ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionMassive bleeding may complicate the course of either acute or chronic pancreatitis. Although the latter is more frequently involved when bleeding occurs in the acute form, a poorer prognosis is to be expected. Abscess, severe inflammation, regional necrosis, and pseudocysts may cause major vessel erosion, with or without pseudoaneurysm formation, whose eventual rupture may result in massive bleeding into the gastrointestinal tract, retroperitoneum, and peritoneal cavity.AimsTo define the most important pathophysiologic mechanisms and factors that might contribute to a better understanding, better prevention, and more efficient treatment of severe hemorrhage complicating acute necrotizing pancreatitis. Awareness of high-risk conditions occurring during the natural evolution of the disease (from extensive local severe enzymatic damage to late septic sequelae), avoidance of a too early and too aggressive approach to sterile pancreatic necrosis, and providing prompt and effective treatment of local septic complications, when they occur, are crucial steps for bleeding prevention.MethodologyForty-four cases of severe bleeding following acute pancreatitis that were reported during the last decade since 1992 (including the six cases reported here) are reviewed, analyzed, and summarized.ResultsThe overall mortality rate was 34.1%. Splenic artery, portal vein, spleen, and unspecified peripancreatic vessels were the most commonly involved sources of bleeding, with associated mortality rates of 33.3%, 50.0%, 30%, and 28.5%, respectively. Massive hemorrhage was more frequently associated with severe necrosis, with a mortality rate of 37.9%.ConclusionThe increased use of diagnostic and interventional radiology, in association with prompt surgical treatment, appears to be the way to improve survival rates in cases of arterial bleeding. Venous bleeding due to lesion of major peripancreatic veins or diffuse bleeding represents a therapeutic challenge, and treatment of these conditions should be tailored to the individual case, as no general rule can be suggested. In extreme cases, open packing or salvage emergency pancreatectomy may represent the only chances for survival.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionProinflammatory cytokines act as mediators of the local and systemic manifestations of acute pancreatitis (AP).AimsTo investigate whether moderate hypothermia (MH) (32°C) can reduce the severity of AP by inhibiting cytokine production in a rat model of caerulein-induced pancreatitis.MethodologyRats were divided into three groups: control rats (Group I), AP rats treated with normothermia (38°C) (Group II), and AP rats treated with MH (Group III). AP was induced by intramuscular injection of caerulein and intraperitoneal infusion of lipopolysaccharide. MH was induced 4 hours after the first caerulein injection. Serum interleukin (IL)-1&bgr;, tumor necrosis factor (TNF)-&agr;, IL-6, amylase, and lipase levels were determined 8 hours after the first injection. The pancreas and lung were examined histologically.ResultsMH in comparison with normothermia significantly reduced serum levels of IL-1&bgr;, TNF-&agr;, IL-6, amylase, and lipase. Histologically, the MH group showed less vacuolization of the acinar cells and cellular infiltration into the interacinar areas of the pancreas than were shown in the normothermia group, but these effects were not evident in the lung.ConclusionOur results suggest that MH may be clinically applicable for reducing the severity of AP.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Introduction and AimsWe examined the effects of a weak base, chloroquine, on the trypsinogen processing in cerulein-induced pancreatitis.MethodologyImmunofluorescence studies were performed using newly generated affinity-purified antibodies to the trypsinogen activation peptide (TAP).ResultsThe present study showed that chloroquine pretreatment blocked intracellular TAP generation in cerulein-induced pancreatitis.ConclusionThese results indicate that intracellular trypsinogen activation, which plays an important role in acute pancreatitis, requires a low-pH compartment, as well as serine protease activity.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionGap junctional intercellular communication has been implicated in the homeostatic regulation of cell growth, differentiation, and apoptosis. Cancer cells, which have been viewed as “partially blocked stem cells,” and which lack the ability for growth control, terminal differentiation, and apoptosis, also lack functional gap junctional communication.Aims and MethodologyA clone of a human pancreatic ductal epithelial cell line, H6c7, derived after immortalization with human papilloma virus, was used to examine gap junctional intercellular communication and the ability to differentiate under different growth conditions.ResultsThe cells showed characteristic epithelial morphology on standard