13C-Hiolein呼气试验对胰腺外分泌功能检测的临床应用

目的测定慢性胰腺炎(CP)13C-Hiolein脂肪酸呼气试验,了解对胰腺功能检测的临床意义.方法A组8例正常志愿者为对照,8例无脂肪泻CP为B组,8例有脂肪泻CP为C组,进食13C-Hiolein后,检测呼气中13CO2,评估胰腺的外分泌功能.C组患者补充胰酶后再行13C-Hiolein试验.结果C组13C-Hiolein呼气试验显示,13C峰值(PDRpeak)和6 h呼出13C累积丰度(cPDR)较A组明显降低[(1.53±0.36)%比(2.87±0.73)%;(6.11±0.59)%比(11.22±1.22)%;P＜0.01],补充胰酶后PDRpeak和cPDR/6h较治疗前明显升高[(2.33±0.47)%,(9.03±0.84)%;P＜0.01],但cPDR/6h低于正常对照组(P＜0.05);B组PDRpeak和cPDR/6h与对照组无明显差异.13C通常在(5.90±1.17)h达到PDRpeak峰值.结论13C-Hiolein能有效地检测胰腺外分泌功能和了解胰酶治疗的疗效.     

13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency

Background—A non-invasive test for assessment offat digestion has been developed based on the intraluminal hydrolysisof cholesteryl-[1-¹³C]octanoate by pancreatic esterase.
Aims—To determine the diagnostic performance ofthis breath test in the assessment of exocrine pancreatic function.
Methods—The test was performed in 20 healthycontrols, 22 patients with chronic pancreatic disease (CPD), four withbiliopancreatic diversion (BPD), and 32 with non-pancreaticdigestive diseases (NPD); results were compared with those of othertubeless tests (faecal chymotrypsin and fluorescein dilaurate test).
Results—Hourly recoveries of¹³CO₂ were significantly lower in CPD whencompared with healthy controls or NPD. In patients with CPD with mildto moderate insufficiency, the curve of ¹³CO₂recovery was similar to that of healthy controls, while in those withsevere insufficiency it was flat. In three patients with CPD withsevere steatorrhoea, a repeat test after pancreatic enzymesupplementation showed a significant rise in¹³CO₂ recovery. The four BPD patients had lowand delayed ¹³CO₂ recovery. Only eight of the32 patients with NPD had abnormal breath test results. There was asignificant correlation between the results of the breath test andthose of faecal chymotrypsin, the fluorescein dilaurate test, andfaecal fat measurements. For the diagnosis of pancreatic disease usingthe three hour cumulative ¹³CO₂ recovery test,the sensitivity was 68.2% and specificity 75.0%; values were similarto those of the other two tubeless pancreatic function tests. In sevenhealthy controls, nine patients with CPD, and nine with NPD a secondbreath test was performed using Na-[1-¹³C]octanoate and apancreatic function index was calculated as the ratio of¹³C recovery obtained in the two tests: at three hours thisindex was abnormal in eight patients with CPD and in three with NPD.
Conclusion—Thecholesteryl-[1-¹³C]octanoate breath test can beuseful for the diagnosis of fat malabsorption and exocrine pancreatic insufficiency.

     

Synthetic 13C-dipeptide breath test for the rapid assessment of pancreatic exocrine insufficiency in rats

OBJECTIVE: (13)C-breath tests have been investigated in order to assess pancreatic exocrine function using various (13)C-compounds, but they have not been accepted for routine clinical use. One of the barriers to their acceptance is that these tests are time-consuming and require up to several hours for breath collection. The purpose of this study was to design a novel (13)C-compound that would make a rapid (13)C-breath test for assessing exocrine pancreatic function possible. MATERIAL AND METHODS: N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was synthesized, and the characteristics of its cleavage in duodenal juice and in the duodenum of rats were examined. Thereafter, a (13)C-breath test was carried out in which N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was given orally to pancreatic exocrine-insufficient and normal control rats. RESULTS: N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was readily cleaved and liberated 1-(13)C-L-alanine in the duodenal juice. Carboxypeptidase was a major contributor to the cleavage. When N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was injected into the duodenum and orally administered to the rats, the (13)C atom% of CO(2) in breath increased rapidly. This indicated that N-benzoyl-L-tyrosyl-1-(13)C-L-alanine in the duodenum liberated (13)C-Ala on cleavage. (13)C-Ala is absorbed and metabolized to liberate (13)CO(2), which is exhaled. It was shown that the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test in the pancreatic exocrine-insufficient rats, in whom the absorption and metabolism of (13)C-Ala was unimpaired, was significantly lower than that in the control rats. CONCLUSIONS: The rate of increase in the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test is expected to be proportional to the rate of N-benzoyl-L-tyrosyl-1-(13)C-L-alanine cleavage by pancreatic proteases in the duodenum. We propose the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test as a rapid test for assessing pancreatic exocrine function.     

