Pancreatic Enzyme Substitution Research Articles

Long-term changes of pancreatic function in patients with complicated walled-off necrosis

Objectives Walled-off necrosis (WON) is a serious complication to necrotizing acute pancreatitis with a high morbidity and mortality. The aim of this study was to investigate the long-term changes in pancreatic function, metabolic function and body composition in patients with WON. Material and methods Observational study including patients with WON who underwent endoscopic transmural drainage and necrosectomy. Patients were prospectively evaluated at baseline, 3–6 months after discharge, and 12 months after discharge. Patients were characterized with fecal elastase, blood samples, computer tomography, dual energy X-ray absorptiometry and Lundh’s test. Results The study includes 17 patients (11 men) with WON. The etiologies were gallstones (53%) alcohol intake (35%) and 12% had an unknown etiology. The body mass index (BMI) dropped during baseline and 3 months after discharge (p = .03) and increased 12 months after discharge (p = .002). Twelve months after discharge, 29% had mild exocrine insufficiency, 7% moderate insufficiency and 50% severe insufficiency based on the Lundh’s test. Fecal elastase was <100 μg/g in 35% and <200 μg/g in 59% 12 months after discharge. Only, 24% required pancreatic enzyme substitution. Endocrine insufficiency developed in 24%. These patients also had exocrine insufficiency. Conclusions A considerable proportion of patients with WON experience both endocrine and exocrine pancreatic insufficiency suggesting that long-term follow-up is needed in order to ensure adequate treatment.

Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota.

Cystic Fibrosis (CF) is an autosomal recessive disorder with life-threatening organ manifestations. 87% of CF patients develop exocrine pancreas insufficiency, frequently starting in utero and requiring lifelong pancreatic enzyme substitution. 99% develop progressive lung disease, and 20-60% CF-related liver disease, from mild steatosis to cirrhosis. Characteristically, pancreas, liver and lung are linked by choline metabolism, a critical nutrient in CF. Choline is a tightly regulated tissue component in the form of phosphatidylcholine (Ptd'Cho) and sphingomyelin (SPH) in all membranes and many secretions, particularly of liver (bile, lipoproteins) and lung (surfactant, lipoproteins). Via its downstream metabolites, betaine, dimethylglycine and sarcosine, choline is the major one-carbon donor for methionine regeneration from homocysteine. Methionine is primarily used for essential methylation processes via S-adenosyl-methionine. CF patients with exocrine pancreas insufficiency frequently develop choline deficiency, due to loss of bile Ptd'Cho via feces. ~ 50% (11-12g) of hepatic Ptd'Cho is daily secreted into the duodenum. Its re-uptake requires cleavage to lyso-Ptd'Cho by pancreatic and small intestinal phospholipases requiring alkaline environment. Impaired CFTR-dependent bicarbonate secretion, however, results in low duodenal pH, impaired phospholipase activity, fecal Ptd'Cho loss and choline deficiency. Low plasma choline causes decreased availability for parenchymal Ptd'Cho metabolism, impacting on organ functions. Choline deficiency results in hepatic choline/Ptd'Cho accretion from lung tissue via high density lipoproteins, explaining the link between choline deficiency and lung function. Hepatic Ptd'Cho synthesis from phosphatidylethanolamine by phosphatidylethanolamine-N-methyltransferase (PEMT) partly compensates for choline deficiency, but frequent single nucleotide polymorphisms enhance choline requirement. Additionally, small intestinal bacterial overgrowth (SIBO) frequently causes intraluminal choline degradation in CF patients prior to its absorption. As adequate choline supplementation was clinically effective and adult as well as pediatric CF patients suffer from choline deficiency, choline supplementation in CF patients of all ages should be evaluated.

Chronic pancreatitis and the heart disease: Still terra incognita?

