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The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic regeneration.The role of PI3K in PDX-1 expression and duct cell differentiation with pancreatic regeneration in mice after partial pancreatectomy (Px) was examined using either wortmannin, a pharmacological PI3K inhibitor, or small-interfering RNA directed to the p85alpha regulatory subunit of PI3K. Akt phosphorylation, a marker of PI3K activation, and PDX-1 expression were assessed by Western blot analysis and immunohistochemistry.Both PDX-1 levels and Akt phosphorylation were concomitantly increased in pancreatic ducts after partial Px and, conversely, blocked by treatment with wortmannin or p85alpha small-interfering RNA. Pancreatic duct cell differentiation, as assessed by appearance of insulin-positive cells 3 days after partial Px, was effectively reduced by wortmannin.The PI3K/Akt activation plays a critical role for both PDX-1 expression and pancreatic duct cell differentiation into insulin-producing cells during pancreatic regeneration.

Summary The porcine MX1 and MX2 promoters were characterized in this study. Sequencing of the 332-bp MX1 promoter region identified 15 substitutions and insertions at three positions in 21 pigs from 15 breeds, in which nine genotypes were classified. Among the nine genotypes, no statistically significant differences in the promoter activities were observed after interferon (IFN-α 2b) treatment of transiently transfected cells containing constructs with luciferase reporter plasmids. The 341-bp MX2 promoter region contained regulatory sequences for ISRE, GC box, Sp1 and AP-1, as well as a TATA box. Nucleotide sequences of the MX2 promoter region revealed four substitutions and one deletion, in which six genotypes were classified. Among the six genotypes, a statistically significant difference (P

The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3.

This retrospective study was conducted to find preoperatively assessable risk factors for postoperative pancreatic fistula (POPF) in patients undergoing laparoscopic distal pancreatectomy (LDP) using a slow compression method with a stapler, which we call pen-firing compression (PFC).Fifty-two patients underwent LDP, of whom 42 underwent PFC for pancreatic division using a stapler. The relationship between preoperatively assessable factors and the incidence of clinical POPF was statistically analyzed.Overall rate of POPF was 7.1% in 42 patients. Univariate analysis showed that greater BMI (p = 0.004) and thicker pancreatic stump (0.0022) were significant risk factors for POPF. BMI and stump thickness remained significant (P0.0001, P0.0001) by multivariate analysis. Cutoff points estimated by ROC curve were 27 kg/m2 for BMI and 27 mm for stump thickness.High BMI value and thick pancreatic stump are significant risk factors for POPF after LDP. Alternative treatment of the pancreatic stump may prevent POPF in high-risk patients.

A single amino acid substitution between Asn and Ser at position 631 in the chicken Mx protein has been reported to determine resistant and sensitive antiviral activity. In this study, we investigate whether various kinds of chicken breeds and jungle fowls carry the resistant or sensitive Mx allelic gene by using the mismatched PCR-restriction fragment length polymorphism (RFLP) technique. In total, 271 samples from 36 strains of 17 chicken breeds and from 3 kinds of jungle fowls were examined. The rates of the resistant Mx gene and sensitive gene were 59.2% and 40.8%, respectively. Only a Red jungle fowl captured in Laos carried the resistant Mx gene, and the other three Red jungle fowls from Indonesia and Gray and Green jungle fowls all had the sensitive Mx gene. These results were confirmed by the determination of amino acid sequences in the GTPase effector domain of jungle fowls.

The molecular mechanism by which sperm triggers Ca2+oscillation, oocyte activation, and early embryonic development has not been clarified. Recently, oocyte activation has been shown to be induced by sperm-specific phospholipase Cζ (PLCζ). The ability of PLCζ to induce oocyte activation is highly conserved across vertebrates. In the present study, porcine PLCζ cDNA was identified and the nucleotide sequence was determined. The expression pattern of porcine PLCζ mRNA during the period of postnatal testicular development was shown to be similar to that of mouse PLCζ. PLCζ mRNA expression in the pig and mouse was detected only in the testes when the elongated spermatids had differentiated, and was detected from day 96 after birth in the pig. Histological examination of porcine testis during the period of postnatal development revealed the presence of spermatozoa from day 110 after birth. These findings suggest that the synthesis of PLCζ mRNA starts when spermiogenesis is initiated. Microinjection of porcine PLCζ complementary RNA into porcine oocytes demonstrated that porcine PLCζ has the ability to trigger repetitive Ca2+transients in porcine oocytes similar to that observed during fertilization. It was also found that porcine PLCζ cRNA has the potential to induce oocyte activation and initiate embryonic development up to the blastocyst stage.

We report a rare case of bleeding ileal varices successfully treated with emergency enterectomy. A 72-year old woman with hepatic cirrhosis due to hepatitis C was admitted to our hospital because of anemia and hematochezia. An endoscopic examination showed no evidence of bleeding in the upper and lower gastrointestinal tracts. Angiographic studies of portal hemodynamics revealed extravasation from the ileal varices and total occlusion of the portal vein due to portal thrombus. This made it difficult to remove the ileal varices using interventional radiology. Therefore, the patient underwent emergency enterectomy for the ileal varices. No further gastrointestinal bleeding occurred during the 1-year follow-up.

