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Summary for primary care

Guidelines for the Diagnosis and Therapy of Chronic Pancreatitis


This Guidelines summary covers key recommendations of the guideline; please refer to the full guideline for the complete set of recommendations.


  • Chronic pancreatitis (CP) is a serious disorder which can have a severe impact on the quality of life in addition to life-threatening long-term sequelae. As well as pain, pancreatic exocrine insufficiency (PEI) can result in malnutrition—in a population apt to neglect their nutrition
  • Long-term complications include diabetes mellitus and pancreatic cancer. The incidence in European countries ranges from 5 to 10 per 100,000 inhabitants. With a median survival of 20 years, the calculated prevalence is around 120/100,000 inhabitants


  • Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of the pancreatic parenchyma by fibrous connective tissue
  • Complications of CP encompass strictures of the pancreatic duct and/or the biliary ducts, pseudocysts, pancreaticolithiasis, duodenal stenosis, malnutrition, vascular complications, and recurrent or persisting pain

Aetiology of Chronic Pancreatitis

  • It is recommended that a comprehensive medical history, laboratory evaluation, and imaging studies are performed in patients with CP
  • A diagnosis of cystic fibrosis needs to be ruled out in all patients with CP onset before the age of 20 years as well as in patients with so-called ‘idiopathic’ CP (regardless of the age of onset)
  • If no other aetiology of CP can be identified in a patient then a diagnosis of autoimmune pancreatitis should be ruled out
  • All patients with a family history or early onset disease (<20 years) should be offered genetic testing for associated variants

Diagnosing Chronic Pancreatitis

  • Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and computed tomography (CT) are the best imaging methods for establishing a diagnosis of CP
  • Computed tomography examination is the most appropriate method for identifying pancreatic calcifications, while for very small calcifications non-enhanced CT is preferred 
  • The presence of typical imaging findings for CP with MRI/magnetic resonance cholangiopancreatography (MRCP) is sufficient for diagnosis; however, a normal MRI/MRCP result cannot exclude the presence of mild forms of the disease
  • The use of i.v. secretin increases the diagnostic potential of MRCP in the evaluation of patients with known/suspected CP
  • Endoscopic ultrasound is the most sensitive imaging technique for the diagnosis of CP, mainly during the early stages of the disease, and its specificity increases with increasing diagnostic criteria

Diagnosing Pancreatic Exocrine Insufficiency

  • Pancreatic exocrine insufficiency refers to an insufficient secretion of pancreatic enzymes (acinar function) and/or sodium bicarbonate (ductal function)
  • The main causes of PEI are loss of the pancreatic parenchyma, obstruction of the main pancreatic duct, decreased stimulation of the exocrine pancreas, and inactivation of pancreatic enzymes
  • Chronic pancreatitis is a progressive disease and exocrine function gradually decreases during the course of the disease
  • In a clinical setting, a non-invasive pancreatic function test (PFT) should be performed. The faecal elastase-1 (FE-1) test is feasible and widely available and is, therefore, most frequently used in this setting, while the 13 C mixed triglyceride breath test (13 C-MTG-BT) offers an alternative. The secretin MRCP (s-MRCP) test may also be used as an indicator of PEI but provides only semi-quantitative data
  • A function test is required for the diagnosis of CP
  • Every patient with a new diagnosis of CP should be screened for PEI
  • In order to detect maldigestion prior to the occurrence of overt clinical symptoms, the presence of PEI should be evaluated annually in patients with CP. Apart from this, function tests should be repeated if previously normal when symptoms occur or deteriorate and can be attributable to PEI
  • To evaluate the efficacy of enzyme replacement therapy, it is sufficient in most cases to verify the normalisation of nutritional parameters and symptomatic improvement. When symptoms of exocrine insufficiency persist in spite of adequate pancreatic enzyme replacement therapy (PERT), function tests (13 -CMTG-BT, acid steatocrit, and quantitative faecal fat) are recommended in order to evaluate treatment efficacy
  • Specific attention is required when screening for PEI in patients with CP and diabetes mellitus, pancreatic carcinoma, or following pancreatic resections or gastric resections
  • Established blood parameters of malnutrition such as prealbumin, retinol-binding protein, 25-OH cholecalciferol (vitamin D), and minerals/trace elements (including serum iron, zinc and magnesium) should be measured 

