Pancreatic function testing. Methods to identify exocrine insufficiency

The diagnosis of chronic pancreatitis is ideally established by an appropriate clinical history and confirmatory radiologic imaging. However, in cases where imaging results are normal or equivocal, pancreatic function testing is necessary. Direct (intubation) tests are generally accepted as the best methods for study of pancreatic exocrine capacity, but indirect tests, which are well tolerated and generally simple to perform, are gaining interest. Their shortcoming is that they are too insensitive to reliably differentiate patients with early exocrine dysfunction (ie, before malabsorption has occurred) from controls. Sensitivity is not improved by combining two or more studies. However, several modified tests (eg, two-stage paraaminobenzoic acid test, pancreolauryl test) have improved specificity and are able to distinguish pancreatic from other causes of steatorrhea. Their reproducibility in individual cases is of value in sequential studies and in patients with established pancreatic exocrine deficiency to seek evidence of improvement or deterioration in function and to determine patient compliance with replacement therapy.     

Diagnosis of pancreatic injury after blunt abdominal trauma

Expeditious diagnosis and treatment of pancreatic injury continues to elude the trauma surgeon and radiologist. Missed or underestimated pancreatic injury is responsible for a high level of morbidity and mortality after blunt or penetrating trauma. Unfortunately, inappropriate therapy can lead to devastating consequences such as severe endocrine or exocrine insufficiency. Abdominal CT is currently the imaging method of choice for evaluating patients with blunt trauma. This article reviews the constellation of CT findings that the radiologist must rely on to establish the diagnosis of pancreatic injury.     

Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?

Exocrine pancreatic insufficiency is frequently associated with diabetes, with high prevalence in both insulin-dependent or insulin-independent patients. Exocrine pancreatic failure has often been perceived as a complication of diabetes. In contrast, recent clinical observations lead to the notion that nonendocrine pancreatic disease is a critical factor for development rather than a sequel to diabetes. The incidence of diabetes caused by exocrine pancreatic disease appears to be underestimated and may comprise 8% or more of the general diabetic patient population. Nonendocrine pancreas disease can cause diabetes by multiple mechanisms. Genetic defects have been characterized, resulting in a syndrome of both exocrine and endocrine failure. Regulation of beta-cell mass and physiological incretin secretion are directly dependent on normal exocrine function. Algorithms for diagnosis and therapy of diabetes should therefore address both endocrine and exocrine pancreatic function.     

重症患者胰腺外分泌功能不全的研究进展

重症患者虽然常常合并胰腺损伤,且胰腺损伤所致外分泌功能不全的直接后果则是营养不良,但迄今未对重症患者胰腺外分泌功能不全的研究引起足够的重视。为此,本文系统回顾了胰腺外分泌功能不全的诊断方法,重症患者胰腺损伤和胰腺外分泌功能不全的流行病学和潜在的高危因素以及胰酶补充治疗的可行性,旨在为重症患者纠正营养不良,改善预后提供新的途径和方法。     

Hereditary pancreatitis in a young adult: Acute to chronic

This report investigates an unusual case of recurrent pancreatitis. A 22-year-old female was admitted to the emergency room for severe abdominal pain, nausea, and weight loss. She reported having these symptoms since she was a toddler. The clinician ordered fecal pancreatic elastase-1, fat-soluble vitamins, molecular studies, and imaging of the pancreas by computed tomography. The screening test result for fecal pancreatic elastase-1 revealed severe pancreatic exocrine insufficiency, and the concentrations of fat-soluble vitamins were also low. Imaging showed scattered calcifications in the pancreas. These findings supported a diagnosis of chronic pancreatitis. Due to the rarity of chronic pancreatitis in young adults, molecular studies were performed. The patient was found to be homozygous for a mutation in the SPINK1 gene, which is associated with hereditary pancreatitis. This case report discusses hereditary pancreatitis and highlights data on the utilization of fecal pancreatic elastase-1 to assess pancreatic exocrine insufficiency.     