BACKGROUNDIt has been suggested that chronic pancreatitis (CP) may be an independent risk factor for development of cardiovascular disease (CVD). At the same time, it seems that congestive heart failure (CHF) and CP share the responsibility for the development of important clinical conditions such as sarcopenia, cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency (PEI), respectively.AIMTo explore the evidence regarding the association of CP and heart disease, more specifically CVD and CHF.METHODSA systematic search of MEDLINE, Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was investigated. The search was limited to articles in the English language. The last search was run on the 1st of May 2019. The primary outcomes were: (1) Incidence of cardiovascular event [acute coronary syndrome (ACS), chronic coronary disease, peripheral arterial lesions] in patients with established CP; and (2) Incidence of PEI in patients with CHF.RESULTSOut of 1166 studies, only 8 were eligible for this review. Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers (vitamin D, selenium, phosphorus, zinc, folic acid, and prealbumin) in patients with CHF. However, after substitution of pancreatic enzymes, it seems that, at least, loss of appetite was attenuated. On the other side, studies investigating cardiovascular events in patients with CP showed that, in CP cohort, there was a 2.5-fold higher incidence of ACS. In another study, patients with alcohol–induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies. Earlier studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary insufficiency. Also, statistically significant higher incidence of arterial lesions was found in patients with CP compared to the control group with the same risk factors for atherosclerosis (hypertension, smoking, dyslipidemia). Moreover, one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP.CONCLUSIONCurrent evidence implicates a possible association between PEI and malnutrition in patients with CHF. Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF. On the other hand, CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

Influence of Clinical pathways on treatment and outcome quality for patients undergoing pancreatoduodenectomy? A retrospective cohort study

Pancreatic surgery demands complex multidisciplinary management. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated the effect of CPs on quality of care for pancreatoduodenectomy. Data of all consecutive patients who underwent pancreatoduodenectomy before (n=147) or after (n=148) CP introduction were evaluated regarding catheter and drain management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates. Catheters and abdominal drainages were removed significantly earlier in patients treated with CP (p<0.0001). First intake of liquids, nutritional supplement and solids was significantly earlier in the CP group (p<0.0001). Exocrine insufficiency was significantly less common after CP implementation (47.3% vs. 69.7%, p<0.0001). The number of patients receiving intraoperative transfusion dropped significantly after CP implementation (p=0.0005) and transfusion rate was more frequent in the pre-CP group (p=0.05). The median number of days with maximum pain level >3 was significantly higher in the CP group (p<0.0001). There was no significant difference in mortality, morbidity, reoperation and readmission rates. Following implementation of a CP for pancreatoduodenectomy, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.

Clinical Pathways For Pancreatic Surgery: Are They A Suitable Instrument For Process Standardization To Improve Process And Outcome Quality Of Patients Undergoing Distal And Total Pancreatectomy? - A Retrospective Cohort Study.

PurposePancreatic surgery demands complex multidisciplinary management, which is often cumbersome to implement. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated if CPs are a suitable tool for process standardization in order to improve process and outcome quality in patients undergoing distal and total pancreatectomy.Patients and methodsData of consecutive patients who underwent distal or total pancreatectomy before (n=67) or after (n=61) CP introduction were evaluated regarding catheter management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates.ResultsThe usage of incentive spirometers for pneumonia prophylaxis increased. The median number of days with hyperglycemia decreased significantly from 2.5 to 0. For distal pancreatectomy, the incidence of postoperative diabetes dropped from 27.9% to 7.1% (p=0.012). The incidence of postoperative exocrine pancreatic insufficiency decreased from 37.2% to 11.9% (p=0.007). There was no significant difference in mortality, morbidity, reoperation and readmission rates between groups.ConclusionFollowing implementation of a pancreatic surgery CP, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.

Vitamin A and beta (β)-carotene supplementation for cystic fibrosis.

People with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines. Thus, a systematic review on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in people with CF would help guide clinical practice. This is an update of an earlier Cochrane Review. To determine if supplementation with vitamin A, carotenes or other retinoid supplements in children and adults with CF reduces the frequency of vitamin A deficiency disorders, improves general and respiratory health and affects the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. Additionally we searched several ongoing trials registries, including ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number Registry.Most recent database searches: 01 June 2018. All randomised or quasi-randomised controlled studies comparing all preparations of oral vitamin A, carotenes or retinoids (or in combination), used as a supplement compared to placebo at any dose, for at least three months, in people with CF (diagnosed by sweat tests or genetic testing) with and without pancreatic insufficiency. Two authors individually assessed study quality and extracted data on outcome measures. The authors assessed the quality of the evidence using the GRADE system. Investigators were contacted to retrieve missing quantitative data. No studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (β)-carotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive β-carotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the low-dose supplementation period should be interpreted with caution, due to the lack of a wash-out period after the high-dose supplementation.The included study did not report on two of the review's primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD) -0.23 (95% confidence interval (CI) -0.89 to 0.43) (low-quality evidence). With regards to secondary outcomes, supplementation with high-dose β-carotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD -15 days (95% CI -27.60 to -2.40); however, this was not maintained in the second three-month section of the study when the level of β-carotene supplementation was reduced, MD -8 days (95% CI -18.80 to 2.80) (low-quality evidence). There were no statistically significant effects between groups in lung function (low-quality evidence) and no adverse events were observed (low-quality evidence). Supplementation affected levels of β-carotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity. Since no randomised or quasi-randomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the low-quality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on β-carotene supplementation can be drawn. Until further data are available, country- or region-specific guidelines regarding these practices should be followed.

