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Background: Point-of-care devices for performing a prothrombin time/international normalized ratio (PT/INR) using capillary blood samples are being increasingly used to monitor patients receiving anticoagulation therapy. However, the performance of some devices has been shown to be suboptimal and there are only limited published data comparing specific devices to various central laboratory coagulation analyzers. We report an evaluation of the iSTAT PT/INR with a comparison to the Tcoag MDA II analyzer., Methods: We obtained simultaneous capillary/venous samples on 20 healthy volunteers for a normal range study and on 50 anticoagulated patients for a clinical evaluation. Testing was performed by phlebotomists. We also obtained 68 near simultaneous capillary/venous test results for assessment of performance by non-laboratory personnel. The criteria for determining clinical equivalence of the iSTAT to the MDA II were (1) same clinical category (subtherapeutic INR<2, therapeutic INR 2-3, and supratherapeutic INR>3) or (2) paired values within ≤ 0.4 INR., Results: Forty nine of 50 patient sample pairs collected by phlebotomists showed acceptable clinical agreement. Sixty one (61) of 68 patient sample pairs collected by nurses showed acceptable agreement. In all discordant cases the differences were minor and would have resulted in either no or minimal change in therapy., Conclusions: The iSTAT PT/INR compares well to the MDA II when performed by phlebotomists or nurses., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We evaluated a new point-of-care (POC) device for urine drugs of abuse (DOA) screening including appropriate clinical interpretation and potential benefits in a large academic medical center. Two hundred consecutive urine samples were tested using Syva Rapid Test (SRT) and existing laboratory methods (Syva EMIT II). Agreement between methods was acceptable with some considerations. Threshold concentration differences, drug interferences, and cross-reactivity profiles of the class-specific assays resulted in performance differences between the POC and central laboratory methods. Clinical interpretation of POC results requires an understanding of these issues as well as the limitations of urine testing. While urine-based screening is used in workplace testing and in a variety of clinical applications, quantitative blood measurements of some drugs (e.g. ethanol, acetaminophen, salicylate, +/-tricyclic antidepressants) will remain important in the emergent setting. Performance of the SRT method takes approximately 10 min. Consequently, the major advantage over laboratory methods is rapid turnaround time. At the Massachusetts General Hospital, the most important application is for samples from the emergency department (about 1700/year). Each institution should assess its own needs and capabilities with regard to POC versus laboratory-based testing for DOA.

Pancreatic proteases are secreted in acute pancreatitis, but their contribution to associated lung injury is unclear. Applying models of mild edematous (intravenous caerulein) and severe necrotizing (intraductal glycodeoxycholic acid) pancreatitis in rats, we showed that both trypsinogen and trypsin concentrations in peripheral blood, as well as lung injury, correlate with the severity of the disease. To isolate the potential contribution of proteases to lung injury, trypsin or trypsinogen was injected into healthy rats or trypsinogen secreted in caerulein pancreatitis was activated by intravenous enterokinase. Pulmonary injury induced by protease infusions was dose dependent and was ameliorated by neutrophil depletion. Trypsinogen activation worsened lung injury in mild pancreatitis. In vitro incubation of leukocytes with trypsinogen showed that stimulated leukocytes can convert trypsinogen to trypsin. In conclusion, this study demonstrates that the occurrence and severity of pancreatitis-associated lung injury (PALI) corresponds to the levels of circulating trypsinogen and its activation to trypsin. Neutrophils are involved in both protease activation and development of pulmonary injury.

Most pancreatic cysts (90%) are inflammatory pseudocysts. Approximately 10% of pancreatic cysts are neoplasms, including serous cystadenomas, and mucinous tumors, some of which are malignant. Analysis of pancreatic cyst fluid obtained by percutaneous or endoscopic fine-needle aspiration is increasingly being used for the preoperative diagnosis of pancreatic or peripancreatic cysts. However, cyst fluid chemical and cytologic features in less common types of pancreatic cysts have not been reported. Lymphoepithelial cyst of the pancreas is exceedingly rare, and only occasional individual reports have described cyst fluid findings. We report on a case of lymphoepithelial cyst of the pancreas developing in a middle-aged man. Cyst fluid aspirated under radiological guidance showed elevated levels of carcinoembryonic antigen (CEA), CA19-9, CA 125, and amylase, and a viscosity greater than that of serum. A cell block preparation of a fine-needle aspiration showed tissue fragments with a keratinized squamous lining and a lymphocytic infiltrate in the wall, and abundant background keratinous debris. The cytologic and biochemical findings in this case exhibit similarities to the findings reported in other reports, and may represent a recognizable pattern on cyst fluid analysis., (Copyright 1999 Wiley-Liss, Inc.)

Background: Mechanisms that mediate cocaine-induced cardiovascular events following vasoconstriction are incompletely understood., Objective: To examine the effects of cocaine in moderate doses on hematologic and hemostatic parameters that influence blood viscosity and thrombotic potential., Methods: Changes in hemoglobin concentration, hematocrit, and red blood cell counts were measured in human subjects who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for long-term cocaine abuse, before and sequentially after moderate intranasal and intravenous doses of cocaine. Hemostatic parameters, including von Willebrand factor, fibrinolytic activity, fibrinogen, plasminogen activator inhibitor antigen, and tissue-type plasminogen activator antigen, were sequentially measured after intravenous cocaine or saline placebo with cardiac troponin subunits T and I., Results: Hemoglobin level (P= .002), hematocrit (P =.01), and red blood cell counts (P = .04) significantly increased from 4% to 6% over baseline from 10 to 30 minutes after intranasal (n = 14) and intravenous (n = 7) cocaine administration in doses of 0.9 mg/kg and 0.4 mg/kg, respectively, with no change in white blood cell or platelet counts. There was a significant increase (P =.03) in von Willebrand factor from 30 to 240 minutes, peaking at 40% over baseline following intravenous cocaine administration in a dose of 0.4 mg/kg (n = 12), with no change after 0.2 mg/kg (n = 3) or placebo (n = 6). Other hemostatic factors, creatinine, blood urea nitrogen, and cardiac troponin subunits T and I showed no changes., Conclusions: Cocaine induced a transient erythrocytosis that may increase blood viscosity while maintaining tissue oxygenation during vasoconstriction. An increase in von Willebrand factor without a compensatory change in endogenous fibrinolysis may trigger platelet adhesion, aggregation, and intravascular thrombosis.