This paper describes experimental results of a high T c superconducting magnet excited by a thermoelectromotive force. This magnet system has an advantage of simple configuration because a thermoelectric element is much smaller than a conventional external power source for a superconducting magnet. It is demonstrated that more than 50 A of transport current is obtained in the present experiment. The heat leakage to the coil is about double amount as compared with a conventional magnet system with an external power source.

The IMF Fiscal Affairs Department's Revenue Administration Gap Analysis Program (RA-GAP) aims to provide a quantitative analysis of the tax gap between potential revenues and actual collections, and this technical note explains the concept of the tax gap for corporate income tax (CIT), and the methodology to estimate CIT gaps. It includes detailed steps to derive the potential CIT base and liability with careful consideration for the theoretical differences between the coverage of statistical macroeconomic data and the actual tax base of CIT, and then compare the estimated results with actual declarations and revenues. Although the estimated gaps following the approach will have margins of errors, it has the advantage of using available data without additional costs of collection and suits initial evaluations of overall CIT noncompliance in a country.

Although recent studies have confirmed the safety of total pancreatectomy (TP), appropriate selection of patients for TP has not been well documented. Because patients require lifelong medical treatment and self-management of pancreatic insufficiency after TP, indications for TP should be determined carefully according not only to disease factors but also to the social background of patients. We aimed to clarify long-term outcomes after TP, including the living conditions and quality of life (QoL), of surviving patients.Medical records of 44 consecutive patients who underwent TP between 1990 and 2013 were reviewed retrospectively; 25 survivors completed cross-sectional clinical surveys and responded to a questionnaire about QoL using Short Form 36v2.Prevalence of morbidity and mortality after TP was 32 and 5 %, respectively. Postoperative complications occurred more frequently in elderly patients than in young patients (48 vs. 14 %; P = 0.02); however, there was no significant difference in mortality, postoperative hospital stay, or survival. Twenty-four of 25 survivors (96 %) could manage pancreatogenic diabetes by themselves, and the median level of glycosylated hemoglobin was 7.4 %. Although one-third of patients after TP complained of diarrhea and the QoL scores of patients with diarrhea were lower than those of patients without diarrhea, QoL scores after TP were virtually comparable with those of the national population, even in elderly patients.TP can be performed safely, even in elderly patients. QoL after TP seems to be acceptable if patients are capable of self-management.

Background. The importance of bile in liver regeneration after hepatectomy is unknown, although we have recently shown that preoperative internal biliary drainage is superior to external biliary drainage for liver regeneration in obstructive jaundiced rats. This study examined the hypothesis that the presence or absence of bile in the intestinal tract modulates cyclins and cyclin-dependent kinases after hepatectomy in rats. Methods. In male Wistar rats, bile was drained externally (ED group) or into the duodenum (ID group) for 7 days before 70% hepatectomy. Relative liver weight, DNA synthesis rate, and proliferating cell nuclear antigen labeling index were determined at the time of hepatectomy (day 0) and on days 1, 3, and 7 after hepatectomy. Posthepatectomy expressions of cyclin D1 and E and of cyclin D1- and E-associated kinases were serially analyzed. Hepatic function tests were performed. Results. No significant difference in liver function was found between the 2 groups at hepatectomy except for the lower albumin level in the ED group. The relative liver weight was lower in the ED group than in the ID group on day 3 after hepatectomy (ED, 2.58% ± 0.06%; ID, 2.84% ± 0.08%; P

Transcriptional activation of nuclear factor (NF)-kappaB, signal transducers and activators of transcription (STAT) 3, activating protein (AP)-1 and CCAAT/enhancer-binding protein (C/EBP) plays an important role in liver regeneration by modulating cell cycle regulators. The regeneration of cirrhotic liver after hepatectomy is inhibited despite intact expression of growth factors. To elucidate the mechanism involved, regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-thirds hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The expression of c-met and epidermal growth factor receptor analyzed by RT-PCR and immunohistochemistry did not differ between the two groups. The activities of C/EBP and AP-1 evaluated by electrophoretic mobility shift assay were significantly inhibited in the cirrhotic group compared with those in the control group, but not those of NF-kappaB and STAT3. The expression of cyclin-D1, -E, and -A assessed by Western blot analysis was significantly decreased in the cirrhotic group compared with the control group. The level in p21(Cip1) or p27(Kip1) did not differ between the two groups. The liver regeneration estimated by the rates of [(3)H]thymidine incorporation into DNA and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic rats than in the controls. In conclusion, downregulation of cyclin -D1, -E, and -A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy.