Exocrine and endocrine pancreatic insufficiency after pancreatic surgery

The pancreas is the central organ for digestion and for control of glucose homeostasis. Indications for major pancreatic surgery are complications of chronic and acute pancreatitis and pancreatic malignancies. The postoperative pancreatic function is determined by type of resection, resection of adjacent organs, the underlying disease and preoperative pancreatic function. Standard treatment following major pancreatic surgery includes the administration of pancreatic enzyme preparations and inhibition of acid secretion by proton pump inhibitors. Postoperatively most patients also develop diabetes mellitus, which requires insulin substitution. Hypoglycemia is the most difficult clinical problem to handle following total pancreatectomy.     

13C-美沙西丁呼气试验对亚临床肝性脑病的临床价值分析

目的探讨13C-美沙西丁呼气试验对亚临床肝性脑病(SHE)发病率和预后判断等方面的临床应用价值.方法随机选择72例肝硬化患者和31例正常人作为研究对象,对所有受试者进行数字连接试验和智商(IQ)检测,以明确有无SHE,并同步进行13C-美沙西丁呼气试验、血氨等检测.比较13C-美沙西丁呼气试验的肝功能分级与临床Child Pugh分级的关系;采用多因素相关分析,比较13C-美沙西丁呼气试验的分级指标、血氨指标对并发SHE的关系;随访所有肝硬化患者的13C-美沙西丁呼气试验分级结果与SHE的关系.结果肝硬化患者13C-美沙西丁呼气试验的肝功能分级与临床Child Pugh分级的差别无统计学意义(P＞0.05).13C-美沙西丁呼气试验分级为病理性肝损害、Child Pugh A级的两组肝硬化患者中无SHE,SHE患者均出现在13C-美沙西丁呼气试验分级为Child B级或Child C级且血氨值为(90.56±13.66)μmol/L或更高的患者中.在肝硬化患者13C-美沙西丁呼气试验的肝功能分级中,Child C级中SHE的发病率高于Child B级(P＜0.05).随访发现,13C-美沙西丁呼气试验为Child B级和Child C级患者存在并发SHE的危险.结论13C-美沙西丁呼气试验可作为SHE发病的重要评判因素之一并有助于对肝硬化并发SHE的预后判断.     

Prevalence of pancreatic exocrine insufficiency after pancreatic surgery measured by 13C mixed triglyceride breath test: A prospective cohort study

BackgroundPatients undergoing pancreatic surgery are at risk of pancreatic exocrine insufficiency (PEI) and needing pancreatic enzyme replacement therapy (PERT).MethodsThis study included 254 patients undergoing pancreatic surgery for oncologic indications. A¹³C mixed triglyceride breath test was performed immediately preoperative and postoperative. This test analyzes the pancreatic remnant lipase activity measuring ¹³CO₂ in breath samples after a test meal with 1.3-distearyl-(¹³C-Carboxyl)octanol-glycerol. Cumulative percent dose recovery after 6 h of less than 23% confirms PEI. In addition, PEI was compared between pathology subgroups.ResultsIn 197 patients undergoing pancreaticoduodenectomy, cPDR-6h decreased significantly from a median of 32.84% before to 15.80% after surgery (p < 0.0001). This decrease in exocrine function was significant in all pathology subgroups except in pancreatic neuroendocrine tumors. Exocrine function decreased most in pancreatic ductal adenocarcinoma (PDAC). In addition, the percentage of patients needing PERT because of PEI increased from 25.9% to 68.0% postoperative (p < 0.001). Overall, patients with an MPD diameter of more than 3 mm had a higher risk of developing postoperative PEI: 62.7% compared to 37.3% (p = 0.009), OR = 3.11.In contrast, the majority of the 57 patients undergoing a distal pancreatectomy did not experience any significant change in exocrine function.ConclusionsThe vast majority of patients undergoing pancreaticoduodenectomy for oncologic indications experience a significant drop in exocrine function, are at high risk of developing pancreatic exocrine insufficiency and consequently need to be treated with pancreatic enzyme replacement therapy. Therefore, systematic screening for pancreatic exocrine insufficiency is needed after pancreaticoduodenectomy.     