Uncommon Solid Pancreatic Neoplasms: Ultrasound, Computed Tomography, and Magnetic Resonance Imaging Features

This article reviews the ultrasound, computed tomography, and magnetic resonance imaging features of rare solid tumors of the pancreas with attention to distinctive imaging appearances, which can help radiologists to discriminate between the different entities. Various uncommon solid pancreatic neoplasms, including exocrine and endocrine epithelial tumors, mesenchymal tumors, and metastases, are reviewed, with emphasis on key differential points, including morphologic features and patterns of contrast enhancement.     

Permissive role of prostaglandins in the action of bradykinin on the pancreas of anesthetized dogs

We have investigated the contribution of prostaglandins (PGs) to the effect of bradykinin on pancreatic blood flow and pancreatic exocrine secretion by examining its actions in the isolated blood-perfused pancreas of pentobarbital-anesthetized dogs. Intra-arterial injections of bradykinin (0.05-5 ng/kg) into the pancreas produced a dose-dependent vasodilation and increased pancreatic blood flow; the rate of flow, bicarbonate concentration, protein content or pH of the pancreatic juice was not altered. Administration of arachidonic acid (0.5-5 micrograms/kg) into the pancreas also produced vasodilation without altering pancreatic exocrine secretion. In animals pretreated with indomethacin or sodium meclofenamate (10 mg/kg i.v.), the vasodilator effect of bradykinin was attenuated, whereas that of arachidonic acid was abolished; the pancreatic exocrine secretion was not altered. The vasodilation produced by sodium nitroprusside (0.3 micrograms/kg i.a.) in the pancreas was not altered by indomethacin. During infusion of PGI2 or PGE2 (10 ng/kg/min i.a.), the effect of indomethacin or sodium meclofenamate to attentuate bradykinin-induced vasodilation was reduced. However, the sodium nitroprusside-induced vasodilation in animals treated with indomethacin was not altered during infusion of PGI2 or PGE2. These data indicate that PGs, presumably PGI2 and PGE2, play a permissive role in the vasodilator effect of bradykinin in the pancreas of anesthetized dogs. Moreover, these studies suggest that neither bradykinin nor PGs contribute to the regulation of pancreatic exocrine secretion.     

Hormones as regulators of pancreatic secretion in man

At the beginning of the century, Pavlov Suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss & Starling published their experiments on secretin and claimed that the nervous regulation is ‘superfluous and improbable’. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural. hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretin modulating the response.     

Current options for the diagnosis of chronic pancreatitis

The diagnostic options for chronic pancreatitis have evolved over recent years. The previous gold standard references for structural imaging and exocrine pancreatic function testing have both been supplanted and redesigned. Endoscopic retrograde pancreatography has now been overtaken by endoscopic ultrasound and magnetic resonance cholangiopancreatography, whilst the old technique for Dreiling tube pancreatic function testing has now been replaced by the endoscopic pancreatic function test. New advances in endoscopic ultrasound elastography have also extended the options for evaluating pancreatic masses to differentiate mass-forming chronic pancreatitis from malignancy. Genetic contribution to chronic pancreatitis is also now more widely recognized than ever before.     

Inhibitory action of antidiuretic hormone on canine pancreatic exocrine flow.

A direct relationship was observed between the percentage inhibition of secretin-stimulated pancreatic exocrine flow and the dose of antidiuretic hormone administered with the minimal effective concentration being 0.75 m units/kg or 0.012 m units/ml. An alteration in the molecular configuration of the antidiuretic hormone modified its ability to inhibit secretin-stimulated pancreatic exocrine secretion.     

