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.     

Intraoperative Radiation Enhances Decline of Pancreatic Exocrine Function After Pancreatic Head Resection

Intraoperative radiation therapy has been introduced to improve survival rates after resection of biliopancreatic cancer. Early and late effects of intraoperative radiation on the exocrine and endocrine functions of the residual pancreas were examined in 54 patients with pancreatic head resection. Of the 54 patients, 20 underwent intraoperative radiation (A group) and the other 34 did not (B group). Fasting blood sugar level, a 120-min value of the 75-g oral glucose tolerance test, N-benzol-l-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value (a pancreatic exocrine function test), and amount of postoperative pancreatic juice drainage were compared between groups A and B at preoperative and early and late postoperative times. Fasting blood sugar level and a 120-min value of the 75-g oral glucose tolerance test (OGTT) showed no change at the early (<2 months) postoperative period of the two groups. At the late (>6 months) postoperative period, fasting blood sugar showed no alteration, while the 75-g OGTT 120-min value increased compared to the preoperative level in both groups. In the group A, the 75-g OGTT 120-min value at the late postoperative period was significantly higher than those at the preoperative and early postoperative periods (289.4 ± 104.9 vs 193.0 ± 58.2 mg/dl, P = 0.0198 and 289.4 ± 104.9 vs 184.4 ± 104.9 mg/dl, P = 0.0285). Preoperative BT-PABA excretion value was not different between the two groups. It decreased at the early postoperative period and returned to the preoperative level at the late postoperative period in both the groups. The decline of BT-PABA in group A was 23 ± 21%, which was significantly larger than 11 ± 24% in group B. The total amount of postoperative pancreatic juice drainage from postoperative days (POD) 4–13 in group A was about half as much as that in group B (720.8 ± 916.4 vs 1433.8 ± 962.1 ml, P = 0.0128). Univariate and multivariate regression analysis of factors concerning the decline of BT-PABA values at the early postoperative period showed that intraoperative radiation was a significant independent determinant. In conclusion, these results suggest that intraoperative radiation causes significant deterioration of pancreatic exocrine function at the early postoperative period. Intraoperative radiation for resectable periampullary carcinoma should be reappraised based on the decline of the pancreatic exocrine function as well as the improvement of the survival curve.     

Pancreatic Polypeptide Secretion in Patients with Chronic Pancreatitis and After Pancreatic Surgery

Aim. We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. Methods. Included were patients with CP without (n=20) and with (n=30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n=20), after Whipple’s procedure (n=19), following distal pancreatectomy (DP; n=12), and healthy controls (n=36). Results. In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01−0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01−0.05) reduced. Conclusion. Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).     

High Prevalence of Steatorrhea in 101 Diabetic Patients Likely to Suffer from Exocrine Pancreatic Insufficiency According to Low Fecal Elastase 1 Concentrations: A Prospective Multicenter Study

Impaired exocrine pancreatic secretion has been frequently observed in diabetic patients by different methods, including direct function tests. However, the clinical importance remained unclear. In the present study, the fecal fat excretion in patients with type 1 or type 2 diabetes mellitus and exocrine dysfunction according to fecal elastase 1 concentrations <100 g/g was investigated. Subjects with a history of gastrointestinal cancer, gastrointestinal surgery, alcohol abuse, or inflammatory diseases were excluded. In 101 patients the mean (±SD) fat excretion was 9.19 ± 5.39 g. Only 41 patients (40.6%) had normal fat excretion <7 g/day. In 40 patients (39.6%), it was higher than 10 g/day, indicating relevant steatorrhea. The fat excretion did not correlate with diabetes type, duration, or clinical symptoms. This finding is of some clinical importance and might influence pathophysiological concepts and the management of diabetic patients.     

Exocrine function of caerulein-induced acute pancreatitis in anesthetized rats

Exocrine function was studied in anesthetized rats that had received two specific doses of caerulein (maximal stimulation and supramaximal stimulation). Male Wistar rats (body weight, 200–250 g) were divided into three groups: the control group (4-h saline infusion), the maximal stimulation group (0.25 g/kg per h caerulein for 4 h), and the caerulein pancreatitis group (10g/kg per h for 4 h). Histologically, inter-stitial edema and cytoplasmic vacuolization were observed only in the caerulein pancreatitis group, with no abnormal findings in the other groups. The volume of pancreatic juice was significantly increased in both the maximal stimulation group and the caerulein pancreatitis group. The protein ouput and the amylase output in the 1st h of caerulein infusion were also significantly increased, to 459% and 338% in the maximal stimulation group, and to 925% and 1430% respectively, in the caerulein pancreatitis compared to the baseline values. We also found that the pancreatic juice of the caerulein pancreatitis group contained precipitated protein, and high trypsin activity, and protein degradation was confirmed by electrophoresis. These findings were not observed in the other groups. These results strongly suggest that hypersecretion and the appearance of trypsin activity in pancreatic juice plays an important role in the induction of histological changes in this pancreatitis model in anesthetized rats.     

