Biomedical subjects

John A Dumot

Publications and source records attributed to John A Dumot.

15 recordsLinked to original sources

PubMed2006

ERCP: current uses and less-invasive options.

Endoscopic retrograde cholangiopancreatography (ERCP) is well suited for the evaluation and treatment of diseases of the bile ducts and pancreas, but it carries the risk of inducing pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography have exceptional value in imaging the gallbladder, common hepatic duct, common bile duct, and pancreas. These imaging studies have replaced ERCP for diagnostic purposes in patients with a low pretest probability of finding lesions amenable to endoscopic therapy, such as bile duct stones.

Bile Duct Diseases↗

PubMed2005

Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam.

BACKGROUND AND AIMS: Although moderate (conscious) sedation is intended during elective gastrointestinal endoscopy, unintended levels of deep sedation occur. The aims of this study were to prospectively evaluate the incidence and risk factors of deep sedation during elective endoscopy with meperidine and midazolam intended to maintain a level of moderate sedation. METHODS: Eighty American Society of Anesthesiology class 1-2, outpatients presenting for elective esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) were offered enrollment. Intravenous meperidine and midazolam were administered according to a standardized protocol. Hemodynamic parameters and levels of sedation were assessed and recorded by a single observer at 3-min intervals. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale (ranging 1-5) is a subjective sedation assessment scale used to assess sedation levels. Occurrence of deep sedation, defined by MOAA/S 1-2, was recorded. Univariable and multivariable analyses were used to assess predictors of deep sedation. RESULTS: Deep sedation occurred in 54/80 (68%) patients for a total of 204/785 (26%) of total sedation assessments. The percentage of deep sedation episodes of all sedation-level observations by procedure was 26% for EGD, 11% for colonoscopy, 35% for ERCP, and 29% for EUS. Deep sedation occurred at least once in 60% of EGD, 45% of colonoscopy, 85% of ERCP, and 80% of EUS. Multivariable analysis showed that only ERCP and EUS were independent risk factors of deep sedation. CONCLUSIONS: Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam used with the intent of moderate sedation. ERCP and EUS are risk factors for the occurrence of deep sedation, independent of sedation dose or length of procedure.

Aged↗

PubMed2005

Endoscopic ultrasound errors in esophageal cancer.

BACKGROUND: Previous assessments of endoscopic ultrasound (EUS) classification of esophageal cancer are dominated by symptomatic patients with advanced stage disease. Fewer data exist on EUS errors in a cohort balanced between early and advanced disease. PURPOSE: Assess EUS errors in classification of esophageal cancer in a more balanced cohort, and identify clinical and tumor characteristics associated with EUS errors. METHODS: A total of 266 patients underwent EUS and esophagectomy without preoperative chemoradiotherapy. Pathologic classification of disease extent: 108 (41%) tumors were confined to the esophageal wall (pTis-pT2, pN0, pM0); 158 (59%) were advanced beyond (pT3-pT4, pN1, or pM1). Logistic regression analysis was performed to identify correlates of error in T classification and disease extent using 10 clinical and tumor characteristics (gender, age, dysphagia, weight loss, tumor length, location, traversability, morphology, histopathologic type, and histologic grade). RESULTS: EUS erroneously predicted pathologic T (pT) in 119 patients (45%). When T classification was dichotomized into tumors whose depth of invasion was not beyond the muscularis propria (pTis-pT2) and those beyond (pT3-pT4), errors occurred in 42 patients (16%). EUS erroneously predicted N classification in 67 patients (25%), and was insensitive to the presence of distant metastases. EUS misclassified disease extent in 40 patients (15%). Logistic regression analysis indicated that weight loss and tumor length were the only clinical and tumor characteristics correlated with EUS errors; more weight loss was associated with decreased odds of misclassification, while the odds of misclassification were four to six times greater for intermediate length tumors than for shorter tumors. CONCLUSIONS: EUS errors, particularly in predicting pT, are more frequent than previously reported. Weight loss and tumor length are the only clinical and tumor characteristics correlated with EUS errors.

Diagnostic Errors↗

PubMed2004

Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects.