Estimation of exocrine pancreatic insufficiency in children with acute pancreatitis using the 13C mixed triglyceride breath test

Background/Objective: The extent of exocrine pancreatic insufficiency (EPI) in the paediatric population with acute pancreatitis (AP) is unknown. The primary objective was to use a 6 h stable-isotope breath test to determine the prevalence of EPI in children with AP. The secondary objective was to determine the diagnostic ability of a 4 h abbreviated breath test in the detection of EPI.Methods¹³C-mixed triglyceride (MTG) breath test was used to measure fat digestibility in 12 children with AP and 12 normal children. EPI was diagnosed based on a cumulative dose percentage recovery (cPDR) cut-off value < 26.8% present in literature. To reduce the test burden, the diagnostic accuracy of an abbreviated 4 h test was evaluated, using a cPDR cut-off that was the 2.5^th percentile of its distribution in control children.ResultsThe cPDR of cases was significantly lower than that of controls (27.71 ± 7.88% vs 36.37 ± 4.70%, p = 0.005). The cPDR during acute illness was not significantly different to that at 1 month follow up (24.69 ± 6.83% vs 26.98 ± 11.10%, p = 0.52). The 4 h and 6 h breath test results correlated strongly (r = 0.93, p < 0.001) with each other. The new 4 h test had 87.5% sensitivity and 93.8% specificity for detecting EPI.ConclusionTwo-thirds (66.7%) of this sample of children with AP had EPI during admission, which persisted at 1 month follow up. The 4 h abbreviated ¹³C-MTG breath test has good diagnostic ability to detect EPI in children and may improve its clinical utility in this age group.     

Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test.

The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration.     

Comparison of bentiromide test and rice flour breath hydrogen test in the detection of exocrine pancreatic insufficiency

Bentiromide test (BT) has been recently approved in the United States for screening patients with chronic pancreatitis for exocrine insufficiency. A few reports have suggested that the rice flour breath hydrogen test (RFBHT)--i.e., breath hydrogen analysis after rice flour ingestion--may also be useful in diagnosing exocrine pancreatic insufficiency. We conducted this study to compare the diagnostic value of these two tests in chronic alcoholic (n = 14) and nutritional or tropical (n = 6) pancreatitis. False-positive results were not noted with either of these two tests in 12 healthy volunteers. BT was positive in 28.6% of patients with chronic alcoholic pancreatitis and in 16.7% of patients with tropical pancreatitis. In comparison, RFBHT was almost twice as sensitive as BT in detecting insufficiency in patients with alcoholic pancreatitis (50 vs. 28.6%) and four times as sensitive in patients with tropical pancreatitis (66.7 vs. 16.7%). Only one patient in our study had a positive BT but a negative RFBHT. We recommend RFBHT as a simple, safe, and inexpensive test in screening patients for exocrine pancreatic insufficiency.     

Exocrine pancreatic insufficiency in distal pancreatectomy: incidence and risk factors

BackgroundExocrine pancreatic insufficiency (EPI) is a known consequence of pancreatic resection; however, its incidence following distal pancreatectomy is not well defined. The aim of this study was to describe the prevalence of EPI in patients undergoing distal pancreatectomy and moreover identify risk factors for developing de-novo EPI after distal pancreatectomy.MethodsA prospectively maintained institutional pancreatic resection database was interrogated to identify patients who underwent distal pancreatectomy from 2005 to 2015. Pre- and post-operative exocrine function, histopathology, demographics and volume of pancreas resected were analyzed.ResultsThe cohort consisted of 324 patients, 22 (6.8%) presented with EPI pre-operatively. 38 (12.6%) patients developed new onset EPI requiring pancreatic enzyme replacement therapy. There was no relationship between patient demographics or diabetes status and requirement for pancreatic enzyme replacement therapy, and no significant effect of resection volume on the need for pancreatic enzyme replacement therapy post-operatively (p ≥ 0.05). Having an underlying obstructive pancreatic pathology (p = 0.002) or a presenting history of acute pancreatitis (p < 0.001) significantly predicted development of de-novo EPI.ConclusionThese results indicate that pre-existing EPI at time of surgery is not uncommon. Patients presenting for distal pancreatectomy should be assessed pre-operatively for the need for pancreatic enzyme replacement therapy.     

13C-egg white breath test: a non-invasive test of pancreatic trypsin activity in the small intestine

BACKGROUND: The recent availability of egg white protein highly enriched with (13)C has allowed breath test technology to be adapted for the study of protein digestion and absorption. Pancreatic trypsin is considered to be the key enzyme in the proteolytic cascade. AIM: To evaluate trypsin activity in the small intestine of healthy volunteers and patients with pancreatic disease by a recently developed (13)C-egg white breath test. METHODS: A total of 48 healthy volunteers and 30 patients with pancreatic disease were studied after ingestion of a test meal consisting of 22 g (13)C-labelled egg protein. Breath samples were taken before and after ingestion of the meal and analysed for (13)CO(2) concentration. Moreover, pancreatic trypsin output after maximal stimulation was measured in 13 patients and nine healthy volunteers. RESULTS: The six hour cumulative (13)CO(2) excretion in breath was significantly lower in patients than controls (mean (SEM): 6.23 (0.82)% v 19.16 (0. 58)%, p<0.0001). An excellent correlation was found between the six hour cumulative (13)CO(2) excretion and trypsin activity after maximal pancreatic stimulation. CONCLUSION: The non-invasive (13)C-egg white breath test is promising as an indirect pancreatic proteolytic function test.     

