Pancrelipase for pancreatic disorders: An update.

Pancrelipase is a porcine pancreatic extract which contains the digestive enzymes lipases, proteases and amylases. In patients with pancreatic exocrine insufficiency (PEI) from conditions such as chronic pancreatitis, pancreatectomy and cystic fibrosis, pancrelipase can be used as pancreatic enzyme replacement therapy (PERT). Pancrelipase can reverse steatorrhea, prevent weight loss, control pain and correct other nutritional deficiencies resulting from exocrine insufficiency. Various forms of pancreatic enzymes were being marketed as over-the-counter medications prior to the recent FDA declaration that all pancreatic enzyme products had to obtain approval as new drugs before marketing. On the basis of evidence from recent randomized controlled trials, three pancrelipase formulations (Creon®, Zenpep® and Pancreaze®) have been approved by the FDA as effective treatments for PEI. Although several tests exist for the detection of PEI, early diagnosis still remains a challenge. Individualization of the timing of treatment initiation and dosage requirements is needed to achieve optimal effectiveness. When used at recommended doses, pancrelipase is a safe medication. Appropriate use of pancrelipase in patients with pancreatic exocrine insufficiency can achieve symptomatic relief, prevent morbidity/mortality and also improve quality of life.

Evaluation of the Ez-HBT Helicobacter blood test to establish Helicobacter pylori eradication.

BACKGROUND: The urea blood test (Ez-HBT) has been shown to compare favourably with the urea breath test in the diagnosis of active Helicobacter pylori infection. AIM: To examine the performance characteristics of the Ez-HBT Helicobacter blood test in establishing success or failure of therapy in H. pylori-infected adults using the 13C urea breath test as the reference method. METHODS: 13C urea breath test and Ez-HBT Helicobacter blood test were performed 4-6 weeks after completion of treatment in H. pylori positive subjects. Basal urea breath samples were collected; basal Ez-HBT Helicobacter blood test samples were not. Ez-HBT Helicobacter blood test results were reported as positive, negative, or indeterminate. RESULTS: Seventy patients generated 126 measurable sets of urea breath and blood tests. The H. pylori cure rate was 93%. The sensitivity, specificity, and accuracy of the Ez-HBT Helicobacter blood test were 100%, 97%, and 97%, respectively. Six of eight false positive and indeterminate Ez-HBT Helicobacter blood test results could be attributed to incomplete fasting or a 13C enriched diet. After correcting for the non-fasting state, the positive predictive value of the Ez-HBT Helicobacter blood test improved from 56% to 86%. CONCLUSION: The performance characteristics of the Ez-HBT Helicobacter blood test are comparable with that of 13C-urea breath test in establishing H. pylori eradication after therapy. Errors related to incomplete fasting can be mitigated by collection of a basal blood sample.

Diagnosis and management of chronic pancreatitis.

Chronic pancreatitis represents a condition that is challenging for clinicians secondary to the difficulty in making an accurate diagnosis and the less than satisfactory means of managing chronic pain. This review emphasises the various manifestations that patients with chronic pancreatitis may have and describes recent advances in medical and surgical therapy. It is probable that many patients with chronic abdominal pain are suffering from chronic pancreatitis that is not appreciated. As the pathophysiology of this disorder is better understood it is probable that the treatment will be more successful.

Chronic pancreatitis: controversies in etiology, diagnosis and treatment.

The pathogenesis of idiopathic chronic pancreatitis remains poorly understood despite the high expectations for ascribing the pancreatic damage in affected patients to genetic defects. Mutations in the cationic trypsinogen gene, pancreatic secretory trypsin inhibitor, and the cystic fibrosis conductance regulator gene do not account for the chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis. Small duct chronic pancreatitis can be best diagnosed with a hormone stimulation test. Endoscopic ultrasonography can detect abnormalities in both the parenchyma and ducts of the pancreas. The true value of endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains to be fully defined and is under active investigation. It is not clear whether endoscopic ultrasonography is more sensitive for early structural changes in patients with small duct disease or is over diagnosing chronic pancreatitis. Pancreatic enzyme supplementation with non-enteric formulation along with acid suppression (H2 blockers or proton pump inhibitors) is an effective therapy for pain in patients with small duct chronic pancreatitis. The role of endoscopic ultrasonography-guided celiac plexus block should be limited to treating those patients with chronic pancreatitis whose pain has not responded to other modalities. Total pancreatectomy followed by autologous islet cell autotransplantation appears to be potential therapeutic approach but for now should be considered experimental.

Synthetic porcine secretin is highly accurate in pancreatic function testing in individuals with chronic pancreatitis.