Sepsis is a life-threatening clinical condition that is particularly serious among the elderly who experience considerably higher mortality rates compared with younger patients. Using a sterile endotoxemia model, we previously reported age-dependent mortality in conjunction with enhanced coagulation and insufficient levels of anti-coagulant factor activated protein C (aPC). The purpose of the present study was to further investigate the mechanisms for age-dependent coagulation and aPC insufficiency during experimental sepsis. Intra-abdominal sepsis was induced by cecal ligation and puncture (CLP) using 21 or 16 gauge (G) needles (double-puncture) on young (4 to 6 mo old) and aged (20 to 25 mo old) male C57BL/6 mice. When compared with young mice, aged mice showed significantly increased mortality (92% vs. 28%), systemic inflammation, and coagulation in the lung and kidney after 21G CLP. Young mice with more severe CLP (16G) showed a mortality rate and inflammation equivalent to aged mice with 21G CLP; however, enhanced coagulation and kidney dysfunction were significant only in the aged. In young mice, increased levels of aPC after CLP were coupled with reduced levels of protein C (PC), suggesting the conversion of PC to aPC; however, PC and aPC levels remained unchanged in aged mice, indicating a lack of PC to aPC conversion. Activation of fibrinolysis, determined by plasma d-dimer levels, was similar regardless of age or CLP severity, and plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, showed severity-dependent induction independent of age. These results suggest that enhanced coagulation in aged mice during sepsis is due to dysfunction of the PC activation mechanism.

Routine endoscopic retrograde pancreatography (ERP) for pancreatic juice cytology (PJC) during management of intraductal papillary mucinous neoplasm (IPMN) is not recommended in the international consensus guidelines 2012. The aim of the present study was to investigate the roles of PJC in relation to the new stratification of clinical findings in the consensus guidelines 2012. Medical records of 70 consecutive patients who underwent preoperative PJC, subsequent pancreatectomy, and a pathological diagnosis of IPMN were reviewed. Diagnostic ability of PJC to detect malignant lesions was calculated by the stratification of clinical findings. Forty patients had malignant lesions, including 29 with malignant IPMN, 10 with concomitant pancreatic adenocarcinoma, and one with both. Accuracies of PJC in all 70 patients and in 59 patients with IPMN alone were 77 and 80 %, respectively. The sensitivity and accuracy of PJC in patients with “worrisome features” were 100 and 94 %, respectively. Eight of 11 patients with concomitant pancreatic adenocarcinoma had non-malignant IPMN without risk factors, and 3 significant lesions could be diagnosed only by ERP/PJC. In addition, the management plan based on imaging study changed from observation to resection in two patients who had the single “worrisome feature” of branch duct IPMN and positive PJC results. As a result, PJC altered the management plan in 5 patients. Pancreatic juice cytology potentially has important roles to determine the adequate treatment choice in patients with IPMNs with “worrisome features,” and to detect significant lesions that could not be detected by other imaging modalities.

The majority of patients with pancreatic cancer present with far advanced disease and jaundice. With the advancement of endoscopic interventional techniques, the role of surgical bypass has declined. However, surgical bypass is still considered to be appropriate in patients who are able to tolerate surgery. We performed hepaticocholecystojejunostomy consecutively as a palliative surgical biliary bypass for the purpose of long-term palliation. The aim of this study was to analyze the results of our palliative surgical biliary bypass, hepaticocholecystojejunostomy.Between January 2001 through December 2009, 69 patients received palliative surgical biliary bypass (bypass group) and 33 patients received endoscopic biliary stenting (stent group) for unresectable pancreatic cancers. Mortality, morbidity and survival between the two groups were compared.There was no in-hospital death in the bypass group, but 2 patients (6%) in the stent group died in the hospital (p = 0.04). The surgical morbidity rate was 15% in the bypass group, while 20 patients (61%) in the stent group developed complications, mainly due to stent blockage. There was no significant difference in overall survival between the two groups. Among patients who underwent systemic chemotherapy but did not present with jaundice at the time of diagnosis, those who underwent prophylactic surgical biliary bypass before chemotherapy showed better survival than those who underwent systemic chemotherapy preceding biliary bypass or biliary stenting after occurrence of jaundice (p = 0.01).Hepaticocholecystojejunostomy resulted in negligible mortality, low morbidity and effective long-term palliation. Prophylactic surgical biliary bypass with gastrointestinal bypass might be a good treatment option for non-jaundiced patients undergoing chemotherapy for unresectable pancreatic cancer.

A 70 -year-old female patient with a palpable mass in the left upper abdomen suffered from abdominal pain and fever. Abdominal computed tomography showed a jejunal tumor 11 cm in diameter with ascites, suggesting rupture of the tumor. Histological diagnosis via endoscopic ultrasound-guided fine needle aspiration indicated c-kit-positive gastrointestinal stromal tumor. Diagnostic laparoscopy demonstrated a large jejunal tumor possibly invading the stomach and pancreas. The patient then underwent tube jejunostomy. Thereafter, preoperative induction chemotherapy with imatinib mesylate(400mg/ body/day)via jejunostomy was administered for 6 months, resulting in 20%reduction of the tumor diameter and disappearance of any indication of stomach and pancreas invasion. The patient then underwent radical partial resection of the jejunum without combined resection of either the stomach or pancreas. Postoperative adjuvant chemotherapy with imatinib mesylate (400mg/body/day)was also indicated. No sign of recurrence has been detected to date after 1 year of follow-up.