Pancreatic Exocrine Insufficiency in Intraductal Papillary Mucinous Carcinoma Presenting with Leg Edema Treated with Pancreatic Exocrine Replacement Therapy

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.     

Recovery of the pancreas after acute pancreatitis is not necessarily complete

Summary In 38 patients, exocrine pancreatic function was tested by means of the secretin-pancreozymin test (SPT) and pancreatic duct system with endoscopic retrograde cholangiopancreatography (ERCP) 34±36 mo (mean±SD, range 1–156 mo) following acute pancreatitis. SPT and ERCP results were both normal in 19 (50%). They were both abnormal in four (11%) patients (group 1). Fourteen (37%) patients with normal SPT had abnormal ERCP test results (group 2), and one (3%) patient with normal ERCP had abnormal SPT (group 3). All patients except one of group 2 could be followed up within a mean observation time of 105±46 mo (range 24–168 mo): Chronic pancreatitis developed in all four patients of group 1, in one patients of group 2, and in the single patient of group 3, and suspected chronic pancreatitis in another patient of group 2. Elevens of the remaining 12 patients with abnormal ERCP results, but normal exocrine pancreatic function (group 2), showed no signs or symptoms of acute or chronic pancreatitis. It is concluded that (1) recovery to normal does not necessarily occur after acute pancreatitis, (2) progression to chronic pancreatitis is possible at a considerable percentage, and (3) duct changes demonstrated by ERCP may persist without any later signs and symptoms of acute or chronic pancreatitis.     

Pancreatic Tissue Fluid Pressure in Chronic Pancreatitis Relation to Pain,Morphology, and Function

The relation between pancreatic tissue fluid pressure and pain, morphology, and function was studied in a cross-sectional investigation. Pressure measurements were performed by percutaneous fine-needle puncture. Thirty-nine patients with chronic pancreatitis were included, 25 with pain and 14 without pain. The pressure was higher in patients with pain than in patients without pain (p = 0.000001), and this was significantly related to a pain score from a visual analogue scale (p < 0.001). Patients with pancreatic pseudocysts had both higher pressure and higher pain score than patients without (p = 0.004 and p = 0.0003, respectively). The pressure was significantly related (inversely) to pancreatic duct diameter only in the group of 19 patients with earlier pancreatic surgery (R = -0.57, p = 0.02). The pressure was not related to functional factors or the presence of pancreatic calcifications. In conclusion, pancreatic tissue fluid pressure is a valuable indicator of pain in chronic pancreatitis.     

Pancreatic stenting for the preservation of pancreatic function in chronic pancreatitis with stricture

Background: Although many reports have documented pain relief achieved by pancreatic stenting, the effect of stenting on pancreatic function is less clear. In addition, the effects of stent caliber and patency have not been considered in most previous studies. Pain and pancreatic function after stenting of the main pancreatic duct (MPD) were examined. Methods: Records of 24 patients with chronic pancreatitis who had an MPD stricture treated with a 10‐Fr stent from June 1996 to June 2002 were reviewed. The average age was 57.0 ± 1 years, and the male : female ratio was 7 : 1. Eleven patients had diabetes mellitus. Stent patency, pancreatic pain and pancreatic endocrine and exocrine function were examined before stenting and 6 months after stenting. Stenting was continued for 1 year or more, with repeated stent exchange every 3 months. Results: The stent became occluded in 29% of cases, migration occurred in 15% of cases, and the 50% patency time was 125 days. Pancreatic pain was relieved by stenting in all cases. The diameter of the MPD, the Bentiromide test value, weight and body mass index were improved. Conclusion: Stenting relieves blockage of the main pancreatic duct and provides both pain relief and preservation of residual pancreatic function.     

粪弹性蛋白酶试验在慢性胰腺炎诊断中的意义

粪弹性蛋白酶试验是通过检测粪便中弹性蛋白酶-1的含量来反映胰腺外分泌情况的一项检查,是间接胰腺外分泌试验中较为简便的一种.此文就其临床研究及应用价值作一综述.     