The secretin stimulation test is the most sensitive and specific test for pancreatic function. It is usually performed using biologically derived porcine secretin. Several shortages of biologic porcine secretin have occurred in the past few years. The aim of this study was to compare synthetic porcine secretin to biologic porcine secretin in pancreatic function testing in subjects with chronic pancreatitis. Twelve patients with a previously abnormal secretin stimulation test were enrolled. After an overnight fast, each patient underwent a secretin stimulation test on 2 consecutive days using 1 CU/kg biologic porcine secretin or 0.2 [microg/kg synthetic porcine secretin in a randomized fashion. The peak bicarbonate concentration in duodenal juice was used as a measure of pancreatic function. The peak bicarbonate concentration (mean +/- SD) obtained by using biologic porcine secretin and synthetic porcine secretin were 70 +/- 25 mEq/L and 68 +/- 31 mEq/L, respectively (p = 0.58, paired t test; R = 0.964). The accuracy of synthetic porcine secretin in diagnosing pancreatic insufficiency was 100% when compared with biologic porcine secretin. We conclude that synthetic porcine secretin is highly accurate and safe in pancreatic function testing. The 100% purity, excellent diagnostic accuracy, and ready availability make synthetic porcine secretin an attractive choice for secretin stimulation testing.

The 13C-urea blood test accurately detects active Helicobacter pylori infection: a United States, multicenter trial.

OBJECTIVES: Current nonendoscopic tests for Helicobacter pylori include antibody tests and the urea breath test. After the administration of 13C-urea, serum bicarbonate measurement can identify those infected with H. pylori. In this study, our aims were to determine the accuracy of the urea blood test, and to compare the accuracy of the urea blood test with that of rapid urease testing of gastric biopsies. METHODS: This was a multicenter trial conducted at five sites within the U.S. Patients scheduled for endoscopy were recruited. During endoscopy, biopsies were obtained from the gastric body and antrum for histology and rapid urease testing. Patients underwent the urea blood test, which required the ingestion of 125 mg of 13C-urea after endoscopy. Thirty minutes later, a 3-ml blood sample was obtained and later analyzed by mass spectrometry for 13C-bicarbonate. Performance characteristics for the urea blood test were calculated using the endoscopic biopsy tests as a gold standard. RESULTS: One hundred and twenty-one patients (54 infected) were enrolled. The urea blood test yielded sensitivity of 89%, specificity of 96%, positive predictive value of 94%, negative predictive value of 91%, and accuracy of 93% using histology as a gold standard. There was no difference between results obtained with the urea blood test and rapid urease testing of gastric biopsies. CONCLUSIONS: The urea blood test accurately identified active H. pylori infection. The performance characteristics of this nonendoscopic test were similar to those of endoscopic rapid urease testing.

Comparison of [13C]urea blood test to [13C]urea breath test for the diagnosis of Helicobacter pylori.

OBJECTIVE: It has been determined that the [13C]urea breath test (UBT) is a safe and effective way of detecting Helicobacter pylori (H. pylori) infection. Some individuals may have difficulty performing the exhalation component of the test, possibly due to age, or mental or physical compromise. Our aim was to determine if a commercially developed [13C]urea blood test could be utilized as a substitute for the UBT to detect H. pylori infection. METHODS: Patients who were referred by their physicians for UBT were offered study inclusion. Patients underwent baseline and 30-min UBT. A simultaneous blood sample of 3 cc was drawn into a heparinized vacutainer at the 30-min period of the UBT. [13C]urea levels in both blood and breath samples were analyzed using isotope ratio mass spectrometry. UBT > or = 6 delta per mil over baseline and urea blood tests > (-17 delta per mil) were considered positive. RESULTS: One hundred sixty-one patients (68 men/93 women) with average age of 47.0 +/- 14.2 yr were tested. Agreement between breath and blood test results occurred in 153/161 (95%) cases. Using the UBT as the diagnostic standard, the urea blood test resulted in 44 true positive, 109 true negative, four false positive, and four false negative results, giving a sensitivity of 92%, specificity of 96%, positive predictive value of 92%, and negative predictive value of 96%. CONCLUSIONS: The urea blood test was found to be comparable to the urea breath test in the detection of H. pylori infection. The urea blood test will be accurate in the diagnosis of active H. pylori infection.

Update on diagnosis and management of chronic pancreatitis.

Chronic pancreatitis should be considered in all patients with unexplained abdominal pain. The importance of small duct disease without obvious radiographic abnormalities is an important new concept. It is meaningful for the clinician to define whether the patient with chronic pancreatitis has small duct or large duct disease. Diagnostic evaluations should begin with a simple, noninvasive, inexpensive test such as serum trypsinogen, to be followed by more complicated testing such as the secretin stimulation test, particularly in those patients with small duct disease. Non-enteric-coated pancreatic enzyme preparations are preferred for the treatment of pain whereas enteric-coated pancreatic enzyme preparations are the drugs of choice for treating steatorrhea. Octreotide may become an important therapy for treating abdominal pain unresponsive to pancreatic enzyme therapy. Endoscopic treatment of the pain of chronic pancreatitis should be used only in highly selected patients and may cause damage to the pancreas. Surgical ductal decompression is appropriate in selected patients.