13C-Mixed Triglyceride Breath Test and Fecal Elastase as an Indirect Pancreatic Function Test in Cystic Fibrosis Infants.

The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.

Research progress of pancreatic enzyme replacement therapy after gastric resection

Gastric resection can cause a multifactorial clinical manifestations of dyspepsia, such as flatulence, diarrhea, weight loss, and fat diarrhea. Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat maldigestion following gastric surgery, the main causes may be related to rapid gastric emptying; asynchrony between gastric emptying and bilio-pancreatic secretion due to new tracts of various reconstructions; bacterial overgrowth after gastrectomy and so on. Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for EPI, due to lack of available evidence so far, the efficacy and safety of pancreatic enzyme substitution in patients following gastric resection remains unclear and cannot be generally recommended. This review will sum up the revelant studies addressing EPI and PERT after gastric resection in recent years, and summarizes the mechanisms, clinical diagnostic methods and PERT treatment perscription of EPI after gastrectomy to improve the cognition of clinicans. Key words: Gastrectomy; Exocrine pancreatic insufficiency; Dyspepsia; Pancreatic enzyme replacement therapy

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Retrospective cohort analysis on pancreatic enzyme substitution in very low birthweight infants with postnatal growth failure

ObjectiveTo evaluate the effects of pancreatic enzyme substitution (PES) in selected very low birthweight (VLBW) infants with poor postnatal growth despite intensified nutritional support.DesignRetrospective historic cohort study with matched controls.SettingSingle...

Enzyme replacement therapy for maldigestion syndrome: clinical surveillances

Maldigestion persists in most patients with chronic pancreatitis (CP) and celiac disease. The objective lipase and amylase insufficiency diagnosis is needed to achieve an adequate clinical response to oral pancreatic enzyme substitution therapy. The novel data are presented in the article on the role of 13C-mixed triglyceride and 13C-corn starch breath tests as tools for exocrine pancreatic insufficiency diagnostics, for evaluating fat and starch malabsorbtion in CP patients. 165 patients (135 with CP and 30 with CP + celiac disease) and 30 healthy volunteers were included in the investigation. Delayed results of enzyme replacement therapy for maldigestion were estimated in 1 and 2 year of surveillance. It has been shown that partial recovery of exocrine pancreatic function is possible, and replacement therapy leads to patients’ nutritional status improving. It has been shown that 13C-breath tests could be useful tools in clinical practice for CP diagnostics. They are well-correlated with fecal elastase-1 level, have high sensitivity and specificity for diagnostics of lipase and amylase deficiency. Tests make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction.

The Risk of Fractures Among Patients With Cirrhosis or Chronic Pancreatitis

Cirrhosis and chronic pancreatitis (CP) are accompanied by inflammation and malnutrition. Both conditions can have negative effects on bone metabolism and promote fractures. We evaluated the risk of fractures among patients with CP or cirrhosis and determined the effect of fat malabsorption on fracture risk among patients with CP. We performed a retrospective cohort study using the Danish National Patient Register to identify patients diagnosed with CP or cirrhosis. We analyzed data collected from January 1, 1995, to December 31, 2010, on 20,769 patients (35.5% women with cirrhosis and 11,972 patients (33.5% women) with CP. Each patient was compared with 10 age- and sex-matched controls. We also assessed the risk of fractures among patients with CP who received pancreatic enzyme substitution (PES) for fat malabsorption. During the study period, bone fractures occurred in 3954 patients with cirrhosis and 2594 patients with CP. The adjusted hazard ratio (HR) for any fracture was 2.4 in patients with cirrhosis (95% confidence interval [CI], 2.2-2.5) and 1.7 in patients with CP (95% CI, 1.6-1.8). The relative risk of low-trauma fractures was highest among individuals younger than 50 years old. Alcohol as an etiology was associated with an increased risk of fracture compared with patients with nonalcoholic cirrhosis (HR, 2.4 vs 1.5; P < .0001) and CP (HR, 2.0 vs 1.5; P < .0001). Patients with CP receiving PES for fat malabsorption had a lower risk of fractures than other CP patients (HR, 0.8; 95% CI, 0.7-0.9). However, increasing the duration of treatment with PES was associated with an increased risk of fracture. Patients, especially younger patients, with cirrhosis or CP have an increased risk of fractures of all types.

