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BMJ Clin Evid. 2008; 2008: 0417.
Published online 2008 December 5.
PMCID: PMC2907985

Chronic pancreatitis

Hemant M Kocher, Senior Lecturer and Honorary Consultant Surgeon# and Fieke EM Froeling, PhD student#

Abstract

Introduction

Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of dietary supplements 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? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: avoiding alcohol consumption, biliary decompression, calcium supplements, ductal decompression (endoscopic or surgical), low-fat diet, nerve blocks, opioid analgesics, pancreatic enzyme supplements, pseudocyst decompression (endoscopic or surgical), resection using distal pancreatectomy, resection using pancreaticoduodenectomy (Kausch–Whipple or pylorus-preserving), and vitamin/antioxidant supplements.

Key Points

Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis.

  • Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

Pancreatic enzyme supplements reduce steatorrhoea in people with chronic pancreatitis, but it seems that they have no effect on pain.

There is consensus that tramadol is the most effective oral opioid analgesic for reducing pain in people with chronic pancreatitis, but is associated with gastrointestinal adverse effects.

There is consensus that endoscopic and surgical pseudocyst decompression and ductal decompression have both benefits and harms; it is unclear which technique is best, and choice often depends on local expertise.

  • There is consensus that, despite complications, biliary decompression is essential in people with chronic pancreatitis who have biliary obstruction.

Resection using pancreaticoduodenectomy may be equivalent to localised excision of the pancreatic head in improving symptoms, but it reduces quality of life and increases intraoperative and postoperative complications. In clinical practice, resection using pancreaticoduodenectomy is usually reserved for when other surgical options, such as pseudocyst or duct decompression, are not feasible because of severity of disease.

  • There is consensus that distal pancreatectomy may be a viable option in people with chronic pancreatitis limited to the tail of the pancreas, with most efficacy when multiple pseudocysts are present. It is associated with complications in 15%–50% of people.

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 three and nine 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%–80%. Diagnosis is usually made between 40 and 48 years 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 (includes intraoperative and postoperative complications).

Methods

Clinical Evidence search and appraisal April 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2008, Embase 1980 to April 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, containing more than 20 individuals of whom more than 80% were followed up. Drug RCTs were required to be double-blinded, non-drug interventions to be at least single-blinded, and for surgical trials "open" studies upwards were included. There was no minimum length of follow-up required to include studies. We also searched for prospective and retrospective cohort, case control, and case series containing more than 20 individuals. Many RCTs include people with both acute and chronic pancreatitis: we excluded RCTs in mixed populations if fewer than 20% of participants had chronic pancreatitis. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the review as required. To aid readability of the numerical data in our reviews, we round percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. 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.

Glossary

Beger procedure
Localised pancreatic head resection with pancreatic neck transection and requiring reconstruction to pancreatic neck as well as tissue covering bile duct. Also called duodenum-preserving pancreatic head resection.
Biliary decompression
Procedure to relieve bile duct obstruction (either surgical or endoscopic or percutaneous).
Cystogastrostomy
A communication between (pancreatic) pseudocyst and stomach, which can be performed endoscopically (stent) or surgically.
Cystojejunostomy
An anastomosis between (pancreatic) cyst and jejunum.
Distal pancreatectomy
Resection of the tail of the pancreas, usually to the left of the portal vein/superior mesenteric vein confluence. This may take place with or without splenectomy.
Frey procedure
Localised pancreatic head resection with pancreaticojejunostomy (anastomosis between pancreatic duct and jejunum).
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.
Pancreaticoduodenectomy
Removal of the head of the pancreas, lower end of the bile duct, and duodenum. It may include surgical resection of the distal end of the stomach (antrum). Also called Kausch–Whipple or Whipple procedure.
Pylorus-preserving pancreaticoduodenectomy (PPPD or Traverso-Longmire procedure)
Surgical resection of the duodenum distal to the pylorus, distal common bile duct, head of the pancreas, and proximal jejunum.
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

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, Department of Health National Clinician Scientist, London, UK.

Fieke EM Froeling, Centre for Tumour Biology, Barts and The London School of Medicine and Dentistry, London, UK.

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36. Izbicki JR, Bloechle C, Broering DC, et al. Extended drainage versus resection in surgery for chronic pancreatitis: a prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy. Ann Surg 1998;228:771–779. [PubMed]
2008; 2008: 0417.
Published online 2008 December 5.

Avoiding alcohol consumption

Summary

We don't know whether avoiding alcohol consumption improves symptoms of chronic pancreatitis.

There is consensus that alcohol abstinence may be beneficial, as it prevents further injury to the pancreas and other organs.

Benefits and harms

Avoiding alcohol consumption:

We found no systematic review, RCTs, or observational studies of sufficient quality.

Further information on studies

Comment

Clinical guide:

Avoiding alcohol consumption may be beneficial in people with alcoholic chronic pancreatitis (where there is usually prolonged exposure to large amounts of alcohol) by preventing further injury to the pancreas and other organs (such as the liver, heart, and nervous system). Randomising people with chronic pancreatitis to continuing alcohol consumption would be unethical.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Low-fat diet

Summary

We don't know whether consuming a low-fat diet improves symptoms of chronic pancreatitis.

Low-fat diets decrease the amount of overall fat presented to the intestine for digestion and absorption, and may be helpful in alleviating steatorrhoea.

Benefits and harms

Low-fat diet:

We found no systematic review, RCTs, or observational studies of sufficient quality.

Further information on studies

Comment

Clinical guide:

Low-fat diet may help symptom control in alleviating steatorrhoea (where this is a major presenting symptom of chronic pancreatitis) by decreasing the amount of overall fat presented to the intestine for digestion and absorption. If people are given pancreatic enzyme supplements, they are usually advised to maintain a normal diet, as there is no need to lower fat intake alongside enzyme supplementation.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Pancreatic enzyme supplements

Summary

Pancreatic enzyme supplements reduce steatorrhoea in people with chronic pancreatitis, but it seems that they have no effect on pain.

Benefits and harms

Pancreatic enzyme supplements versus placebo:

We found one systematic review (search date not reported, 6 RCTs, 189 people with chronic pancreatitis, 91 men), one additional RCT, and two subsequent RCTs comparing pancreatic enzyme supplements versus placebo. See further information on studies for data on participant preference and protein absorption.

Pain

Pancreatic enzyme supplements compared with placebo We don't know whether pancreatin is more effective than placebo at reducing pain in people with chronic pancreatitis (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain relief

Systematic review
189 people, 91 men with chronic pancreatitis, age range not reported, 69 people with steatorrhoea, alcohol intake not reported
6 RCTs in this analysis
Pain 2 weeks–4 months
with pancreatin
with placebo
Absolute results reported graphically

Reported as not significant
P value not reported
Not significant

No data from the following reference on this outcome.

Steatorrhoea

Pancreatic enzyme supplements compared with placebo Pancreatin may be more effective than placebo at increasing faecal fat absorption at 2 weeks, reducing faecal fat at 2–4 weeks, and decreasing stool frequency at 2 weeks in people with chronic pancreatitis (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Faecal fat

RCT
Crossover design
11 people with chronic pancreatitis and steatorrhoea
Subgroup analysis
Faecal fat (after cross-over) in people with steatorrhoea 4 weeks
10 g/day with pancreatin (2 capsules at meal times and 1 with snack)
24 g/day with placebo

P <0.001
Effect size not calculatedpancreatin

RCT
Crossover design
9 people with chronic pancreatitis and no steatorrhoea Faecal fat (after cross-over) in people without steatorrhoea 4 weeks
3 g/day with pancreatin (2 capsules at meal times and 1 with snack)
2 g/day with placebo

Reported as not significant
P value not reported
Not significant

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, with faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Faecal fat reduction from baseline 2 weeks
57 g/day with pancreatin (4 capsules at meal times and 2 with snacks)
11 g/day with placebo

P = 0.02
Effect size not calculatedpancreatin
Fat absorption

RCT
Crossover design
29 people with chronic pancreatitis, 27 (93%) alcohol-induced, 28 men, mean age 53 years, with faecal fat >10 g/day Fat absorption at 15 days
81% with pancreatin for 2 weeks (4 capsules at meal times and 2 with snack)
54% with placebo
Absolute numbers not reported

P = 0.002
Effect size not calculatedpancreatin

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Fat absorption increase from baseline to 2 weeks
37% with pancreatin (4 capsules at meal times and 2 with snacks)
12% with placebo
Absolute numbers not reported

P = 0.02
Effect size not calculatedpancreatin
Stool frequency

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Stool frequency reduction from baseline 2 weeks
5 stools/day with pancreatin (4 capsules at meal times and 2 with snacks)
11 stools/day with placebo

P = 0.0015
Effect size not calculatedpancreatin

No data from the following reference on this outcome.

Global symptom improvement

Pancreatic enzyme supplements compared with placebo Pancreatin may be more effective than placebo at improving investigator-assessed global symptom scores (measured by the Clinical Global Impression Disease Symptom Scale) in people with chronic pancreatitis, but not at improving patient-assessed global symptom scores (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Global symptom improvement

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Mean difference in patient-scored Clinical Global Impression Disease Symptoms Scale (CGIDS) from baseline 2 weeks
–0.3 with pancreatin (4 capsules at meal times and 2 with snacks)
+0.4 with placebo

P = 0.06
Not significant

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10g/day and/or a fat absorption < 80% Improvement in investigator-scored CGIDS from baseline 2 weeks
–0.3 with pancreatin (4 capsules at meal times and 2 with snacks)
+0.4 with placebo

P = 0.04
Effect size not calculatedpancreatin

No data from the following reference on this outcome.

Mortality

No data from the following reference on this outcome.

Weight gain/maintenance

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Pancreatic enzyme supplements compared with placebo Pancreatin may be associated with major changes in fasting glucose levels over 4 weeks in people with chronic pancreatitis (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
Crossover design
29 people with chronic pancreatitis, 27 (93%) alcohol-induced, 28 men, mean age 53 years, with faecal fat >10 g/day Blood glucose control 4 weeks
with pancreatin (4 capsules at meal times and 2 with snack)
with placebo

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Non-serious adverse effects (include nausea, mild tremor, mild weakness and abdominal pain) 2 weeks
6/13 (46%) with pancreatin (4 capsules at meal times and 2 with snacks)
11/14 (79%) with placebo

P = 0.5
Not significant

RCT
27 people with chronic pancreatitis, 9 men, mean age 51 years, faecal fat values greater than or equal to 10 g/day and/or a fat absorption <80% Serious adverse effects 2 weeks
0/13 (0%) with pancreatin (4 capsules at meal times and 2 with snacks)
0/14 (0%) with placebo

No data from the following reference on this outcome.

Further information on studies

The review found no significant difference in the proportion of people preferring pancreatic enzymes (time frame for outcome measurement not reported: 52%, 95% CI 45% to 60%; P = 0.52, absolute results presented graphically).

The RCT found significant increase in protein absorption with pancreatin compared with placebo at 15 days (86% with pancreatin v 81% with placebo, P = 0.004).

Comment

Clinical guide:

Pancreatic enzyme supplementation is the most commonly used treatment for steatorrhoea as there is consensus that pancreatic enzymes ameliorate exocrine insufficiency. However, change in pancreatic enzyme levels can exacerbate pancreatic endocrine dysfunction, and supplementation may need monitoring if introduced suddenly. Fat absorption seems best if pancreatic enzyme supplements are taken during or after meals.

Substantive changes

Pancreatic enzyme supplements One RCT added, which found that pancreatic enzyme supplements caused a greater reduction in faecal fat from baseline to 2 weeks, compared with placebo. It found no significant difference in overall symptom relief between groups. Categorisation unchanged (Likely to be beneficial).

2008; 2008: 0417.
Published online 2008 December 5.

Calcium supplements

Summary

We don't know whether calcium is effective.

Reduction in calcium intake is advised for people with hyperparathyroidism or renal failure associated with chronic pancreatitis (to manage the underlying disease).

Benefits and harms

Calcium supplements:

We found no systematic review, RCTs, or observational studies of sufficient quality.

Further information on studies

Comment

Clinical guide:

In current clinical practice, calcium supplements are no longer considered as useful treatment for most people with chronic pancreatitis. Reduction in calcium intake is advised for people with hyperparathyroidism or renal failure associated with chronic pancreatitis (to manage the underlying disease).

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Vitamin/antioxidant supplements

Summary

We don't know whether vitamin/antioxidant supplements are effective in people with chronic pancreatitis.

Benefits and harms

Oral citrate versus placebo:

We found one RCT comparing oral citrate 20–40 g/day versus placebo. See further information on studies for data on calcification.

Pain relief

Vitamin/antioxidant supplements compared with placebo We don't know whether oral citrates are more effective at reducing pain at 18 months in people with chronic pancreatitis (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain

RCT
Crossover design
44 people aged 36–64 years with symptoms of chronic pancreatitis for a median 11 years, 37 of whom consumed more than 80 g alcohol/day, 17 with diabetes, steatorrhoea, or both Proportion of people pain-free 18 months
14/19 (74%) with oral citrate 20–40 g/day
13/17 (76%) with placebo/no treatment

Significance not assessed

Mortality

No data from the following reference on this outcome.

Steatorrhoea

No data from the following reference on this outcome.

Global symptom improvement

No data from the following reference on this outcome.