tissue culture dishes. When placed on Matrigel they showed phenotypical changes with extensive ductal organization and budding structures. In growth medium containing hormones and growth factors, these cells were gap junctional intercellular communication (GJIC)–incompetent. In the presence of c-AMP elevating agents, isobutylmethylxanthine, and forskolin, in basal medium that did not contain the hormones and growth factors, the cells became GJIC-competent and expressed connexin43 gap junction protein within 48 hours after treatment. RT-PCR analyses of the cells under different growth conditions showed that the cells expressedconnexin 32, 36, and43genes when cultured in the basal medium with c-AMP elevating agents. They also expressed theconnexin 45gene that did not change with c-AMP treatment. H6c7 cells also have the capacity to turn on an ectopic insulin promoter reporter gene.ConclusionOur data suggest that the immortalized H6c7 cells retain stem-like characteristics and have the potential to differentiate into duct-like structures and perhaps insulin-producing cells.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionChronic pancreatitis is a significant risk factor for pancreatic cancer and is associated with the generation of reactive oxygen species. Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. There are three major types of primary intracellular antioxidant enzymes in mammalian cells: superoxide dismutase (SOD), catalase, and peroxidase, of which glutathione peroxidase is the most prominent.AimTo determine the level of antioxidant enzymes in human pancreas from normal, chronic pancreatitis, and pancreatic cancer specimens.MethodologyImmunohistochemical analysis for manganese SOD, copper/zinc SOD, catalase, and glutathione peroxidase expression using the avidin–biotin–peroxidase complex method was performed on pancreatic specimens previously fixed in formalin and embedded in paraffin. A quantitative digital imaging methodology was used to examine antioxidant staining in the pancreatic tissue. Cytoplasmic regions of ductal and acinar cells were identified and digitized. Mean gray-level pixel values were then obtained for each of these regions.ResultsCytoplasmic values of manganese SOD, catalase, and glutathione peroxidase were decreased in pancreatic cells from chronic pancreatitis specimens when compared with normal pancreas. In pancreatic carcinoma specimens, mean cytoplasmic gray-level values of all antioxidant enzymes were decreased when compared with normal pancreas.ConclusionThere appears to be a gradual decrease in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionAfrican Americans have a higher incidence of pancreatic adenocarcinoma than do Caucasians for unknown reasons. Whether other clinicopathologic differences exist between these two groups is not known. This study was undertaken to compare the clinical, pathologic, and biologic findings for a group of patients with a histologic diagnosis of pancreatic ductal adenocarcinoma of the usual type in a single institution.MethodologyWe studied 410 patients (166 African Americans and 244 Caucasians) with a histologic diagnosis of pancreatic ductal adenocarcinoma of the usual type and analyzed (a) the clinicopathologic characteristics of the tumors, (b) the immunohistochemical expression of biomarkers implicated in pancreatic carcinogenesis (Fas, Fas ligand, HER2, p21/waf-1, p27, and p53), and (c) the presence and types of K-rasmutations at codon 12 as determined by polymerase chain reaction–mediated amplification. All elements of data were not available for all patients.ResultsAfrican Americans had significantly higher rates of K-rasmutations to valine than did Caucasians (58% versus 22%, respectively;p= 0.015) and were less likely to have received chemotherapy (45% versus 70%, respectively;p= 0.001) or radiation therapy (34% versus 57%, respectively;p= 0.003). African Americans also had more frequent positive surgical margins than did Caucasians (56% versus 25%, respectively;p= 0.001), although mean tumor size was similar between the two groups (African Americans, 3.4 cm; Caucasians, 3.5 cm). Other clinicopathologic variables were similar between the two groups, including median survival (African Americans, 8.5 months; Caucasians, 10.1 months), 5-year survival (African Americans, 3%; Caucasians, 6%), and stage at presentation. Differences in biomarker immunoreactivity included less frequent Fas expression (4% versus 24%, respectively;p= 0.048) and a trend toward more frequent strong HER2 expression (39% versus 18%, respectivelyp= 0.11) in African Americans than in Caucasians.ConclusionAlthough African American and Caucasian patients had similar survival rates associated with usual type pancreatic ductal adenocarcinoma, there were differences in management and expression of biologic markers between these two groups. African Americans were significantly less likely to receive radiation therapy or chemotherapy than were Caucasians, which may assume more importance as treatment improves. At the molecular level, African Americans had more frequent K-rasmutations to valine than did Caucasians.