Background & Aims: Intracellular activation of trypsinogen is currently believed to initiate pancreatitis. Factors responsible for the progression of mild to necrotizing pancreatitis are poorly understood. This study evaluated the significance of interstitial protease release and activation in this process., Methods: In rats with cerulein-induced pancreatitis, concentrations of trypsinogen and its activation peptide TAP were measured in lymph and blood, and pancreatic injury was determined. Activation of extracellular trypsinogen was induced by intravenous infusion of enterokinase, which does not enter the acinar cell. Gabexate mesilate (acinar cell permeable) or soybean trypsin inhibitor (acinar cell nonpermeable) was administered to distinguish the effects of intracellular or extracellular protease activation., Results: In cerulein pancreatitis, trypsinogen levels increased prominently and were highest in lymph and portal vein blood, whereas TAP increments were modest. Combined cerulein/enterokinase infusions resulted in marked TAP increases in lymph and blood and in severe necrohemorrhagic pancreatitis. Gabexate mesilate as well as soybean trypsin inhibitor significantly decreased TAP levels in both lymph and blood and reduced pancreatic injury, with no significant differences between groups., Conclusions: In secretagogue-induced pancreatitis, large amounts of trypsinogen are present in the interstitium and drain via the portal and lymphatic circulation. Activation of this extracellular trypsinogen induces hemorrhagic necrosis in a setting of mild edematous pancreatitis. This phenomenon may be the central event in the progression to fulminant necrotizing pancreatitis.

Objective: To analyze the time points and levels of the expression of adhesion molecules in the pancreas and lung in pancreatitis of different severities, and to assess whether treatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) can reduce local and systemic complications., Background: The outcome of severe acute pancreatitis relates to its pulmonary and septic complications. Leukocyte adhesion and infiltration, both mediated by ICAM-1, are central events in the pathogenesis of necrotizing pancreatitis., Methods: Expression of ICAM-1 at different time points was assessed by immunohistochemistry and Western blot analysis in pancreas and lungs from rats with mild edematous or severe necrotizing pancreatitis. ICAM-1 expression was correlated with leukocyte infiltration and histologic changes. The possible therapeutic effect of monoclonal antibodies against ICAM-1 was assessed by measuring pancreatic and lung injury., Results: In edematous pancreatitis, increased ICAM-1 expression in pancreas was evident by 6 hours but did not occur in lung. In contrast, ICAM-1 was upregulated at 3 hours in the pancreas and at 12 hours in lung in necrotizing pancreatitis. Increased expression of ICAM-1 preceded leukocyte infiltration. Treatment of severe necrotizing pancreatitis with monoclonal antibodies against ICAM-1 decreased both local pancreatic injury and systemic lung injury compared with untreated controls., Conclusions: Upregulation of ICAM-1 and subsequent leukocyte infiltration appear to be significant mediators of pancreatic and pulmonary injury in pancreatitis, and both the onset and extent correlate with severity. The time course should permit effective prevention of tissue damage by treatment with ICAM-1 antibodies.

Conclusion: Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors., Background: Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance., Methods: Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays., Results: Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges.

Conclusion: Lexipafant administration fails to improve survival or lessen the disease severity in two experimental models of severe acute pancreatitis., Background: The potent platelet activating factor antagonist Lexipafant has been shown to attenuate the biochemical and histologic changes associated with some animal models of acute pancreatitis, suggesting an important role for this cytokine in its pathogenesis. However, a survival advantage following Lexipafant administration has not been demonstrated. This study evaluates the effect of this platelet activating antagonist on survival in rat models of necrotizing and fulminant hemorrhagic pancreatitis., Methods: Sprague-Dawley rats underwent induction of either acute necrotizing (n = 40) or hemorrhagic pancreatitis (n = 36) with a time- and pressure-controlled bile duct infusion of 10 mM glycodeoxycholic acid (GDOC) or enterokinase 15 U/mL, in combination with supramaximal cerulein stimulation (5 micrograms/kg/h). Immediately after pancreatitis induction, rats were randomly divided into three groups and received Lexipafant (1 mg or 10 mg) or saline as a continuous intravenous infusion over 9 h. Twenty-four-hour survival rates were determined and severity of pancreatitis was assessed by pancreatic histology scores., Results: The survival rates for GDOC treated rats were 55% (saline), 50% (1 mg Lexipafant) and 50% (10 mg Lexipafant). As expected, all rats induced with enterokinase and treated with saline died with hemorrhagic pancreatitis within 24 h. The same was true of those treated with high- and low-dose Lexipafant, and there was no difference in survival time. Histology scores did not differ between Lexipafant-treated and control rats in either GDOC or enterokinase rats.

Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the occurrence of sudden cardiac death during marathon running. Serum creatine kinase MB (CK-MB) may be elevated in asymptomatic marathon runners after competition from exertional rhabdomyolysis of skeletal muscle altered by training, limiting its utility for evaluating acute cardiac injury in such athletes. Myoglobin and CK-MB2 isoform levels are emerging as earlier markers of AMI and troponin subunits as more specific than serum CK-MB mass. We tested runners before and sequentially after the 1995 Boston Marathon for conventional and newer markers including myoglobin, CK-MB mass and isoforms, cardiac troponin T, and cardiac troponin I using standard laboratory methods and rapid format assays if available. The mean serum values for myoglobin, CK-MB mass, CK-MB/myoglobin rapid panel tests, and CK-MB2 isoforms were normal or negative pre-race and elevated or positive 4 and 24 h after competition. These markers lack specificity for acute cardiac injury in trained runners. While the mean serum values for cardiac troponins T and I remained normal, 9 of 45 runners (20%) showed an increase in subunits by first-generation assays. All runners remained asymptomatic for cardiac disease and completed subsequent marathons 1 year later, making reversible myocardial injury or stunning unlikely. Elevated values of serum markers for AMI, including first-generation assays for both troponin subunits should be interpreted with caution in trained runners.

