suggest that HMGB1 may act as a key mediator for inflammation and organ failure in SAP.

Fig 1. Dynamic CT imaging showing pancreatic tissue completely encircling the superior mesenteric vein (SMV; arrow) and a dilated main pancreatic duct in the tissue behind the SMV (arrow head). A PREVIOUSLY HEALTHY 81-YEAR-OLD WOMAN with general fatigue was admitted to our hospital in June 2009. Her blood chemistry data were within normal limits except for slightly elevated liver function values. Serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen were both normal. Gastroduodenoscopy showed an erosive tumor in the ampulla of Vater. Dynamic computed tomography (CT) revealed bilateral intrahepatic biliary dilatation, and the superior mesenteric vein (SMV) circumferentially embedded in the body of the pancreas, as well as a slightly dilated main pancreatic duct (MPD) in the tissue behind the SMV (Fig 1). The MPD was found posteriorly to the SMV and the accessory pancreatic duct (APD) was seen anteriorly to the SMV. The 2 ducts joined in the body of the pancreas to the left side of the

Pancreatic stellate cells (PSCs) are thought to be responsible for pancreatic fibrosis. Although fibrosis is a major characteristic of chronic pancreatitis (CP) induced by pancreatic duct obstruction, it is unclear whether pancreatic duct obstruction itself activates PSCs.To test the hypothesis that pancreatic duct obstruction activates PSCs, clinical and experimental analyses were performed using alpha smooth muscle actin (alpha-SMA) as a marker of their activation. In clinical analysis, surgical specimens from the patients with pancreatic cancer or cancer of the papilla Vater were classified into two groups with or without duct obstruction. alpha-SMA expression was examined on these specimens, and the difference between two groups was evaluated. In animal experiment, duct ligation-induced pancreatitis was developed in rats by ligating the secondary pancreatic duct in duodenal segment, and the expression of alpha-SMA was examined.In clinical analysis, the specimens from the pancreas with duct obstruction (14 cases) expressed alpha-SMA significantly stronger than those from the pancreas without duct obstruction (7 cases). All specimens in the former expressed alpha-SMA, but 4 specimens from the latter did not at all (P0.05). In animal experiment, alpha-SMA expression was detected 7 days after the ligation and was increased on the 10th day.We can assume that pancreatic duct obstruction itself activates PSCs. This mechanism may play roles in the development of CP from multiple origins.

Adjuvant chemotherapy (AC) is recommended as a standard treatment after curative resection in patients with pancreatic adenocarcinoma (PA). Although patients who failed to complete AC had significantly worse survival compared with those who completed AC for cancers in various organs, the effects of complete AC on survival in patients with PA have not been investigated. The purpose of this study was to clarify the impact of complete AC on PA patient survival and to identify independent risk factors for incomplete AC. Medical records of 236 consecutive PA patients who planned to undergo surgical resection with curative intent between January 2000 and September 2012 at Kobe University Hospital were retrospectively reviewed. Of these, the complete AC (n = 75) and the incomplete AC (n = 30) groups due to adverse events were compared. Patient survival was significantly better in the complete AC group than in the incomplete AC group (median survival time 48.9 vs. 17.9 months; 5-year survival rate 42.7 vs. 17.1 %; p

The objective of the present study was to reappraise the clinical value of peritoneal washing cytology (CY) in 984 pancreatic ductal adenocarcinoma patients who underwent margin-negative resection. In a 2001–2011 database from seven high-volume surgical institutions in Japan, 69 patients (7 %) had positive CY (CY+ group) indicative of M1 disease and 915 patients had negative CY (CY− group). Clinicopathological data and survival were compared between groups. Significant correlations between CY+ and high CA19-9 level, pancreatic body and tail cancer, lymph node metastasis, and a lower frequency of R0 resection were observed. Overall survival (OS) of CY+ patients was significantly worse than that of CY− patients (median survival time [MST], 16 vs. 25 months; 3-year OS rate, 6 vs. 37 %; p