BACKGROUND: Traditional pancreatic function tests are sensitive for the diagnosis of pancreatic exocrine insufficiency but are cumbersome and difficult to perform. A sedationless endoscopic pancreatic function test that has the potential for wide clinical application was developed by us, but data on the results of this method in healthy subjects are lacking. This study analyzed endoscopically collected duodenal fluid from healthy subjects after synthetic porcine secretin stimulation. METHODS: Healthy subjects underwent the sedationless endoscopic pancreatic function test. After secretin stimulation, duodenal aspirates were obtained every 5 minutes for 1 hour. The collected fluid was analyzed for electrolyte concentrations. RESULTS: Sixteen healthy subjects (8 women, 8 men; median age 34.5 years) underwent the endoscopic pancreatic function test. The concentrations of the sodium ([Na+]) and potassium ([K+]) cations remained constant, similar to normal concentrations in plasma (median [Na+], 155 mEq/L; median [K+], 4.3 mEq/L). The concentrations of the bicarbonate ([HCO 3 - ]) and chloride anions increased and decreased, respectively, in an inverse and reciprocal manner, similar to the previously characterized "secretory curve." The median peak [HCO 3 - ] was 108 mEq/L IQR: 99-110). By the 20-minute collection, the [HCO 3 - ] was greater than 80 mEq/L for 94% (15/16) of subjects, the historic cut point for [HCO 3 - ] in studies based on traditional methods of pancreatic function testing. CONCLUSIONS: Endoscopic collection of pancreatic fluid reproduces the anion-cation secretory curve described by prior studies of pancreatic secretory physiology based on traditional collection methods.

Adult↗

PubMed2004

Analysis of pancreatic elastase-1 concentrations in duodenal aspirates from healthy subjects and patients with chronic pancreatitis.

Fecal pancreatic elastase 1 (PE-1) has been advocated as a noninvasive marker of pancreatic function and allows detection of moderate and severe exocrine insufficiency. Few studies have evaluated the utility of measuring PE-1 in duodenal fluid for the diagnosis of pancreatic insufficiency. Our purpose was (1) to determine the feasibility of measuring PE-1 concentrations in duodenal aspirates obtained through our endoscopic pancreatic function test (ePFT) in healthy subjects and patients with chronic pancreatitis (CP) and (2) to determine correlations between duodenal PE-1 concentrations and bicarbonate and lipase concentrations in duodenal fluid. Healthy subjects (HS) and CP patients underwent an ePFT with CCK or secretin. CP was defined as endoscopic retrograde pancreatography (ERP) Cambridge class III-IV, endoscopic ultrasound (EUS) score >5, or presence of pancreatic calcifications on CT scan. Duodenal fluid PE-1, lipase, and bicarbonate concentrations were measured in each study group. Duodenal lipase and bicarbonate concentrations were measured using an autoanalyzer (Roche Diagnostics, Indianapolis, IN). PE-1 was measured using an ELISA (Genova Diagnostics, Asheville, NC). Ten HS and 10 CP patients were studied. In the CCK test the median peak lipase for HS and CP was 1605 and 113 IU/L, respectively (P < 0.008). In the secretin test the median peak bicarbonate for HS and CP was 102 and 40 mEq/L, respectively (p < 0.008). Median PE-1 concentrations for HS and CP were 317 and 63 microg/ml, respectively, after CCK stimulation (p = 0.046) and 87 and 17 microg/ml, respectively, after secretin stimulation (p = 0.033). Statistically significant correlations were found between [PE-1] and peak [lipase] (r = 0.83, P < 0.001), as well as [PE-1] and peak [HCO3(3)-] (r = 0.65, P = 0.037). Conclusions are as follows: (1) PE-1 concentrations can be measured from duodenal fluid obtained by endoscopic aspiration. (2) Duodenal fluid PE-1 concentrations are decreased in CP compared to HS. (3) Duodenal fluid [PE-1] has an excellent correlation with [lipase] and therefore is a marker of acinar cell function. (4) Secretin-stimulated endoscopic function testing with measurement of bicarbonate and PE-1 may provide a simultaneous assessment of both ductal cell and acinar cell function.