Objective: The purpose of the study was to determine the prevalence of activating K-ras mutations in the pancreas of patients with intraductal papillary mucinous tumors (IPMT) and to analyze their relation to the degree of site-specific histopathologic abnormality., Background: Intraductal papillary mucinous tumors of the pancreas have a biologic behavior that is significantly different from pancreatic ductal adenocarcinoma. Activating K-ras mutations, which may be important events in a multistage process of carcinogenesis, have been reported in IPMT., Methods: Forty-six different histologic specimens (comprising normal pancreatic ducts, hyperplasia, low-grade dysplasia, high-grade dysplasia-carcinoma in situ, and carcinoma) from 16 patients with IPMT and 9 specimens from patients with pancreatic ductal adenocarcinomas were designated by a pathologist. Genomic DNA was extracted from paraffin-embedded tissue sections after microdissection. The K-ras gene was amplified by polymerase chain reaction and subjected to DNA sequencing., Results: The K-ras mutations were detected in at least one specimen in 13 (81.2%) of 16 patients with IPMT. All mutations were found in codon 12. No codon 13 mutations were detected. The relative frequency of K-ras mutations in the different stages of IPMT was 16.7% in normal epithelium and papillary hyperplasia, 28.6% in low-grade dysplasia, and 57.1% in high-grade dysplasia-carcinoma in situ and invasive carcinoma. The K-ras mutations were detected in 6 (66%) of 9 pancreatic ductal adenocarcinomas., Conclusions: The K-ras codon 12 point mutations are as frequent in IPMT as in ductal adenocarcinoma. A stepwise increase in the frequency of codon 12 mutations correlated with the stage of neoplastic evolution to cancer. This finding is consistent with an important role of K-ras gene mutations in the transformation from normal epithelium to invasive carcinoma in the majority of patients with IPMT.

Background & Aims: The mechanism by which alcohol injures the pancreas remains unknown. Alcohol-intoxicated humans have high levels of fatty acid ethyl esters (FAEEs), nonoxidative products of ethanol metabolism, in blood, pancreas, and liver. The aims of this study were to determine whether FAEEs are toxic to the pancreas in vivo and, if so, to assess whether this injury is specific to the pancreas and to compare it to the injury observed in acute pancreatitis., Methods: FAEEs were infused into Sprague-Dawley rats. Levels of FAEEs in plasma and pancreas were measured, and pancreatic injury was assessed during a 48-hour period for edema formation and ectopic trypsinogen activation and by light and electron microscopy., Results: FAEEs induced highly significant increases in pancreatic edema, pancreatic trypsinogen activation, and vacuolization of acinar cells. These findings were specific to the pancreas and were not found in liver, lung, myocardium, skeletal muscle, or subcutaneous fat., Conclusions: FAEEs at concentrations found in human plasma produce a pancreatitis-like injury in rats, providing direct evidence that FAEEs can produce organ-specific toxicity. Thus, FAEEs may contribute to acute alcohol-induced damage to the pancreas.

Objective: The purpose of the study is to review a single institutional experience with mucinous ductal ectasia (MDE) and intraductal papillary neoplasms (IPNs) and to compare the clinicopathologic features of the two groups of tumors., Summary Background Data: Mucinous ductal ectasia and IPNs represent newly recognized categories of pancreatic exocrine tumors, previously confused with pancreatic cystic neoplasms. The natural history of MDE and IPN is not well understood, and it is unclear whether MDE and IPN represent two distinct tumors or the same clinicopathologic entity., Methods: The authors reviewed the clinical presentation, treatment, histopathology, and outcomes of 23 patients diagnosed with MDE or IPN at their institution over the past 6 years., Results: The mean age at presentation for the cohort of patients with MDE and IPN was 62.5 years. The prevalence of abdominal pain was 75%, jaundice 25%, weight loss 42%, steatorrhea 37.5%, diabetes 37.5%, and history of pencreatitis 29%. Serum CA 19-9 levels ranged from 0 to 5350 units/mL with high levels reflecting advanced disease. There were no significant differences between MDE and IPN with respect to these parameters. Both MDE and IPN comprised papillary villous epithelial neoplasms involving the main and large pancreatic ducts. The tumors ranged from a few millimeters in size to panductal and were distinguished easily from cystic neoplasms in all cases. Invasive carcinoma was present in 11 (46%) of 24 patients, carcinoma in situ in an additional 10 (42%) of 24 patients, and low grade dysplasia in the remaining 3 (12%) of 24 patients. Mucinous ductal ectasia and IPN differed histopathologically only in degree of mucin secretion and tumor location. Mucinous ductal ectasia, but not IPN, was characteristically mucin-hypersecreting and more frequently involved the head of the gland than did IPN (11/16 vs. 1/8 p < 0.04). All patients were explored surgically and 20 (83%) of 24 of the tumors were resectable with frozen section control of the duct margins (9 pancreatoduodenectomies, 4 distal pencreatectomies, 7 total pancreatectomies). Despite the 88% prevalence of cancer, the overall survival at a mean follow-up of 21 months was 13 (87%) of 15 for MDE and 5 (71%) of 7 for IPN., Conclusions: Intraductal papillary neoplasms with or without MDE represent a spectrum of main duct papillary tumors ranging from adenoma to carcinoma with differing amounts of extracellular mucin production. Malignant IPNs with or without MDE typically exhibit extensive intraductal growth but are slow to invade the periductal tissues and slow to metastasize. The majority of patients with these tumors have resectable disease and a favorable prognosis; endoscopic therapy is inappropriate. The encompessing term intraductal papillary-mucinous tumors is appropriate.

Purpose: Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol., Materials and Methods: Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity., Results: We observed that the FAEE synthase activity is present in whole blood, primarily within white blood cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained approximately 3.5-fold higher activity than the granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/10(6) cells) was the natural killer (NK) cell population. B cells contained approximately 40% of the enzyme activity found in NK cells, and the B-cell activity was slightly greater than that found in CD4+ and CD8+ T cells. Having shown that FAEE synthase exists in a blood cell, we subsequently demonstrated that alcoholic individuals have approximately half the white blood cell FAEE synthase activity of that found in normal controls. We also demonstrated that white blood cell FAEE synthase could be induced nearly 2-fold upon ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned to baseline levels despite ingestion of 2 oz of scotch whiskey/day for 3 additional days., Conclusions: These data indicate that ethanol ingestion results in increased FAEE production, particularly by NK cells. FAEE synthesis after ethanol ingestion may explain the presence of FAEE in the serum. The lower enzyme activity observed in white blood cells of alcoholics from a detoxification center may be the result of years of ethanol abuse or it may be that alcoholics congenitally have low levels of FAEE synthase. If the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse.