Weight gain/maintenance

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The RCT found that oral citrate significantly reduced calcification at 18 months compared with placebo (proportion of people with reductions in calcification: 7/19 [37%] with oral citrate 40 g/day v 1/17 [6%] with placebo; P <0.05).

Comment

Clinical guide:

Vitamin supplements may benefit people with chronic pancreatitis independent of altering the clinical course of the disease, because of underlying nutritional deficiency, especially in people with pancreatitis associated with heavy alcohol consumption.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Opioid analgesics

Summary

There is consensus that tramadol is the most effective oral opioid analgesic for reducing pain in people with chronic pancreatitis, but is associated with gastrointestinal adverse effects.

Benefits and harms

Opioid analgesics versus each other:

We found one RCT.

Pain relief

Opioid analgesics compared with each other Tramadol may be more effective than morphine at increasing the proportion of people who rate their pain relief as excellent at 4 days in people with chronic pancreatitis (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain

RCT
25 people with chronic pancreatitis, 80% alcohol-induced Proportion of people who rated pain relief as "excellent" at day 4
67% with tramadol
20% with morphine
Absolute numbers not reported

P <0.001
Effect size not calculatedtramadol

Mortality

No data from the following reference on this outcome.

Steatorrhoea

No data from the following reference on this outcome.

Global symptom improvement

No data from the following reference on this outcome.

Weight gain/maintenance

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Opioid analgesics compared with each other Morphine may be associated with more adverse effects (such as increasing gastrointestinal transit times, headaches, drowsiness, dizziness) than tramadol in people with chronic pancreatitis (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
25 people with chronic pancreatitis, 80% alcohol-induced Orocaecal and colonic transit times
with tramadol
with morphine
Absolute results reported graphically

P <0.05
Effect size not calculatedtramadol

RCT
25 people with chronic pancreatitis, 80% alcohol-induced Headache
33% with tramadol
60% with morphine
Absolute numbers not reported

P <0.001
Effect size not calculatedtramadol

RCT
25 people with chronic pancreatitis, 80% alcohol-induced Dizziness
13% with tramadol
40% with morphine
Absolute numbers not reported

P <0.001
Effect size not calculatedtramadol

RCT
25 people with chronic pancreatitis, 80% alcohol-induced Drowsiness
13% with tramadol
40% with morphine
Absolute numbers not reported

P <0.001
Effect size not calculatedtramadol

Further information on studies

Comment

Clinical guide:

Pain is a major symptom in most people with chronic pancreatitis, which may be continuous or intermittent. Non-opioid analgesics rarely alleviate visceral pain (as in chronic pancreatitis). Clinical consensus suggests that tramadol may be the most effective oral opioid analgesic, but is associated with gastrointestinal adverse effects.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Nerve blocks

Summary

We don't know whether nerve blocks are effective.

Benefits and harms

Nerve block versus placebo or other non-drug treatments:

We found no clinically important results from RCTs or observational studies about the effects of nerve blocks compared with placebo or other non-drug treatments in people with chronic pancreatitis.

Endoscopic ultrasound-guided nerve block versus computerised tomography-guided nerve block:

We found one RCT comparing endoscopic ultrasound-guided nerve block versus computerised tomography-guided nerve block.

Pain relief

Endoscopic ultrasound-guided nerve block compared with computerised tomography-guided nerve block Endoscopic ultrasound-guided nerve block may be more effective than computerised tomography-guided nerve block at improving median pain scores at 4 weeks in people with chronic pancreatitis (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain relief

RCT
22 people with chronic pancreatitis (10 alcohol-induced, mean age 45 years, 45% male, duration of pancreatitis not reported) Median pain score (VAS scale 0–10 where 0 = no pain) 4 weeks
1 with EUS-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)
9 with CT-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)

P <0.02
Effect size not calculatedEUS-guided nerve block

Mortality

No data from the following reference on this outcome.

Steatorrhoea

No data from the following reference on this outcome.

Global symptom improvement

No data from the following reference on this outcome.

Weight gain/maintenance

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
22 people with chronic pancreatitis (10 alcohol-induced, mean age 45 years, 45% male, duration of pancreatitis not reported) Diarrhoea
1/10 (10%) with EUS-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)
2/8 (25%) with CT-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)

RCT
22 people with chronic pancreatitis (10 alcohol-induced, mean age 45 years, 45% male, duration of pancreatitis not reported) Postural hypotension
0/10 (0%) with EUS-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)
1/8 (13%) with CT-guided nerve block (bupivacaine 10 mL 0.75% plus 3 mL triamcinolone 40 mg)

Further information on studies

30% of people receiving EUS-guided nerve block had pain relief at 24 weeks; 12% receiving CT-guided nerve block had pain relief at 12 weeks, with 75% returning to pretreatment pain scores by 18 weeks.

Comment

Clinical guide:

Coeliac plexus block is technically demanding and tends to be reserved for people with pain that is refractory to opioid analgesics — usually those with small-duct chronic pancreatitis and without large-duct obstruction. In people with large-duct obstruction, endoscopic or surgical drainage is usually performed instead. The need for technical expertise with either ultrasound- or CT-guided nerve block must be weighed against the relatively short-term pain relief offered.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Biliary decompression

Summary

Biliary decompression may prevent jaundice and biliary cirrhosis, and there is consensus that despite complications, it is essential in people with obstruction to the biliary tree.

Benefits and harms

Endoscopic versus surgical biliary decompression:

We found no systematic review, RCTs, or observational studies of sufficient quality assessing endoscopic or surgical biliary decompression (see comment).

Further information on studies

Comment

Clinical guide:

Biliary obstruction secondary to chronic pancreatitis may occur in 3%–10% of people admitted to hospital with chronic pancreatitis, and in 6%–46% of people having surgery for chronic pancreatitis, resulting in a lifetime risk of 5%–10% in all people with chronic pancreatitis. Biliary decompression may prevent the effects of jaundice, such as cholangitis, which may happen in 9% of people (27/288 in a collection of case reports from 1976–1988), and long-term biliary cirrhosis, in 7% (21/288 in a collection of case series from 1976–1988). While endoscopic decompression may offer relief in the short term, surgical decompression will be required when chronic pancreatitis causes biliary obstruction (and this may be combined with operation for the pancreatic disease). Rarely, when cancer cannot be ruled out, a surgical resection (pancreaticoduodenectomy) may be carried out (see option on resection using pancreaticoduodenectomy (Kausch–Whipple or pylorus-preserving) in people with more severe disease limited to head of the pancreas).

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Ductal decompression

Summary

There is consensus that endoscopic and surgical pseudocyst decompression and ductal decompression have both benefits and harms; it is unclear which technique is best, and choice often depends on local expertise.

Surgery has attendant morbidity, mortality, and slow recovery rates.

Benefits and harms

Endoscopic versus surgical ductal decompression:

We found two RCTs and one cohort study.

Mortality

Endoscopic compared with surgical ductal decompression We don't know how endoscopic ductal decompression and surgical ductal decompression compare at reducing mortality (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Mortality

RCT
39 patients with pancreatic duct obstruction associated with chronic pancreatitis and severe recurrent pancreatic pain, 54% alcohol-induced, mean age 49 years, 67% male Mortality 2 years
1/19 (5%) with endoscopic treatment
0/20 (0%) with surgical treatment

Significance not assessed

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male Mortality
0% with endoscopic treatment
0% with surgical treatment

No data from the following reference on this outcome.

Pain relief

Endoscopic compared with surgical ductal decompression Surgical ductal decompression may be more effective than endoscopic ductal decompression in reducing pain at 2 and 5 years (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain relief

RCT
39 patients with pancreatic duct obstruction associated with chronic pancreatitis and severe recurrent pancreatic pain, 54% alcohol-induced, mean age 49 years, 67% male Mean Izbicki scores 2 years
51 with endoscopic treatment
25 with surgical treatment

Mean difference 24
95% CI 11 to 36
P <0.001
Effect size not calculatedsurgical ductal decompression

RCT
39 patients with pancreatic duct obstruction associated with chronic pancreatitis and severe recurrent pancreatic pain, 54% alcohol-induced, mean age 49 years, 67% male Proportion of people with complete or partial pain relief at 2 years
6/19 (32%) with endoscopy
15/20 (75%) with surgery

P = 0.007
Effect size not calculatedsurgical ductal decompression

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male People pain-free at 5 years
15% with endoscopic decompression
34% with surgical decompression

P <0.05
Effect size not calculatedsurgical ductal decompression

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male People pain-free 1 year and 3 years
with endoscopic decompression
with surgical decompression
Absolute results reported graphically

Significance not assessed
1018 people with pancreatic duct obstruction associated with chronic pancreatitis, 72% alcohol-induced, mean age 50 years, 71% male Proportion who had no pain or weak pain at mean 4.9 years
87% (of 758 people) with endoscopic treatment only
79% (of 238 people) with surgical intervention after failed endoscopic treatment
Absolute numbers not reported

Weight gain/maintenance

Endoscopic compared with surgical ductal decompression Surgical ductal decompression may be more effective than endoscopic ductal decompression at increasing the proportion of people with increased body weight at 5 years, but we don't know about at 1 and 3 years (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Weight gain/maintenance

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male People with increased body weight 5 years
29% with endoscopic decompression
47% with surgical decompression
Absolute numbers not reported

P <0.05
Effect size not calculatedsurgical ductal decompression

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male People with increased body weight 1 year and 3 years
with endoscopic decompression
with surgical decompression
Absolute results reported graphically

Significance not assessed

No data from the following reference on this outcome.