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease.

BACKGROUND AND AIMS: Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. METHODS: We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. RESULTS: On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. CONCLUSIONS: In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.     

Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis.

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).     

A systematic review and meta-analysis of the accuracy and methodology of the 13C mixed triglyceride breath test for the evaluation of pancreatic function

IntroductionThe diagnosis of pancreatic exocrine insufficiency (PEI) is challenging. The ¹³C mixed triglyceride breath test (¹³C MTGT) has emerged as a promising diagnostic method. However, there is need to assimilate high quality evidence to understand its accuracy and address variation in the conduct of the test. This systematic review aims to appraise the existing literature on the methodology and accuracy of the ¹³C MTGT.MethodsA systematic literature search of PUBMED, MEDLINE, and EMBASE databases identified articles describing the use of the ¹³C MTGT in the analysis of pancreatic function in adults. Data extraction addressed each methodological step in detail. These were combined in a narrative synthesis. For quantitative analysis, those studies within this search that assessed the accuracy of the ¹³C MTGT were selected.Results37 studies were included for qualitative review, 6 assessed sensitivity and specificity of the ¹³C MTGT against another measure of PEI and were included in quantitative synthesis. Areas with a majority consensus were pre-test overnight fasting, a test meal with a lipid load of at least 10 g, within-test control of exercise and dietary intake, breath sampling every 30 min and the preference of isotope ratio mass spectrometry (IRMS) for analysis. Good evidence suggests there is no benefit to extend the total timeframe of breath sampling beyond 6 h. Areas of uncertainty are a) Duration of PERT cessation b) the addition of metoclopramide, c) the ideal test meal and d) if the time frame can be shortened. Quantitative analysis among 6 studies demonstrated a pooled sensitivity and specificity of the ¹³C MTGT for diagnosing PEI of 0.84 (95% CI: 0.73–0.91) and 0.87 (95% CI: 0.79–0.93) respectively.ConclusionThere is yet to emerge a clear standard of breath test methodology that is validated for all causes of PEI and suitable for routine use. The accuracy of the ¹³C MTGT for diagnosing PEI is encouraging when compared to other measures. We present a suggested set protocol based on the current literature and identify areas that need further, high quality evidence. With refinement, the ¹³C MTGT could become a valuable, non-invasive PEI diagnostic tool that could be used outside of specialist centres.     

Diagnostic value of amino acid consumption test on exocrine pancreatic insufficiency

INTRODUCTION Amino acid consumption test (AACT) has a high sensitivity and specificity in evaluating exocrine pancreatic insufficiency[1,2], but its diagnostic value to exocrine pancreatic insufficiency in Chinese has not been well understood. In this study, the oral reagent stimulating pancreatic secretion (O-AACT) was used instead of cerulein (I-AACT) for amido acid consumption test and the dignostic efficiency of O-AACT was evaluated and compared with I-AACT on the exocrine pancreatic insufficiency in Chinese.     

Diagnostic accuracy of the C-urea breath test in children: adjustment of the cut-off value according to age

BACKGROUND AND AIMS: The (13)C-urea breath test ((13)C-UBT) is a reliable non-invasive method of diagnosing Helicobacter pylori infection in adults and children. However, only a few validation studies have been performed on the (13)C-UBT in very young children. The purpose of the present study was to evaluate the diagnostic accuracy of the (13)C-UBT according to age, and to determine the optimal cut-off value in children. METHODS: A total of 307 (13)C-UBT were performed in 274 children. All were compared with the results of endoscopic biopsy-based methods to confirm H. pylori infection. Seventy-five milligrams of (13)C-urea was ingested without a test meal. Two breath samples were collected at 0 and 30 min. The optimal cut-off value of the (13)C-UBT was assessed by determining the sensitivity, specificity, false negative, and false positive results, at cut-off values ranging from 2.0 to 10.0 per thousand. RESULTS: The delta over baseline (DOB) values of the (13)C-UBT showed a significant negative correlation with age in both the H. pylori-positive group (r = -0.309; P = 0.005) and the H. pylori-negative group (r = -0.162; P = 0.015). High false positive results and low specificity were noted in children aged 6 years or less compared with children older than 6 years at a cut-off value of 4.0 per thousand (false positives; 8.3%vs 0.85%, specificity; 89.8%vs 98.8%). After adjusting the cut-off value, the optimal cut-off values were found to be 4.0 per thousand in children older than 6 years and 7.0 per thousand in children aged 6 years or less. CONCLUSIONS: The cut-off value of the (13)C-UBT recommended regardless of age must be adjusted in preschool children to reduce the false positive results.