We rarely have an opportunity to perform pancreatoduodenectomy (PD) following the onset of severe acute pancreatitis (SAP) for patients with periampullary cancer. The perioperative risks and optimal timing of subsequent PD have, therefore, remained unclear.Between January 2006 and December 2012, we performed PD in six patients with SAP. We reviewed these six cases, and compared the perioperative risks of morbidity and mortality with those of 81 concurrent PD patients matched for primary cancer without preoperative SAP.The six patients were classified as having SAP based on the Japanese criteria developed in 2008. The SAP in five patients was caused by ERCP procedures. The median interval from SAP onset to the operation was 111 days. The rate of Grade B/C postoperative pancreatic fistula formation in the SAP patients was significantly higher than that of the 81 control patients (83 vs. 26 %, P0.001). In addition, the median postoperative hospital stay was significantly longer in the six SAP patients relative to that of the control patients (40 vs. 30 days, P0.001).An interval of at least 3 months after surgery may be needed to decrease the inflammation of the peripancreas region after SAP. Therefore, unnecessary and low-yield ERCP procedures should be avoided in these patients.

Graft thrombosis is the most common cause of early graft loss after pancreas transplantation. The grafted pancreas is difficult to salvage after complete thrombosis, especially arterial thrombosis, and graft pancreatectomy is required. We describe a patient presenting with a functioning pancreas graft with thromboses of the splenic artery (SA) and superior mesenteric artery (SMA) after simultaneous pancreas-kidney transplantation (SPK). A 37-year-old woman with a 20-year history of type 1 diabetes mellitus underwent SPK. The pancreaticoduodenal graft was implanted in the right iliac fossa with enteric drainage. A Carrel patch was anastomosed to the recipient's right common iliac artery, and the graft gastroduodenal artery was anastomosed to the common hepatic artery using an arterial I-graft. The donor portal vein was anastomosed to the recipient's inferior vena cava. Four days after surgery, graft thromboses were detected by Doppler ultrasound without increases in the serum amylase and blood glucose levels. Contrast enhanced computed tomography revealed thromboses in the SA, splenic vein and SMA. Selective angiography showed that blood flow was interrupted in the SA and SMA. However, pancreatic graft perfusion was maintained by the I-graft in the head of the pancreas and the transverse pancreatic artery in the body and tail of the pancreas. We performed percutaneous direct thrombolysis and adjuvant thrombolytic therapy. However, we had to stop the thrombolytic therapy because of gastrointestinal hemorrhage. Thereafter, the postoperative course was uneventful and the pancreas graft was functioning with a fasting blood glucose level of 75 mg/dL, HbA1c of 5.1%, and serum C-peptide level of 1.9 ng/mL at 30 months post-transplantation.

Background Living donor pancreas transplantation (LDPT) reduces the number of deaths of diabetic patients on dialysis and of candidates on the waiting lists and helps to overcome the organ shortage. Stringent criteria must be applied to minimize the risk of metabolic complications for living donors. The Japanese Pancreas and Islet Transplantation Association (JPITA) proposed LDPT guidelines in 2010. In this study, we retrospectively evaluated glucose metabolism of the patients who underwent distal pancreatectomy (DP) according to the donor criteria of the LDPT guidelines proposed by the JPITA. Methods Fifty-two nondiabetic patients who underwent DP were divided into 2 groups according to the donor criteria: indication group (IG, n = 14) who had age ≤ 65, hemoglobin A1c (HbA1c) 2 . The other patients were placed in the no indication group (NG, n = 38). Clinical data and percent resected volume (PRV) of each pancreas as determined by multi–detector row computed tomography volumetry were compared between the 2 groups. Results During the follow-up period (median 12 months), 14 patients (27%) developed new-onset diabetes within a median onset time of 10 months (range 3–24 months) postoperatively. No patient in the IG developed new-onset diabetes. On the other hand, 37% of the patients in the NG developed new-onset diabetes. There were significant between-group differences in changes in preoperative serum fasting glucose and HbA1c levels, whereas there were no significant between-group differences in preoperative serum albumin or body weight. Multivariate analysis identified preoperative HbA1c (odds ratio 51.6, P = .002) and PRV (odds ratio 2.07, P = .033) as independent risk factors for new-onset diabetes. Conclusion Living donor criteria in the LDPT guidelines proposed by the JPITA are appropriate for prevention of glucose metabolic complications in donors. Further long-term follow-up studies of living donors' metabolic function are needed to clarify the safety of the donor.

