Showing papers on "Pancreatitis published in 2000"
TL;DR: Analysis of the gene encoding the serine protease inhibitor, Kazal type 1, a pancreatic trypsin inhibitor, indicates that mutations in SPINK1 are associated with chronic pancreatitis.
Abstract: Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.
952 citations
TL;DR: These results support nonsurgical management, including early antibiotic treatment, in patients with sterile pancreatic necrosis, and for them surgical treatment seems preferable.
Abstract: Objective
To determine benefits of conservative versus surgical treatment in patients with necrotizing pancreatitis.
755 citations
TL;DR: These experiments provide the first conclusive evidence to the authors' knowledge that cathepsin B plays a role in intrapancreatic trypsinogen activation and the onset of acute pancreatitis.
Abstract: Autodigestion of the pancreas by its own prematurely activated digestive proteases is thought to be an important event in the onset of acute pancreatitis. The mechanism responsible for the intrapancreatic activation of digestive zymogens is unknown, but a recent hypothesis predicts that a redistribution of lysosomal cathepsin B (CTSB) into a zymogen-containing subcellular compartment triggers this event. To test this hypothesis, we used CTSB-deficient mice in which the ctsb gene had been deleted by targeted disruption. After induction of experimental secretagogue‐induced pancreatitis, the trypsin activity in the pancreas of ctsb ‐/‐ animals was more than 80% lower than in ctsb +/+ animals. Pancreatic damage as indicated by serum activities of amylase and lipase, or by the extent of acinar tissue necrosis, was 50% lower in ctsb ‐/‐ animals. These experiments provide the first conclusive evidence to our knowledge that cathepsin B plays a role in intrapancreatic trypsinogen activation and the onset of acute pancreatitis. J. Clin. Invest. 106:773‐781 (2000).
530 citations
TL;DR: The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies.
Abstract: Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.
497 citations
TL;DR: Modeling and familial clustering suggest that SPINK1 mutations are disease modifying, possibly by lowering the threshold for pancreatitis from other genetic or environmental factors, but by themselves do not cause disease.
478 citations
TL;DR: The results suggest that local mediator release, with a probable IL-1β-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators.
Abstract: Background—The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown. Patients and methods—In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)1‚, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1‚ receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured. Results—Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1‚/ IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure. Conclusion—Our results suggest that local mediator release, with a probable IL-1‚-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP. (Gut 2000;47:546‐552)
362 citations
TL;DR: EUS-FNAB is a useful and safe method for the investigation of pancreatic masses, with a high feasibility rate even when lesions are small, and overall diagnostic accuracy seems to depend on the tumour type.
Abstract: Aim—To assess the feasibility and diagnostic accuracy of endoscopic ultrasound guided fine needle biopsy (EUS-FNAB) in patients with solid pancreatic masses. Methods—Ninety nine consecutive patients with pancreatic masses were studied. Histological findings obtained by EUS-FNAB were compared with the final diagnosis assessed by surgery, biopsy of other tumour site or at postmortem examination, or by using a combination of clinical course, imaging features, and tumour markers. Results—EUS-FNAB was feasible in 90 patients (adenocarcinomas, n = 59; neuroendocrine tumours, n = 15; various neoplasms, n = 6; pancreatitis, n = 10), and analysable material was obtained in 73. Tumour size (> or < 25 mm in diameter) did not influence the ability to obtain informative biopsy samples. Diagnostic accuracy was 74.4% (adenocarcinomas, 81.4%; neuroendocrine tumours, 46.7%; other lesions, 75%; p<0.02). Overall, the diagnostic yield in all 99 patients was 68%. Successful biopsies were performed in six patients with portal hypertension. Minor complications (moderate bleeding or pain) occurred in 5% of cases. Conclusions—EUS-FNAB is a useful and safe method for the investigation of pancreatic masses, with a high feasibility rate even when lesions are small. Overall diagnostic accuracy of EUS-FNAB seems to depend on the tumour type. (Gut 2000;46:244‐249)
349 citations
TL;DR: The risk of diabetes mellitus is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy in patients with chronic pancreatitis and this risk seems to be largely caused by progression of the disease because it increased by more than 3-fold after the onset of pancreatic calcifications.
299 citations
TL;DR: Hemoconcentration with an admission hematocrit ≥44% and/or failure of admission heMatocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure.
Abstract: In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.