Adult↗

PubMed2003

An endoscopic pancreatic function test with cholecystokinin-octapeptide for the diagnosis of chronic pancreatitis.

BACKGROUND & AIMS: Current pancreatic function tests are cumbersome and unavailable to the clinical gastroenterologist. We have developed a function test that can be modified to a purely endoscopic collection method (ePFT). The aim of this study was to compare the endoscopic and traditional Dreiling tube collection methods. METHODS: Two separate groups of healthy subjects and patients with chronic pancreatitis underwent pancreatic function testing. One group underwent the endoscopic collection method (ePFT). Intravenous cholecystokinin (CCK 40 ng x kg(-1) x h(-1)) was started in preprocedure area. Duodenal fluid was collected with upper endoscope during endoscopy at 30, 40, 50, and 60 minutes during infusion. Another group underwent the traditional Dreiling collection method. Intravenous CCK was started in postprocedure area after endoscopic tube placement. Duodenal fluid was collected at 0, 20, 40, 60, and 80 minutes during infusion. Lipase concentration was determined (IU/L) on laboratory autoanalyzer. RESULTS: Seventy-three patients were studied. Thirty-four underwent endoscopic collection and 39 underwent Dreiling collection. The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the endoscopic collection method group were 1612500 +/- 556152 IU/L and 369594 +/- 281624 IU/L, respectively (P < 0.001). The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the Dreiling tube collection method group were 1670324 +/- 786731 IU/L and 478956 +/- 406061 IU/L, respectively (P < 0.001). There was no statistical difference between collection methods at distinguishing healthy subjects and patients with chronic pancreatitis. Receiver operating characteristic curves (ROC) for the endoscopic and Dreiling collection methods were 0.993 (standard error of mean, 0.009) and 0.921 (standard error of mean, 0.041). A lipase concentration cut point of 810600 IU/L distinguishes healthy subjects from patients with chronic pancreatitis with a sensitivity and specificity of 92% and 95%, respectively. The ePFT was safe, short in duration, minimized costs (US dollars 1890 vs. US dollars 2659), required small amounts of fluid for analysis (1-3 mL), and eliminated radiation exposure. CONCLUSIONS: Analysis of timed endoscopic aspirations of pancreatic juice after hormonal stimulation can distinguish healthy subjects from patients with chronic pancreatitis. This new endoscopic collection method (ePFT) is less cumbersome and more time efficient, when compared to traditional collection methods. The ePFT broadens the availability of function testing to the practicing clinical gastroenterologist.

Adult↗

PubMed2003

An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis.

BACKGROUND: Pancreatic function tests are the most reliable methods for the diagnosis or exclusion of chronic pancreatitis in patients without obvious radiologic changes, but they are cumbersome, time consuming, and unavailable in clinical practice. Synthetic porcine secretin, a 27 amino acid peptide identical to the biologic form, is available for exocrine function testing. This study examined the utility of a simple, newly developed, purely endoscopic pancreatic function test with synthetic porcine secretin. METHODS: Three groups of patients were studied: patients with chronic abdominal pain with and without risk factors for chronic pancreatitis, and patients with advanced chronic pancreatitis. All patients with abdominal pain had "pancreatic type" pain for greater than 6 months and negative radiographic imaging studies. All patients with chronic pancreatitis had advanced disease based on retrograde pancreatography and/or CT findings. Participants underwent the following protocol: (1) standard endoscopy to the descending duodenum with the patient under conscious sedation; (2) intravenous administration of secretin (0.2 microgram/kg); (3) endoscopic duodenal fluid collection at 0, 15, 30, 45, and 60 minutes after secretin injection; and (4) fluid analysis for bicarbonate concentration. RESULTS: Eighteen patients were studied (5 abdominal pain without risk factors, 7 abdominal pain with risk factors, and 6 advanced chronic pancreatitis). Median peak (interquartile range) bicarbonate concentrations in meq/L for each group were, respectively, 87 (6, range 84-108), 72 (10, range 68-90), and 35 (27, range 18-88). Median peak bicarbonate concentration values for the 3 groups are significantly different (p = 0.010; Kruskal-Wallis test). Bicarbonate secretion in patients with chronic pancreatitis was markedly reduced compared with that in patients with abdominal pain without risk factors (p = 0.038; the Fisher exact test). The secretory function curve for patients with abdominal pain with risk factors was markedly abnormal, resembling the attenuated secretory curve seen in patients with chronic pancreatitis. The test was safe and well tolerated. CONCLUSIONS: A simple endoscopic pancreatic function test with synthetic porcine secretin appears to distinguish patients with known chronic pancreatitis from those with chronic abdominal pain without chronic pancreatitis. This simple, practical endoscopic test can be performed during upper endoscopy and may decrease the need for invasive procedures in patients with abdominal pain and normal radiographic imaging studies.

