ABSTRACT
Objectives:
To identify factors that increase the risk of gastrointestinal‐related (GI‐related) hospitalization of infants with cystic fibrosis (CF) during the first year of life.
Methods:
...The Baby Observational and Nutrition Study was a longitudinal, observational cohort of 231 infants diagnosed with CF by newborn screening. We performed a post‐hoc assessment of the frequency and indications for GI‐related admissions during the first year of life.
Results:
Sixty‐five participants had at least one admission in the first 12 months of life. High pancreatic enzyme replacement therapy (PERT) dosing (>2000 lipase units/kg per meal; hazard ratio HR = 14.75, P = 0.0005) and use of acid suppressive medications (HR = 4.94, P = 0.01) during the study period were positively associated with subsequent GI‐related admissions. High levels of fecal calprotectin (fCP) (>200 μg/g) and higher relative abundance of fecal Klebsiella pneumoniae were also positively associated with subsequent GI‐related admissions (HR = 2.64, P = 0.033 and HR = 4.49, P = 0.002, respectively). During the first 12 months of life, participants with any admission had lower weight‐for‐length z scores (WLZ) (P = 0.01). The impact of admission on WLZ was particularly evident in participants with a GI‐related admission (P < 0.0001).
Conclusions:
Factors associated with a higher risk for GI‐related admission during the first 12 months include high PERT dosing, exposure to acid suppressive medications, higher fCP levels, and/or relative abundance of fecal K pneumoniae early in life. Infants with CF requiring GI‐related hospitalization had lower WLZ at 12 months of age than those not admitted as well as those admitted for non‐GI‐related indications.
We compared pancreatogenic (DM3c) and type 2 diabetes mellitus.
We compared age-, sex-, and diabetes mellitus duration-matched DM3c cases (n = 142) and type 2 diabetes mellitus (n = 142). ...Pancreatogenic diabetes was considered when it appeared after the diagnosis of pancreatitis or after pancreatic surgery.
Pancreatogenic diabetes presented lower body mass index (BMI) odds ratio (OR), 1.2; 95% confidence interval (CI), 1.13-1.28; P < 0.001, worse glycemic control (OR, 1.196; 95% CI, 1.058-1.35; P = 0.004), required insulin more frequently (OR, 4.21; 95% CI, 2.57-6.93; P = 0.0001), had more hypoglycemic episodes (OR, 3.65; 95% CI, 1.64-8.16; P = 0.001) but lower frequency of dyslipidemia (OR, 0.42; 95% CI, 0.26-0.68; P = 0.001) and arterial hypertension (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01). Pancreatogenic diabetes cases on pancreatic enzyme replacement therapy had lower glycosylated hemoglobin (8.52% vs 9.44%; P = 0.026), serum carotenes (79.1 vs 116.1; P = 0.03), and BMI (23.4 vs 26.1; P = 0.0005) than those not on pancreatic enzyme replacement therapy. Pancreatogenic diabetes onset occurred earlier in necrotizing pancreatitis and after pancreatic surgery.
Pancreatogenic diabetes presents with low BMI and lacks metabolic syndrome components. The type of pancreatic disease or surgery defines its onset time.
Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at ...diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.
BACKGROUNDHigh daily doses of pancreatic enzyme replacement therapy (PERT) were historically associated with risk of fibrosing colonopathy (FC) in people with cystic fibrosis (pwCF), leading to ...development of PERT dosing guidelines and reformulated products. This study quantified incidence of FC in pwCF treated with PERT following those measures.METHODSThis large prospective cohort study included eligible pwCF enrolled in the Cystic Fibrosis Foundation Patient Registry with ≥1 clinic visit in 2012-2014 and follow-up through 2020. Data on PERT exposure, demographics, and medical history were collected. Clinical data, imaging, and histopathology of suspected cases were examined by an independent adjudication panel of physicians familiar with this complication.RESULTSBase Study Population included 26,025 pwCF who contributed 155,814 person-years mean (SD) 6.0 (2.0) years of follow-up. Over 7.8 years, 29 pwCF had suspected FC; three cases were confirmed by adjudication, 22 cases were confirmed as not FC, and four cases were indeterminate. There were 22,161 pwCF exposed to any PERT, with mean PERT use time of 5.583 person-years and mean daily dose of 8328 U lipase per kg per day. All three confirmed cases and four indeterminate cases of FC occurred during current use of PERT. Incidence rates per 1000 person-years exposed were 0.0242 (95 % CI 0.0050, 0.0709) for confirmed FC and 0.0566 (95 % CI 0.0227, 0.1166) for indeterminate or confirmed FC.CONCLUSIONSThe incidence of FC in pwCF is very low in the era of current treatment guidelines and more stringent quality standards for PERT products.
Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism ...of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.
•Oral supplementation of pancrelipase alters composition of intestinal microbiota.•Over-represented taxa include bacteria promoting intestinal homeostasis.•Akkermansia muciniphila and Lactobacillus reuteri are over-represented.•Pro-inflammatory bacteria is inhibited by supplementation of pancrelipase.•Pancrelipase may help treat chronic pancreatitis by altering intestinal microbiota.
Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to ...the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI.
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations.
Best Practice Advice Statements
EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery.
EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger–Ellison syndrome).
Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition.
Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100–200 μg/g are indeterminate for EPI.
Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy.
Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use.
Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis.
Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease.
Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States.
Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life.
PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non–enteric-coated preparations.
PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content.
Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets.
Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels.
EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1–2 years.
Exocrine pancreatic insufficiency (EPI) is characterized by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption. Numerous conditions account for the etiology of EPI, with the most ...common being diseases of the pancreatic parenchyma including chronic pancreatitis, cystic fibrosis, and a history of extensive necrotizing acute pancreatitis. Treatment for EPI includes dietary management, lifestyle changes (i.e., decrease in alcohol consumption and smoking cessation), and pancreatic enzyme replacement therapy.
Many diagnostic tests are available to diagnose EPI, however, the criteria of choice remain unclear and the causes for a false-positive test are not yet understood. Despite multiple studies on the treatment of EPI using exogenous pancreatic enzymes, there remains confusion amongst medical practitioners with regard to the best approach to diagnose EPI, as well as dosing and administration of pancreatic enzymes. Appropriate use of diagnostics and treatment approaches using pancreatic enzymes in EPI is essential for patients. This opinion piece aims to address the existing myths, remove the current confusion, and function as a practical guide to the diagnosis and treatment of EPI.
Exocrine pancreatic insufficiency (EPI), which leads to malabsorption and poor weight gain, is seen in 85% of patients with cystic fibrosis (CF). EPI is treated with pancreatic enzyme replacement ...therapy taken with each meal. The highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator, ivacaftor, restores CFTR function in patients with responsive mutations. It is a widely held view that EPI in CF is irreversible due to the complete destruction of pancreatic ducts and acinar cells. We describe three pediatric CF patients with EPI who were started on ivacaftor, and subsequently showed evidence of restored exocrine pancreatic function with clinical and biochemical parameters.
The clinical consequences of pancreatic exocrine insufficiency and its treatment in advanced pancreatic ductal adenocarcinoma (PDAC) are poorly investigated. This retrospective study aims at ...investigating the pancreatic enzyme replacement therapy (PERT) use and its impact on survival and maldigestion-related symptoms in advanced PDAC patients undergoing chemotherapy.
A retrospective analysis was conducted on advanced PDAC patients, treated with first-line gemcitabine plus
-paclitaxel at two academic institutions (March 2015-October 2018). Data were correlated with overall survival (OS) using Cox regression model. Kaplan-Meier curves were compared using Log-Rank test.
Data from 110 patients were gathered. PERT was administered in 55 patients (50%). No significant differences in baseline characteristics with those who did not receive PERT were found. Median OS for the entire group was 12 months (95% CI 9-15). At multivariate analysis, previous surgical resection of the primary tumor, (HR 2.67,
), weight gain after 3 months (HR 1.68,
) and PERT (HR 2.85,
) were independent predictors of OS. Patients who received PERT reported an improvement of maldigestion-related symptoms at 3 months more frequently than patients who did not (85.2% vs 14.8%,
).
PERT is associated with significantly prolonged survival and maldigestion-related symptoms alleviation in advanced PDAC patients.
Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we ...conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients.
Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival.
A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070).
In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.
PDF