266 citations
TL;DR: It is feasible to presume that the use of MRCP may prevent inappropriate explorations of the pancreatic and common bileducts in cases of suspected pancreatic carcinomas, where interventional endoscopic therapy (ie, palliative common-bileduct drainage) is unlikely.
255 citations
TL;DR: Although in this study AP in DKA appeared to be mild, a definite conclusion with regard to the severity should be based only on a much larger number of patients, as only 20% of patients with AP in general have serious disease.
TL;DR: PPPD results in higher frequencies of postoperative delayed gastric emptying compared with the Whipple procedure, and both operations achieve comparable long-term nutritional results, cause new insulin dependence in surprisingly few patients, and provide equivalent pain relief to 65% of selected patients.
Abstract: Surgical therapy for chronic pancreatitis is reserved for patients with complications of the disease, intractable abdominal pain, or suspected underlying carcinoma. 1 The choice of operation for chronic pancreatitis is predicated on the two anatomical variants of the disease, which are distinguished by the size of the main pancreatic duct. 2 Large duct disease (>6 mm in diameter) accounts for approximately 40% of cases and is thought to develop from increased pressure in the pancreatic ductal system. 3 In this circumstance, the longitudinal pancreaticojejunostomy (or modified Puestow procedure) has been the treatment of choice, benefiting close to 80% of patients. 4,5 Patients with small duct disease (<6 mm in diameter) generally are thought not to be candidates for that operation and require pancreatic resection. Because of the historical ineffectiveness of distal resections 6,7 and the complications associated with total pancreatectomy, 1 resections targeting the head of the pancreas are the primary operations for patients with chronic pancreatitis of the small duct form that is refractory to medical treatment. Three main operations are available to these patients today: the Whipple-type pancreaticoduodenectomy (with antrectomy), 8 the pylorus-preserving pancreaticoduodenectomy (PPPD), 9 and the Beger duodenum-preserving pancreatic head resection. 10
Regarding pancreaticoduodenectomy for chronic pancreatitis, controversy exists with respect to the choice of operation and the expected rate of successful outcomes. The PPPD was first described by Watson in 1944 11 and reintroduced by Traverso and Longmire in 1978 9 to improve on the nutritional deficiencies associated with the classic Whipple. Large published series, however, report successful weight maintenance or gain in more than 80% of patients after either operation. 12,13 Relief of pain after pancreaticoduodenectomy is another focus of debate. Information from the literature is commonly based on anecdotal experience of a single approach, often with small cohorts or inadequate follow-up information. 12–17 There are few studies comparing alternative surgical treatments. 1 Evaluation of published reports is further complicated by a lack of standard measurements to assess success. 1,18 Successful pain relief after pancreaticoduodenectomy by either technique is reported over the wide range of 60% to 100% of patients.
In this study, we reviewed our experience with pancreaticoduodenectomy in the treatment of chronic pancreatitis for the past 7 years. During this time, we performed an almost equal number of Whipple and PPPD operations. Our goals were twofold. First, we wished to ascertain the advantages or disadvantages of one operation over the other, both in the short term and the long term. Secondly, and perhaps more important, we performed an outcome analysis of these patients in the hopes of providing prospective selection criteria that will improve the likelihood of successful surgical results.
TL;DR: The results suggest that MT1‐MMP is involved in the progression of pancreatic cancer via activation of MMP‐2, which itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreaticcancer.
Abstract: Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matrix metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MT1-MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the development of the desmoplastic reaction characteristic of pancreatic cancer tissues. Northern blot analyses revealed that transcript levels of MT1-MMP and MT2-MMP, but not MT3-MMP, were enhanced in pancreatic cancer tissues (n = 18) compared with both chronic pancreatitis (n = 9) and healthy pancreas (n = 9). A good correlation was found between MT1-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, expression and activation of MMP-2 were strongly associated with the extent of the desmoplastic reaction in pancreatic cancer tissues. Invasion assays showed a good correlation between MMP-2 expression and activity and the invasive potential of pancreatic cancer cell lines. In cell lines with high levels of MMP-2 expression and activity, the MMP inhibitor Batimastat led to significant reduction of the number of invading cells. Our results suggest that MT1-MMP is involved in the progression of pancreatic cancer via activation of MMP-2. MMP-2 itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreatic cancer.
TL;DR: The administration of secretin improves visualization of the pancreatic ducts and helps in the evaluation of exocrine reserve.
Abstract: PURPOSE: To assess whether secretin stimulation improves visualization of the pancreatic ducts at magnetic resonance (MR) cholangiopancreatography (MRCP) in patients with severe chronic pancreatitis or suspected pancreatic disease. MATERIALS AND METHODS: Thirty-one patients (group 1) with chronic pancreatitis and 84 patients (group 2) with clinical and/or laboratory findings suggestive of pancreatic disease who did not have ductal alterations at ultrasonography (US) and/or computed tomography (CT) underwent MRCP before and up to 10 minutes after secretin stimulation. Size of the main pancreatic duct (head, body, tail) and duodenal filling before and after secretin stimulation were measured quantitatively. Image quality, number of main pancreatic ductal segments visualized, visualization of side branches, ductal narrowing, endoluminal filling defects, and presence of pancreas divisum were analyzed qualitatively. RESULTS: In both groups, the size of the main pancreatic duct increased significantly 3 minutes...
TL;DR: Current management of acute pancreatitis is suboptimal when compared with evidence based UK guidelines but the mortality rate was within the guideline standard.
Abstract: BACKGROUND The incidence of acute pancreatitis shows regional variations in the UK. AIMS To document the incidence and presentation of acute pancreatitis in hospitals in Wessex, and to audit the process and outcome of management of patients against the UK guidelines. METHODS A prospective survey was carried out of all patients with acute pancreatitis in a one year period, in eight geographically adjacent acute hospitals in the Wessex region. RESULTS 186 patients with acute pancreatitis were identified, an incidence of 152 per million in the adult population. Aetiology was: gallstones 33%, alcohol 20%, idiopathic 32%, other 15%. There were 60 severe cases with 17 deaths. Age and APACHE-II score had significant relations to outcome, but delay to admission, serum amylase level, aetiology, and sex did not. The mortality rate (9.1%) was within the audit standard of 10%. Some management goals were not met: in mild cases, only one third of patients with gallstone pancreatitis had definitive treatment within four weeks. In severe cases, there was poor use of objective severity stratification (19%), low admission rates to a high dependency unit or intensive care unit (67%), and only 33% of patients had computed tomography. Only seven of 17 patients with severe gallstone pancreatitis had an urgent endoscopic retrograde cholangiopancreatography. CONCLUSIONS The incidence of clinically diagnosed acute pancreatitis in England continues to rise. Current management of acute pancreatitis is suboptimal when compared with evidence based UK guidelines but the mortality rate was within the guideline standard.
TL;DR: Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, but a bulky homogeneous tumoral mass without alteration of Wirsung's duct or the peripancreatic vessels should suggest the diagnosis.
Abstract: When the radiologist is faced with a well-circumscribed tumoral mass in the pancreas, knowing when to direct the patient toward nonsurgical biopsy instead of surgical biopsy and staging is critical. Lymphoma does not require surgical staging or a palliative Whipple's procedure before chemotherapy or radiation therapy. A better overall prognosis with nonsurgical treatment is additional impetus to search for secondary signs of primary pancreatic lymphoma. In patients with primary pancreatic lymphoma, no marked pancreatic ductal dilatation is present even with ductal invasion. Adenocarcinoma commonly dilates the more distal pancreatic duct when more proximal ductal invasion has taken place. Lymph node involvement below the level of the renal veins was another finding not seen with adenocarcinoma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, but a bulky homogeneous tumoral mass without alteration of Wirsung's duct or the peripancreatic vessels should suggest the diagnosis. In patients with diffuse infiltration of the pancreatic gland without clinical signs of pancreatitis, the radiologist should be alert to the possibility of pancreatic lymphoma.
TL;DR: Oxygen-derived free radicals and many cytokines are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.
Abstract: Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.
TL;DR: In this article, the authors found that smoking increases the risk of developing pancreatic cancer and lowers the age of onset by approximately 20 years, compared with the background population. And smoking appears to be an additional risk factor in these patients.
TL;DR: The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective.
TL;DR: Cholelithiasis is detected by EUS in a large number of patients classified as having idiopathic pancreatitis by conventional radiologic examinations, thereby reducing the risk of recurrent pancreatitis with its associated morbidity and mortality.
TL;DR: In this retrospective study the observed incidence of acute pancreatitis increased by 28% between 1985 and 1995, and due to a decrease in the case-fatality proportion, the mortality remained stable during this period.
