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Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. METHODS:Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. RESULTS:A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk?=?3.36, 1.07-10.54; p?=?0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

SUBMITTER: Iglesia D

PROVIDER: S-EPMC7724551 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

Iglesia Daniel de la D Avci Bartu B Kiriukova Mariia M Panic Nikola N Bozhychko Maryana M Sandru Vasile V de-Madaria Enrique E Capurso Gabriele G

United European gastroenterology journal 20200706 9

<h4>Background</h4>Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic can ...[more]

PMID: 32631175

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Project description:BACKGROUND & AIMS:Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI. METHODS:We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis. RESULTS:We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives). CONCLUSIONS:In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.

Project description:BackgroundExocrine pancreatic insufficiency (EPI) is common in patients with type 2 diabetes. However, the prevalence of EPI varies significantly in different studies. Untreated EPI in these patients can adversely affect their nutrition and metabolism. The aim of this study is to estimate the pooled prevalence of EPI in patients with type 2 diabetes and to explore the potential risk factors.MethodsA systematic search was performed in PubMed, Web of Science, and Embase, which included studies meeting inclusion criteria from 1960 to 1 April 2022. Relevant articles were searched using the combination of Medical Subject Heading (MeSH) terms of "Type 2 diabetes" and "pancreatic exocrine insufficiency." The Stata 16.0 software was used for data analyses. The random-effects model was used to estimate the pooled prevalence rates and 95% CI using "metaprop program."ResultsThe pooled prevalence of EPI was 22% (95% CI: 15%-31%) in patients with type 2 diabetes and 8% (95% CI: 4%-14%) of them developed severe pancreatic insufficiency. In the subgroup analyses, the prevalence of EPI in type 2 diabetes was correlated with geographic location. The prevalence in Asian countries (35%, 95% CI: 22%-49%) is higher than in Europe (18%, 95% CI: 10%-29%) and Australia (9%, 95% CI: 4%-16%). Furthermore, patients with higher insulin requirements, who are more likely to be insulin-deficient, have a higher prevalence of EPI. The pooled prevalence was 27% (95% CI: 17%-37%) in type 2 diabetes with higher insulin requirement (1 group) and 15% (95% CI: 1%-40%) in patients with lower insulin requirement (2 group). In addition, the morbidity of severe EPI in the higher insulin requirement group (12%, 95% CI: 7%-19%) was sextuple as much as the lower insulin requirement group (2%, 95% CI: 0%-13%). EPI was more common in subjects younger than 60 compared with elderlies (25% vs. 19%).ConclusionThe prevalence of EPI in type 2 diabetes may be overestimated. Furthermore, the higher prevalence may be closely related to β-cell function. Endocrine disease therapy would potentially represent a novel therapeutic approach for patients with type 2 diabetes and EPI.

Project description:Exocrine pancreatic insufficiency (EPI) is a clinically defined syndrome based on the physician's assessment of a patient's maldigestion. However, current clinical definitions are inadequate in determining (1) the threshold of reduced pancreatic digestive enzyme secretion that determines "pancreatic insufficiency" in an individual patient; (2) the role of pancreatic function tests; (3) effects of differing metabolic needs, nutrition intake, and intestinal function/adaptation (4) when pancreatic enzyme replacement therapy is needed; and (5) how to monitor and titrate multiple therapies. Experts and key opinion leaders were invited to PancreasFest 2021 to discuss and help clarify mechanistic issues critical to defining EPI and to address misconceptions and barriers limiting advancements in patient care. Clinically EPI is defined as inadequate delivery of pancreatic digestive enzymes to meals to meet nutritional needs and is reversed with appropriate treatment. A new mechanistic definition of EPI was proposed that includes the disorders essence and character: (1) EPI is a disorder caused by failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of a series of individual snacks and meals over time to meet nutritional and metabolic needs, given (a) the specific macronutritional and micronutritional needs; (b) nutrient intake; (c) exocrine pancreatic function; and (d) intestinal anatomy, function, diseases, and adaptative capacity. (2) EPI is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, by gastrointestinal symptoms of nutrient maldigestion and by improvement or correction of nutritional state with lifestyle changes, disease treatment, optimized diet, dietary supplements, and/or administration of adequate pancreatic enzyme replacement therapy. EPI is complex and individualized and multidisciplinary approaches are needed to optimize therapy. Better pancreas function tests and biomarkers are needed to diagnose EPI and guide treatment.

Dataset Information

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

Publications

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

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