Abdominal Pain↗

PubMed2002

Cytokeratin expression patterns in noncardia, intestinal metaplasia-associated gastric adenocarcinoma: implication for the evaluation of intestinal metaplasia and tumors at the esophagogastric junction.

BACKGROUND: Barrett esophagus (BE)/Barrett adenocarcinoma and distal gastric intestinal metaplasia (IM)/adenocarcinoma are similar histologically, but they differ in their clinical presentation, epidemiology, and pathogenesis. Differentiating BE from gastric IM and Barrett adenocarcinoma from gastric adenocarcinoma is difficult, especially when IM is short or tumors are large and involve both sides of the esophagogastric junction. Previously, the authors identified unique cytokeratin (CK) immunoreactivity patterns that were associated strongly with BE and Barrett adenocarcinoma. The specificity of CK7 and CK20 (CK7/20) expression patterns in patients with IM-associated gastric adenocarcinoma, which is distinct epidemiologically from BE/Barrett adenocarcinoma, has not been evaluated. The objective of the current study was to evaluate the CK7/20 expression patterns in noncardia, IM-associated gastric adenocarcinoma in a Chinese population with a low risk for BE and esophageal adenocarcinoma and a high risk for Helicobacter pylori infection and gastric carcinoma. METHODS: Endoscopic biopsy specimens of gastric IM and adjacent tumor from 50 consecutive patients with advanced noncardia gastric carcinoma were immunostained for CK7 and CK20. Clinical and endoscopic features and H. pylori status were documented. Two gastrointestinal pathologists, blinded to clinical and endoscopic data, independently assessed CK7/20 immunohistochemistry. RESULTS: H. pylori infection was present in 43 of 50 patients (86%). In the area of IM, patchy CK7 staining was seen in 9 patients (18%), and diffuse CK20 staining was seen in all 50 patients (100%). The BE CK7/20 pattern characterized by CK7 staining in superficial and deep glands and the CK20 staining in surface epithelium was not seen in any of the 50 patients. Only one patient (2%) demonstrated a CK7 positive/CK20 negative immunophenotype characteristic of Barrett adenocarcinoma. The remaining 49 patients (98%) showed non-Barrett adenocarcinoma patterns of CK7/20 staining, i.e., a CK7 positive/CK20 positive pattern was seen in 33 patients (66%), a CK7 negative/CK20 positive pattern was seen in 12 patients (24%), and a CK7 negative/CK20 negative pattern was seen in 4 patients (8%). CONCLUSIONS: In a patient population without risk factors for the development of BE/esophageal adenocarcinoma, the CK7/20 pattern characteristic of BE was not present in gastric IM adjacent to adenocarcinoma, and the CK7/20 pattern characteristic of Barrett adenocarcinoma also was extremely rare. These results support the hypothesis that, despite the presence of intestinalized mucosa in both disorders, BE/Barrett adenocarcinoma and gastric IM/adenocarcinoma are two distinct clinical entities with unique demographic, clinical, and CK immunophenotypic findings. These results may have application to the evaluation of patients with IM and adenocarcinoma arising at the esophagogastric junction.

Adenocarcinoma↗

PubMed2002

Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial.