Immunoglobulin A Secretion into Pancreatic Juice as a Novel Marker of Local Immune Defense and Exocrine Pancreatic Function

The importance of secretory immunoglobulin A (IgA) of local immune defense in the gastrointestinal tract has gained increasing acceptance. Bacterial contamination is a major factor related to mortality in acute pancreatitis. However, very little is known about IgA in pancreatic juice. Pure pancreatic juice was collected from 40 patients undergoing pancreatoduodenectomy. The patients were divided into three groups according to the degree of preoperative pancreatic duct obstruction, as follows: normal, narrowed, and obstructed. IgA concentration, amylase activity, and daily volume of pancreatic juice were measured. Daily IgA secretion into pancreatic juice was constant during the early period after the operation. The concentration of IgA in the control group was 5 ± 0.8 g/ml, and IgA daily secretion was 1.2 ± 0.2 mg/day. Pancreatic duct obstruction resulted in a marked decrease in both amylase and pancreatic juice secretion. The concentration of IgA, however, was markedly increased in the narrowed group (11.1 ± 2.4 g/ml) and the obstructed group (32.5 ± 5.4 g/ml). The concentration of amylase increased with the increase in pancreatic juice. Conversely, the concentration of IgA increased with the decrease in volume of pancreatic juice. Similarly, the increased in IgA concentrations positively correlated with the decrease in amylase activity. In conclusion, the mechanisms that modulate IgA secretion in the human pancreas are essentially different from those that modulate digestive enzyme and fluid secretion. IgA in pancreatic juice may play an important role in pathological conditions such as pancreatic duct obstruction. As such, the measurement of IgA in pancreatic juice may potentially be used as a new marker of local immune defense and exocrine pancreatic function.     

Pancreatic calcifications in patients with normal pancreatic function

This is a report on five patients who had acute attacks of pancreatitis (three cases complicated by pseudocysts). They all showed pancreatic calcifications on plain abdominal X-ray(n = 5), computed tomography (n = 3), or at postmortem examination (n = 1). Despite calcifications, the exocrine pancreatic function, as tested with the secretin-pancreozymin test and fecal fat analysis, was either normal or returned to normal. The conclusion is that pancreatic calcifications do not indicate severe exocrine pancreatic insufficiency and the necessity for pancreatic enzyme substitution. Calcifications are not necessarily a sign of chronic pancreatitis. They may result rather from scars following acute pancreatitis.     

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis

Summary Conclusion Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis. Background Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis. Methods WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1–6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by iv administration of cerulein at a rate of 10 μg/kg/h for 4 h 4 after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration. Results In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant, at 3–6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopcially showed prominent intersitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and chole-cystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.     

Autonomic Dysfunction and Cholelithiasis in Patients with Cirrhosis

Gallstones are seen in 33–46% of patients with cirrhosis, and their prevalence is known to increase with the duration and severity of liver disease. We hypothesized that autonomic neuropathy may contribute to the formation of gallstones or gallbladder disease, as in diabetics with autonomic neuropathy, due to impaired gallbladder emptying. The objective of our study was to determine the prevalence of gallstones or gallbladder disease in cirrhotic patients with and without autonomic neuropathy. We determined autonomic function tests, gallstones, and other gallbladder disease in 123 (male 71) with varying severity of liver disease (Child classes: A, 40; B, 45; C, 35). In all, 54 patients had gallstones and an additional 22 patients had other gallbladder disease (cholecystitis, common bile duct stones, or debris). Autonomic neuropathy was seen in 97 patients (one abnormal test in 48 and two or more in 49). The prevalence of gallstones was similar in Child A (57%), Child B (64%), and Child C (63%) cirrhosis. The gallstones or gallbladder disease was not increased in women, blacks, diabetics, or alcoholic cirrhotics. The prevalence of gallbladder disease was increased in patients with autonomic neuropathy (51% vs 35%, P = 0.08); in patients with Child C cirrhosis, gallstones (P = 0.018) and gallbladder disease (P = 0.03) were seen more commonly in patients with autonomic neuropathy. Our findings suggest that autonomic neuropathy may contribute to the formation of gallstones in patients with advanced cirrhosis, perhaps by impairing gallbladder and sphincter of Oddi dysmotility.     

B cell function in patients with chronic pancreatitis and its relation to exocrine pancreatic function

Summary Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The C-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88,p < 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72,p < 0.001), amylase (r=0.64,p < 0.05) and to amylase output (r = 0.64,p < 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.     