Background: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables. Study Design: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model. Results: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17–129.94, p=0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08–108.33, p=0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08–108.33, p=0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34–13.82, p=0.0142) and surgical margin (OR 7.41, 95% CI 2.19–25.13, p=0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62–400.72, p=0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%. Conclusions: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Aberrant expression of several microRNAs (miRs) has been reported in various neoplasms including intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. MicroRNA-196a (miR-196a) is up-regulated in Barrett esophagus (characterized by intestinal metaplasia) and in colorectal cancer; this relationship between intestinal characteristics and miR-196a might also be applicable to intestinal-type IPMNs. The aim of this study was to evaluate whether intestinal-type IPMNs can be discriminated from non-intestinal-type IPMNs by the expression level of miR-196a in tissue and pancreatic juice samples.Thirty-seven formalin-fixed paraffin-embedded tissue samples (including 3 of normal pancreatic ducts) and 36 pancreatic juice samples were obtained. The expression level of miR-196a measured by quantitative reverse transcription-polymerase chain reaction assays was compared between intestinal-type and non-intestinal-type IPMNs.MicroRNA-196a expression in intestinal-type IPMN tissue samples (n = 18) was significantly higher than that of non-intestinal-type IPMNs (n = 16) (P0.001). Similarly, miR-196a expression in pancreatic juice samples of intestinal-type IPMNs (n = 6) was significantly higher than that of non-intestinal-type IPMNs (n = 30) (P = 0.008), and the sensitivity and specificity for prediction of intestinal-type IPMNs using pancreatic juice samples were both 83%.Elevated expression of miR-196a in pancreatic juice samples is predictive of intestinal-type IPMNs.

A 5-cm pheochromocytoma located in segment 7 of the liver was found incidentally in a 45-year-old man with mild diabetes mellitus and hypertension, and resected. The tumor was demonstrated by computed tomography and magnetic resonance imaging to have completely invaginated itself into the liver and to be receiving blood from a dilated right hepatic artery alone. Surgery revealed the hepatic mass to be tightly adherent to the right adrenal gland. The histopathologic diagnosis was pheochromocytoma growing exophytically from the right adrenal gland. There was no association with multiple endocrine neoplasia type 1 and type 2. A postoperative 131I metaiodobenzylguanidine scan revealed no accumulation, and the patient is currently doing well without recurrence or hypertension one year after the operation. A pheochromocytoma deeply invaginating into the liver should be considered in the differential diagnosis of primary hypervascular hepatic tumors.

Several recent studies have suggested that Braun enteroenterostomy (BEE) during conventional pancreatoduodenectomy might decrease delayed gastric emptying (DGE). However, the advantages and disadvantages of performing BEE during pylorus-preserving pancreatoduodenectomy (PPPD) remain controversial.The medical records of 185 patients who underwent PPPD either with or without BEE between January 2008 and June 2013 were retrospectively reviewed, and the postoperative course of the 2 groups was compared.Ninety-eight patients underwent PPPD with BEE and 87 without BEE. DGE occurred in 4% of patients with BEE and in 21% of those without BEE (P.01). The addition of BEE did not affect postoperative complications other than DGE. By multivariate analysis, the omission of BEE was the only independent factor associated with DGE (odds ratio 5.04, 95% confidence interval: 1.59 to 19.66; P.01).BEE during PPPD reduced the incidence of DGE.

Background Mucinous cystic neoplasms (MCN) of the pancreas frequently develop in the distal pancreases of young women. Laparoscopic surgery can enhance cosmetic benefits and ease of surgery. This study assessed the feasibility of laparoscopic surgery for MCN. Methods The medical records of 21 patients pathologically diagnosed with benign MCN after laparoscopic resection were reviewed. Clinical data were compared in the 11 patients with tumors ≥45 mm (large tumor group) and the 10 patients with tumors

The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

Schwannomas arising in the retroperitoneum are very rare. A case of malignant retroperitoneal schwannoma in a patient with von Recklinghausen's disease is reported. A 17-year-old man with von Recklinghausen's disease was admitted to the hospital in 1994 because of a left lower abdominal mass and pain of he left thigh which started in 1992 and were gradually getting worse. On physical examination, an elastic hard, tender mass with smooth suface, about 13 cm in diameter, was palpated in the left lower abdomen. Computed tomography, ultrasonography and angiography showed a solid and mild hypervascular tumor in the retroperitoneal space. The tumor was extirpated completely. The extirpated speciemen was a 15×11×10cm yellowish solid tumor and 790 g in weight. Histopathological diagnosis was malignant schwannoma. Retroperitoneal malignant schwannoma is hardly diagnosed in an early stage and it's prognosis is relatively poor especially with von Recklinghausen's disease. The patients with von Recklinghausen's disease should be followed by a periodic check-up including computed tomography and ultrasonography for early detection of such a neoplasm.