Lymphoepithelial cyst (LEC) of the pancreas is a rare benign lesion, which is difficult to diagnose preoperatively. We describe a case of a 60-year-old male, incidentally diagnosed as having LEC of the pancreas, which was managed by laparoscopic distal pancreatectomy. Most of the reported cases of LEC were asymptomatic and diagnosed incidentally. A high index of suspicion under EUS may help in making a diagnosis and avoiding unnecessary surgery in asymptomatic patients. In particular, the unique “cheerios-like” appearance of the lesion in EUS, which was also found in this case, might be helpful in the differential diagnosis of pancreatic cystic lesions.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucin production and cystic dilatation of the pancreatic ducts. The clinical presentation often involves recurrent episodes of pancreatitis associated with the temporal obstruction of the main pancreatic duct caused by the hypersecretion of mucin. We herein describe a case in which the patient repeatedly experienced the occurrence of idiopathic acute pancreatitis in the head of the pancreas over a 9-year period, and who was ultimately was cured by distal pancreatectomy for IPMNs in the pancreatic tail. This case illustrates the potential pitfalls in the diagnosis of IPMNs owing to a discrepancy between the site of pancreatitis and that of the IPMN. The possible mechanisms linking acute pancreatitis with the formation of IPMNs are also reviewed.

A 57-year-old woman with a history of diabetes mellitus underwent simultaneous pancreas–kidney transplantation. The pancreaticoduodenal graft was implanted in the right iliac fossa. The donor’s portal vein was anastomosed to the recipient’s inferior vena cava (IVC). Seven days after the surgery, a thrombus was detected in the graft veins. Percutaneous thrombolysis was immediately performed; however, venous congestion was still present. We therefore attempted selective embolectomy using a Fogarty Thru-Lumen Catheter. Thrombi were directed from the graft veins toward the IVC and captured in the IVC filter with complete elimination of the thrombus without any major complications. We present our technique for the successful treatment of pancreas graft thrombosis within a short time period by percutaneous selective embolectomy using a Fogarty Thru-Lumen Catheter.

In acute pancreatitis (AP), disorders of the coagulation-fibrinolysis system are closely related to the severity of the AP and to organ dysfunctions. We previously reported that plasma tissue factor (TF) levels were elevated in patients with AP, particularly in cases of alcoholic AP with pancreatic necrosis. Tissue factor pathway inhibitor (TFPI) is a key regulator of the extrinsic coagulation pathway, but plasma TFPI levels in AP have not yet been determined.Plasma TFPI concentrations were measured by enzyme-linked immunosorbent assay in 44 patients with AP on admission. The relationships between AP severity, pancreatic necrosis, organ dysfunction, infection, and prognosis were analyzed.Plasma TFPI levels were increased in AP patients compared with healthy volunteers. Plasma TFPI levels in severe AP were greater than those in mild AP. Plasma TFPI levels significantly correlated with Ranson score, APACHE II score, and Japanese severity score. Plasma TFPI levels in patients with pancreatic necrosis were greater than those in patients without pancreatic necrosis. Plasma TFPI levels in patients with organ dysfunction were greater than those in patients without organ dysfunction. In patients with pancreatic necrosis, the TF/TFPI ratios in non-survivors were lower than those in survivors. Moreover, the mortality rates in patients with TF/TFPI ratiosor = 2.0 were lower than those in patients with TF/TFPI ratios2.0.Plasma TFPI levels were significantly increased in patients with AP, and the elevation was markedly related to the severity, pancreatic necrosis and organ dysfunctions. The imbalance of TF and TFPI may influence the disease state and thereby the prognosis in AP.