BACKGROUND & AIMS: Propofol is increasingly used for gastrointestinal endoscopy because of its rapid recovery profile. There has been no prospective, randomized comparison of gastroenterologist-administered propofol to meperidine and midazolam for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. Additionally, its cost-effectiveness has not been studied. METHODS: Seventy-five randomized patients received either gastroenterologist-administered propofol (n = 38) or meperidine/midazolam (n = 37) for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. Monitoring with capnography allowed for rapid titration of propofol at the earliest signs of respiratory depression. Visual analogue scales measured tolerance and satisfaction. A cost-effectiveness analysis was performed by using return to baseline for both activity and food intake 24 hours after the procedure as the effectiveness measure. RESULTS: The groups had similar physiological outcomes and satisfaction. Patients receiving propofol had shorter recovery times (P < 0.001) and a higher recovery of both baseline activity level and dietary intake 24 hours after the procedure (P = 0.028). With incremental cost-effectiveness analysis, gastroenterologist-administered propofol cost an additional $403.00 per additional patient at 100% of baseline for both activity level and food intake when compared with standard sedation and analgesia. Sensitivity analysis indicated that the only model in which propofol administration would become the dominant strategy was with its administration by a registered nurse. CONCLUSIONS: Gastroenterologist-administered propofol using monitoring with capnography is similar to meperidine/midazolam for both physiological outcomes and patient/endoscopist satisfaction. Propofol leads to significantly improved recovery of baseline activity and food intake 24 hours after the procedure. Our model suggests that propofol would be more cost-effective than meperidine and midazolam for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography if registered nurse administration were possible.

Analgesics, Opioid↗

PubMed2002

Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy.

BACKGROUND: Recommendations from the American Society of Anesthesiologists suggest that monitoring for apnea using the detection of exhaled carbon dioxide (capnography) is a useful adjunct in the assessment of ventilatory status of patients undergoing sedation and analgesia. There are no data on the utility of capnography in GI endoscopy, nor is the frequency of abnormal ventilatory activity during endoscopy known. The aims of this study were to determine the following: (1) the frequency of abnormal ventilatory activity during therapeutic upper endoscopy, (2) the sensitivity of observation and pulse oximetry in the detection of apnea or disordered respiration, and (3) whether capnography provides an improvement over accepted monitoring techniques. METHODS: Forty-nine patients undergoing therapeutic upper endoscopy were monitored with standard methods including pulse oximetry, automated blood pressure measurement, and visual assessment. In addition, graphic assessment of respiratory activity with sidestream capnography was performed in all patients. Endoscopy personnel were blinded to capnography data. Episodes of apnea or disordered respiration detected by capnography were documented and compared with the occurrence of hypoxemia, hypercapnea, hypotension, and the recognition of abnormal respiratory activity by endoscopy personnel. RESULTS: Comparison of simultaneous respiratory rate measurements obtained by capnography and by auscultation with a pretracheal stethoscope verified that capnography was an excellent indicator of respiratory rate when compared with the reference standard (auscultation) (r = 0.967, p < 0.001). Fifty-four episodes of apnea or disordered respiration occurred in 28 patients (mean duration 70.8 seconds). Only 50% of apnea or disordered respiration episodes were eventually detected by pulse oximetry. None were detected by visual assessment (p < 0.0010). CONCLUSIONS: Apnea/disordered respiration occurs commonly during therapeutic upper endoscopy and frequently precedes the development of hypoxemia. Potentially important abnormalities in respiratory activity are undetected with pulse oximetry and visual assessment.

Adult↗

PubMed2002

Quantitative assessment of psychomotor recovery after sedation and analgesia for outpatient EGD.