In patients with pancreatic ductal carcinoma (PDAC), EUS-FNA carries a risk of cancer seeding. To avoid this risk, we attempted to obtain preoperative cytological confirmation of adenocarcinoma by ERCP. The aim of this study was to assess the validity of our diagnostic strategy. The medical records of 124 consecutive patients who were investigated for potentially resectable PDAC were retrospectively reviewed, and the ability to detect adenocarcinoma by ERCP was evaluated. ERCP was performed in 115 patients, 69 of whom had positive cytology results. Thirty-four patients underwent EUS-FNA, 29 of whom had positive cytology results. A total of 98 patients (79 %), therefore, had preoperative cytological confirmation of adenocarcinoma, which was more frequent in patients with lesions of the head of the pancreas than in those with lesions of the body or tail of the pancreas. The postoperative pathological diagnosis demonstrated malignant pancreatic neoplasms in 122 patients (98 %), including 111 with PDAC. EUS-FNA did not affect the rate of postoperative peritoneal dissemination. Our strategy using ERCP as the initial diagnostic modality for obtaining cytological confirmation of potentially resectable PDAC seems to be adequate, yielding a high rate of positive cytology, especially in cases with tumors of the head of the pancreas.

We investigate how large a size of primary deficit to GDP ratio the Japan’s government can sustain. For this investigation, we construct an overlapping generations model, in which multi-generational households live and the government maintains a constant ratio of primary deficit to GDP. We numerically show that the primary deficit cannot be sustained unless the rate of economic growth is unrealistically high, which is more than five percent according to our settings. Our result implies that Japan’s government needs to achieve a positive primary balance in the long-run in order to avoid the divergence of the public debt to GDP ratio.

Cancer stem cells (CSCs) play pivotal roles in cancer growth, invasion, metastasis and recurrence. Several proteins have been reported as CSC markers for pancreatic ductal adenocarcinoma (PDAC). In the present study, we examined the correlation between pancreatic intraepithelial neoplasias (PanINs) and CSC markers including CD24, CD44, CD133, CXCR4, ESA and nestin using immunohistochemical analysis. Furthermore, we examined the roles and clinical significance of these CSC markers in PDAC. CD24-, CD44-, CXCR4-, ESA- and nestin-positive cells were detected in the following tissues, listed in order of increasing percentage: normal ducts < low-grade PanINs < high-grade PanINs < PDACs. CD133 did not increase according to the malignancy grade. In PDAC, cells positive for each of the following CSC markers were detected, listed according to increasing percentage: nestin < CD133 < CD44 < CD24 < CXCR4 < ESA. CXCR4 and ESA expression correlated with well-differentiated PDAC. Venous invasion was positively associated with CD133 and inversely associated with ESA. CSC marker expression levels detected in PDAC cell lines using flow cytometry showed lowest expression of CD133 and highest of CD44, differing from the results obtained using immunohistochemistry. In two PDAC subtypes, adenosquamous carcinoma and anaplastic carcinoma, ESA was expressed more abundantly in adenocarcinoma components, whereas CD44 and nestin showed high expression in anaplastic components. Together, these results suggest that most CSC markers correlate with pancreatic carcinogenesis through the PanIN-to-PDAC sequence. Each CSC marker was related in a different manner with proliferation, differentiation, invasiveness or tissue type of PDAC.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are known as incretins to stimulate insulin secretion. The aims of this study were to investigate the postoperative β-cell function and hormonal responses of GLP-1 and GIP after pancreatoduodenectomy (PD) and distal pancreatectomy (DP).Oral glucose tolerance tests were performed in 34 patients (20 PD and 14 DP) before and 1 month after operation. The changes in the serum glucose and insulin concentrations, homeostasis model assessment of insulin resistance, and pancreatic β-cell function (BCF) were analyzed. GLP-1 and GIP were also measured.There was no patient with postoperative deterioration of glucose tolerance after PD, whereas impairment of glucose metabolism was observed after DP. Homeostasis model assessment of insulin resistance decreased after PD, whereas those after DP showed no change. The postoperative BCF were lower than preoperative values in both groups. GLP-1 increased after DP but not after PD, whereas GIP decreased after PD but not after DP.The changes in glucose metabolism and incretin responses were different between PD and DP. The increased level of GLP-1 after DP might reflect the relatively insufficient BCF; and thus, perioperative administration of GLP-1 might improve the diabetic condition after DP.

Resectability of hepatic metastases which have developed from lung cancer is limited and only a few reports have been published. We report two cases of a surgical resection of liver metastases arising from lung cancer. A 77-year-old male underwent a lower left lobectomy to treat a primary large cell lung carcinoma. Eight months later, abdominal computed tomography revealed a slightly enhanced heterogeneous tumor measuring 50 mm in diameter in the right liver, segment 8. We performed a hepatic anterior sectionectomy. The pathological findings were similar to those of the primary carcinoma. After six months, there was no evidence of a recurring lesion. A 65-year-old female underwent an upper right lobectomy to treat a primary adenocarcinoma. Twenty months later, abdominal computed tomography revealed a heterogeneous tumor measuring 20 mm in diameter in the right liver, segment 7. We performed a hepatic posterior sectionectomy. The pathological findings were similar to those of the primary lung carcinoma. After twenty months, the patient died from an unresectable recurrent carcinoma in the lung and brain. No recurrence was detected in the liver. We recommend that surgical resection be considered for solitary metastatic liver tumors which develop from lung cancer.

