Abstract
Introduction
Chronic pancreatitis affects 3 to 9 people in 100,000; 70% of cases are alcohol-induced.
Methods and outcomes
We conducted a systematic overview aiming to answer the following clinical question: What are the effects of dietary supplements in people with chronic pancreatitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 73 studies. After deduplication and removal of conference abstracts, 41 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 20 studies and the further review of 21 full publications. Of the 21 full articles evaluated, two systematic reviews were added at this update. We performed a GRADE evaluation for four PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for three interventions based on information about the effectiveness and safety of calcium, pancreatic enzyme, and vitamin/antioxidant supplements.
Key Points
Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis.
Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.
Pancreatic enzyme supplements reduce steatorrhoea in people with chronic pancreatitis, but they may have no effect on pain.
We don't know whether calcium supplements or vitamin/antioxidant supplements are effective.
Clinical context
General background
Pancreatitis is inflammation of the pancreas. The inflammation may be sudden (acute) or on-going (chronic). Acute pancreatitis usually involves a single 'attack', after which the pancreas returns to normal. Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis.
Focus of the review
Because alcohol is the most common cause of chronic pancreatitis, we sought to identify if dietary modifications could help such patients. The cited evidence varies on the role of dietary modification for chronic pancreatitis. We sought to review the evidence for such recommendations.
Comments on evidence
Most available sources of evidence are not randomised controlled trials. Rigorous review reveals minimal effect of dietary medication.
Search and appraisal summary
The update literature search for this review was carried out from the date of the last search, August 2011, to October 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 73 studies. After deduplication and removal of conference abstracts, 41 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 20 studies and the further review of 21 full publications. Of the 21 full articles evaluated, two systematic reviews were added at this update.
About this condition
Definition
Pancreatitis is inflammation of the pancreas. The inflammation may be sudden (acute) or ongoing (chronic). Acute pancreatitis usually involves a single 'attack', after which the pancreas returns to normal. Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Symptoms of chronic pancreatitis include recurring or persistent abdominal pain and impaired exocrine function. The most reliable test of exocrine function is the demonstration of increased faecal fat — although, this test is frequently not performed if imaging is consistent (particularly calcification of the pancreatic gland on computerised tomography scan). Diagnosis There is no consensus on the diagnostic criteria for chronic pancreatitis. Typical symptoms include pain radiating to the back and people may present with malabsorption, malnutrition, and pancreatic endocrine insufficiency. However, these symptoms may be seen in people with more common disorders such as reflux disease and peptic ulcers (also more common in heavy drinkers), and also in people with more serious diseases such as pancreatic or periampullary cancers. Diagnostic tests for chronic pancreatitis include faecal elastase measurement (to prove pancreatic insufficiency) and imaging. Biopsy may be required to resolve diagnostic uncertainty.
Incidence/ Prevalence
The annual incidence of chronic pancreatitis has been estimated in one prospective study and several retrospective studies to be between 3 and 9 cases/100,000 population. Prevalence is estimated at between 0.04% and 5%. Alcoholic chronic pancreatitis is usually diagnosed after a long history of alcohol abuse, and is the most common cause.
Aetiology/ Risk factors
The TIGAR-O system describes the main predisposing factors for chronic pancreatitis as: toxic-metabolic (which includes alcohol-induced [70% of all cases], smoking, hypercalcaemia, hyperlipidaemia, and chronic renal failure); idiopathic (which includes tropical pancreatitis and may form up to 20% of all cases); genetic (which includes cationic trypsinogen, CFTR, and SPINK1 mutation); autoimmune (which includes solitary and syndromic); recurrent and severe acute pancreatitis (which includes postnecrotic and radiation-induced); and obstructive (which includes pancreatic divisum and duct obstruction owing to various causes). Although 70% of people with chronic pancreatitis report excessive consumption of alcohol (>150 g/day) over a long period (>20 years), only 1 in 10 heavy drinkers develop chronic pancreatitis, suggesting underlying genetic predisposition or polymorphism, although a link has not been established conclusively.
Prognosis
Mortality in people with chronic pancreatitis is higher than in the general population, with mortality at 10 years after diagnosis estimated at 70% to 80%. Diagnosis is usually made between 40 and 48 years of age. Reported causes of mortality in people with chronic pancreatitis are: complications of disease as well as treatment; development of pancreatic cancer or diabetes; and continual exposure to risk factors for mortality, such as smoking and alcohol.
Aims of intervention
To minimise pain of chronic pancreatitis, alleviate symptoms and sequelae of pancreatic exocrine insufficiency, improve quality of life, and reduce complications, with minimal adverse effects of treatment.
Outcomes
Mortality; pain relief; reduction of steatorrhoea (includes alleviation of nutritional insufficiency); global symptom improvement; weight gain/maintenance; quality of life; development of complications (includes incidence of diabetes and incidence of pancreatic cancer); adverse effects.
Methods
Search strategy BMJ Clinical Evidence search and appraisal date October 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to October 2014, Embase 1980 to October 2014, The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, at least single-blinded, and containing 20 or more individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our pre-defined criteria for inclusion in the benefits and harms section may have been reported in the 'Further information on studies' or 'Comment' sections (see below). Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributor may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following previously reported questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of drug interventions in people with chronic pancreatitis? What are the effects of nerve blocks for pain relief in people with chronic pancreatitis? What are the effects of different invasive treatments for specific complications of chronic pancreatitis? Data and Quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Chronic pancreatitis: dietary supplements.
| Important outcomes | Development of complications, Global symptom improvement, Mortality, Pain relief, Quality of life, Steatorrhoea, Weight gain/maintenance | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of dietary supplements in people with chronic pancreatitis? | |||||||||
| 4 (not reported) | Pain relief | Pancreatic enzyme supplements versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results, inclusion of poor-quality RCTs, and no significance assessment between groups |
| 3 (55) | Steatorrhoea | Pancreatic enzyme supplements versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (27) | Global symptom improvement | Pancreatic enzyme supplements versus placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and short follow-up; directness point deducted for use of subjective outcome |
| 1 (36) | Pain relief | Oral citrate versus placebo | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results; directness point deducted as only 16 people had pain before trial started |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Hemant M. Kocher, Barts Cancer Institute, Queen Mary University of London, London, UK.
Raghu Kadaba, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, London, UK.
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