Objective: To assess the role of peritoneal cytology in the management of mucinous cystadenocarcinoma., Study Design: A review of the peritoneal fluid cytologic findings in eight selected cases of pancreatic mucinous cystadenocarcinomas., Results: Four of eight cases (50%) were positive for malignant cells. All four patients with positive peritoneal cytology had unresectable tumors and extensive intraabdominal metastases. Of the four patients with negative cytology, three had unresectable, locally invasive tumors without metastases, and one had a resectable tumor confined to the pancreas., Conclusion: Peritoneal cytology is frequently positive in unresectable mucinous cystadenocarcinomas with intraabdominal metastases, but cytology may often be negative in unresectable cases. Therefore, negative cytologic findings in these cases do not reliably ensure resectability, while positive findings clearly correlate with the presence of intraabdominal metastases. A larger study of unselected patients, including more with resectable tumors, will be required to define the full utility of this technique in preoperative assessment.

Background: Benign and malignant pancreatic mucinous tumors differ in proliferative activity, production of tumor markers, and expression of growth factors. DNA ploidy is a useful index of aggressiveness and poor survival in ductal adenocarcinoma, but has not been studied in pancreatic cystic tumors., Methods: The DNA ploidy status of Fuelgen-stained tissue sections of pancreatic mucinous cystic tumors was evaluated by image cytometry and related to clinical outcome obtained by case record review., Results: Ploidy status correlated with malignancy and poor clinical outcome. All benign mucinous cystadenomas (n = 13) were diploid and cured by resection. Patients with diploid cystadenocarcinomas (n = 6) had an 83% survival rate following resection, while patients with aneuploid cystadenocarcinomas (n = 5) all died (four of disease and the fifth of another cause). The difference in survival between the diploid and aneuploid carcinomas was significant (P = 0.04)., Conclusions: DNA ploidy status of pancreatic mucinous tumors by image analysis provides quantifiable information that may be predictive of clinical outcome. DNA aneuploidy appears to be a significant differential factor in pancreatic mucinous tumors and is associated with shortened survival in mucinous cystadenocarcinomas.

Background: Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies have shown that malignant mucinous tumors differ from benign pancreatic cysts in proliferative activity, secretion of tumor markers, and expression of growth factor receptors. Analysis of aspirated cyst fluid for tumor markers, viscosity, and cytologic examination has been proposed as an aid to preoperative differential diagnosis. Tissue polypeptide antigen (TPA) is a soluble proliferation antigen produced by rapidly dividing tissues, including conventional ductal pancreatic carcinoma. TPA levels in pancreatic cyst fluids have not been reported., Methods: Tissue polypeptide antigen levels were determined in 46 pancreatic cyst fluids using a commercial immunoassay technique., Results: Mucinous cystadenocarcinomas exhibited significantly higher levels of cyst fluid TPA than benign cystic lesions, including pseudocysts, serous cystadenomas, and benign mucinous cystadenomas (mean 910,672 U/mL, median 300,900 U/mL, range 16,600 to 4,210,000 U/mL for malignant mucinous cystadenocarcinomas; versus mean 16,082 U/mL, median 2,455 U/mL, range 0 to 155,000 U/mL for benign cystic lesions considered as a group; P < 0.0002). In 75% of the malignant cysts, the TPA values were in excess of 100,000 U/mL. Pseudocysts exhibited the lowest TPA levels (mean 2,108 U/mL, median 604 U/mL, range 0 to 20,240 U/mL) and were significantly lower than the values observed in cystic tumors (P < 0.0005). Serous and benign mucinous tumors had intermediate levels of TPA., Conclusions: Elevated levels of the proliferation antigen TPA in malignant pancreatic cysts correlate with earlier observations of increased proliferative activity and overexpression of growth factor receptors in these tumors. The TPA measurement may be a useful addition to previously reported cyst fluid markers to aid in preoperative differential diagnosis. Markedly elevated or very low values indicate a malignant or benign cyst, respectively.

Background: Calcium infusion and hypotension have been described as the most important risk factors for pancreatic injury after cardiopulmonary bypass., Methods: Rats were randomly allocated to three experimental groups undergoing either sham operation and saline infusion (Control, n = 30), hemorrhagic reduction of mean arterial pressure to 30 mmHg for 30 min alone (hypotension, n = 51), or hypovolemic hypotension followed by bolus infusion of CaCl2 (200 mg.kg-1; hypercalcemia, n = 85). Serum ionized calcium, amylase activity, trypsinogen activation peptide in pancreatic tissue homogenates, pancreatic wet/dry weight ratio, histologic changes, and mortality were assessed for 24 h., Results: Control rats showed no significant changes of any parameter throughout the experiments. In contrast, hypotension significantly increased serum amylase (P < 0.001), tissue trypsinogen activation peptide (P < 0.01), wet/dry weight ratio (P < 0.001), and histologic scores for edema (P < 0.001) and pancreatic necrosis (P < 0.05). Subsequent CaCl2 administration transiently increased [Ca2+] (P < 0.001) with the concentration rapidly returning to baseline within 3 h. That infusion of CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation peptide (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evidence of pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) when compared with hypotension alone. Whereas all Control animals survived the experiments, 22% (P < 0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and hypercalcemia groups, respectively., Conclusions: Temporary hypotension alone causes ectopic trypsinogen activation and lethal acute pancreatitis. Super-imposed hypercalcemia significantly aggravates hypotension-induced pancreatic injury and mortality in rats.

This report describes the quality control and quality assurance programs for bedside glucometry at our institution. From our 3-year experience, a regular schedule of inspections is necessary for maintenance of high-quality bedside glucose testing. The most common violation of quality control/quality assurance in bedside glucometry in our institution was the failure to perform regular proficiency testing, in which one random patient's bedside capillary blood glucose value during each inspection period was compared to his or her venous plasma or serum glucose value obtained from the central laboratory. Failure to perform instrument maintenance and document operator certification were the next most common violations of quality control/quality assurance in our bedside glucometry program. Regarding the cost analysis for bedside glucometry, we conclude that bedside glucose testing is not inherently more expensive than testing performed within the clinical laboratory. The increased cost of bedside glucometry over laboratory testing can be significantly minimized by involvement of a limited number of health care workers and performance of bedside glucometry only on clinical units where testing is required more than five times per day.

We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.