Abstract: Background: The incidence of acute pancreatitis seems to have increased in Western countries. It has been suggested that this increase can be explained by improved diagnostic procedures. We performed a nationwide study to assess the annual sex- and age-specific incidence and mortality rates of acute pancreatitis in the Netherlands between 1985 and 1995, a period in which diagnostic procedures did not change considerably. Methods: We conducted a population-based retrospective follow-up study in which we used automated hospital discharge data accumulated by Prismant Health Care Information. All patients admitted with acute pancreatitis (ICD-9CM, 577.0) in the Netherlands were identified. We accounted for referrals to other hospitals to avoid double counting and for miscoding of chronic pancreatitis as acute pancreatitis. The annual population size was retrieved from the Netherlands Central Statistics Office. Results: The observed incidence of acute pancreatitis increased from 12.4/100,000 person-years (95% ...
TL;DR: Autoimmune mechanism may be involved in some patients with idiopathic pancreatitis associated with hypergammaglobulinemia, and segmental stenosis of the main pancreatic duct by ERCP is shown.
TL;DR: OfRs are important mediators of tissue damage, however, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis, and factors other than OFRs must be involved for triggering acute Pancreatitis in vivo.
Abstract: Acute pancreatitis leads to various degrees of interstitial edema, acinar cell damage, hemorrhage, and the recruitment of leukocytes into the damaged gland. 1,2 Oxygen free radicals (OFRs) have been implicated as an important factor in the pathogenesis and progress of this disease. As highly reactive biochemical species, OFRs exert their pathophysiologic effects by directly attacking lipids 3 and proteins 4 in the biologic membranes at the local site of generation and cause their dysfunction. 5,6 Indirectly, they act on the arachidonic acid cascade by two mechanisms. First, they increase the production of thromboxane, which lowers tissue circulation by its potent platelet-aggregating and vasoconstricting effects. 7 Second, they enhance the production of leukotriene B4, which promotes the activation of leukocytes 8 and the discharge of lysosomal enzymes. 9 These changes contribute to further cell damage.
Since the first study by Sanfey et al, 10 many publications have addressed the role of OFRs in acute pancreatitis in both experimental 11,12 and clinical respects. 13 In most of these reports, an indirect approach was chosen to investigate their pathophysiologic role by applying different types of radical scavengers. 11,13 Most of these studies showed that free radical scavengers significantly ameliorated, but did not inhibit the characteristic changes observed with acute pancreatitis; OFRs are thus considered to be important mediators within this disease.
From in vitro studies, there is clear evidence that pancreatic acinar cells are susceptible to oxidative stress. Different oxygen radical species induce severe acinar cell damage in a dose- and time-dependent manner, which led to the conclusion that OFRs may be the crucial event for initiating the pathophysiologic changes of acute pancreatitis. 12 Surprisingly, only a few studies have been performed to investigate the potential of OFRs to induce the typical enzymatic and morphologic alterations of acute pancreatitis in vivo, and their results are controversial. 14,15 As a consequence, the question of whether OFRs act as mediator or as initiating event in acute pancreatitis under in vivo conditions remains unanswered. In the present study we aimed to address this issue in an in vivo experimental set-up.
TL;DR: A patient who had BD complicated with radiologically-proven hepatic veins involvement (Budd-Chiari syndrome) and complete occlusion of hepatic portion of inferior vena cava is presented and who had a good response to colchicine and penicillin treatment.
Abstract: Behcet's disease (BD) is a multisystem, chronic, relapsing vasculitis of unknown origin that affects nearly all organs and systems. While recurrent oral ulcerations are a "sine qua non" of BD, the frequency of extra-oral parts of the gastrointestinal involvement varies widely in different countries. The most frequent extra-oral sites of gastrointestinal involvement are the ileocecal region and the colon. The liver (except with Budd-Chiari syndrome), pancreas, and spleen are rarely involved. The symptoms associated with these extra-oral manifestations of BD are abdominal pain, nausea, vomiting, diarrhea with or without blood, and constipation. The lesions typically are resistant to medical treatment and frequently recur with surgical treatment. We review the literature regarding the gastrointestinal and hepatobiliary systems in BD. Also, we present a patient who had BD complicated with radiologically-proven hepatic veins involvement (Budd-Chiari syndrome) and complete occlusion of hepatic portion of inferior vena cava and who had a good response to colchicine and penicillin treatment.
TL;DR: The findings suggest that syndecan‐1 expression by Pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies.