Steatorrhoea

No data from the following reference on this outcome.

Global symptom improvement

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
72 people with pancreatic duct obstruction associated with chronic pancreatitis, 88% alcohol-induced, mean age 41.7 years, 85% male Complications after procedure
8% with endoscopic decompression
8% with surgical decompression
Absolute numbers not reported

RCT
39 patients with pancreatic duct obstruction associated with chronic pancreatitis and severe recurrent pancreatic pain, 54% alcohol-induced, mean age 49 years, 67% male Complications
11/19 (58%) with endoscopic treatment
7/20 (35%) with surgical treatment

P = 0.15
Not significant

No data from the following reference on this outcome.

Different types of surgical ductal decompression versus each other:

We found one RCT comparing Beger ductal decompression and Frey ductal decompression. For further information on the outcomes of exocrine or endocrine insufficiency, see further information on studies.

Mortality

Different types of surgical ductal decompression compared with each other We don't know how Beger ductal decompression and Frey ductal decompression compare at reducing mortality at 8.6 years (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Mortality

RCT
74 people with chronic pancreatitis with an inflammatory mass limited to the pancreatic head, 51 evaluated, alcohol intake and age not reported Late mortality median 8.6 years
8/26 (31%) with Beger ductal decompression
8/25 (32%) with Frey ductal decompression

Reported as not significant
P value not reported
Not significant

Pain relief

Different types of surgical ductal decompression compared with each other We don't know how Beger ductal decompression and Frey ductal decompression compare at reducing pain at 8.6 years (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain

RCT
74 people with chronic pancreatitis with an inflammatory mass limited to the pancreatic head, 51 evaluated, alcohol intake and age not reported Pain score on VAS (0–100) median 8.6 years
20 with Beger ductal decompression
20 with Frey ductal decompression

P = 0.499
Not significant

Quality of life

Different types of surgical ductal decompression compared with each other We don't know how Beger ductal decompression and Frey ductal decompression compare at improving global quality-of-life scores at 8.6 years (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Quality of life

RCT
74 people with chronic pancreatitis with an inflammatory mass limited to the pancreatic head, 51 evaluated, alcohol intake and age not reported Global quality of life score (range 0–100 where 100 = higher function) median 8.6 years
66.7 with Beger ductal decompression
58.4 with Frey ductal decompression

P = 0.48
Not significant

No data from the following reference on this outcome.

Steatorrhoea

No data from the following reference on this outcome.

Global symptom improvement

No data from the following reference on this outcome.

Weight gain/maintenance

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Adverse effects

Different types of surgical ductal decompression compared with each other We don't know how Beger ductal decompression and Frey ductal decompression compare at reducing postoperative complications (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
74 people with chronic pancreatitis with an inflammatory mass limited to the pancreatic head, 51 evaluated, alcohol intake and age not reported Postoperative complications median 8.6 years
32% with Beger ductal decompression
22% with Frey ductal decompression
Absolute numbers not reported

Reported as not significant
P value not reported
Not significant

Further information on studies

The RCT found no significant difference between Beger and Frey ductal decompression in exocrine or endocrine insufficiency at median 104 months (exocrine insufficiency: 22/25 [88%] with Beger v 18/25 [72%] with Frey; P = 0.16; endocrine insufficiency: 14/25 [56%] with Beger v 15/25 [60%] with Frey; P = 0.16).

Comment

Clinical guide:

Endoscopic ductal decompression may be the preferred treatment because of its relatively quick recovery rates. Surgery may have better long-term results, but has attendant morbidity and mortality. In clinical practice, the choice between Beger or Frey ductal decompression depends on local expertise. Other more extensive surgical procedures, such as resection, may have higher attendant risks, and may be used based on the extent of disease.

Substantive changes

Method of ductal decompression One RCT added, which compared endoscopic ductal decompression versus surgical ductal decompression. It found that surgical decompression reduced pain at 2 years. Categorisation unchanged (Trade-off between benefits and harms).

2008; 2008: 0417.
Published online 2008 December 5.