Background & Aims: Clinical and experimental observations have associated acute and chronic hypercalcemia with pancreatitis. The aim of this study was to determine whether acute hypercalcemia can induce acute pancreatitis and, if so, whether the pathogenesis involves premature protease activation., Methods: Rats given bolus infusions of CaCl2 (200 mg/kg; n = 76) were compared with saline-treated controls (n = 40). Serum [Ca2+], serum amylase activity, trypsinogen activation peptide (TAP) concentration in serum and pancreatic tissue, pancreatic wet/dry weight ratio, and histology were assessed for 24 hours. For dose-response analysis, CaCl2 was injected at a dose of 50-200 mg/kg, and the aforementioned indices were assayed for 1 hour (n = 5 each)., Results: There were no significant changes in the controls. Calcium infusion increased serum [Ca2+] 3-fold after 5 minutes (P < 0.001). Within 1 hour, serum amylase (2.5-fold) and tissue TAP (3-fold) levels increased along with macroscopic and microscopic edema formation and leukocytic infiltration. The extent of the changes at 1 hour correlated with the calcium dose. Amylase and tissue TAP concentrations remained elevated until 24 hours when serum TAP concentration had increased (P < 0.001) and focal acinar necrosis became evident., Conclusions: Acute experimental hypercalcemia induces dose-dependent morphological alterations characteristic of acute pancreatitis, acute hyperamylasemia, and early ectopic trypsinogen activation. This supports the pathophysiological relevance of excess calcium and offers a possible pathogenetic mechanism for its association with clinical pancreatitis.

Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished.

Objective: The potential of pancreatic ischemia to cause acute pancreatitis as indicated by morphologic changes and ectopic trypsinogen activation was investigated., Background: Experimental evidence has shown that pancreatic ischemia is important in the evolution of severe pancreatitis, but whether ischemia can initiate pancreatitis has been disputed., Methods: Pancreatic ischemia was induced in rats by hemorrhagic hypotension (30 mm Hg for 30 min; n = 64). Changes of pancreatic microcirculatory perfusion were studied using diffuse reflectance spectroscopy. Serum amylase, trypsinogen activation peptide (TAP) in serum and pancreatic tissue, wet/dry weight ratio, and histology were determined over 24 hours and compared with sham-operated control subjects (n = 35)., Results: In control animals, serum amylase (47.9 +/- 2.1 units/L), serum (7.9 +/- 0.7 nmol/L) and tissue TAP (63.0 +/- 5.4 nmol/L x g), wet/dry weight ratio (2.8 +/- 0.1), and histology remained unchanged. Temporary hypotension markedly decreased pancreatic perfusion with incomplete recovery after reperfusion. Pancreatic isoamylase activity increased within 1 hour (110 +/- 5 units/L, p < 0.05) and further to 151 +/- 18 units/L at 24 hours. Tissue TAP was elevated at 1 hour (134 +/- 16 nmol/L x g, p < 0.05) and increased to 341 +/- 43 nmol/L x g (p < 0.001) after 24 hours, whereas serum TAP remained unchanged (8.3 +/- 0.5 nmol/L). Morphologic alterations included elevated wet/dry weight ratio (4.1 +/- 0.3, p < 0.01) and increased histologic scores for edema (p < 0.05) and acinar necrosis (p < 0.05) at 24 hours. Trypsinogen activation preceded the development of pancreatic necrosis., Conclusions: In addition to its potentiating role, severe pancreatic ischemia can play a pathogenetic role in the initiation of acute pancreatitis.

Recent epidemiologic studies confirm that heavy physical exertion can trigger myocardial infarction. Diagnosis of acute myocardial injury in marathon runners is complicated by elevations of serum creatine kinase MB isoenzyme activity in asymptomatic finishers with normal post-race infarct-avid myocardial scintigraphy. Such isoenzyme elevations can arise from exertional rhabdomyolysis of skeletal muscle biochemically altered by training, from silent injury to the myocardium or from a combined tissue source. To assess silent myocardial cell necrosis in marathon runners, we performed quantitative anti-myosin myocardial scintigraphy after competition with serum immunoassays for creatine kinase MB isoenzyme and troponin T. Therefore, 8 male marathon runners with a mean age of 52 years underwent quantitative antimyosin myocardial scintigraphy immediately following the 1988 and 1993 Boston Marathons. Serum immunoassays for creatine kinase MB isoenzyme by a chemiluminescent method (CLIA) and troponin T by an enzyme-linked immunosorbent assay were performed in 4 runners after the 1993 race. Quantitative antimyosin myocardial scintigraphy was normal in all runners including 3 who participated after both races 5 years apart. Post-race serum creatine kinase MB isoenzyme and/or troponin T levels were in a range otherwise diagnostic of acute myocardial infarction in 3 of 4 subjects. Normal quantitative antimyosin myocardial imaging in asymptomatic marathon runners excludes silent myocardial cell necrosis as the source of elevated serum protein markers. Such imaging may be the optimal diagnostic modality for detection of myocardial cell necrosis in symptomatic athletes when results of conventional testing are inconclusive.

Objective: To evaluate the role of epidermal growth factor receptor (EGF-R) and pS2 protein in the evolution of malignancy in mucinous cystic tumors of the pancreas., Background: Mucinous cystic tumors of the pancreas include histologically benign but premalignant mucinous cystic neoplasms and mucinous cystadenocarcinoma. The molecular events leading to transformation from a benign to a malignant mucinous tumor are not known. Overexpression of EGF-R and detection of an estrogen-induced protein (pS2) has been demonstrated in ductal adenocarcinomas of the pancreas, but these factors have not been evaluated in mucinous cystic tumors., Design: Twenty-six mucinous tumors were examined for EGF-R, pS2 protein, and estrogen and progesterone receptors., Results: Eight (61.2%) of 13 malignant tumors exhibited increased expression of EGF-R, whereas EGF-R was not detected in any of the 13 benign tumors (P = .002). The pS2 protein was detected in nine of 11 malignant and 11 of 11 benign tumors (P = .480). Estrogen and progesterone receptors were not detected in the epithelium of either tumor type. The median survival time of the patients with EGF-R-negative tumors was 29.0 months compared with 14.5 months for those with EGF-R-positive tumors, but this difference did not reach significance owing to the small population size., Conclusions: Overexpression of EGF-R in mucinous cystic tumors, as in ductal adenocarcinomas, may be an important feature associated with malignancy and may have prognostic significance. Failure to detect EGF-R in histologically benign epithelium suggests that the upregulation of EGF-R may be important in the evolution of aggressive behavior. The expression of pS2 protein appears to be independent of estrogen and may play a role in the proliferative activity of mucinous tumors. However, pS2 expression is not a feature associated exclusively with malignancy.