Mutations of the trypsinogen activation peptide in hereditary pancreatitis

Mutations of the trypsinogen activation peptide in hereditary pancreatitis

Effects of exocrine pancreatic insufficiency (EPI) and pancreatic enzyme substitution on bone mineral content of growing pigs – used as a model for children

Effects of exocrine pancreatic insufficiency (EPI) and pancreatic enzyme substitution on bone mineral content of growing pigs – used as a model for children

Pancreatic Resections for Solid or Cystic Pancreatic Masses in Children

The aim of the study was to assess the diagnosis and management of solid pancreatic neoplasm in children and the type of surgical treatment, focusing on short- and long-term outcomes. We retrospectively reviewed the charts of all children who had undergone pancreatic resection for suspicion of pancreatic tumor in Kremlin Bicêtre Hospital, Paris, between 1986 and 2008. We studied the symptoms at diagnosis, the type of surgery, and the short- and long-term morbidity and mortality. Of 18 patients identified, there were 7 pseudopapillary tumors, 3 neuroblastomas, 2 rhabdomyosarcomas, 1 acinar cell carcinoma, 1 endocrine cell carcinoma, 1 renal angiomyolipoma, and 3 pancreatic cysts. Symptoms at diagnosis were abdominal trauma, abdominal mass, and jaundice. Operative procedures were duodenopancreatectomy (11), mid-pancreatic resections (2), splenopancreatectomy (2), distal pancreatectomy (1), and tumorectomy (2). There were no deaths related to surgery. The postoperative morbidity rate was 45%, including 2 cases of fistula (11%) occurring after a mid-pancreatic resection and a pancreaticoduodenectomy. The median follow-up was 4.2 years (range 2-11). There was no diabetes mellitus, but there was 1 case of fat diet intolerance requiring pancreatic enzyme substitution. All of the children had a growth curve within normal limits. In this experience, pancreatic resections have proven to be a safe and efficient procedure, with low long-term morbidity, for the treatment of tumoral and selected nontumoral pancreatic masses.

Severe gastroparesis associated recurrent hypoglycemic unconsciousness in diabetic neuropathy

The gastric emptying rate has a decisive role in the regulation of blood glucose in diabetic patients. In some cases the gastric hypomotility might result an insufficient glucose absorption leading to extreme metabolic instability. Here we describe the diagnostic and the therapeutic strategy of this motility disorder. A 45 years old man was admitted to the department of neurology with severe recurrent convulsions and transient unconsciousness. His pancreatic diabetes developed 10 years before when the head of the pancreas was removed due to a pseudocyst. As the neurological diagnostic procedures did not reveal any organic central nervous disorder and the glucose levels were unstable, he was transfered to our clinic. The careful analysis of the daily blood glucose profile revealed severe recurrent hypoglycemias after breakfast besides the gradual reduction of the pre-breakfast insulin. Although he did not have digestive symptoms, a scintigraphic gastric emptying was done. The half-time of gastric emptying (HTE) after breakfast was extremely long (HTE: 487.6min, normal range: ≤67.6min.). The cardiovascular reflex tests reflected a severe autonomic neuropathy (score: 8, normal range: ≤2), with a dominance of parasympathetic dysfunction. The subcutaneous blood glucose was measured via an inserted electrode on 6 consecutive days by the application of a continuous blood glucose measuring system (CGMS). On all of the 6 days the post-breakfast glucose was much lower than the fasting value and on 2 of the 6 days it fell down to the hypoglycemic range. Parenteral, later oral metoclopramid and alpha lipoic acid were administered with oral pancreatic enzyme substitution. The insulin treatment and the diet were also adjusted. 6 months later the patient was hypoglycemia- and symptom-free, the HTE was less longer (245.8min.), the CGMS did not reveal post-breakfast glucose lowering while the autonomic neuropathy remained severe (score: 10). Conclusions: The measurement of the gastric emptying might be a part of the differenzial diagnostics of newly appearing convulsive disorder in diabetic patients with long-term disease. The application of cardiovascular tests and a CGMS method strengthens the diagnostic accuracy. The treatment of gastric hypomotility, neuropathy and exocrine insufficiency ensures a stable metabolism and an improvement in quality of life.