急性胰腺炎患者胰腺外分泌功能不全识别及护理的研究进展

急性胰腺炎发病率逐年上升。急性胰腺炎后近1/3患者发生胰腺外分泌功能不全,导致患者出现消化吸收障碍、营养不良等症状。该文回顾国内外文献,对护理人员关注急性胰腺炎患者胰腺外分泌功能不全的重要性、胰腺外分泌功能不全的识别与监测、护理措施等方面进行综述,为护理人员的相关临床工作提供科学依据。     

Predictive factors for pancreatic cancer in patients with chronic pancreatitis in association with K-ras gene mutation

BACKGROUND AND STUDY AIMS: Chronic pancreatitis is considered to be a predisposing factor for pancreatic ductal adenocarcinoma (PAC). The purpose of this study was to examine the prognostic value of a finding of mutated (K- ras) gene in predicting the development of PAC in patients with chronic pancreatitis. PATIENTS AND METHODS: The pancreatic duct brushings of 146 patients with chronic pancreatitis were examined in order to identify K- ras gene mutations. A total of 112 patients were followed up (median duration 42 months) using clinical evaluation, serum CA19 - 9 levels, and imaging studies. RESULTS: One or more K- ras mutations were found in 57 of the 146 patients with chronic pancreatitis (39 %). Patients harboring K- ras mutations had a higher incidence of persistent alcohol consumption ( P = 0.041) and of prior rupture of the main pancreatic duct ( P = 0.040). A finding of nuclear atypia in brushing cytology was also more common in patients with K- ras mutation ( P = 0.048). Out of the 112 patients who were followed up, PAC occurred in four of the 44 patients who had a K- ras mutation, but in none of the 68 patients with the wild genotype ( P = 0.022). PAC occurred in three of the 25 patients who did not have pancreatic calcifications ( P = 0.034) and in four of the 54 patients who had demonstrated exocrine insufficiency, but in none of the 58 patients with preserved exocrine function ( P = 0.051). Using stepwise logistic regression, the absence of calcifications, the presence of exocrine insufficiency, and the presence of K- ras mutation were identified as independent predictive factors for cancer development in all patients with chronic pancreatitis. CONCLUSIONS: K- ras gene mutations occur in chronic pancreatitis and are associated with evolution towards PAC. The absence of pancreatic calcifications and the presence of exocrine insufficiency were identified as additional predictive factors for the development of PAC.     

Changes of duodenal pH and pancreatic exocrine function after upper G-I intraluminal ethanol administration

Using 3 outbred dogs with pancreatic, gastric and jejunal fistulas, we examined changes in pancreatic exocrine secretion, duodenal pH and plasma CCK concentration after intragastric or intrajejunal administration of ethanol. Intragastric administration of 20% or 40% ethanol significantly lowered the pH in the duodenal cavity, and pancreatic fluid secretion and bicarbonate excretion were stimulated. Intrajejunal administration of ethanol elicited stronger responses. Plasma CCK concentration was not changed or was only slightly lowered by ethanol administration in the digestive tract. It is assumed that stimulation of pancreatic exocrine secretion was mediated by the secretion of gastric acid.     

The effect of equicaloric medium-chain and long-chain triglycerides on pancreas enzyme secretion

It has been shown previously that medium chain triglycerides (MCT) do not affect gallbladder emptying and cholecystokinin (CCK) release. The effect of MCT on exocrine pancreas secretion in humans is unknown. We have compared the effect of enteral administration of MCT versus long chain triglycerides (LCT) on exocrine pancreatic secretion. Eight healthy subjects (three female, five male; mean age 22 +/- 1.9 years) participated in two experiments, performed in random order. Duodenal contents, obtained by aspiration, were used to calculated the output of pancreatic enzymes and bilirubin. An equicaloric amount of either MCT or LCT (2 kcal min-1) oil was continuously administered in the proximal jejunum for 2 h. Gallbladder volume was measured by ultrasonography and blood samples were drawn for determination of CCK. The experiments consisted of 1 h basal secretion, 2 h of continuous oil administration and 1 h poststimulation. During the LCT feeding the pancreatic enzyme secretion, bilirubin output, gallbladder emptying and CCK release increased significantly (P < 0.05) over basal levels. MCT had no effect on pancreatic enzyme secretion nor gallbladder emptying or CCK release. We conclude that enteral administration of MCT in the proximal jejunum does not stimulate exocrine pancreatic secretion nor gallbladder contraction or CCK release, in contrast to an equicaloric amount of LCT.     