BACKGROUND: Sedation and analgesia are routinely used to improve patient tolerance for GI endoscopy. Currently, assessment of postprocedure recovery uses cardiovascular and respiratory parameters but not psychomotor function. The two aims of this study were to determine degree of psychomotor recovery after conscious sedation for endoscopy when patients meet established discharge criteria, and to identify a sensitive method of testing psychomotor recovery, and thereby provide meaningful predictions regarding the ability of patients to return to daily activities. METHODS: Outpatients undergoing elective EGD were recruited. Four psychometric tests were used to establish baseline psychomotor function before sedation and analgesia: Critical Tracking, Manual Dexterity, Multiple-Choice Reaction Time, and Letter Cancellation. Meperidine and midazolam were administered intravenously per standard nomogram. The tests were repeated immediately after the procedure and at 15-minute intervals until patients were deemed ready for discharge by recovery room personnel. Discharge criteria included an Aldrete discharge score of 10 and the ability to ambulate unhindered and carry on a simple conversation. Recovery personnel were blinded to psychometric test results. Psychomotor scores at discharge were compared with baseline scores to determine percent recovery. RESULTS: Thirty-one patients (12 men, 19 women; mean age 43 years, range 18-72 years) were enrolled. When Aldrete discharge criteria were met, the average psychomotor recovery was only 60% to 70% compared with baseline. At the time of discharge, average psychomotor recovery was 86.5% of baseline. Letter Cancellation and Multiple-Choice Reaction Time had the highest sensitivity in detecting depression of psychomotor function versus baseline, with mean recovery of, respectively, 64% and 63% (p < 0.0001). CONCLUSIONS: Psychomotor function remains significantly impaired when patients reach an Aldrete discharge score of 10. The Letter Cancellation test was most sensitive in detecting psychomotor impairment and recovery. Incorporating psychometric tests with current discharge criteria may identify patients who are better able to resume normal daily activities without supervision.

Adolescent↗

PubMed2002

Prospective preoperative determination of mucinous pancreatic cystic neoplasms.

BACKGROUND: Optimal management of pancreatic cystic neoplasms includes identification and resection of mucinous neoplasms. This study was performed to assess the accuracy of preoperative variables in determining a mucinous lesion. METHODS: Patients referred for a cystic neoplasm were prospectively assessed by presenting symptoms, blinded radiologic review, and endoscopic ultrasound-guided cyst aspirate analysis. Patients who were symptomatic, or had aspirate findings of a mucinous neoplasm were resected. RESULTS: Eighty-seven patients were enrolled over a 22-month period ending in December 2001. There were 56 (64%) women and 31 (36%) men, with a mean age of 63 (27-86) years. Thirty-five (40%) patients were resected including 24 (69%) women and 11 (31%) men with a mean age of 58 years. Twenty-eight (80%) patients who had resection were symptomatic. Specimen histology included 18 (51%) mucinous neoplasms, 8 (23%) serous neoplasms, 4 (11%) ductal or neuroendocrine carcinomas, and 3 (9%) pseudocysts. The positive predictive value (PPV) for cyst-aspirate extracellular mucin (83%) was significant in predicting a mucinous neoplasm (P =.009). No other aspirate variables (amylase, carcinoembryonic antigen, CA15-3, viscosity), or patient characteristics were predictive of final histology. Diagnostic agreement between all 3 radiologists was 8% (P =.98). At a median follow-up of 12 months, no patients who were observed required resection. CONCLUSIONS: Patients with suspected pancreatic cystic neoplasms can be selectively treated on the basis of symptoms and cyst-aspirate mucin analysis. Symptomatic and mucin containing lesions should be resected.

Adenocarcinoma, Mucinous↗

PubMed2002

Analysis of duodenal drainage fluid after cholecystokinin (CCK) stimulation in healthy volunteers.