Background Previous studies demonstrated the efficacy of the two-layer method (TLM) using oxygenated perfluorochemicals (PFC) for pancreas preservation. The current study investigated the effect of oxygenated PFC on isolated islets during transportation. Materials and Methods Purified rat islets were stored in an airtight conical tube for 24h in RPMI culture medium at 22°C or University of Wisconsin solution (UW) at 4°C, either with or without oxygenated PFC. After storage, the islets were assessed for in vitro viability by static incubation (SI), FDA/PI staining, and energy status (ATP, energy charge, and ADP/ATP ratio) and for in vivo viability by a transplantation study. Results UW at 4°C and RPMI medium at 22°C maintained islet quality almost equally in both in vitro and in vivo assessments. The ATP levels and energy status in the groups with PFC were significantly lower than those without PFC. The groups with PFC showed a significantly higher ADP/ATP ratio than those without PFC. In the transplantation study, blood glucose levels and AUC in the UW + PFC group were significantly higher than those in UW group. Conclusions UW at 4°C and RPMI medium at 22°C maintained islet quality equally under the conditions for islet transportation. The addition of oxygenated PFC, while advantageous for pancreas preservation, is not useful for islet transportation.

Hemosuccus pancreaticus (HP) is mostly induced by a ruptured pseudoaneurysm or hemorrhage from a pseudocyst in chronic pancreatitis. We herein report a rare case with HP induced by tumor hemorrhage. The present patient is a 71-year-old woman referred to us with a diagnosis of severe progressive anemia. Endoscopy revealed hemorrhage from the papilla of Vater. Computed tomography showed a multilocular cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy. The histopathological diagnosis was carcinoma in mucinous cystadenoma. No cancer infiltration into the pancreatic duct was detected. Pancreatography of the resected specimen demonstrated an overt communication between the main pancreatic duct and the cystic cavity of the tumor, which was not demonstrated preoperatively by endoscopic retrograde pancreatography. Although the cause of HP is mainly acute or chronic pancreatitis, we should bear in mind that a pancreatic tumor may be a possible cause of HP and that, as such, prompt and proper treatment is mandatory.

The Japanese severity score (JSS) for acute pancreatitis was revised in 2008. As special therapies for severe acute pancreatitis (SAP), continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI) and enteral nutrition (EN) are now utilized in Japan. We investigated the usefulness of the new JSS and the indications for CRAI and EN based on the new JSS. We assessed the new JSS in 138 patients with SAP according to the previous Japanese criteria. Usefulness of the new JSS for the prediction of mortality rates was compared with conventional scoring systems by receiver-operator characteristic curve analysis. We analyzed the relationship between the new JSS and prognosis in patients with and without CRAI and EN, respectively. Forty-five patients (33%) were assessed as having mild acute pancreatitis, and 93 patients (67%) were assessed as having SAP. Their mortality rates were 7 and 40%, respectively. The area under the curve for the prediction of mortality rates with the new JSS was 0.822 and was the highest among conventional scoring systems. In patients with new JSS ≥ 6, the mortality rate was lower in patients with CRAI than in patients without CRAI (P = 0.129). In patients with new JSS ≥ 4, the mortality rate was lower in patients with EN than in patients without EN (P = 0.016). The new JSS is useful and easier to use for the prediction of prognosis compared to the conventional scoring systems. EN was effective in reducing the mortality rate in patients with a new JSS ≥ 4.

In pancreaticojejunostomy (PJ), the occurrence of an injury during the removal of a stented tube is sometimes related to pancreatitis or late-onset stenosis of the pancreatic duct. In this study, we compare the outcomes of a PJ with an external stent versus an internal stent in a randomized study.We compared the complications including pancreatic fistula, mortality, and postoperative hospital stay of 43 patients who had PJ with an external stent (group E) or PJ with an internal stent (group I) after a pancreaticoduodenectomy (PD).Pancreatic fistula occurred in 8 patients (36.4%) in group E, while it only was seen in 7 patients (33.3%) in group I. Pancreatitis was recognized in 3 patients in group E, while there was no patient in whom an obstruction due to an internal stent was suspected.Pancreaticojejunostomy with an internal stent is therefore considered to be an effective treatment alternative after PD, with an acceptable morbidity and no mortality.

