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Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test.

BACKGROUND: Breath tests using stable isotopes of carbon or hydrogen are increasingly becoming established for the evaluation of various gastrointestinal functions, including measurement of exocrine pancreatic insufficiency. We wanted to evaluate the clinical relevance of the non-invasive, non-radioactive 13C-mixed triglyceride breath test in comparison with the secretin-caerulein test as the 'gold standard' of pancreatic function testing and with faecal chymotrypsin and elastase 1 in patients with mild and severe exocrine pancreatic insufficiency. METHODS: The secretin-caerulein test, faecal fat analysis, 13C-mixed triglyceride breath test, faecal elastase 1, and chymotrypsin and various morphologic investigations were done in 26 patients with mild (n = 13) or severe (n = 13) exocrine pancreatic insufficiency and 25 patients with gastrointestinal diseases of non-pancreatic origin. Twenty-seven healthy volunteers served as normal controls. After a 12-h fast 200 mg mixed triglyceride (1,3-distearyl,2(carboxyl-13C)octanoyl glycerol) were orally administered with a test meal, and breath samples were taken before and at 30-min intervals for 5 h thereafter, and the increase in 13C/12C isotopic ratio in breath was analysed by mass spectrometry. Various modifications of the test procedure were investigated. RESULTS: Specificity for impaired pancreatic function was higher for faecal elastase (90%) and equal for faecal chymotrypsin (82%) as compared with the various variables of the 13C-mixed triglyceride breath test (69-85%). The sensitivity of the 13C-mixed triglyceride breath test for total and separately for mild and severe exocrine pancreatic insufficiency was higher (total, 69-81%) than that of faecal chymotrypsin (total, 56%) but lower than faecal elastase (total, 92%). CONCLUSION: The 13C-mixed triglyceride breath test very sensitively reflects severe exocrine pancreatic insufficiency (steatorrhoea) but has limited sensitivity for the detection of mild cases. With regard to the higher sensitivity and specificity, the higher practicability, and the much lower cost, determination of faecal elastase 1 concentrations is superior to the 13C-mixed triglyceride breath test and therefore remains the most reliable indirect pancreatic function test available today.

Adult↗

Value of combinations of pancreatic function tests to predict mild or moderate chronic pancreatitis.

UNLABELLED: Pancreatic function tests share an insufficient accuracy concerning the detection of mild or moderate forms of chronic pancreatitis. It was evaluated here whether by combination of different assays the prediction or exclusion of chronic pancreatitis could be improved. METHODS: 62 patients with chronic abdominal pain and suspected chronic pancreatitis underwent an endoscopic retrograde pancreaticography. The duct alterations were classified according to the Cambridge criteria. In all individuals the pancreolauryl test in serum (PLT-S) and urine (PLT-U) was performed and elastase 1-immunoreactivity (E) as well as chymotrypsin (Chy) activity in stool were measured. Sensitivities, specificities, receiver-operator-curves as well as cut-off points at optimal accuracies were calculated for each single assay and all test combinations. Cut offs were optimized by a mathematical model to achieve highest accuracies. RESULTS: In 30 patients the pancreatic duct was normal and in 32 patients alterations of the duct system were found. These were classified as mild in 10 patients, as moderate in 8 patients and as severe in 14 patients. In those with mild and moderate disease all pancreatic function tests showed sensitivities/specificities of 60-65% and 65-70%, respectively. Only in severe chronic pancreatitis elastase was superior to the other tests. Combinations of function tests did not lead to improved accuracy. After mathematical optimization the accuracy (sensitivity 80%, specificity 80%) was best for the combination of PLT-S (cut off 4.7 micrograms/ml) and E (cut off 500 micrograms/g). Both parameters had to be below these newly defined cut offs to diagnose chronic pancreatitis. CONCLUSIONS: The accuracy of pancreatic function tests may be improved by use of altered cut offs and a combination of serum pancreolauryl test and elastase. These newly defined cut offs will have to be evaluated in a much larger study.

Adult↗

13C-labeled trioctanoin breath test for exocrine pancreatic function test in patients after pancreatoduodenectomy.