Pseudocyst decompression

Summary

We found no direct results from RCTs or observational studies comparing the effects of endoscopic or percutaneous pseudocyst decompression versus surgical pseudocyst decompression in people with chronic pancreatitis, or different types of surgical pseudocyst decompression versus each other in people with chronic pancreatitis.

Pseudocysts are drained if they are complicated or long-standing, to reduce the risk of life-threatening complications, such as haemorrhage, infection, or rupture. Both procedures are associated with serious postoperative complications.

Benefits and harms

Endoscopic or percutaneous versus surgical pseudocyst decompression:

We found no systematic review, RCTs, or observational studies directly comparing endoscopic versus surgical pseudocyst decompression (see comment).

Different types of surgical pseudocyst decompression versus each other:

We found no systematic review or RCTs directly comparing different surgical pseudocyst decompression techniques (see comment).

Further information on studies

Comment

Endoscopic or percutaneous versus surgical pseudocyst decompression:

Retrospective data suggest that endoscopic drainage is successful in 62%–84% of people in the long term. Recurrence was seen in up to 20% of people. Two retrospective studies assessed surgical drainage performed after failure of conservative management or endoscopic drainage (see clinical guide). One study suggested that recurrence after surgery may occur in up to one third of people, but another study reported no recurrence. Retrospective data suggest that complications (infection and bleeding) are seen in up to 34% of people receiving endoscopic or percutaneous drainage, and up to 10% of procedures may require emergency surgery. Surgical drainage has a complication rate of 8%–20% (infection, bleeding, perforation, and fistula; see table 1 ).

Table 1
Pseudocyst decompression.

Different types of surgical pseudocyst decompression versus each other:

One comparative case series suggested that cystogastrostomy had a shorter operative time than cystojejunostomy. There was no significant difference between procedures in length of hospital stay or recurrence rates (see table 1 ). The case series also suggested that cystogastrostomy had a shorter operative time and caused less intraoperative blood loss than cystojejunostomy, but caused more postoperative haemorrhage. There was no significant difference between procedures in overall complications or perioperative mortality (see table 1 ).

Clinical guide:

Clinical experience suggests that in people with chronic pancreatitis, most pseudocysts larger than 6 cm in diameter or present for more than 6 weeks will not regress spontaneously. However, reported case series assessing initial conservative management of pseudocysts are in mixed populations (people with acute and chronic pancreatitis) and it is therefore difficult to draw conclusions about whether conservative management is possible. Nearly 40%–60% of people with chronic pancreatitis will require surgical intervention for failed conservative management, with up to 10% requiring emergency surgery for life-threatening complications such as haemorrhage or infection. Need for intensive care is greater with emergency surgery compared with planned surgery (46% with emergency surgery v 1% with planned surgery), and the length of intensive care stay is longer. Endoscopic, percutaneous, and surgical drainage have attendant morbidity and failure rate.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Resection using distal pancreatectomy in people with disease limited to the tail of the pancreas

Summary

We found no direct information from RCTs about the effects of distal pancreatectomy in people with chronic pancreatitis whose disease is limited to the tail of the pancreas, compared with no treatment or other treatments.

There is consensus that distal pancreatic resection may be a viable option in people with chronic pancreatitis limited to the tail of the pancreas, with most efficacy when multiple pseudocysts are present.

Benefits and harms

Resection using distal pancreatectomy in people with disease limited to tail of the pancreas:

We found no systematic review, RCTs, or observational studies comparing surgical resection versus endoscopic decompression, or different surgery techniques versus each other. We found four case series in people with chronic pancreatitis (see comment for further information from these case series).

Further information on studies

Comment

Three case series found that distal pancreatectomy was associated with reduction in pain in up to three-quarters of people. Results concerning improvements in endocrine function were inconclusive (see table 2 ). Case series suggested that distal pancreatectomy was associated with low perioperative mortality (0%–0.9%). Postoperative complications occurred in 15%–46% of people. There may be new-onset or worsening diabetes mellitus in 25%–45% of people (see table 2 ).

Table 1
Resection using distal pancreatectomy in people with disease limited to the tail of the pancreas.

Clinical guide:

Distal pancreatic resection may be a viable option in people with chronic pancreatitis limited to the tail of the pancreas, with most efficacy when multiple pseudocysts are present.

Substantive changes

No new evidence

2008; 2008: 0417.
Published online 2008 December 5.

Resection using pancreaticoduodenectomy (Kausch–Whipple or pylorus-preserving) in people with more severe disease limited to the head of the pancreas

Summary

Resection using pancreaticoduodenectomy may be equivalent to localised excision of the pancreatic head in improving symptoms, but it reduces quality of life and increases intraoperative and postoperative complications. In clinical practice, resection using pancreaticoduodenectomy is usually reserved for when other surgical options, such as pseudocyst or duct decompression, are not feasible because of severity of disease.

