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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.

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．

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.

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

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.

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.

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.

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.

Background. In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. In this study, immunologic alterations in patients with SAP were analyzed, and immunologic parameters related to infectious complications were clarified. Methods. A total of 101 patients with SAP were analyzed retrospectively. Various immunologic parameters on admission were analyzed and compared between the infection group and noninfection group during SAP. Furthermore, chronologic change in the lymphocyte count was investigated, and its utility for predicting infection was compared with conventional scoring systems. Results. Serum immunoglobulin G (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer cell activity were low, and the incidence of abnormally low values was 50.0%, 65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was significantly negatively correlated with the APACHE II score. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte counts were below the normal range, and CD4- and CD8-positive lymphocyte counts were significantly lower in the infection group. The lymphocyte count on day 14 after admission was significantly lower in the infection group and was more useful for predicting infection than conventional scoring systems. Conclusions. Immunosuppression occurs from the early phase in SAP, and quantitative impairment of lymphocytes, mainly T lymphocytes, may be closely related to infectious complications during SAP. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection.

section(indirect PPJ; see picture 5). In the outer-layer reinforced stitch seromuscular layer of the jejunum was sutured with the pancreas envelope or peripancreatic connective tissue interruptedly. Results: The time of PPJ was from eight minutes to eighteen minutes(average ten minutes). None presented C grade postoperative pancreatic fistula according to ISGPF. Ten cases presented A grade postoperative pancreatic fistula. Four cases presented B grade pancreatic fistula. The cases with A or B grade postoperative pancreatic fistula had nothing to do with pancreatic anastomotic failure through the radiography (see picture 6). No case was postoperative dead. There was neither pancreatic anastomotic haemorrhage nor reoperation. No case showed obvious expansion of pancreatic duct in twenty-eight cases during postoperative following up for three months. Conclusions: The design idea of PPJ is that the pancreas stump should be anastomosed to the jejunum in a way as a parenchymal organ rather than a hollow organ. This anastomosis is time-saving and easy to grasp. It is clear that PPJ is the simplest and a reliable pancreaticojejunostomy to today.

重症急性膵炎105例を対象とし肺障害合併例を検討した．経過中の肺障害合併例は50%であった．肺障害合併例の入院時重症度や壊死性膵炎の頻度は有意に高かった．肺障害合併群と非合併群の間で入院時に有意差を認めた因子はBE，BUN，クレアチニン，血糖，LDH，CRP，リンパ球数，カルシウム，総蛋白，好中球エラスターゼであった．肺障害合併例の感染併発率は48%，死亡率は58%と有意に高かった．肺障害合併例を肺障害単独例と多臓器障害例に分けると，多臓器障害例の感染併発率は56%，死亡率は68%と有意に高かった．肺障害合併例の入院時予後予測因子はAST，ALT，総ビリルビン，クレアチニン，カルシウム，LDHであった．入院時肺障害，早期肺障害，後期肺障害での膵手術施行率は，それぞれ47%，0%，75%であり，死亡率はそれぞれ63%，10%，83%であった．いずれの時期の肺障害においても肺障害単独例に比して多臓器障害例で死亡率は高かった．重症急性膵炎において肺障害合併率は高く，肺障害合併例（特に多臓器障害例）の感染併発率や死亡率は高かった．入院時や後期の多臓器障害としての肺障害は予後不良であり，感染対策を含めた全身管理が必要である．

重症急性膵炎における血液凝固線溶系の異常をretrospectiveに検討した．自験例では入院時から凝固線溶系の異常が高率に認められた．特にThrombin-antithrombin III complex（TAT）とD-dimerの異常発現率は100%であった．厚生労働省重症度スコアとの相関関係はProthrombin time-international normalized ratio（PT-INR）とTATが正の相関関係を，血小板が負の相関関係を示した．また，入院時TATはStage 2よりもStage 3, 4において高値を示した．生存群に比して死亡群において，PT-INRは有意に延長し，TATは高値を示した．入院時PT-INRが1.15以上の症例や入院時TATが45ng/ml以上の症例では死亡率が有意に高かった．以上より，重症急性膵炎において入院時TATは重症度や予後予測のマーカーとして有用である可能性が示唆された．

Background & Aim: Organ dysfunction is a serious complication in severe acute pancreatitis (SAP), and pulmonary dysfunction (PD) is most frequently experienced. Incidence of PD complicating AP varies from 15 to 55%, and the severity of PD varies from mild hypoxemia without clinical abnormality to severe ARDS. It is conceivable that the presence of PD is correlated with the mortality rate in SAP, but there have been few clinical studies. This study aimed to clarify the clinical characteristics of PD associated with SAP. Methods: We analyzed the data of 105 patients with SAP according to the Japanese criteria. Pulmonary dysfunction was defined as PaO2

AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS: SAP was induced by creating closed duodenal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 μg). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS: Anti-HMGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAP. Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP.