cyst; 4. adult; Presenting Author: ZHONG GAO WANG Additional Authors: ZHI WEI HU, JI MIN WU, JIAN JUN LIU, YU ZHANG, SHU RUI TIAN, GUANG CHANG ZHU, WEI TAO LIANG Corresponding Author: ZHONG GAO WANG Affiliations: Center for GERD, General Hospital of Second Artillery; Xuanwu Ivacaftor Hospital of Capital Medical University Objective: Childhood-to-adult persistent asthma is usually considered to be an atopic disease. However gastroesophageal reflux disease (GERD) may also play an important role in this phenotype of asthma. Methods: An investigation of 57 consecutive patients with decades of childhood-to-adult persistent asthmatic symptoms which were refractory to pulmonary medication.

GERD was assessed by endoscopy, reflux monitoring and manometry, and treated by Stretta radiofrequency (SRF) or laparoscopic Nissen fundoplication (LNF). The outcomes were followed up in January Autophagy inhibitor mw 2013 for an average of 3.3 ± 1.1 years. Results: Evident typical GERD symptoms, pathological acid reflux, and esophagitis were found in 51.9%, 64.9% and 47.4% of the patients. Meanwhile, Hiatus hernia (HH) was shown in 35.1% of the

patients; upper esophageal sphincter (UES) hypotonia, lower esophageal sphincter (LES) hypotonia, shortened LES and esophageal body dyskinesia were demonstrated by esophagus manometry in 50.9%, 43.9%, 35.1% and 45.6% of the patients respectively. The symptom score of heartburn, regurgitation, coughing, wheezing and chest tightness significantly decreased (P < 0.001) from 5.8 ± 2.0, Fluorouracil manufacturer 5.6 ± 2.0, 7.3 ± 1.6, 8.4 ± 1.2 and 8.1 ± 1.5 to 1.2 ± 1.8, 1.1 ± 1.6, 2.8 ± 2.5, 3.8 ± 2.7 and 3.9 ± 2.7 respectively after anti-reflux treatment. Cure, excellent, and good outcome in the overall asthma status were obtained in 7.0%, 31.6%

and 26.3% of the patients, while 21.1% and 14.0% of the patients had fair and poor response to the anti-reflux treatment. Conclusion: The prevalence esophagus dysfunction is high in GERD related childhood-to-adult persistent asthmatic patients who had inadequate response to medical treatment for asthma. The SRF and LNF are both effective in esophagus symptoms as well as GERD related persistent asthmatic symptoms. Evaluating the asthmatic patients for possible treatment of the underlying cause such as GER may improve symptoms and prevent disease persistency. Key Word(s): 1. GERD; 2. asthma; 3. radiofrequency; 4. fundoplication; Presenting Author: WEI LI Additional Authors: HUANONG LU Corresponding Author: HUANONG LU Affiliations: the First Affiliated Hospital of NanChang University Objective: Helicobacter pylori (H.pylori) is a major inducement of peptic ulcers, intestinal metaplasia (IM), dysplasia and gastric carcinoma (GC), whereas the exact pathological mechanism is still unknown. The present study was undertaken to determine possible pathological role of H.pylori in DNA damage response and repair pathways by establishing a H.pylori infected Mongolian gerbil model. We verified the hypothesis that chronic H.

In patients, Shc expression correlated with malignant potential and overall survival. Blocking Erk1/2 reduced proliferation and EMT-like changes of heat-treated HCC cells. Implantation of heat-exposed HEPG2 cells into nude mice induced significantly larger, more aggressive tumors than untreated cells. Conclusions: Sublethal heat treatment skews HCC cells toward EMT and transforms them to a progenitor-like, highly

proliferative cellular phenotype in vitro and in vivo, which is driven significantly by p46Shc-Erk1/2. Suboptimal RFA accelerates HCC growth and spread by transiently inducing an EMT-like, more aggressive cellular phenotype. (Hepatology 2013;58:1667–1680) Radiofrequency ablation (RFA) is Silmitasertib molecular weight accepted as a potentially curative therapy for the early stages of primary hepatocellular carcinoma (HCC).[1] RFA induces tumor necrosis with low complication rates and is superior to percutaneous ethanol injection in tumor Selleck PLX4032 ablation.[2] However, suboptimal RFA treatment for HCC has been reported as a risk factor of early diffuse recurrence.[3] Large tumor size is a major risk factor of local recurrence because of poorly defined margins.[4] Such recurrent HCC appears to behave more aggressively

than before RFA[5-8] and significantly reduces overall survival (OS) of HCC patients.[9] Phenotypic and functional alterations of HCC cells subjected to heat treatment have not been studied. Epithelial-mesenchymal transition (EMT) is thought to be a critical factor in progression of cancer and dictating metastasis. Several oncogenic pathways (such as those of growth and transcription factors, integrins, Wnt/β-catenin, and Notch) can induce EMT.[10] In particular, the Ras/extracellular signal-related kinase (Erk)1/2 pathway has been shown to activate two EMT-related transcription factors, else namely, Snail and Slug.[11] A recent clinical study has shown a correlation of Snail transcript levels with

capsular and portal invasion of HCC.[12] Other inducers of EMT in HCC are TWIST1 and CHD1L.[13, 14] Moreover, expression of type I procollagen (COL1A1) is a useful marker of transition to a mesenchymal phenotype.[15] Src homology and collagen (Shc) is a central SH2-containing cytoplasmic adaptor protein, which directly binds to tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor beta (PDGFRβ), insulin-like growth factor 1 receptor (IGF-1R), and fibroblast growth factor receptor (FGFR). Notably, Shc is a central player in malignant transformation.[16-20] Mitogenic, transforming, and proinvasive signal transduction from Shc to mitogen-activated protein kinases (MAPKs) by Grb2-Sos has been well studied,[21-23] with p46-Shc and p52-Shc being central upstream regulators of MAPK activation, whereas the alternatively spliced p66-Shc isoform appears to promote apoptosis.

[9] Four of the six had evidence of gastric varices

on imaging studies. One of these had presented with hematemesis from gastric varices and another patient had findings of portal hypertensive gastropathy on endoscopic evaluation. Takahashi et al. reported vascular involvement in 44% (11/25) of AIP patients.[10] In this issue of the Journal, these findings are extended by Ishikawa et al. who report on the prevalence and long term outcome of peripancreatic vascular involvement in 54 AIP p38 MAPK activation patients.[11] Peripancreatic vascular involvement of any form was observed using multidetector computed tomography (CT) scan in 24 (44%) patients. There was occlusion or stenosis of splenic vein in 22, superior mesenteric or portal veins in 13, and development of collaterals in 18 patients. This prevalence is higher than reported by our group,[9] but similar to that of the Mayo group.[10] The difference may be due to a broader definition for vascular involvement. CP-673451 mw The only patient characteristic increasing the risk of vascular involvement was diffuse

enlargement of the pancreas (56 versus 22%). Corticosteroid treatment was administered to 20 of the 24 patients with vascular involvement who also had symptoms (jaundice or abdominal pain). On a follow-up CT scan, improvement in vascular lesions, including resolution of portal vein thrombosis, was seen in 14 of 16 patients treated with steroids. Of the four patients with vascular involvement who did not receive treatment, interval worsening of vascular lesions occurred in two, while no change was seen in the other two patients. Among patients who did not receive steroids, new vascular lesions were not detected in any

patient who had a follow up CT scan. The pathogenesis of vascular involvement in AIP remains unclear. Similar to pancreatitis from other causes, a pre-existing hypercoagulable factor does not appear to play a role.[9, 11] One possible explanation is the extension of inflammatory changes from the pancreas to the surrounding vessels. This possibility is supported by the preferential involvement of vessels in close proximity to the inflamed pancreas. It is important to note that AIP patients Rucaparib typically do not develop pancreatic necrosis or pancreatic/peripancreatic fluid collections. The other possibility is involvement of vessels by the primary inflammatory process typical for IgG4 related systemic disorder. Although Ishikawa et al. did not find this to be present in the patient who underwent pancreatic resection,[11] Kamisawa et al. have demonstrated obliterative phlebitis in pancreatic and peripancreatic veins in resection specimens of AIP patients.[8] In addition to defining the pathogenesis and factors that determine vascular involvement, there are three other questions that should be answered by future investigations.

[9] Four of the six had evidence of gastric varices

on imaging studies. One of these had presented with hematemesis from gastric varices and another patient had findings of portal hypertensive gastropathy on endoscopic evaluation. Takahashi et al. reported vascular involvement in 44% (11/25) of AIP patients.[10] In this issue of the Journal, these findings are extended by Ishikawa et al. who report on the prevalence and long term outcome of peripancreatic vascular involvement in 54 AIP Navitoclax purchase patients.[11] Peripancreatic vascular involvement of any form was observed using multidetector computed tomography (CT) scan in 24 (44%) patients. There was occlusion or stenosis of splenic vein in 22, superior mesenteric or portal veins in 13, and development of collaterals in 18 patients. This prevalence is higher than reported by our group,[9] but similar to that of the Mayo group.[10] The difference may be due to a broader definition for vascular involvement. selleckchem The only patient characteristic increasing the risk of vascular involvement was diffuse

enlargement of the pancreas (56 versus 22%). Corticosteroid treatment was administered to 20 of the 24 patients with vascular involvement who also had symptoms (jaundice or abdominal pain). On a follow-up CT scan, improvement in vascular lesions, including resolution of portal vein thrombosis, was seen in 14 of 16 patients treated with steroids. Of the four patients with vascular involvement who did not receive treatment, interval worsening of vascular lesions occurred in two, while no change was seen in the other two patients. Among patients who did not receive steroids, new vascular lesions were not detected in any

patient who had a follow up CT scan. The pathogenesis of vascular involvement in AIP remains unclear. Similar to pancreatitis from other causes, a pre-existing hypercoagulable factor does not appear to play a role.[9, 11] One possible explanation is the extension of inflammatory changes from the pancreas to the surrounding vessels. This possibility is supported by the preferential involvement of vessels in close proximity to the inflamed pancreas. It is important to note that AIP patients Adenosine typically do not develop pancreatic necrosis or pancreatic/peripancreatic fluid collections. The other possibility is involvement of vessels by the primary inflammatory process typical for IgG4 related systemic disorder. Although Ishikawa et al. did not find this to be present in the patient who underwent pancreatic resection,[11] Kamisawa et al. have demonstrated obliterative phlebitis in pancreatic and peripancreatic veins in resection specimens of AIP patients.[8] In addition to defining the pathogenesis and factors that determine vascular involvement, there are three other questions that should be answered by future investigations.

[9] Four of the six had evidence of gastric varices

on imaging studies. One of these had presented with hematemesis from gastric varices and another patient had findings of portal hypertensive gastropathy on endoscopic evaluation. Takahashi et al. reported vascular involvement in 44% (11/25) of AIP patients.[10] In this issue of the Journal, these findings are extended by Ishikawa et al. who report on the prevalence and long term outcome of peripancreatic vascular involvement in 54 AIP Wnt inhibitors clinical trials patients.[11] Peripancreatic vascular involvement of any form was observed using multidetector computed tomography (CT) scan in 24 (44%) patients. There was occlusion or stenosis of splenic vein in 22, superior mesenteric or portal veins in 13, and development of collaterals in 18 patients. This prevalence is higher than reported by our group,[9] but similar to that of the Mayo group.[10] The difference may be due to a broader definition for vascular involvement. Opaganib mw The only patient characteristic increasing the risk of vascular involvement was diffuse

enlargement of the pancreas (56 versus 22%). Corticosteroid treatment was administered to 20 of the 24 patients with vascular involvement who also had symptoms (jaundice or abdominal pain). On a follow-up CT scan, improvement in vascular lesions, including resolution of portal vein thrombosis, was seen in 14 of 16 patients treated with steroids. Of the four patients with vascular involvement who did not receive treatment, interval worsening of vascular lesions occurred in two, while no change was seen in the other two patients. Among patients who did not receive steroids, new vascular lesions were not detected in any

patient who had a follow up CT scan. The pathogenesis of vascular involvement in AIP remains unclear. Similar to pancreatitis from other causes, a pre-existing hypercoagulable factor does not appear to play a role.[9, 11] One possible explanation is the extension of inflammatory changes from the pancreas to the surrounding vessels. This possibility is supported by the preferential involvement of vessels in close proximity to the inflamed pancreas. It is important to note that AIP patients Etomidate typically do not develop pancreatic necrosis or pancreatic/peripancreatic fluid collections. The other possibility is involvement of vessels by the primary inflammatory process typical for IgG4 related systemic disorder. Although Ishikawa et al. did not find this to be present in the patient who underwent pancreatic resection,[11] Kamisawa et al. have demonstrated obliterative phlebitis in pancreatic and peripancreatic veins in resection specimens of AIP patients.[8] In addition to defining the pathogenesis and factors that determine vascular involvement, there are three other questions that should be answered by future investigations.

Early hepatocellular carcinomas with a high incidence of iso-density or low density (signal) areas throughout the arterial, portal and equilibrium phases (LF1213816

level 1), hepatocellular carcinoma with a nodule-in-nodule finding (LF1214517 level 1), and dysplastic nodules (LF1214018) were not included in the studies. Of the articles adopted this time, the histological diagnostic criteria for hepatocellular carcinoma were mentioned in five articles. Three articles (LF121031 level 1, LF105467 level 1, LF0620011 level 1) cited the International Working Party (LF1214018), and two articles (LF058794 level 1, LF020016 level 1) made a reference to the diagnostic criteria established by Ferrell et al. (LF1213919

level 1). Of the three articles on lipiodol CT, only lipiodol was used in two studies (LF058794 level 1, LF103715 level 1), selleck compound and lipiodol plus anticancer drug plus/minus gelatin sponge were used in the third study (LF004742 level 1). With regard to the diagnostic performance of each diagnostic imaging technique, the merits and demerits of studies using isolated or resected livers as the gold standards may be as follows: (1) Usually, the sensitivity is higher for resected livers than for VX-809 solubility dmso isolated livers. This is probably attributable to small cancer nests not being identifiable at the time of surgery but being found in the explanted livers. More sensitive diagnosis is considered to be possible in isolated livers. However, (2) the time Anidulafungin (LY303366) from the final imaging test to liver transplantation (range : 32 days to 6 months, Table 1) is generally longer than that from the final imaging to resection. If a new focus develops during the waiting period for transplantation, the preoperative diagnostic imaging examination may have yielded a false-negative

result, reducing the sensitivity of diagnosis. (3) The main candidates for liver transplantation in Western countries are patients with advanced cirrhosis (Child–Pugh class C), and hepatocellular carcinoma is only a secondary indication. The diagnostic performance of imaging decreases as the severity of cirrhosis increases. Whereas, hepatectomy is often performed in patients with good liver function (Child–Pugh class A). (4) A section of resected liver and a CT/MRI image plane can be compared relatively easily, whereas it is difficult to maintain an isolated liver in a 3-D anatomical form as it is in the body after explantation. Therefore, comparison with CT/MRI is not always easy. (5) The slice thickness of an isolated liver tends to be generally thicker than that of a resected liver, and small lesions may be missed in thicker slices.

Early hepatocellular carcinomas with a high incidence of iso-density or low density (signal) areas throughout the arterial, portal and equilibrium phases (LF1213816

level 1), hepatocellular carcinoma with a nodule-in-nodule finding (LF1214517 level 1), and dysplastic nodules (LF1214018) were not included in the studies. Of the articles adopted this time, the histological diagnostic criteria for hepatocellular carcinoma were mentioned in five articles. Three articles (LF121031 level 1, LF105467 level 1, LF0620011 level 1) cited the International Working Party (LF1214018), and two articles (LF058794 level 1, LF020016 level 1) made a reference to the diagnostic criteria established by Ferrell et al. (LF1213919

level 1). Of the three articles on lipiodol CT, only lipiodol was used in two studies (LF058794 level 1, LF103715 level 1), Alisertib and lipiodol plus anticancer drug plus/minus gelatin sponge were used in the third study (LF004742 level 1). With regard to the diagnostic performance of each diagnostic imaging technique, the merits and demerits of studies using isolated or resected livers as the gold standards may be as follows: (1) Usually, the sensitivity is higher for resected livers than for check details isolated livers. This is probably attributable to small cancer nests not being identifiable at the time of surgery but being found in the explanted livers. More sensitive diagnosis is considered to be possible in isolated livers. However, (2) the time over from the final imaging test to liver transplantation (range : 32 days to 6 months, Table 1) is generally longer than that from the final imaging to resection. If a new focus develops during the waiting period for transplantation, the preoperative diagnostic imaging examination may have yielded a false-negative

result, reducing the sensitivity of diagnosis. (3) The main candidates for liver transplantation in Western countries are patients with advanced cirrhosis (Child–Pugh class C), and hepatocellular carcinoma is only a secondary indication. The diagnostic performance of imaging decreases as the severity of cirrhosis increases. Whereas, hepatectomy is often performed in patients with good liver function (Child–Pugh class A). (4) A section of resected liver and a CT/MRI image plane can be compared relatively easily, whereas it is difficult to maintain an isolated liver in a 3-D anatomical form as it is in the body after explantation. Therefore, comparison with CT/MRI is not always easy. (5) The slice thickness of an isolated liver tends to be generally thicker than that of a resected liver, and small lesions may be missed in thicker slices.

Then, saline, 5×104, 2×105, or 1×106 freshly isolated (no expansion) and expanded CD34+ cells/kg body weight were transplanted via spleen, respectively. The administration of CCl4 was continued for three more weeks until the rats were sacrificed. Examination items were as follows. 1)FACS, real-time PCR and gene array analysis of freshly isolated and expanded CD34+ cells, 2) morphometry AZD0530 chemical structure of fibrotic areas in Azan-Mallory stained liver, 3) immunohistochemistry using anti-α-smooth

muscle actin (SMA), CD31, keratin19, albumin and PCNA antibodies, and 4) the expression of metalloproteinase and tissue inhibitor of metalloproteinase-1 by gelatin zymography and real-time PCR. Results: For 7 days in culture, CD34+ cells were effectively expanded to 8-fold. Increased expression of VE-cadherin, KDR and Tie2 was determined by FACS analysis. The expression of VEGF, transforming growth factor-α, fibroblast growth factor-2, endothelial nitric oxide synthase and angiopoietin-2

in expanded CD34+ cells was increased compared with that in freshly isolated CD34+ cells. Gene array analysis showed that the most up-regulated gene in expanded CD34+ cells compared with freshly isolated CD34+ cells was integrin-3β. Expanded CD34+ cell transplantation reduced liver fibrosis with the decrease of αSMA positive cells. The transplanted cells differentiated into CD31+ and smooth myosin heavy chain-1+ cells. The transplantation of expanded CD34+ cells significantly up-regulated the number of PCNA positive hepatocyte compared with the transplantation of freshly isolated CD34+ in 3 different groups of cell number, respectively. Conclusion: Lapatinib These observations suggest that ex vivo expanded CD34+ cell transplantation may become a promising therapeutic strategy for patients with decompensated liver cirrhosis. Disclosures: Michio Sata – Speaking and Teaching: MSD K. K., Chugai Aspartate Pharmaceutical Co., The following people have nothing to disclose:

Toru Nakamura, Takuji Torimura, Hiroshi Masuda, Hideki Iwamoto, Hironori Koga, Mitsuhiko Abe, Yu Ikezono, Osamu Hashimoto, Takato Ueno Hepatocyte transplantation is a potential treatment for a myriad of liver disorders that are currently only curable by liver transplantation. A major limiting factor of hepatocyte transplantation is an inability to non-invasively and longitudinally monitor engraftment and expansion of transplanted cells. We hypothesized that the sodium iodide symporter (NIS) gene could be used to visualize transplanted hepatocytes and set out to test this reporter system in a rodent model of liver repopulation. FAH+ C57BI/6J mouse hepatocytes were transduced ex vivo using a lentiviral vector containing the mouse Slc5a5 (NIS) gene under the control of a liver specific promoter. Transduction efficiencies of 70-80% were achieved and NIS-labeled cells could robustly concentrate radiolabeled iodine in vitro.

Patients were fairly evenly apportioned between each of the three survival groups, each group having a similar

percentage of males to females. There was a slightly higher proportion of patients in the poor survival group with higher alcohol intake and with cirrhosis and with ascites, a consequence of cirrhosis. Likewise, the poorer survival group had patients with slightly larger tumors and numbers of http://www.selleckchem.com/products/sch772984.html tumors. However, the incidence of PVT was similar in all three survival groups. Most significantly, the poorer survival group had the highest GGTP levels and the highest AFP levels, even though the AFP range was quite low, with all being <400 ng/mL. GGTP levels thus seem to distinguish between worse and better tumor Selleckchem Alvelestat phenotypes, even in this relatively low AFP range. We found a broadly bi-linear correlation of serum AFP with bilirubin levels, as shown in Figure 3. This observation emphasizes novel information that

can be extracted from the study of inter-correlations between the various clinical parameter values. The most important observation in Figure 3a is a clearly discernible change in the trends of the AFP to bilirubin relationship for AFP levels below and above 15 ng/mL. For the lower part of the AFP interval, patients are typically with normal bilirubin and the bilirubin level does not increase with increasing AFP levels. By contrast, when AFP levels are above 15 ng/mL, patient bilirubin levels start to increase, correlating linearly with the increasing AFP levels. Figure 3b shows the Kaplan–Meier representation of the survival in the two patient subgroups defined by this novel, trend-identified threshold, and shows that there is a significant difference in the survival for these subgroups. This correlation also explains why bilirubin levels did not feature in our scoring system, since bilirubin levels remain typically normal and constant (i.e. non-informative) for the AFP < 15 ng/mL subgroup, while in the AFP > 15 ng/mL subgroup, the prognostic information in bilirubin levels is represented by the AFP levels, due to the linear correlation between the

two parameter levels. These patient groupings are shown in summary form in Table 2, which provides a guide to survival estimation Bcl-w for these unresectable HCC patients with low AFP levels at presentation. In the last 15 years, several scoring and staging systems have been proposed and tested, to enhance the original idea of Okuda1 that both tumor factors and liver factors need to be taken into account, to assess disease extent, treatability and survival. Some have focused on treatment selection,3 but all are concerned with prognostication. Several of them have incorporated AFP levels, but most studies on HCC survival after therapy include AFP levels, including resection,5,9 liver transplant19 and chemoembolization studies.

While haemophilia

A and B are characterized by haemorrhages into joints and muscle, it is notable that bleeding occurs frequently into skeletal, but rarely cardiac muscle. This observation suggests that the clotting system does not function in an identical fashion in all vascular beds, even within organs with seemingly analogous physiological functions. Mice expressing low levels of TF (≈1% FDA approved Drug Library of normal; sufficient to avoid the intra-uterine lethality associated with complete deficiency [8]) have contributed to our understanding of the role of vessel wall TF in haemophilic patterns of bleeding. Specifically, in the perivascular space of normal mice and humans, TF is abundant in the heart, lung, brain, testis, uterus and placenta, click here but not in joints or skeletal muscle. However, these ‘low TF’ mice – as well as those

lacking factor VII expression – develop age-dependent bleeding into the heart, lungs, brain, testis, uterus and placenta [9]. Collectively, these observations suggest that haemostasis in joints and skeletal muscles is critically dependent on factors VIII (FVIII) and IX (FIX), whereas the ‘extrinsic pathway’ comprising TF and FVIIa is more pertinent in the maintenance of haemostasis in other organs, such as the heart [10]. Factor VIII is normally produced by specialised endothelium such as sinusoidal endothelial cells in the liver [11]. Utilizing gene transfer or cellular therapy, successful targeting of FVIII expression to this specialized form of endothelium has been achieved in mouse models of haemophilia A [12,13], although equally satisfactory haemostatic outcomes can be obtained by non-selective endothelial expression of FVIII [14,15]. On the other hand, mice engineered to express mutant FIX that fails to bind to collagen

type IV (while retaining normal procoagulant activity in standard clotting assays) exhibit a mild haemorrhagic phenotype [16]. This observation is likely explained by the fact that the full haemostatic effect of FIX is partially dependent on its binding to sub-endothelial collagen IV, but it remains unclear whether haemostasis is equally impaired in all vascular beds. Finally, the vessel wall contribution to heptaminol haemostasis offers some special opportunities and challenges in the development of bypassing therapies for haemophilic patients with inhibitors. High-dose recombinant factor FVIIa probably works primarily through TF-independent activation of factor X. However, abnormal endothelial expression of TF in the patient with atherosclerotic disease (or possibly sepsis) may pose a risk of thrombosis. It remains to be seen whether other emerging bypassing therapies, such as those that inhibit TF pathway inhibitor [17], exhibit a favourable risk–benefit profile in haemophilia, particularly in the presence of abnormal vessel wall TF expression.