Benefits and harms

Resection using pancreaticoduodenectomy versus other surgical techniques:

We found no systematic review. We found one RCT comparing resection using pylorus-preserving pancreaticoduodenectomy versus Frey ductal decompression. See further information on studies for data on proportion of people returning to work.

Mortality

Resection using pancreaticoduodenectomy compared with other surgical techniques We don't know how pylorus-preserving pancreaticoduodenectomy and Frey ductal decompression compare at reducing mortality in people with more severe disease limited to the head of the pancreas (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Mortality

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Mortality
0% with pylorus-preserving pancreaticoduodenectomy
3.2% with Frey ductal decompression

Significance not assessed

Pain relief

Resection using pancreaticoduodenectomy compared with other surgical techniques We don't know how pylorus-preserving pancreaticoduodenectomy and Frey ductal decompression compare at reducing composite pain scores at 24 months in people with more severe disease limited to the head of the pancreas (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Pain

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Pain (measured by combining mean scores on VAS, frequency of pain, use of medication, and inability to work and dividing by 4) median 24 months
18.1 with pylorus-preserving pancreaticoduodenectomy
6.1 with Frey ductal decompression

Reported as not significant
P value not reported
Not significant

Global symptom improvement

Resection using pancreaticoduodenectomy compared with other surgical techniques We don't know how pylorus-preserving pancreaticoduodenectomy and Frey ductal decompression compare at reducing symptoms (not further defined) at 24 months in people with more severe disease limited to the head of the pancreas (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Symptoms

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Proportion with relief of symptoms median 24 months
26/30 (87%) with pylorus-preserving pancreaticoduodenectomy
28/31(90%) with Frey ductal decompression

Reported as not significant
P value not reported
Not significant

Weight gain/maintenance

Resection using pancreaticoduodenectomy compared with other surgical techniques We don't know how pylorus-preserving pancreaticoduodenectomy and Frey ductal decompression compare at increasing weight gain in people with more severe disease limited to the head of the pancreas (very low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Weight gain

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Weight gain
1.9 kg with pylorus-preserving pancreaticoduodenectomy
6.7 kg with Frey ductal decompression

Significance not assessed

Quality of life

Resection using pancreaticoduodenectomy compared with other surgical techniques Pylorus-preserving pancreaticoduodenectomy may be less effective than Frey ductal decompression at increasing global quality-of-life scores in people with more severe disease limited to the head of the pancreas (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Quality of life

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Global quality of life (scale 0–100)
57.1 with pylorus-preserving pancreaticoduodenectomy
85.7 with Frey ductal decompression

P <0.05
Effect size not calculatedFrey ductal decompression

Steatorrhoea

No data from the following reference on this outcome.

Development of complications

No data from the following reference on this outcome.

Adverse effects

Resection using pancreaticoduodenectomy compared with other surgical techniques Pylorus-preserving pancreaticoduodenectomy may be associated with increased rates of postoperative complications, operating time, and requirement for blood transfusion compared with Frey ductal decompression in people with more severe disease limited to the head of the pancreas (low-quality evidence).

Ref (type)PopulationOutcome, InterventionsResults and statistical analysisEffect sizeFavours
Adverse effects

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Postoperative complications
53% with pylorus-preserving pancreaticoduodenectomy
19% with Frey ductal decompression
Absolute numbers not reported

P <0.05
Effect size not calculatedFrey ductal decompression

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Blood transfusion requirements
3.2 units with pylorus-preserving pancreaticoduodenectomy
1.2 units with Frey ductal decompression

P <0.05
Effect size not calculatedFrey ductal decompression

RCT
61 people, 47 with alcohol-induced pancreatitis, mean age 44 years, mean duration of symptoms 4.8–5.5 years Operating time
328 minutes with pylorus-preserving pancreaticoduodenectomy
245 minutes with Frey ductal decompression

P <0.05
Effect size not calculatedFrey ductal decompression

Further information on studies

The RCT found that a significantly lower proportion of people returned to work after pylorus-preserving pancreaticoduodenectomy compared with Frey ductal decompression (43% with PPPD v 68% with Frey; P <0.05).

Comment

Clinical guide:

In clinical practice, resection using pancreaticoduodenectomy is usually reserved for when other surgical options, such as pseudocyst or duct decompression, are not feasible. It is required for disease limited to gland (typically in absence of dilated pancreatic duct).

Substantive changes

No new evidence


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