The role of gastrectomy for patients with positive peritoneal cytology, but a negative macroscopic peritoneal implant (P−/cy+), remains unclear. The aim of this study was to evaluate laparoscopic gastrectomy for P−/cy+ patients. This study reviewed a prospectively maintained gastric cancer database of gastric-cancer patients those underwent surgical resection. P−/cy+ gastric cancer that had invaded the subserosa, or deeper layers, of the stomach wall without distant organ metastases was considered operable in this institution. P−/cy+ patients underwent either open or laparoscopic gastrectomy with D2 lymphadenectomy. The short-term results were examined to assess differences in outcome between the two groups. Eighteen P−/cy+ patients without distant organ metastases underwent surgery between 2000 and 2010. Laparoscopic gastrectomy was performed in nine patients and open gastrectomy in nine patients. The estimated blood loss was significantly smaller, the resumption of food intake earlier, and the length of postoperative hospital stay shorter in the patients that underwent laparoscopic gastrectomy than in the patients that underwent open gastrectomy. There were no significant differences in the 2-year survival rates between the groups. Laparoscopic gastrectomy for P−/cy+ patients is a minimally invasive and safe oncologic procedure with good short-term results.

The fibroblast growth factor receptor (FGFR) family consists of four members, named FGFR1, 2, 3, and 4. All 4 FGFRs and their ligands, fibroblast growth factors (FGFs), are expressed in colorectal cancer (CRC). Recent studies have shown that FGFR2 plays important roles in cancer progression; therefore, it is of great interest as a novel target for cancers. Expression of FGFR2 regulates migration, invasion, and growth in CRC. Expression of the FGFR2 isoform FGFR2 IIIb was associated with well-differentiated histological types, and its specific ligand, FGF7, enhanced angiogenesis and adhesion to type-IV collagen via FGFR2 IIIb in CRC. FGFR2 IIIc is detected in CRC, but its roles have not been well elucidated. Interactions between FGFR2 IIIb and IIIc and FGFs may play important roles in CRC via autocrine and/or paracrine signaling. Several kinds of molecular-targeting agents against FGFR2 have been developed; however, it is not clear how a cancer treatment can most effectively inhibit FGFR2 IIIb or FGFR2 IIIc, or both isoforms. The aim of this paper is to summarize the roles of FGFR2 and its isoforms in CRC and clarify whether they are potent therapeutic targets for CRC.

Lymph node (LN) metastases from hepatocellular carcinoma (HCC) are considered uncommon. We describe the surgical resection of a solitary para-aortic LN metastasis from HCC. A 65-year-old Japanese man with B-type liver cirrhosis was admitted for the evaluation of a liver tumor. He had already undergone radiofrequency ablation, transcatheter arterial chemoembolization, and percutaneous ethanol injection therapy for HCC. Despite treatment, viable regions remained in segments 4 and 8. We performed a right paramedian sectionectomy with partial resection of the left paramedian section of the liver. Six months later, serum concentrations of alpha-fetoprotein (189 ng/mL) and PIVKA-2 (507 mAU/mL) increased. Enhanced computed tomography of the abdomen revealed a tumor (20 mm in diameter) on the right side of the abdominal aorta. Fluorine-18 fluorodeoxyglucose positron emission tomography revealed an increased standard uptake value. There was no evidence of recurrence in other regions. Esophagogastroduodenoscopy and colonoscopy revealed no malignant tumor in the gastrointestinal tract. Para-aortic LN metastasis from HCC was thus diagnosed. We performed lymphadenectomy. Histopathological examination revealed that the tumor was largely necrotic, with poorly differentiated HCC on its surface, which confirmed the suspected diagnosis. After 6 mo tumor marker levels were normal, with no evidence of recurrence. Our experience suggests that a solitary para-aortic LN metastasis from HCC can be treated surgically.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor. We report on a patient who underwent hepatectomy for malignant HEH associated with abdominal pain due to rapid progression. An 83-year-old man was admitted to Nippon Medical School Hospital because of acute, severe upper abdominal pain. Seven months before admission, a hepatic tumor, 3 cm in diameter, had been detected in the left lateral sector. The diagnosis was hepatic cavernous hemangioma. Abdominal ultrasonography revealed a heterogeneous hyperechoic tumor with a smooth border, 6 cm in diameter, in the left lateral sector (segment 3). Contrast-enhanced computed tomography of the abdomen showed that the tumor was enhanced from the early to the late phase. Abdominal angiography revealed a cotton wool-like appearance of the tumor. The diagnosis was hepatic cavernous hemangioma. A malignancy could not be ruled out because of the tumor's rapid growth, which had caused abdominal pain. Left hepatectomy was performed. Histopathological examination showed necrosis throughout the tumor. Slightly pleomorphic neoplastic cells with rounded, spindle-like nuclei and scant cytoplasm were sporadically found in vascular channels. Intracytoplasmic lumina occasionally contained red cells. Neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34. The Mib-1 index was high. The tumor was diagnosed as malignant HEH. The postsurgical course was uneventful, and the patient was discharged on postoperative day 11. After 3 months, multiple metastatic tumors appeared in right hepatic lobe. Transcatheter arterial chemoembolization was performed.

Background Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. Methods The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. Results The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1–18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014–0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13–22.73; P = .03). Conclusion This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis.

Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction. We describe a patient with a huge caudate lobe of the liver due to Budd-Chiari syndrome. A 49-year-old woman was referred to Nippon Medical School Hospital to receive treatment for enlarged gastric varices. She had been followed up for idiopathic portal hypertension with deformity of the liver for 7 years and had undergone surgery for pharyngeal carcinoma 5 years earlier. Upper gastrointestinal endoscopy revealed solitary gastric varices without esophageal varices. Abdominal computed tomography revealed obstructions and scars of the right, middle, and left hepatic veins. The caudate lobe was enlarged, and the portal vein was displaced ventrally, without thrombus. The drainage vein of the caudate lobe, the short hepatic vein on the left side of the inferior vena cava, was dilated. The portal vein and drainage vein of segment 6 were visualized and showed no atrophy. Venography revealed no obstruction of the inferior vena cava. Budd-Chiari syndrome with solitary gastric varices was diagnosed on the basis of these findings. We performed balloon-occluded retrograde transvenous obliteration and partial splenic embolization to treat the gastric varices. The posttreatment course was uneventful, and the patient was discharged 8 days after embolization. The gastric varices shrank.

A 73-year-old man was admitted with bloody stool. Duodenoscopy showed a hemorrhagic ulceration in the duodenum on the side opposite to the papilla of Vater. Abdominal CT demonstrated a well-defined hypervascular mass, adjacent to the lesion of the duodenum. Although as duodenal GIST was diagnosed, histologic examination for frozen sections during the procedure revealed tubular adenocarcinoma of the duodenum and pancreaticoduodenal lymph node metastasis of neuroendocrine carcinoma. He underwent a subtotal stomach-preserving pancreaticoduodenectomy. Clinicopathologically, the neuroendocrine carcinoma of the pancreaticoduodenal lymph node was considered to be metastasis from an unknown primary lesion.

Systemic inflammatory response syndrome (SIRS), a serious clinical condition characterized by whole-body inflammation, is particularly threatening for elderly patients, who suffer much higher mortality rates than the young. A major pathological consequence of SIRS is acute lung injury caused by neutrophil-mediated oxidative damage. Previously, we reported an increase in protein tyrosine nitration (a marker of oxidative/nitrosative damage) and a decrease in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in the lungs of young mice during endotoxemia-induced SIRS. Here we demonstrate that during endotoxemia, down-regulation of EC-SOD is significantly more profound and prolonged, whereas up-regulation of iNOS is augmented, in aged compared to young mice. Aged mice also showed 2.5-fold higher protein nitration levels, compared to young mice, with particularly strong nitration in the pulmonary vascular endothelium during SIRS. Additionally, by two-dimensional gel electrophoresis, Western blotting, and mass spectrometry, we identified proteins that show increased tyrosine nitration in age- and SIRS-dependent manners; these proteins (profilin-1, transgelin-2, LASP 1, tropomyosin, and myosin) include components of the actin cytoskeleton responsible for maintaining pulmonary vascular permeability. Reduced EC-SOD in combination with increased oxidative/nitrosative damage and altered cytoskeletal protein function due to tyrosine nitration may contribute to augmented lung injury in the aged with SIRS.

We report a case of esophageal squamous cell carcinoma (ESCC) directly invading the liver and causing a pyogenic liver abscess. The patient was a 66-year-old man who presented with dysphagia. Esophagography, endoscopic study, and computed tomography (CT) showed a mass lesion in the lower third of the esophagus. A high fever developed on hospital day 17 and another CT scan revealed a liver abscess, 50 × 45 mm, in the left lateral lobe of the liver. Although imaging demonstrated a liver abscess continuous with the tumor, we performed percutaneous transhepatic drainage, followed thereafter by distal esophagectomy and total gastrectomy with a left lateral segmental resection of the liver. The pathological findings confirmed a diagnosis of ESCC with direct invasion (T4N1M0, stage IVa in the TNM classification). The patient had an uneventful postoperative recovery. Microscopic examination of the resected specimen revealed the expansive growth of tumor cells into the hepatocellular tissues. To our knowledge, this is the first report of the direct invasion of esophageal cancer to the liver causing a pyogenic liver abscess; however, it should be borne in mind when a patient with esophageal cancer becomes febrile.