Surgery in Chronic Pancreatitis

  • Surgery is superior to endoscopy in terms of mid-term and long-term pain relief in patients with painful CP
  • To achieve optimal long-term pain relief in patients suffering from CP, early surgery is favoured over surgery at a more advanced stage of the disease
  • The risk of developing PEI is lower after early surgery for CP than after surgery performed at an advanced disease stage. Pancreatic resection techniques have a higher risk of PEI than drainage techniques
  • No recommendation can be drawn from the evidence regarding the effect of early surgery on developing endocrine pancreatic function during follow-up since few studies exist and those that do are contradictory
  • Long-term quality of life (QoL) is improved after early surgery (<3 years from onset) compared to surgery at a more advanced stage of disease
  • A normal pancreatic head varies considerably in size, although a diameter of >4 cm on CT or MRI imaging is usually considered as enlarged
  • In adult patients, a main duct diameter of 5 mm in the pancreatic body seems amenable to ductal drainage for the majority of pancreatic surgeons. This threshold of 5 mm is, therefore, proposed as the definition of a ‘dilated main duct’
  • A total pancreatectomy should be considered in patients without duct system dilatation, who are resistant to conventional medical, endoscopic, and previous surgical treatment and who have severe pain
  • For these patients, a lateral pancreaticojejunostomy with a Roux-en-Y loop and Frey’s procedure provide comparable pain control. However, no recommendation can be made for the preferred surgical technique in these patients
  • Both a lateral pancreaticojejunostomy with a Roux-en-Y loop and Frey’s procedure seem to provide equivalent pain control in patients with main duct dilatation and a normal size pancreatic head
  • An experienced high volume pancreatic centre is recommended for the surgical treatment of CP
  • Surgery should be performed when medical and endoscopic options have failed. Surgery should be aimed at pain relief and/or complete pain resolution, and should solve the patient’s malnutrition status (body weight gain), on condition that the patient stops alcohol and drug abuse
  • The initial treatment of groove pancreatitis should involve medical treatment and occasionally endoscopic drainage procedures may be helpful. If these approaches fail, the patient should be referred for surgery
  • In expert hands, pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis 

Medical Therapy for Exocrine Pancreatic Insufficiency

  • Pancreatic enzyme replacement therapy (PERT) is indicated for patients with CP and PEI in the presence of clinical symptoms or laboratory signs of malabsorption. An appropriate nutritional evaluation is recommended to detect signs of malabsorption
  • Enteric-coated microspheres or mini-microspheres of <2 mm in size are the preparations of choice for PEI. Micro- or mini-tablets of 2.2–2.5 mm in size may be also effective, although scientific evidence in the context of CP is more limited. Comparative clinical trials of different enzyme preparations are lacking
  • Oral pancreatic enzymes should be distributed along with meals and snacks
  • A minimum lipase dose of 40,000–50,000 PhU is recommended with main meals, and half that dose with snacks
  • The efficacy of PERT can be evaluated adequately by the relief of maldigestion-related symptoms (e.g. steatorrhoea, weight loss, flatulence) and the normalisation of the nutritional status of the patients. In non-responder patients, the use of pancreatic function tests (CFA or 13 C-MTG-BT) with oral enzymes may be of help
  • In cases of unsatisfactory clinical response, the enzyme dose should be increased (doubled or tripled) or a proton pump inhibitor (PPI) should be used. If these strategies fail, another cause for maldigestion should be sought
  • The addition of a PPI to oral pancreatic enzymes is of help in patients with an unsatisfactory response to PERT