Abstract: Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastrointestinal malignancies, and it is thought that high levels of syndecan-1 correlate with the maintenance of epithelial morphology and inhibition of invasiveness. In our study, we characterized the expression of syndecan-1 in normal, chronic pancreatitis and primary and metastatic human pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines expressed syndecan-1 mRNA and protein at variable levels. In addition, these cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues markedly over-expressed syndecan-1 mRNA in comparison with both chronic pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6-fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression between early and advanced tumors. By in situ hybridization and immunohistochemistry, syndecan-1 expression was evident at relatively low levels in the ductal cells and less frequently in acinar cells of the normal pancreas. In chronic pancreatitis, syndecan-1 was present at low to moderate levels in areas with atrophic acinar cells and ductular complexes. In contrast, in pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in the majority of the cancer cells within the tumor mass and also in metastatic lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal malignancies (esophageal, gastric, colon and liver cancers) were not significantly different from the levels observed in the corresponding normal samples. Together, our findings suggest that syndecan-1 expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies. Int. J. Cancer 88:12–20, 2000. © 2000 Wiley-Liss, Inc.
Journal Article•
TL;DR: The pathogenetic relationship between pancreatic pseudocysts and acute and chronic pancreatitis and the natural history of pseudocyst will be discussed and a brief description of a few non-neoplastic pancreatic cysts is given.
TL;DR: Magnetic resonance cholangiopancreatography (MRCP) is used for noninvasive work-up of patients with pancreaticobiliary disease and a potential use of MRCP is the demonstration of aberrant bile duct anatomy before cholecystectomy.
Abstract: Magnetic resonance cholangiopancreatography (MRCP) is used for noninvasive work-up of patients with pancreaticobiliary disease. MRCP is comparable with invasive endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis of extrahepatic bile duct abnormalities. In patients with choledocholithiasis, calculi appear as dark filling defects within the high-signal-intensity fluid at MRCP. Benign strictures due to sclerosing cholangitis are multifocal and alternate with slight dilatation or normal-caliber bile ducts, producing a beaded appearance. Dilatation of both the pancreatic and bile ducts at MRCP is highly suggestive of a pancreatic head malignancy. Side-branch ectasia is the most prominent and specific feature of chronic pancreatitis. MRCP is more sensitive than ERCP in detection of pancreatic pseudocysts because less than 50% of pseudocysts fill with contrast material. Because the mucin secreted by biliary cystadenomas and cystadenocarcinomas causes filling defects and partial obstruction of co...
TL;DR: T lymphocytes, particularly CD4(+) T cells, play a pivotal role in the development of tissue injury during acute experimental pancreatitis in mice and are recruited during acute pancreatitis.
TL;DR: Concomitant splenectomy should be strongly considered in patients undergoing operative treatment of symptomatic chronic pancreatitis if sinistral portal hypertension and gastroesophageal varices are also present.
Abstract: Background: Sinistral portal hypertension, a localized (left-sided) form of portal hypertension may complicate chronic pancreatitis as a result of splenic vein thrombosis/obstruction. Aim: To determine appropriate surgical strategy for patients with splenic vein thrombosis/obstruction secondary to chronic pancreatitis. Methods: We reviewed our experience with operative management of 484 consecutive patients with histologically documented chronic pancreatitis treated between 1976 and 1997. The diagnosis of sinistral portal hypertension was based on clinical presentation, preoperative endoscopic and radiographic imaging, and operative findings. “Symptomatic,” herein defined, denotes those patients with sinistral hypertension and either gastrointestinal bleeding or hypersplenism. “Asymptomatic” patients were those with sinistral hypertension alone. Results: Sinistral portal hypertension was present in 34 of the 484 patients (7%). Gastric or gastroesophageal varices were confirmed in 12 patients (35%), of whom 6 had variceal bleeding and 4 had hypersplenism (25%). All symptomatic patients were treated by splenectomy alone or in conjunction with distal pancreatectomy. Splenectomy at the time of pancreatectomy for primary pancreatic symptoms was also performed in 15 patients with (asymptomatic) sinistral portal hypertension. None of the 23 patients who had splenectomy rebled in mean follow-up of 4.8 years. In contrast, 1 of the 11 patients with asymptomatic sinistral portal hypertension who underwent pancreatic surgery without splenectomy died of later variceal bleeding 3 years after lateral pancreatojejunostomy. Conclusions: Symptomatic sinistral portal hypertension is best treated by splenectomy. Concomitant splenectomy should be strongly considered in patients undergoing operative treatment of symptomatic chronic pancreatitis if sinistral portal hypertension and gastroesophageal varices are also present.
TL;DR: Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem and diabetes secondary to exocrine disease could be much more frequent than believed so far.
Abstract: Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 patients with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenetic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.