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionSelective cyclooxygenase-2 (COX-2) inhibition reduces the growth of many cancer cell lines, and this effect may be mediated through induction of apoptosis. This study was designed to investigate the effects of the COX-2 inhibitor nimesulide on the growth of human pancreatic cancer cells.MethodologyReverse transcriptase–polymerase chain reaction analysis, northern blotting, and immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering, and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by measuring caspase-3 cellular activity and by determining the effects of two caspase inhibitors on cell viability.ResultsCOX-2 mRNA was detected in both cell lines. Immunoblotting confirmed COX-2 protein expression in only the BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth in both cell lines. Incubation with 100 &mgr;mol/L nimesulide increased the fraction of apoptotic cells and the floating cell/attached cell ratio in both cell lines. DNA laddering was observed after incubation with nimesulide for 96 hours. There was no increase in caspase-3 activity within 96 hours.ConclusionThe selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer cells, which is independent of COX-2 expression. This effect in part is mediated by the induction of apoptosis.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Introduction and AimsSerous and mucinous cystic pancreatic tumors have different clinical behavior. We evaluated whether they also have genotypic differences by analyses of the tumor suppressor genesp16INK4a,p53, andDPC4.MethodologySeven serous cystadenomas (SCA) and seven malignant mucinous cystadenocarcinomas (MCC) were analyzed for alterations in the tumor suppressor genesp16INK4a,p53, andDPC4by single-strand conformational variant analysis, direct sequencing, and immunohistochemical analysis. Methylation-specific polymerase chain reaction analysis was performed to identifyp16INK4apromoter hypermethylation. Clinical data were compared with genetic data.ResultsNone of the seven patients with SCAs but five of the seven patients with MCCs died of the tumor after a median follow-up of 44.5 months (range, 4–169 months). All seven MCCs had alterations in at least one tumor suppressor gene compared with none of the seven SCAs. Of the seven MCCs, three had inactivatingp16INK4apromoter hypermethylation, five hadp53alterations, and three hadDPC4mutations.ConclusionsThe tumor suppressor genesp16INK4a,p53, andDPC4appear to play an important role in the tumorigenesis of MCCs but not SCAs. These molecular data underscore the clinical and histologic differences of serous and mucinous cystic pancreatic tumors.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

IntroductionReceptor-binding cancer antigen expressed on SiSo cells (RCAS1) is one of the membrane molecules expressed on human cancer cells and is presumed to play a protective role for tumor cells against immune surveillance by inhibition of clonal expansion and induction of cell death in immunocytes.AimsTo address whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic evaluation is useful compared with that of carbohydrate antigen 19–9 (CA19–9) and soluble Fas ligand.MethodologyImmunohistochemical expression of RCAS1 was examined by staining with a 22–1-1 monoclonal antibody, and serum RCAS1 concentrations were determined by an enzyme-linked immunosorbent assay in 20 cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases.ResultsImmunohistochemically, RCAS1 detection occurred in 100% (20/20) of ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary–mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with chronic pancreatitis (p< 0.0001), acute pancreatitis (p< 0.005), and autoimmune pancreatitis (p< 0.001). RCAS1 concentrations in patients with intraductal papillary–mucinous adenoma of the pancreas were also significantly higher than those in patients with chronic pancreatitis (p< 0.05) and autoimmune pancreatitis (p< 0.05). Positive serum RCAS1 samples (concentration, ≥10 U/mL) were found most often in cases of pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60% [3/5], intraductal papillary–mucinous adenoma of the pancreas). By contrast, in cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4% (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19–9 for ductal adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was higher than that of CA19–9. Serum soluble Fas ligand concentrations were not considerably different among these patients.ConclusionsRCAS1 was highly expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with other inflammatory pancreatic diseases. Our results indicate that serum RCAS1 concentrations could be a new marker in screening procedures for pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:2003

数据来源: OVID