This study was undertaken to evaluate the post-discharge outcome of severe acute pancreatitis (SAP) and to clarify the prognostic factors for poor outcome. In 45 patients, recurrence of acute pancreatitis (AP), transition to chronic pancreatitis (CP), and development of diabetes mellitus (DM) were evaluated. Relationships of the outcome with the findings on admission and the presence/absence of alcohol intake were analyzed. The mean follow-up period was 56 ± 6 months. Recurrence of AP was noted in 19% of the patients. The recurrence rate was higher in patients with necrotizing pancreatitis than in those without this feature. C-reactive protein and white blood cell (WBC) count were higher in patients with recurrence of AP. Transition to CP was noted in 22% of patients. The transition rate was higher in those with alcoholic SAP than in those with biliary SAP. In patients with transition to CP, the WBC count, hematocrit, Ranson score, and Japanese severity score were higher, and base excess (BE) was lower, compared with these features in patients without this transition. Development of DM was noted in 39% of patients. Blood glucose and BE were higher in patients who developed DM than in those who did not. The degree of inflammation and pancreatic necrosis found on admission for SAP may be related to the recurrence of AP. Alcoholic SAP in which the disease is very severe may contribute to the transition to CP. Patients with impaired glucose tolerance readily develop DM after SAP.

In severe acute pancreatitis (SAP), it is clinically important at the time of admission to predict the likelihood of early death. This investigation aimed to clarify the factors predicting early death in SAP.Early death was defined as death within 10 days after disease onset. Prediction factors for early death were evaluated from data obtained on admission from 93 patients with SAP, and the characteristics of patients who died early were analyzed.Between the early-death and early-survival groups, significant factors were base excess (BE), serum creatinine (Cr), blood sugar, serum glutamate oxaloacetic transaminase, and serum calcium. Multivariate analysis revealed that BE was an independent prediction factor for early death. The early-death rate in patients with BE-5.5 mEq/l and Cror= 3.0 mg/dl was 31% and 36%, respectively. The combination of BE and Cr raised the positive predictive value to 50%, and was equally able to predict early death as the Japanese Severity Score (JSS), which was the most useful of the three conventional scoring systems used. All early-death patients had pancreatic necrosis, and their JSS wasor= 15 (stage 4). Characteristically, early-death patients had lactate dehydrogenase (LDH)1300 IU/l, or they had serious preexisting comorbidities.As a single parameter, BE was most useful for predicting early death. The combination of BE and Cr could predict early death as well as the JSS. An extreme rise of LDH and serious preexisting comorbidity may also be risk factors for early death.

Multiple organ dysfunction and infection are major contributors to the high mortality associated with severe acute pancreatitis (SAP). Toll-like receptor 4 (TLR4) recognizes the lipopolysaccharide of gram-negative bacilli and is involved in inflammatory response and host defense. We examined the effects of TLR4-deficiency in SAP in mice.Closed duodenal loop-induced pancreatitis was induced in C3H/HeN (wild-type) and C3H/HeJ (TLR4-deficient) mice. We compared the severity of pancreatitis, liver and kidney dysfunction, and bacterial translocation to the pancreas between the two types of mice 12 h after the induction of SAP.The severity of pancreatitis was similar in the two types of mice. The TLR4-deficient mice had significantly lower serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine; significantly lower serum levels of interleukin-1 and tumor necrosis factor; reduced apoptosis of the liver and kidney; and a significantly higher rate of positive gram-negative bacterial cultures of the pancreas. TLR4 protein expression in the liver, kidney, and small intestine was increased 4 h after the induction of SAP, and decreased 12 h after the induction of SAP.TLR4 is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP, and TLR4 may trigger the inflammatory response and function defensively against infection.