The Clinical Significance of Salivary Amylase in Duodenal Aspirates in Evaluation of Exocrine Pancreas Function

Salivary and pancreatic amylases in duodenal aspirates were quantitated in 419 consecutive tests performed on 378 patients suspected of having insufficiency of the exocrine pancreatic function. Salivary amylase was detected in samples from 31% of the tests. However, the amount of salivary amylase was sufficient to cause a misinterpretation in 13 tests only. Five of these tests originated from patients with a history of surgery for peptic ulcer disease. This group of patients tended to have large amounts of salivary amylase in the duodenal aspirates. In the unoperated patients (n = 336) 200 tests yielded values for the total amylase concentration above the lower level of the reference interval, and only in 8 of these tests (4%) did correction for salivary amylase change the results to values below the reference interval. It it concluded that quantitation of isoamylase activity in duodenal samples is unlikely to be of significant value in patients without a history of surgery for peptic ulcer disease.     

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far. Received: 8 September 1999 / Accepted: 16 November 2000     

Exocrine pancreatic insufficiency in long-term follow-up after curative gastric resection with D2 lymphadenectomy: A cross-sectional study

BackgroundExocrine pancreatic insufficiency (EPI) can be a problem following gastrectomies. This study aimed to reveal the EPI prevalence and its possible causes in gastric cancer patients that underwent subtotal or total gastrectomy, with completed oncological treatments, and with long-term disease-free survival success. Additionally, we also sought to determine whether there were any relations between EPI and blood biomarkers, weight change, malnutrition parameters, and quality of life after gastrectomy.MethodsA total of 69 gastric cancer patients whose oncological treatments had already been completed, with a minimum follow-up period of 16 months, were included in the study. Fecal samples were taken from all patients for the Fecal Elastase-1 Test, and patients were stratified into three groups based on the results: low (<100 μg/g), moderate (100–200 μg/g), and normal (>200 μg/g). These results were compared with patients’ clinical characteristics, blood nutrition biomarkers, Maastricht indexes (MI), Bristol stool scale, and Gastrointestinal Quality of Life Index (GIQLI) scores.ResultsFE-1 levels were low in 33 (47.8%) of the patients, moderate in 11 (15.9%), and normal in 25 (36.2%). The rate of patients receiving chemoradiotherapy (CRT) in the low FE-1 group was higher than the normal FE-1 and moderate FE-1 groups (P < 0.001 and P = 0.012, respectively). The serum total protein and lipase levels were lower in the low FE-1 group than in the normal FE-1 group (P = 0.023 and P < 0.001, respectively). When compared to the normal FE-1 group, the MI score of the low FE-1 group was higher (P = 0.018). The low FE-1 group had lower GIQLI gastrointestinal symptom scores than the normal FE-1 group (P = 0.046).ConclusionsDuring long-term follow-up, EPI can be seen in more than half of patients with gastric cancer after curative gastrectomy. Radiotherapy as an adjunct to adjuvant treatment in the postoperative period is considered a serious risk factor for EPI development. EPI contributes to malnutrition development after gastrectomy and negatively affects the patients’ quality of life, especially in terms of gastrointestinal symptoms.     

壶腹周围癌胆胰双支架引流随机对照临床研究

目的探讨壶腹周围癌胆胰管双支架引流的成功率及对胰腺外分泌功能的影响。方法胆管、胰管扩张及粪弹力蛋白酶-1小于200μg/g、无法手术切除的壶腹周围癌病例随机分为2组，试验组在内镜下置入胆管和胰管双支架，对照组于内镜下置入胆管支架，比较2组间支架置入成功率、并发症发生率、2组引流前后及组间引流15d后粪弹力蛋白酶-1水平的变化。结果试验组引流前粪弹力蛋白酶-1水平为（70．7±40．5）μg/g，引流后为（264．5±101．3）μg／g，（P〈0．001）；对照组引流前粪弹力蛋白酶-1水平为（80．3±43．6）μg／g，引流后为（84．3±45．3）μg／g，（P〉0．05）；试验组支架引流前后粪弹力蛋白酶-1水平变化（193．8±66．4）μg／g显著高于对照组（3．9±5．8）μg／g，（P〈0．001）；试验组胆胰管双支架及对照组胆管支架均置入成功，无近期并发症发生，试验组及对照组各有3例出现支架阻塞，差异无统计学意义（P〉0．05）。结论胆胰管双支架引流明显改善壶腹周围癌患者胰腺外分泌功能；初步结果表明壶腹周围癌胆胰管双支架引流是一种安全、有效的治疗方法。