Objective: To evaluate the factors thought to be involved in the pathogenesis of acute pancreatitis associated with alcohol., Background: The mechanism of alcohol-induced pancreatitis is believed to involve synergistic effects of various pathogenetic factors. The present study was designed to evaluate the possible contribution of pancreatic duct obstruction, physiologic exocrine stimulation, or secretory hyperstimulation to alcohol-induced pancreatic injury., Methods: Wistar rats were allocated randomly to a control group (group 1), or to a group with pancreatic duct obstruction (group 2), physiologic exocrine stimulation (group 3), ductal obstruction and exocrine stimulation (group 4), or exocrine hyperstimulation with the cholecystokinin analogue cerulein (group 5). Three hours after this pretreatment, animals in each experimental group were randomly divided into two subgroups for intragastric administration of either water (groups 1A through 5A) or beer (groups 1B through 5B). Test solutions were instilled over 9 hours (total amount of alcohol administered, 4.8 g/kg). Twenty-four hours after beginning the test infusion, animals were killed for histologic evaluation of pancreatic edema and determination of an acinar cell necrosis score. Serum amylase levels were determined at 3, 9, and 24 hours., Results: No increase in amylase levels or significant morphologic changes were found in control animals (group 1A) or in animals subjected to physiologic exocrine stimulation (group 2A). Pancreatic duct obstruction, with or without physiologic exocrine hyperstimulation (groups 3A and 4A), and exocrine hyperstimulation (group 5A) induced pancreatitis of similar severity with minor acinar cell damage. Alcohol superimposed on exocrine hyperstimulation (group 5B) increased acinar cell injury (group 5A, 0.4 +/- 0.1 points vs 5B, 1.0 +/- 0.2 points; P < .05) and serum amylase levels at 24 hours (group 5a, 41 +/- 6 U/L vs group 5B, 72 +/- 11 U/L; P < .05), whereas no differences between subgroups A and B (water vs beer) were found in groups 1 through 4., Conclusion: Our findings suggest that the pathogenesis of acute alcoholic pancreatitis may require a state of exocrine hyperstimulation, perhaps via cholecystokinin, but do not support a role for constriction or obstruction of Oddi's sphincter.

Background: Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans., Objective: The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis., Methods: Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours., Results: No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours., Conclusion: Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.

Background: Inappropriate extraluminal activation of trypsin is assumed to play a part in the pathogenesis of acute pancreatitis (AP), but proof has been elusive because active trypsin is transient and difficult to measure. We have previously shown increased levels of trypsinogen activation peptides (TAP), a direct measure of trypsin activation, to correlate with severity of AP, tissue necrosis, and survival in a rodent model induced by cerulein hyperstimulation and bile salt infusion. The present study seeks to show that increased trypsinogen activation also characterizes three other models of experimental AP in rodents to give credence to the generality of the phenomenon and to its potential relevance to human AP., Methods: Experimental AP was induced in mice by a choline-deficient diet supplemented with ethionine and in rats by creation of a closed duodenal loop or by ligation of the biliopancreatic duct plus physiologic stimulation. TAP were quantified by an immunoassay in tissue and plasma at various time points after onset of AP., Results: In the group with choline-deficient diet supplemented with ethionine a significant increase in tissue and plasma TAP was found at 48 and 72 hours, respectively. In the group with closed duodenal loop significant TAP elevations were found in plasma as early as 6 hours and in the group with ligation of the biliopancreatic duct plus physiologic stimulation at 24 hours., Conclusions: These experiments provide further evidence that extraluminal protease activation is a pathophysiologic event common to the evolution of various models of experimental acute pancreatitis and therefore increase the likelihood that this phenomenon is important in the human disease as well.

Pancreatic cystic lesions include inflammatory pseudocysts, benign serous cystadenomas, and mucinous neoplasms, some of which are malignant. Cytologic analysis of cyst fluid has been proposed to diagnose pancreatic cysts before definitive therapy. The authors report an analysis of 31 pancreatic cyst aspirates: 9 pseudocysts, 5 serous cystadenomas, 8 mucinous cystic neoplasms, 4 mucinous cystadenocarcinomas, 2 papillary cystadenocarcinomas, 1 mucinous ductal adenocarcinoma with cystic degeneration, and 2 cystic islet cell tumors. All pseudocysts were correctly classified as probable inflammatory lesions, because of the presence of abundant acute inflammation and histiocytes and the absence of glandular epithelium. Three of five serous cystadenomas were correctly classified, based on the presence of small cuboidal cells in clusters with microvesicular cytoplasm containing glycogen. Eleven of 12 mucinous tumors contained round cells with large cytoplasmic mucin vacuoles or columnar cells containing cytoplasmic mucin. Malignancy was diagnosed in 5 of 7 carcinomas, 1 case was classified as suspicious for malignancy, and 1 case was nondiagnostic because of the absence of a cellular component. The authors concluded that pancreatic cyst fluid cytologic analysis is useful in differentiating mucinous from nonmucinous pancreatic cysts and may provide definitive evidence of malignancy. In some cases, serous cystadenoma can be diagnosed based on cytologic analysis. An inflammatory smear without epithelial cells suggests a pseudocyst, but these findings are nonspecific, as a similar pattern may occur when a cystic neoplasm undergoes degenerative changes. Therefore, pseudocyst remains a diagnosis of exclusion.