Acid steatocrit: a simple, rapid gravimetric method to determine steatorrhea.

OBJECTIVES: The detection and evaluation of steatorrhea in a rapid, quantitative fashion are clinically needed in patients with suspected steatorrhea. Our aim was to evaluate the acid steatocrit method, on random spot stools in adults with and without steatorrhea, relative to the qualitative (microscopic) and quantitative assessments for fecal fat. METHODS: Stool samples were collected 72 h after a diet of 100 g of fat per day and randomly from 15 healthy controls, 14 patients with chronic pancreatitis, and seven patients with small bowel disease. All stools had quantitative, qualitative, and acid steatocrit analyses performed for fecal fat. RESULTS: The sensitivity and specificity for the detection of steatorrhea by the spot stool qualitative fecal fat were 78 and 70%, respectively. The spot stool acid steatocrit correlated linearly with the 72-h stool quantitative fecal fat (g/24 h), r = 0.761 and p < 0.001. The acid steatocrit on random spot stools, compared with the 72-h stool quantitative fecal fat, revealed a sensitivity of 100%, a specificity of 95%, and a positive predictive value of 90% for the detection of steatorrhea. It also estimated the quantitative fecal fat. CONCLUSIONS: The acid steatocrit can be performed accurately on random spot stools and can be used to detect the presence of steatorrhea and estimate the quantitative fecal fat. This assay can be done with readily available equipment for rapid evaluation. Use of a spot stool sample simplifies the acid steatocrit, further improving on the practicality of this test. This study also confirms the clinical usefulness of this simplified method to detect steatorrhea.

Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Fecal pancreatic elastase 1 is inaccurate in the diagnosis of chronic pancreatitis.

Many tests are available to assess pancreatic function. The ideal test would be simple and have adequate sensitivity in mild to moderate chronic pancreatitis (MCP) and severe CP (SCP). Fecal pancreatic elastase 1 (FPE1) assay (ScheBo Tech) has been proposed as a reliable test to evaluate pancreatic exocrine function, with sensitivities of up to 100% in diagnosing CP. Cutoff values (microgram/g stool) of < 100 have been suggested as SCP, 100-200 as MCP, and > 200 as normal. The test's ability to detect MCP distinguished by the absence of steatorrhea, and its specificity among various etiologies of malabsorption, has not been fully evaluated. The aim of this study was to evaluate this assay in subjects including patients with SCP with steatorrhea, patients with MCP with no steatorrhea, healthy controls, and diseased controls with nonpancreatic malabsorption. Thirty-six subjects [15 healthy controls, 7 malabsorption controls, and 14 subjects with CP (7 MCP, 7 SCP)] had FPE1 assays. One hundred fifty-four assays for FPE1 were run for analysis. The intraassay and interassay intraclass correlation coefficients were 0.93 and 0.90, respectively. All SCP had values of < 100 micrograms/g but more than half of the MCP subjects had FPE1 levels within the normal range. The subjects with nonpancreatic malabsorption had FPE1 values ranging from 55 to > 500 micrograms/g of stool. Although the assay detected SCP with steatorrhea, it did not consistently separate the MCP patients from normals. The majority of those with nonpancreatic malabsorption had false-positive values. These results may differ from previously described data because of the purposeful inclusion of MCP subjects, documented by the lack of steatorrhea, and the inclusion of disease controls with nonpancreatic malabsorption. Although PE1 concentrates in the stool and is not significantly degraded, subtle changes in this enzyme, as in MCP, do not seem to be detectable by this assay. This group continues to be the most difficult group to diagnose clinically.

Future roles and training of internal medicine subspecialists. American Board of Internal Medicine Task Force on Subspecialty Internal Medicine.

While fellowship training programs are being reduced in size to better conform to societal needs, the training of subspecialist basic scientists and clinical investigators must be protected to ensure continued discovery and the scholarly application of knowledge to patient care. Fewer subspecialist clinicians must be appropriately trained to serve as consultants, as principal care providers, and as scholarly leaders and educators in their subspecialties. This article describes the recommendations of the American Board of Internal Medicine for subspecialty training. To encourage physicians to choose careers as investigators, overlapping but different training paths are delineated for subspecialist clinicians and investigators. More didactic coursework is recommended for both paths. To maximize the contribution of fewer subspecialists, it is essential to provide rigorous training that is appropriately relevant and realistically matched with career opportunities.