The measurement of 75selenium in duodenal juice--an advance in the diagnosis of pancreatic function (author's transl)]

The radioactivity in the duodenal juice following the intravenous injection of 75Se-1-selenomethionine was measured in 17 normal subjects and in 14 patients with exocrine pancreatic insufficiency. The mean values of radioactivity were significantly lower during certain periods of the investigation in the patients with pancreatic insufficiency as compared with the normal subjects. The individual values, however, scattered widely and the standard deviations were large. There was a highly significant correlation between the volume of duodenal juice and the 75Se radioactivity, but no significant correlation was established between the duodenal juice radioactivity and bicarbonate or enzyme concentration i.e. specific parameters of exocrine pancreatic function. It is possible that observation period may bring less equivocal results, but this appears of doubtful practicability. Measurement of the 75Se-1-selenomethione radioactivity in the duodenal juice is only an indirect indicator of exocrine pancreatic function. It does not appear to represent any significant advance in the diagnosis of pancreatic insufficiency, since the information provided by these older-established methods is more reliable and is obtained within a similar space of time.     

Complications following pancreatic transplantations: imaging features

Whole organ vascularized pancreatic transplant is a recognized treatment for diabetes and is increasingly being performed worldwide. The procedure itself is complex and is associated with significant mortality and morbidity. Despite improvements in surgical techniques, postoperative complications of pancreatic transplantation are still common and include graft rejection, pancreatitis, peripancreatic fluid collections, exocrine leaks, vascular thrombosis, and hemorrhage. In this pictorial essay, we review clinical presentation and imaging features of these complications. We also briefly discuss technique and complications of islet cell transplants.     

Modern principles of the diagnostics and enzyme therapy of exocrine pancreatic insufficiency

The author considers the main reasons for the development of exocrine pancreatic insufficiency, discusses the advantages and disadvantages of modern direct and indirect techniques of exocrine pancreatic insufficiency diagnostics, and states the main requirements pancreatic enzymes used as means of substitutive therapy should meet.     

新生昆明小鼠胰腺干细胞体外分离、培养及自然分化的潜能

背景：关于胰腺干细胞在胰腺组织中的分布情况,以及如何有效的将其分离、体外优化培养,目前仍有一定的困难。目的：从新生昆明小鼠胰腺组织中分离出胰腺干细胞,在体外条件下培养观察其形态学和生物学特征,并进行初步鉴定。方法：取新生SPF级昆明小鼠的胰腺组织,使用Ⅴ型胶原酶消化,采用Percoll不连续密度梯度离心,使胰腺组织内、外分泌部细胞分离,分布在3个不同的密度界面;收集各界面的细胞,以无血清、添加碱性成纤维细胞生长因子和表皮细胞生长因子的DMEM培养基培养。结果与结论：通过细胞形态学和细胞生长特性的观察,结合双硫腙染色证实：采用Percoll不连续密度梯度离心,第一、二密度界面的细胞来源于胰腺内分泌部;第三密度界面细胞来源于胰腺外分泌部。分别从胰腺内、外分泌部获取胰腺组织细胞,在体外培养观察发现均存在一类大、圆、单个核的细胞,呈集落样附壁生长,具有较活跃的分裂增殖能力,碱性磷酸酶染色阳性,表达胰腺干细胞的特异性标志巢蛋白,即为胰腺干细胞;随着体外培养时间的延长,分别表达PDX-1和CK-19,呈现向胰腺内分泌部细胞和外分泌部细胞分化的趋势。     

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201–995 in acromegalic patients

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.