To assess exocrine pancreatic function in patients before and after pancreatoduodenectomy (PD), we used the breath test, with nonradioactive 13C-labeled trioctanoin, in 14 patients before pancreatic resection because of localized pancreatic mass (preop-PD group), and in 13 patients who had undergone pancreatoduodenectomy more than 5 yr before (post-PD group). The results were compared with those of the secretin test, N-benzolyl-L-tyrosyl-p-amino benzoic acid (BT-PABA) test, and fecal chymotrypsin. Means +/- SD and frequencies of low values of the recovery of the breath test were 42.0 +/- 3.4%, 0/5 in the control; 24.2 +/- 10.5%, 14/14 in the preop-PD group; and 18.6 +/- 8.0, 13/13 in the post-PD group. The overall sensitivities in the preop- and post-PD groups were 100% for the recovery and 93% for the maximal mass ratio of the breath test, 89% for the secretin test, 67% for the BT-PABA test, and 64% for fecal chymotrypsin. The recovery of the breath test correlated significantly with the duodenal outputs of lipase, amylase, and chymotrypsin, and was not affected in patients with obstructive jaundice or with low D-xylose absorption. The breath test is as sensitive as the secretin test, more reliable than the conventional tubeless tests, and is available to follow up the exocrine pancreatic function before and after pancreatoduodenectomy.

4-Aminobenzoic Acid↗

Pancreatic function tests in the diagnosis of pancreatic cancer.

Based on the relevant literature data and on personal experience, the author discusses the mechanisms of pancreatic function impairment in patients with pancreatic cancer, and the role of pancreatic function tests in the diagnosis of this disease. Although pancreatic function is reduced in the vast majority of patients with pancreatic cancer, at present pancreatic function tests are of limited value in the diagnostic approach to this tumor. This is mainly due to the fact that in most cases, patients with pancreatic cancer are seen when the cancer is in an advanced stage, and it can be rather easily diagnosed with currently available imaging techniques.

Humans↗

13C-starch breath test--comparative clinical evaluation of an indirect pancreatic function test.

The clinical relevance of the 13C-starch breath test was evaluated in comparison to the secretin-caerulein test as the "gold standard" of pancreatic function testing, fecal elastase concentration, and fecal chymotrypsin activity in 30 patients with mild (n = 15) or severe (n = 15) exocrine pancreatic insufficiency. 23 patients with gastrointestinal diseases of non-pancreatic origin and 31 healthy volunteers served as controls. 50 g of natural starch of maize were orally administered after a 12-h fast and breath samples were taken before and in 30 min intervals for five hours after oral ingestion and the increase of 13C/12C-isotopic ratio was analyzed by mass spectrometry. Specificity of fecal elastase (93%) and fecal chymotrypsin (93%) for impaired pancreatic function were much higher compared to the various parameters of the 13C-starch breath test (69-74%). Sensitivities of the 13C-starch breath test for all and separately for mild and severe exocrine pancreatic insufficiency were higher (total 70-77%) compared to fecal chymotrypsin (total 60%), but lower compared to fecal elastase (total 93%). With regard to the higher sensitivity and specificity, the higher practicability, and the lower costs determination of fecal elastase concentrations is superior to the 13C-starch breath test and therefore remains to be the most reliable indirect pancreatic function test available today.

Adult↗

Pancreatic function testing in cystic fibrosis.

None of the currently available clinical techniques for measuring pancreatic function in patients with CF can be considered "ideal". The "direct" pancreatic stimulation test provides the most information and remains the only truly accurate test of exocrine function, particularly in those individuals with pancreatic sufficiency. The invasive, complex nature of the pancreatic stimulation tests precludes its use as a routine method of assessing pancreatic function in all patients and limits its value for monitoring function in those individuals who are expected to deteriorate with time. Many of the indirect tests of pancreatic function are of value for identifying CF patients with complete pancreatic insufficiency who may require therapy with pancreatic enzyme supplements and fat soluble vitamins. However, none of the currently available "indirect" tests of exocrine function are sensitive enough to evaluate or monitor CF patients with pancreatic sufficiency. Blood tests, capable of measuring pancreatic enzymes in the circulation, such as immunoreactive trypsinogen, may be of value for monitoring pancreatic function in patients with CF, but further longitudinal studies are necessary to fully evaluate this approach. More sophisticated "indirect" tests of exocrine pancreatic function are vitally needed to facilitate adequate assessment of this important digestive organ in patients with cystic fibrosis.

Cystic Fibrosis↗

Pancreatic function tests in the rat model of chronic pancreatic insufficiency.

It has recently been shown that the infusion of oleic acid into the rat pancreaticobiliary duct causes a reproducible and long-lasting atrophy of the exocrine pancreas. The effects of this pancreatic atrophy on non-invasive pancreatic function tests have not been fully characterized. This study was undertaken to determine which pancreatic function test was most useful in determining pancreatic insufficiency in this model. Pancreatic insufficiency (PI) was induced in male Wistar rats by oleic acid infusion and three pancreatic function tests were compared in these animals and saline controls. The coefficient of fat absorption on a 5 or 45% fat diet and bentiromide testing could not differentiate animals with or without PI, but fecal chymotrypsin levels were excellent discriminators. All animals with PI had fecal chymotrypsin levels below 67 U/g feces whereas all saline controls were above this level. We conclude that, in this model of PI, the fecal chymotrypsin concentration is the best non-invasive test to determine pancreatic insufficiency.

Absorption↗

Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis.

The oral (PABA) pancreatic function test (PFT), the secretin-pancreozymin test and endoscopic retrograde pancreatography (ERCP) have been carried out in 32 patients with suspected chronic alcohol induced pancreatitis (CAIP) in order to evaluate which, if any, test was most likely to confirm the provisional diagnosis. Thirty one patients had changes of minimal (n = 6) moderate (n = 7) or advanced (n = 18) chronic pancreatitis on pancreatography, whilst one patient had a pancreas divisum. Eight hour urinary PABA excretion was significantly reduced in patients with moderate and advanced structural changes (p less than 0.001) and correlated significantly with all parameters of the PFT, although eight patients with an abnormal pancreatogram and pancreatic function test had a normal PABA value. The PFT was abnormal in 23 patients, but normal in five patients with an abnormal pancreatogram and low PABA value. Most patients with minimal change pancreatitis had a normal PABA test and PFT. We conclude that pancreatography appears to be the most sensitive method for detecting chronic pancreatic damage and for confirming a clinical diagnosis of chronic alcohol induced pancreatitis. Both the PFT and PABA test are useful confirmatory tests and whilst the PFT is slightly more sensitive for assessing pancreatic exocrine function, the PABA test is well tolerated and simple to perform. It may therefore be the complementary investigation of choice for this group of patients.

4-Aminobenzoic Acid↗

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↗

Evaluation of 60-minute blood p-aminobenzoic acid concentration in pancreatic function testing of dogs.

For evaluation of pancreatic function testing, a peptide that releases p-aminobenzoic acid (PABA) on digestion by chymotrypsin was given to clinically normal dogs and to dogs with unexplained diarrhea. Blood concentration of PABA and percentage of PABA excretion in the urine at 6 hours after oral administration were determined. One-hour blood values did not reflect pancreatic exocrine secretion as well as did the 6-hour urinary excretion values.

4-Aminobenzoic Acid↗

Exocrine pancreatic function test by endoscopic retrograde aspiration of pure pancreatic juice.

The validity of endoscopic retrograde aspiration of pure pancreatic juice (PPJ) as an exocrine pancreatic function test was evaluated in terms of coefficients of variation in control subjects, reproducibility on repeated examinations, and sensitivity for detecting patients with chronic pancreatitis (CP). PPJ was obtained from, nine control subjects, four patients with suspected CP and 13 with CP. PPJ was collected from within the pancreatic duct by endoscopic retrograde catheterization of the papilla at 2-min intervals for 20 minutes after a bolus intravenous injection of secretin (1U/kg) and then for further 20 minutes after a bolus intravenous injection of CCK-PZ (1U/kg). It was recognized that endoscopic aspiration of PPJ was at least as useful and reliable as the traditional pancreozymin secretin test. Useful parameters included 10-min secretory volume and 10-min bicarbonate output after secretin stimulation, and 10-min enzyme output after CCK-PZ stimulation (lipase output showed higher sensitivity than amylase output). Maximal bicarbonate concentration showed poorer reproducibility and sensitivity despite better coefficients of variation. Lower limits in controls (mean-1.5SD) were 22.5ml for 10-min secretory volume, 2.7mEq for 10-min bicarbonate output, 24.5 x 10(3)U for 10-min amylase output and 3.4 x 10(3)IU for 10-min lipase output.

Adult↗

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↗