Laparoscopic distal pancreatectomy (Lap-DP) is one of the most accepted laparoscopic procedures in the field of pancreatic surgery. However, pancreatic fistula remains a major and frequent complication in Lap-DP, as in open surgery. The aim of this retrospective study is to clarify the advantages of prolonged peri-firing compression (PFC) with a linear stapler for prevention of pancreatic fistula after laparoscopic distal pancreatectomy. Incidence of pancreatic fistula in clinical levels (equivalent to grades B and C defined by the International Study Group of Pancreatic Fistula (ISGPF)) was retrospectively compared between patients who underwent Lap-DP with PFC (PFC group, n = 17) and those who underwent Lap-DP without PFC (no-PFC group, n = 25). Incidence of clinical pancreatic fistula was significantly lower in the PFC group than in the no-PFC group. Consistent with the results for pancreatic fistula, peritoneal drainage period and postoperative hospital stay were shorter in the PFC group than in the no-PFC group. Our data show that PFC effectively prevents pancreatic fistula and shortens postoperative hospital stay after Lap-DP.

The authors point to the difficulty of assessing fiscal sustainability when revenues fluctuate sharply and unexpectedly. They note that in recent years tax revenues in Japan have been considerably unstable, so it is no longer appropriate to calculate the amount of structural tax revenue using a standard elasticity. The paper examines the fluctuation of Japan’s corporate tax revenue and its elasticity since 1980. In particular, it evaluates the role of structural and cyclical changes in the distribution of value-added, the relationship between interest rates and return on capital, asset price movements and return from foreign investment, the divergence of economic fluctuations among sectors and the deductions of carried-over losses. Finally, the paper discusses appropriate methods for the estimation of structural corporate tax revenue.

In bovine Mx1, only an amino acid substitution between Ile and Met at position 120 was detected by the nucleotide sequence and mismatched PCR-RFLP technique. The Ile variant was assumed to distribute mainly in the bovine population since the gene frequency was 79.3%. Furthermore, we cloned water buffalo Mx1 cDNA, which showed 51 nucleotide and 20 amino acid substitutions in comparison with that of the cow. Another kind of Mx1 cDNA, bovine Mx1B cDNA, was found and it was deduced to cause 27 amino acid substitutions at the N-terminus compared to the original Mx1 by alternative splicing. However, no variation was detected in 27 amino acids specific for Mx1B among 29 cows and a water buffalo. We established four kinds of mRNA-expressing 3T3 cells and Vero cells. When infection experiments were performed using recombinant vesicular stomatitis virus (VSVDeltaG*-G), bovine Ile and Met types and water buffalo Mx1 mRNA-expressing cell lines showed equally positive antiviral activities (p0.05). On the other hand, bovine Mx1B mRNA-expressing cell lines did not have activity against VSVDeltaG*-G. Intracellular localization of bovine Mx1 and Mx1B proteins was examined by a transiently GFP-fused expression system in 3T3 cells. Bovine Mx1 was localized in the cytoplasm, while bovine Mx1B was mainly localized in the nucleus. An arginine-rich nuclear localization signal was found in 27 amino acids specific for Mx1B. N-terminus-deleted Mx1B was only localized in the cytoplasm, and the deleted Mx1B-expressing cell lines showed significantly positive antiviral activities (p0.05) against VSVDeltaG*-G.

We describe a 71-year-old man with an inflammatory tumor arising in segment 5 of the liver. The patient was admitted because of acute pain in the right upper quadrant of the abdomen and fever. Initial laboratory tests revealed the following: serum alkaline phosphatase concentration, 634 IU/L; serum gamma glutamic transpeptidase concentration, 1,378 IU/L; serum C-reactive protein concentration, 0.89 mg/dL; and total bilirubin concentration, 8.9 mg/dL. Abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging showed a mass, 3 cm in diameter, in segment 5 of the liver. Magnetic resonance cholangiopancreatography showed a lesion of moderate-to-high signal intensity on T2-weighted images of segment 5. Endoscopic retrograde cholangiopancreatography revealed a common bile duct stone. The intrahepatic bile ducts of segment 5 could not be visualized after the use of contrast material. Endoscopic sphincterotomy was performed to remove the common bile duct stone. Antibiotics were administered soon after stone removal, and fever gradually resolved. Positron emission tomography revealed hot spots in segment 5 of the liver. Three weeks after discharge, the patient was readmitted with an acute pain in the right upper quadrant of the abdomen. Abdominal ultrasonography, CT, and magnetic resonance imaging showed enlargement of this area. Inflammatory changes of segment 5 due to cholangitis with intrahepatic bile duct stones was diagnosed. Because malignant disease could not be completely ruled out, segment 5 of the liver was resected. Macroscopic examination of the resected specimen revealed a gray, fibrotic, solid tumor associated with intrahepatic bile duct stones. Microscopic examination of the tumor showed proliferation of spindle-shaped myofibroblastic cells in a mixed myxoedematous, dense fibrotic stroma, associated with infiltration by various acute and chronic inflammatory cells. The postoperative course was uneventful, and the patient was discharged on postoperative day 16.