Endoscopic Therapy

  • In patients with uncomplicated painful CP and a dilated main pancreatic duct (MPD), we recommend endoscopic therapy (ET) as the first-line treatment after failed medical therapy following discussions by a multidisciplinary team. The clinical response should be evaluated at 6–8 weeks; if it appears unsatisfactory, the patient’s case should be discussed again by a multidisciplinary team of endoscopists, surgeons, and radiologists, and surgical options should be considered, in particular for patients with a predicted poor outcome following ET
  • Pre-treatment factors useful to identify the best responders to ET are the location of obstructing stones in the head of the pancreas, the absence of MPD stricture, a short disease duration, and a low frequency of pain attacks before ET
  • Extracorporeal shock wave lithotripsy (ESWL) can be considered as first-step treatment for larger, radiopaque stones (≥5 mm) obstructing the MPD, and is usually followed by the endoscopic extraction of stone fragments; although, in centres with expertise, ESWL alone may be a more cost-effective option. We suggest performing non-contrast enhanced computed tomography before ESWL to determine the location, size, number, and density of stones
  • Extracorporeal shock wave lithotripsy should target stones with a minimal diameter of 2–5 mm, starting in the head of the pancreas and progressing to the head to permit elimination of stone fragments
  • Extracorporeal shock wave lithotripsy alone may be the most cost-effective option but it should be reserved for centres with expertise in this technique
  • At long-term, pain relapses requiring analgesics or more invasive treatment has been reported in 5–45% of patients
  • Dominant MPD strictures in the head of the pancreas are defined as strictures with an upstream MPD dilation ≥6 mm in diameter or strictures that prevent the outflow of contrast medium. Stricture dilation alone has yielded disappointing results while satisfactory long-term results have been reported in more than two-thirds of patients with temporary plastic stenting
  • In children with uncomplicated painful CP and an obstructed MPD, we recommend ET as the first-line treatment after failed medical therapy

Treatment of Pancreatic Pseudocysts

  • We recommend ET for those patients with uncomplicated chronic pancreatic pseudocysts (PPCs) for which treatment is indicated and that are within endoscopic reach. Transpapillary drainage is preferred over transmural (TM) drainage for small (<6 cm) PPCs communicating with the MPD in the head or body of the pancreas, or if TM drainage is contraindicated or not feasible. If TM pseudocyst drainage is elected:
    • it should be performed under echoendoscopic guidance if there is no luminal bulging and
    • several double-pigtail plastic stents (not self-expandable metal stents) should be inserted to drain the PPC into the digestive lumen until cyst resolution with a minimum of two months of stenting
  • A surgical approach should be chosen for a suspected malignant cystic lesion
  • Visualisation of the pancreatic duct can be performed before endoscopic or surgical drainage of the pseudocyst
  • In the presence of pancreatic duct stones, a pseudocyst should be treated as part of an overall therapeutic concept
  • Endoscopic therapy of pancreatic duct obstruction can be undertaken in patients with a PPC, prestenotic duct dilatation, or fistula formation
  • Vascular pseudoaneurysms that develop secondary to CP should be treated
  • Angiographic embolisation is the method of choice for haemorrhagic pseudoaneurysms
  • In the presence of a recent episode of acute pancreatitis or if the PPC was not detected on prior examinations, the PPC should be observed for at least 6 weeks to allow for either spontaneous resolution or maturation of the cyst wall

Pancreatic Pain

  • Pain is the first presentation of CP in the majority of patients
  • There is no evidence that pain symptoms ‘burn out’ in all patients with ongoing CP
  • There is no convincing evidence that endocrine and exocrine pancreatic insufficiencies are associated with pain relief
  • Pain intensity and the pain pattern over time (constant vs intermittent pain) have been shown to reduce QoL in patients with CP
  • Pancreatic and extra-pancreatic complications may contribute to pain in the individual patient and should be thoroughly investigated at the time of diagnosis and if pain symptoms are worsening
  • Pain in CP should be assessed using a multidimensional approach, including evaluation of pain intensity, pain pattern, and its impact on daily function and QoL
  • Cessation of alcohol, and possibly smoking, improves pain in CP
  • Pancreatic enzyme supplementation is not recommended for pain treatment in CP
  • Antioxidants are not recommended for pain treatment in CP
  • The standard guideline for medical analgesic therapy in CP follows the principles of the ‘pain relief ladder’ provided by the World Health Organization
  • Endoscopic therapy is effective in patients with an obstructive type of pancreatic pain and in patients with a pancreatic duct dilatation
  • Endoscopic therapy could be useful as a bridge to surgery
  • Endoscopic drainage treatment is less effective and has a shorter-term effect compared with surgery
  • Extracorporeal shock wave lithotripsy therapy is effective for disintegrating stones in the main pancreatic duct
  • Extracorporeal shock wave lithotripsy provides pain relief in patients with CP
  • Treatments such as EUS-guided plexus block, splanchnic nerve block, spinal cord stimulation, transcranial magnetic stimulation and acupuncture may be effective in selected cases of painful CP
  • Resection, decompression or mixed surgical techniques achieve pain relief that is maintained over time in approximately 80% of patients. However, as studies are not sham-controlled the effect of surgery is still debatable