INTRODUCTION AND AIMS: Hormonal stimulatory agents are used to assess pancreatic function. Biologically derived secretin, the most widely used pancreatic secretagogue, is no longer available in the United States. Existing secretory tests using cholecystokinin alone are cumbersome, requiring a unique dual tube (gastric and duodenal) collection system and constant perfusion of a nonabsorbable marker to calculate enzyme output (in international units [IU]). A simpler, quantitative cholecystokinin stimulation test that measures enzyme concentrations (in international units per liter [IU/L]) instead of total output would obviate need for marker perfusion/collection. The aim of our experiment was to study the secretory patterns of pancreatic enzyme concentration in duodenal fluid after cholecystokinin stimulation in healthy volunteers. METHODOLOGY: Healthy subjects had a Dreiling tube inserted endoscopically into the ligament of Treitz. Gastric and duodenal aspiration ports were connected to low intermittent suction. A 20-minute baseline was obtained to clear the gastric and duodenal lumina of residual fluid. Cholecystokinin was infused at a constant rate of 40 ng/kg per hour. Duodenal fluid was collected on ice for 80 minutes in four 20-minute aliquots. Aspirated fluid was analyzed for enzyme concentration with an automated chemistry analyzer in the hospital biochemistry laboratory. RESULTS: Nineteen healthy volunteers were studied. The mean volume (+/-SEM) of duodenal fluid collected was 85 +/- 4.4 mL (range, 48 to 118 mL). Fluid analysis revealed a significant rise in mean lipase concentration (+/-SEM) from a baseline of 595,680 +/- 11,930 IU/L to a peak of 1,778,847 +/- 171,204 IU/L (mean difference = 1,183,167 IU/L; 95% CI= 664,459 IU/L to 1,701,875 IU/L; < 0.001, Student test). Increases in amylase concentrations were markedly less pronounced and did not reach statistical significance. Mean peak lipase concentration occurred within 50 minutes of acinar cell stimulation. All patients tolerated tube placement, and there were no episodes of acute pancreatitis or abdominal pain. CONCLUSIONS: Pancreatic lipase concentrations in duodenal fluid increase nearly threefold after cholecystokinin stimulation in healthy volunteers. This magnitude of enzyme secretory response may be a marker of pancreatic function and could potentially lead to a more clinically useful and simpler pancreatic function test. This physiologic study serves as the basis for our further investigations of cholecystokinin-stimulated lipase concentrations as a new test in the assessment of pancreatic insufficiency.

Amylases↗

PubMed2002

Telomerase activity in pancreatic endocrine tumors.

OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr +/- 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type I and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.

Adenoma, Islet Cell↗

PubMed2002

Cholecystokinin-stimulated peak lipase concentration in duodenal drainage fluid: a new pancreatic function test.

OBJECTIVE: Hormonal stimulation with secretin or cholecystokinin (CCK) is the most sensitive means of assessing pancreatic function. Secretin is not available, and current CCK tests are cumbersome, requiring dual tube intubation and marker perfusion techniques. The aim of this study was to test the efficacy of a new CCK-stimulated pancreatic function test measuring peak lipase concentration. METHODS: A Dreiling gastroduodenal tube was inserted to the ligament of Treitz, and fluid was collected on ice for 80 min in four 20-min aliquots. CCK was infused i.v. at a constant rate of 40 ng/kg/h. Gastric aspirations were discarded. Duodenal aspirates were analyzed for volume and enzyme concentration with a clinical laboratory autoanalyzer. RESULTS: Nineteen healthy volunteers and 18 chronic pancreatitis patients were studied. Lipase concentration and secretory volume showed a peak response by 40 min of stimulation, whereas amylase response was variable. The mean peak lipase concentrations (+/-SEM) for normal volunteers and mild, moderate, and advanced chronic pancreatitis patients were 16.9+/-1.9, 7.9+/-1.7, 3.7+/-1.2, and 2.1+/-0.6 x 10 5 IU/L, respectively. Lower peak lipase concentrations were significantly associated with more advanced chronic pancreatitis (p < 0.001). The receiver operating characteristic curve area for all chronic pancreatitis patients was 0.944 (95% CI = 0.825-0.985). A peak lipase concentration of 780,000 IU/L provided a sensitivity and specificity of 0.833 and 0.867, respectively. This CCK test was well tolerated and without complications. CONCLUSIONS: Lipase concentration in duodenal fluid increases nearly 3-fold from baseline after CCK stimulation in healthy volunteers but is markedly reduced in patients with chronic pancreatic disease. Peak lipase concentration is a significant predictor of chronic pancreatitis and correlates with severity of pancreatic disease. Aspiration of duodenal drainage fluid with a Dreiling tube and analysis with a laboratory autoanalyzer are less cumbersome than marker perfusion and back titration techniques. Measurement of enzyme concentration instead of output could lead to the development of an endoscopic or through-the-scope screening method for assessing patients with suspected chronic pancreatitis or chronic abdominal pain.

Adult↗