Trypsinogen activation peptides (TAP) can be found in patients with acute pancreatitis (AP) as well as in different models of experimental AP. First experience has suggested that early elevation of TAP indicates development of necrotizing AP and that the amount of TAP correlates with the extent of acinar cell necrosis and mortality. It is however unknown whether TAP similarly assess severity of AP in the later course of the disease. The present study monitores TAP in plasma, urine and ascites during the initial development of pancreatic injury and correlates the amount of TAP and the extent of pancreatic necrosis over 48 h in a rodent model of AP. While there was no elevation of TAP in control animals or animals with edemantous AP, significant amounts of TAP im plasma were found as early as 30 min following induction of severe necrotizing AP. Serum amylase returned to normal values within 24 h, TAP maintained at high levels until the end of the 48 h observation period. During the first 24 h TAP paralleled the development of acinar cell necrosis, but decreased thereafter despite further progression of pancreatic injury. Our results provide further evidence suggesting that TAP initially precede morphological changes in AP. Early in the course of the disease TAP parallel development of pancreatic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The authors evaluated cyst fluid CA 72-4 as a tumor marker in the differential diagnosis of pancreatic cystic lesions., Summary Background Data: Pancreatic cystic lesions include inflammatory pseudocysts, serious cystadenomas, and mucinous tumors. Mucinous tumors can be further subdivided into mucinous cystadenocarcinomas and premalignant mucinous cystic neoplasms. The clinical and radiologic features of these lesions are unreliable to make a preoperative diagnosis of these diagnostically difficult lesions. Analysis of aspirated cyst fluid was proposed as an aid to making the preoperative differential diagnosis. Currently, a number of parameters have been reported as useful markers in cyst fluid aspirates, including the tumor markers carcinoembryonic antigen and CA 15.3, enzymes (amylase, lipase, and amylase isoenzymes), relative viscosity, and cytologic analysis. However, owing to the rarity of pancreatic cystic tumors, experience with cyst fluid analysis is limited. To define additional markers that might be useful in the differential diagnosis of pancreatic cysts, the authors measured the tumor-associated glycoprotein 72 (TAG-72) in aspirates from 19 pancreatic cystic lesions., Methods: Cyst fluid from 19 pancreatic cysts was obtained by needle aspiration. The tumor marker TAG-72 was measured by a commercial (CA 72-4) immunoassay., Results: Cyst fluid CA 72-4 levels in mucinous cystadenocarcinomas were markedly elevated (mean, 10,027 U/mL; range, 780 to 34,853 U/mL) compared with that in pseudocysts (mean, 3.8 U/mL; range, < 3 to 5.7 U/mL) and serous cystadenomas (mean and range, < 3 U/mL; p < 0.001). The level of CA 72-4 in benign mucinous cystic neoplasms was intermediate (mean, 44.2 U/mL; range, < 3 to 137 U/mL), but it was statistically different from either carcinomas (p = 0.009) or benign cysts (p < 0.001).

Background/aims: Contrast-enhanced computed tomography (CECT) is used to show areas of decreased pancreatic perfusion in severe acute pancreatitis (AP). To evaluate possible adverse effects of the contrast medium (CM) on the course of AP, the impact of intravenous CM in AP of graded severity in the rat was studied., Methods: Pancreatitis of three levels of severity was induced in Sprague-Dawley rats with intravenous cerulein hyperstimulation plus time- and pressure-controlled intraductal infusion of saline or glycodeoxycholic acid. At 7 hours, control and pancreatitis animals received intravenous ionic CM, nonionic CM, or saline. The principal outcome measures were 24-hour survival, trypsinogen activation peptides (TAP) in ascites, and histological acinar necrosis score., Results: There was no measurable effect of CM on the index features in control animals or animals with mild or moderate AP. In severe AP, CM caused a significant increase in mortality, ascites TAP, and necrosis score., Conclusions: Intravenous CM increases pancreatic injury when administered early in the course of severe experimental AP. Because CM may convert borderline ischemia to irreversible necrosis, CECT performed early in pancreatitis to show poor perfusion and predict areas of necrosis may depict a self-fulfilling prophecy. Early CECT should be reconsidered and perhaps avoided.

Background: Inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors comprise most cystic lesions of the pancreas. The mucinous tumors include mucinous cystic neoplasms, which are benign on histologic examination but have the potential for malignant transformation, and mucinous cystadenocarcinomas. Accurate preoperative classification of pancreatic cysts with clinical and radiologic criteria is often impossible, and as a result many cystic tumors are inappropriately treated as pseudocysts. Analysis of percutaneous needle-aspirated cyst fluid for tumor markers, enzymes, viscosity, and cytologic study has been proposed as a useful modality to distinguish mucinous from nonmucinous cystic lesions. However, no reliable cyst fluid parameter distinguishes benign from malignant mucinous tumors., Methods: The concentration of the tumor marker CA 15-3 was measured by immunoassay in cyst fluid from six pseudocysts, five serous cystadenomas, three mucinous cystic neoplasms, and six mucinous cystadenocarcinomas., Results: The concentration of CA 15-3 in the cyst fluid of mucinous cystadenocarcinomas was higher (mean, 178 units/ml; range, 40 to 392) than that of mucinous cystic neoplasms (mean, 4.7 units/ml; range, 0 to 14), serous cystadenomas (mean, 9.2 units/ml; range, 0 to 32), and pseudocysts (mean, 15.3 units/ml; range, 0 to 66). An upper cutoff value of 30 units/ml distinguished mucinous cystic neoplasms from mucinous cystadenocarcinomas with 100% sensitivity and 100% specificity (p = 0.01)., Conclusions: Production of CA 15-3 appears to coincide with malignant transformation in pancreatic mucinous cystic neoplasms. We conclude that measurement of CA 15-3 levels in the cyst fluid is useful in the differentiation of benign from malignant pancreatic mucinous cysts.

The procedure of percutaneous aspiration and analysis of cyst contents has been advocated to provide a preoperative diagnosis of pancreatic cystic lesions (pseudocysts and cystic tumors), but it is not known whether variation in the contents of separate loculi of a multilocular neoplasm might misrepresent the identity of the tumor. The authors measured the cyst fluid carcinoembryonic antigen (CEA) level, fluid viscosity, and amylase content and performed cytologic analysis on aspirates rates from ten different loculi of a single mucinous cystic neoplasm of the pancreas. The CEA levels were highly variable (median, 6,326 ng/mL; range, 962-64,670 ng/mL) but in all cases were diagnostic of a mucinous tumor. Fluid relative viscosity values were also variable (median, 2.4; range, 1.3-10+) but diagnostic in eight of nine aspirates. The amylase content in all of the loculi was low (< 91 U/L), and values were consistent with a cystic tumor. Cytologic analysis showed diagnostic mucin-secreting epithelial cells in nine of ten loculi. Although cytologic examination was nondiagnostic in one loculus, there were no false-positive results for malignancy. The combination of all four tests would not have resulted in misclassification of any of the tumors. The authors conclude that the characteristics of the contents of different loculi of pancreatic cystic neoplasms may be variable, but the use of a combination of tests still ensures accurate diagnosis.