Nutrition and Malnutrition

  • Malnutrition is common among patients with CP
  • Pancreatic exocrine insufficiency, anorexia secondary to abdominal pain, nausea and vomiting, alcohol and other substance abuse, and diabetes mellitus may all contribute to malnutrition in patients with CP
  • Patients with CP should undergo initial screening for body mass index (BMI) either with the community malnutrition universal screening tool (MUST) or hospital nutritional risk screening (NRS-2002). More specifically, dietary intake should be documented as well as symptoms consistent with malnutrition and those symptoms that have an increased risk of secondary anorexia (pain, nausea, and vomiting)
  • A physical examination should be performed, if ascites or oedema are present and should include anthropometric measurements of mid-arm circumference, triceps skin-fold and hand-grip strength
  • Screening for a deficiency of fat-soluble vitamins (A, D, E, and K), zinc, magnesium, and glycated haemoglobin (HbA1c) should be considered
  • Patients who are well nourished should be encouraged to follow normal healthy eating advice. PEI should be corrected in those patients who are nutritionally compromised. Improved nutritional status can be achieved with nutritional assessment and individualised dietary counselling by an experienced dietician
  • Dietary fat restriction and very high fibre diets should be avoided
  • Small, frequent, high-energy meals should be recommended for those with malnutrition
  • Nutritional intervention should be carried out alongside PERT
  • For most patients with CP, oral nutritional supplements are not required. For those who are undernourished and cannot meet their nutritional requirements orally despite dietary intervention, oral nutritional supplements may be useful
  • Medium-chain triglycerides supplements are not recommended
  • Specific recommendations on the supplementation of vitamins A, E and K are not possible, as there are few studies. Clinical evaluation is advised, along with adequate PERT and dietary intervention
  • Vitamin D deficiency may be treated with oral supplementation or by a single i.m. injection
  • Parenteral nutrition is indicated in patients with gastric outlet obstruction secondary to duodenal stenosis, in patients with complex fistulating disease and in patients with apparent severe malnutrition prior to pancreatic surgery if enteral feeding is not possible
  • Enteral nutrition is indicated in patients with malnutrition who are not responding to oral nutritional support
  • It is recommended that enteral nutrition be administered via the naso-jejunal route in patients with pain, delayed gastric emptying, persistent nausea, or vomiting
  • Jejunostomy feeding tube insertion should be considered in those requiring enteral nutrition for longer than 30 days. Peptide, medium chain triglyceride-based enteral feeds may be used in patients with PEI
  • Enteral nutrition is indicated with PERT administered alongside where necessary
  • Patients with CP are at high risk of developing osteoporosis and osteopaenia, and are at high risk of suffering a low trauma fracture 
  • to identify those at risk, regular assessment of bone density by dual-energy X-ray absorptiometry (DXA), along with regular measurement of serum 25(OH)D should be undertaken
  • Basic preventative measures (adequate diet, particularly calcium and vitamin D intake, regular weight-bearing exercise, and smoking/alcohol avoidance) should be encouraged for all CP patients. For those with osteopaenia, basic preventative measures should be implemented and DXA should be repeated every two years. Patients with osteoporosis (or vertebral fractures) should receive appropriate medication, screening for other causes, and/or referral to a bone specialist, along with basic preventative measures