Pancreatic exocrine insufficiency: Diagnosis and treatment

Pancreatic insufficiency is a major consequence of pancreatic diseases leading to a loss of pancreatic parenchyma, obstruction of the main pancreatic duct, decreased pancreatic stimulation, or acid-mediated inactivation of pancreatic enzymes. In addition, gastrointestinal and pancreatic surgical resections are frequent causes. Clinical manifestations include abdominal cramps, steatorrhea and malnutrition. Malnutrition, the main contributing factor of weight loss, has been related to a high morbidity and mortality secondary to an increased risk of malnutrition-related complications and cardiovascular events. Assessments of exocrine pancreatic function, such as fecal fat quantification and (13) C-triglyceride breath test, are the method of choice for diagnosis. In clinical practice, high-risk patient populations include those with severe necrotizing pancreatitis, gastrointestinal and pancreatic surgery, cancer of pancreas head, and those with pancreatic calcifications. Apart from relief of maldigestion-related symptoms, the main goal of pancreatic enzyme substitution therapy is to ensure a normal nutritional status. Therapy of pancreatic insufficiency is based on the oral administration of exogenous pancreatic enzymes. Restriction of fat intake, though traditionally important in conventional treatment, should be reconsidered. Enzyme substitution therapy should ideally mimic the physiological pattern of pancreatic exocrine secretion, and pancreatic enzymes in the form of enteric-coated minimicrospheres are considered as the most elaborated commercially available enzyme preparations. In general, pancreatic exocrine insufficiency in patients after surgery may be managed similarly to patients with chronic pancreatitis. This review focuses on current perspectives in diagnosis and treatment of pancreatic exocrine insufficiency and practical suggestions on its clinical management.

Exocrine pancreatic function in patients with end-stage renal disease

malnutrition is a common problem in patients with end-stage renal disease (ESRD). Several studies showed 30 years ago that more than half of patients with ESRD suffered from exocrine pancreatic insufficiency. However, the studies never investigated whether the functional impairments led to morphological changes of the pancreas or to steatorrhea and thus indicating the need for lifelong pancreatic enzyme substitution. Our goal was therefore not only to establish the frequency but also the severity of exocrine pancreatic insufficiency in hemodialysis patients. the study included 50 hemodialysis patients with no history of acute or chronic pancreatitis or upper abdominal symptoms of uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or (partial) small bowel resection, or chronic inflammatory bowel disease were excluded. In all 50 patients, fecal elastase-1 was determined using two different methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal weight were measured. mild to moderate exocrine pancreatic insufficiency (elastase-1 100 - 200 microg/g stool) was found in 10% of patients. It was not correlated with age, sex, and underlying renal disease, duration of hemodialysis, or diarrhea and steatorrhea. In no patient was the enzyme content < 100 microg/g stool, i.e., it never sank to a level at which pancreatic enzyme substitution would have been recommended. Nine patients (18%) had mild diarrhea (200 - 300 g stool/ day), and 10 (20%) had mild steatorrhea (7 - 15 g fat/day in the stool). Five patients had both diarrhea and steatorrhea. mild to moderate but not severe exocrine pancreatic insufficiency is not infrequent in patients on hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non-pancreas-related steatorrhea is also not uncommon. This finding requires further analysis because steatorrhea might influence nutrition, thus potentially opening the way to new therapeutic approaches.

13C Breath Tests for the Assessment of Exocrine Pancreatic Function

The secretin-pancreozymin test is regarded as the most accurate of the pancreatic exocrine function tests but is cumbersome, time consuming, and invasive because it requires duodenal intubation and hormonal stimulation of the pancreas. Fecal analysis of fat, fecal elastase, or chymotrypsin are more practicable but far less sensitive to detect early stages of pancreatic exocrine insufficiency. Several (13)C-labeled substrates that are digested by pancreatic enzymes have been proposed for breath tests, thus assessing the intraluminal activity of pancreatic enzymes and therewith the pancreatic exocrine function. Particularly in pediatrics, (13)C breath tests are suited not only for diagnosis of pancreatic exocrine disorder, but also for therapy control under pancreatic enzyme substitution. However, the costs of substrates, the high time expenditure, and the lack of standardization still limit the clinical use of these breath tests. This review aims to place into perspective the traditional pancreatic exocrine function tests and the newer (13)C breath tests.

Neurological Features and Enzyme Therapy in Patients With Endocrine and Exocrine Pancreas Dysfunction Due to CEL Mutations

OBJECTIVE—To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy.RESEARCH DESIGN AND METHODS—Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months.RESULTS—Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P < 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common.CONCLUSIONS—Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.