Pancreatic cystic lesions include inflammatory pseudocysts, benign serous tumors, and mucinous neoplasms, some of which are malignant. Clinical and radiologic indices are often inadequate to discriminate reliably among these possibilities. In an attempt to develop new preoperative diagnostic criteria to assist in decisions regarding therapy, the authors have performed cyst fluid analysis for tumor markers (carcinoembryonic antigen: CEA, CA 125, and CA 19.9), amylase content, amylase isoenzymes, relative viscosity, and cytology on 26 pancreatic cysts. The cases included nine pseudocysts, five serous cystadenomas, 4 mucinous cystic neoplasms, 7 mucinous cystadenocarcinomas, and one mucinous ductal adenocarcinoma with cystic degeneration. Carcinoembryonic antigen levels were high (> 367) in all benign and malignant mucinous cysts, but were low (< 23) in the pseudocysts and benign serous cystadenomas, an indication that CEA discriminates between mucinous and nonmucinous cysts (p < 0.0001). Values for CA 125 were high in all malignant cysts, low in pseudocysts, and variable in mucinous cystic neoplasms and serous cystadenomas. Levels of Ca 19.9 were nondiscriminatory. Cyst fluid amylase and lipase content were variable but were generally high in pseudocysts and low in cystic tumors. Amylase isoenzyme analysis was useful to differentiate pseudocysts from cystic tumors. Measurement of the relative viscosity in cyst fluid showed high (> serum viscosity) values in 89% of mucinous tumors and low values (< serum) in all pseudocysts and serous cystadenomas (p < 0.01). Cytologic analysis of cyst fluids was of limited value in differentiating pseudocysts from serous cystadenoma, but in seven of eight mucinous tumors provided useful diagnostic information and correctly classified three of five malignant tumors. The authors conclude that cyst fluid analysis can provide a preoperative classification of these diagnostically difficult lesions. The combination of viscosity, CEA, CA 125, and cytology can reliably distinguish malignant cystic tumors and potentially premalignant mucinous cystic neoplasms from pseudocysts and serous cystadenomas. Amylase content with isoenzyme analysis is useful to identify pseudocysts.

Acinar necrosis in patients with acute pancreatitis can be due to enzymatic injury, ischemia, or both. We hypothesized that novel therapy aimed at an improvement of pancreatic microcirculation early in the course of pancreatitis may reduce the lethality and acinar damage. Forty-six dextran-resistant rats received controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L), followed by intravenous cerulein (5 micrograms/kg/h) for 6 hours. Beginning 30 minutes after the induction of pancreatitis, all animals were resuscitated with Ringer's lactate (RL) (8 mL/kg/h intravenously for 9 hours). In addition, they were given intra-aortic bolus infusions (2 mL/kg at 30, 60, 90, and 150 minutes) of either RL, sodium chloride (NaCl) (7.5%) and dextran 60,000 (10%) (HHS-60), NaCl (7.5%) and dextran 500,000 (10%) (HHS-500), or NaCl (0.9%) and dextran 500,000 (10%) (DEX-500). Despite high-volume fluid resuscitation in the groups that received RL and HHS-60, 70% of the animals in each of these groups died within 24 hours. In contrast, the mortality rates in the groups of animals that received HHS-500 and DEX-500 were dramatically reduced to 0% and 10%, respectively (p = 0.005, p = 0.02). Histopathologic scores for acinar necrosis were significantly lower in the group of animals that received DEX-500 (p < 0.009) compared with those that received RL and HHS-60. Finally, total amounts of trypsinogen activation peptides in ascites were significantly lower in the animals that received HHS-500 (p < 0.004) and DEX-500 (p < 0.02) compared with those that received RL and HHS-60. Rapid bolus infusion of hyperoncotic ultrahigh molecular weight dextran solution with or without hypertonic saline but not RL or hypertonic-hyperoncotic saline-dextran significantly reduced pathologic trypsinogen activation, prevented acinar necrosis, and improved survival in acute experimental pancreatitis. We speculate that a sustained improvement of pancreatic microcirculation by ultrahigh molecular weight dextran is the mechanism of action.

We describe a giant cell tumor of the pancreas composed of a mixture of osteoclastic and pleomorphic cell types. This rare tumor had a unique immunohistochemical profile. Both types of tumor giant cells stained for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, synaptophysin, muscle actin, and neuron-specific enolase, but not for epithelial markers. Electron microscopy showed cells which resembled primitive fibroblasts and osteoclast with no epithelial features. These findings are most consistent with mesenchymal differentiation. The extensive homologies in immunohistochemical staining of both osteoclastic and pleomorphic giant cells in this case indicates that these cells are histogenetically related.

We reviewed 30 cases of breast cancer originally diagnosed as medullary carcinoma during a 10-year period. Of the 30, only 9 proved to be "typical medullary carcinoma" with the associated favorable prognosis. Seven of the remaining 21 cancers were reclassified as "atypical medullary carcinoma," and the remaining 14 were nonmedullary cancers. Overdiagnosis of medullary carcinoma could lead to inappropriately conservative therapy, since medullary carcinoma is a prognostically favorable neoplasm. Those involved with diagnosis and treatment of patients with breast cancer should be aware of this potential problem.

Aortoesophageal fistula is a rare disorder that may result from many causes. In this report, we describe the unique case of a 71-year-old woman who developed an aortoesophageal fistula following prolonged placement of a nasogastric tube. The presence of dense fibrous adhesions between the aorta and esophagus may have facilitated the development of aortoesophageal fistula in this patient.

Adrenal pseudocysts are cystic lesions arising within the adrenal gland surrounded by a fibrous tissue wall devoid of a recognizable lining layer. This study comprised eight adrenal pseudocysts surgically excised at the Massachusetts General Hospital. The median age of the patients was 41 years. Seven of the eight individuals were women. There was no apparent etiologic relationship to prior trauma or pregnancy. Half of the patients described symptoms that resolved following pseudocyst removal. The remaining individuals were asymptomatic with adrenal pseudocysts discovered incidentally during the work up of other medical problems. Adrenal pseudocyst size ranged from 1.8 to 10 cm. Pseudocyst size did not correlate with the presence of symptoms. The histologic and immunohistochemical findings in this study suggest that at least some adrenal pseudocysts are of vascular origin. In two lesions, small foci of residual cells lining the inner pseudocyst wall were found that expressed factor VIII antigen (also Ulex Europaeus lectin in one case) but not vimentin, keratin, or epithelial membrane antigen. In both cases, abundant elastic tissue was present in the pseudocyst wall, and in one lesion, adrenal vein smooth muscle was present as well. In both cases, dilated sinusoids were found at the periphery of the pseudocysts and, in one lesion, the sinusoids appeared to coalesce to form the pseudocyst cavity. In the majority of the remaining six cases there was also some histologic evidence to suggest a vascular origin. In five and three cases, respectively, abundant elastic tissue and adrenal vein smooth muscle were found within the pseudocyst wall. In two lesions, both elastic tissue and smooth muscle were present. In addition, adrenal sinusoids were prominently dilated at the periphery of four pseudocysts and, in one case, the sinusoids appeared to coalesce to form the pseudocyst cavity.