Diabetes Mellitus

  • The risk of developing diabetes increases with surgical intervention (especially distal pancreatectomy) and with increasing age
  • The evidence appears to support an association between (heavy) smoking and the development of diabetes. Most studies support a link between the presence of calcifications and the risk of developing diabetes
  • Most studies show that the risk of diabetes increases with the duration of disease
  • There is some evidence of an association with gender and family history
  • There is insufficient evidence of a relationship between diabetes and BMI or zinc status
  • There is no evidence that a higher dietary fat intake influences the development of diabetes in CP
  • The development of diabetes does not appear to be influenced by the presence of various genetic mutations
  • The initial evaluation of a patient with CP should include fasting plasma glucose (FPG) and HbA1c. Criteria for a diagnosis of pancreatogenic diabetes (Type IIIc diabetes mellitus [T3cDM]) are FPG ≥126 mg/dl (7.0 mmol/l) or HbA1c ≥6.5% (48 mmol/mol)
  • An HbA1c <6.5% does not rule out T3cDM due to the limitations of this test in this patient population. Therefore, normal HbA1c (<6.5%) should always be confirmed by FPG
  • In the absence of unequivocal hyperglycaemia (random plasma glucose ≥200 mg/dl [11.1 mmol/l]) or in cases of doubt, results should be confirmed by repeat testing or by the evaluation by a standard 75 g oral glucose tolerance test (OGTT, 2 h fasting glucose ≥200 mg/dl [11.1 mmol/l])
  • these tests should be performed annually, even in the absence of typical clinical symptoms of diabetes mellitus
  • An absent pancreatic polypeptide response to mixed-nutrient ingestion seems to be a specific indicator of T3cDM as compared to the other types of diabetes
  • Due to feasibility, this test is only recommended in cases of doubt. As differentiating between the two types of diabetes is not easy, the criteria below might be helpful:
    • major criteria (must be present):
    • established diagnosis of CP
    • absence of type 1 diabetes mellitus associated autoimmune markers
    • minor criteria (two of four must be present):
    • impaired beta-cell function (e.g. homeostatic model assessment for beta-cell dysfunction (HOMA-B), C-peptide/glucose ratio)
    • no excessive insulin resistance
    • impaired incretin secretion (e.g. glucagon-like peptide-1 [GLP-1], pancreatic polypeptide)
    • deficiencies of fat-soluble vitamins and/or presence of micronutrient deficiency/insufficiency (in the absence of enzyme therapy and/or nutrient supplementation)
  • Laboratory tests to classify the patient as accurately as possible should be performed at least once. They should include diabetes-associated antibodies, C-peptide/glucose ratio, and assessment of exocrine pancreatic function, as well as pancreatic imaging
  • Patients with T3cDM are generally considered difficult to manage, with potential lifethreatening acute complications (hypoglycaemia and ketoacidosis). Up to 25% of the patients with T3cDM have ‘brittle diabetes’ with rapid swings in glucose levels
  • Chronic microangiopathic complications are as frequent in T3cDM patients as in other diabetic patients. The incidence of retinopathy is reportedly similar to that observed in type 1 diabetes and its prevalence increases with diabetes duration
  • Early signs of renal dysfunction, such as microalbuminuria or glomerular hyperfiltration, are similar to that reported in type 1 diabetes mellitus, while macroalbuminuria and overt renal disease are unusual
  • Neuropathy is also described as a common complication of T3cDM
  • There is a general acceptance that T3cDM is not associated with macrovascular complications
  • No evidence-based study relating to treatment practice in T3cDM has been reported to date. Treatment should include efforts to promote lifestyle changes, which may improve glycaemic control and minimise the risk of hypoglycaemia. In patients with severe malnutrition, insulin therapy is commonly used as a first choice due to the desired anabolic effects of insulin in this special subset of patients
  • If hyperglycaemia is mild and concomitant insulin resistance is additionally diagnosed or suspected, therapy with metformin may be a choice in the absence of contraindications
  • Ensuring adequate and appropriate PERT is essential

Assessments and Quality of Life

  • There is no specific, widely accepted questionnaire for assessing smoking status. Several studies have reported positive findings regarding the relationship between smoking and CP using different questionnaires
  • The key components for the treatment of smoking dependence are combinations of therapeutic education, behavioural support, and medication
  • There is some evidence to suggest that cessation of smoking and/or drinking may improve the course of CP; however, the global benefits of stopping smoking and/or abusive alcohol consumption are unquestionable
  • Smoking seems to be an independent aetiologic factor for the development of CP
  • Validated questionnaires should be applied for the assessment of QoL in patients with CP
  • Health-related QoL should be assessed in both in- and outpatients and during their follow-up
  • Assessment of QoL should be included as an endpoint in clinical treatment studies of CP
  • The 36-Item Short Form Survey (SF36), its shorter version 12-Item Short Form Survey (SF12), European Organisation for Research and Treatment of Cancer quality of life questionnaire-core 36 (EORTC QLQ-C30) with, and without the supplementary EORTC pancreatic cancer module (QLQ-PAD26) questionnaire, and Gastrointestinal Quality of Life Index (GIQLI) can be used for assessing QoL in patients with CP. It takes 12 minutes to complete the SF36 form but only 2 minutes to fill out the SF12 questionnaire—making this test suitable as a screening tool even for the daily busy clinical practice