Chronic pancreatitis

What is it?

Chronic pancreatitis is a disease caused by a persistent inflammatory damage to the pancreas that causes irreversible alterations of the pancreatic gland, characterized by fibrosis, with a progressive atrophy and a consequent progressive reduction of both exocrine function (malabsorption) and endocrine function (glucose intolerance and diabetes), resulting in pancreatic insufficiency. Habitual alcohol consumption and smoking are the two main causes. Other less frequent causes or concomitant causes are genetic mutations in some genes (CFTR, PRSS1, SPINK1, CTRC), chronic pancreatic duct obstruction (congenital or acquired) or autoimmune forms. In addition, recurrence of acute pancreatitis events (link) may result in pancreatitis. 

The typical symptom of disease is abdominal pain, but in some cases symptoms are nuanced and related to organ failure. Diagnosis is based on the clinic pattern, typical appearance at radiologic examinations, and tests that evaluate pancreatic function. Pain control, management of pancreatic insufficiency, and prevention of complications are the cornerstones of the care pathway.

The clinical course of the disease is characterized by phases of acute pain with flare-ups and phases of greater symptom control, although the pain is often continuous. In the acute phases, there may be complications common to acute pancreatitis such as pseudocysts and others typical of the chronic form such as stenosis of the pancreatic duct, bile duct and duodenum. In addition, malabsorption can lead to vitamin deficits and complications such as osteopathy. In addition, patients with chronic pancreatitis have an increased risk of cardiovascular, infectious, and respiratory disease, thrombohemorrhagic events, and pancreatic adenocarcinoma.

Causes and risk factors

The most common cause is chronic alcohol intake, but the disease can also be due to genetic causes or chronic obstruction of pancreatic juice discharge. A rare form of chronic pancreatitis is autoimmune pancreatitis, in which the pancreatitis is due to a reaction of the immune system against pancreatic cells.

Which are the symptoms?

The most common cause is chronic alcohol intake, but the disease can also be due to genetic causes or chronic obstruction of pancreatic juice discharge. A rare form of chronic pancreatitis is chronic pancreatitis. In the early stages, chronic pancreatitis may be asymptomatic, that is, it may not cause any discomfort. Instead, as the disease progresses, the following symptoms may appear:

  • Chronic abdominal pain, i.e., long-lasting, capable of recurring even after fairly long periods of relative well-being. The pain typically occurs after the intake of food, but can also be present after meals.
  • Maldigestion of food, i.e. food passes through the intestine without being sufficiently digested and absorbed. This phenomenon is due to a reduced production of digestive juices by the pancreas. The result is poorly formed, sometimes diarrheal or greasy stools. In the long run, maldigestion causes a progressive slimming of the patient.
  • Diabetes, which is the increase in blood sugar levels (glycemia). Diabetes is also due to insufficient pancreatic function. In this case it is the reduction in the production of insulin, whose function is to lower blood sugar, that is responsible for the appearance of diabetes.oi the autoimmune one, in which pancreatitis is due to a reaction of the immune system against pancreatic cells.

How is it diagnosed?

The diagnosis of chronic pancreatitis is based on clinical evaluation, radiologic examinations, and pancreatic function tests. 

In patients without a typical history but with suggestive symptoms (e.g., abdominal pain, weight loss, new onset of diabetes), abdominal Computed Axial Tomography (CT) is generally recommended in the first instance to rule out pancreatic cancer, but also to detect calcifications and other pancreatic abnormalities. In early forms, however, the CT scan may be normal.

Nuclear Magnetic Resonance Imaging (MRI) with Cholangio-Pancreatography (CP-RM) provides an optimal representation of pancreatic and possibly biliary ductal changes and does not expose the patient to radiation. It can detect minimal ductal alterations better than CT, but does not detect calcification.

Echoendoscopy (EUS) (link) is more sensitive method for the diagnosis of chronic pancreatitis, particularly in its early stages, as it allows the detection of subtle abnormalities of the pancreatic parenchyma and its ducts. EUS also has a diagnostic role when it is necessary to sample the pancreas for cytohistological examination by needle aspiration under ultrasound guidance for the diagnosis of specific forms of chronic (autoimmune) pancreatitis or to exclude a neoplasm. 

The most widely used pancreatic function test is the fecal elastase assay, which measures the concentration of this enzyme in the stool, independent of diet and the possible administration of replacement therapy. On the endocrine side, blood glucose and glycated hemoglobin allow the diagnosis of diabetes to be made.

Biochemical alterations of the nutritional status and further examinations such as computerized bone mineralometry (MOC) are also evaluated in the specialist outpatient pathway to assess bone density. Symptoms of patients with chronic pancreatitis may also be related to bacterial overgrowth of the small intestine, which is present in about a quarter of cases.

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Suggested exams

How is it treated?

Treatment and follow-up of the patient with chronic pancreatitis varies according to the presence and intensity of pain and the stage of the disease. 

The first objective is to remove, where possible, risk factors and pro-inflammatory stimuli, including through specific therapies. It is important to make patients with chronic pancreatitis aware of smoking cessation and alcohol abstinence and to educate them to lead a healthy life, possibly with the help of specialized facilities. 

When the cause of chronic pancreatitis does not appear to be clear, specific tests should be performed to rule out rare etiologies, including genetic testing. However, it is estimated that about10% of cases remain without a recognized cause (idiopathic).

Management of chronic abdominal pain is the most significant clinical problem. Pain therapy is generally chronic and, therefore, non-steroidal anti-inflammatory drugs that may be useful in the acute phase for limited periods of time are not the most widely used. The treatment involves in the first instance the use of paracetamol, alone or in combination with minor opioids, which instead represent a second line of treatment. If control fails, other adjuvant therapies (e.g., pregabalin, etc.) may be used in combination, possibly with the help of fellow specialists in chronic pain management. Resolution of pain that can become central in nature is often not achievable without endoscopy or surgery.

In patients with exocrine pancreatic insufficiency, enzyme replacement therapy is intended to replace exocrine function at each meal to allow nutrient absorption, as well as make malabsorption symptoms disappear. It is made with tablets that must be taken with each meal and snack in appropriate dosage. 

Pancreatic endocrine insufficiency is usually managed in collaboration with fellow specialists who educate the patient on home blood glucose detection and taking oral and/or subcutaneous therapy.

Some additional methods are reserved for the treatment of complications. 

Stenosis of the pancreatic duct or bile duct, or the presence of pancreatic duct stones are part of the clinical presentation of chronic pancreatitis, and can be addressed with ERCP (Endoscopic Retrograde Cholangio-Pancreatography), an endoscopic method that accesses the pancreatic or biliary ductal system from the point where these structures exit into the intestine. ERCP can facilitate the transit of pancreatic secretions by "sphincterotomy," placing plastic stents across stenoses or removing pancreatic duct stones. If standard retrograde drainage cannot be performed, access to the pancreatic duct can be achieved by echo-guided one. Biliary tract stenoses can also be treated endoscopically with stent placement.

Pancreatic pseudocysts that are symptomatic, i.e., causing pain, compression symptoms, or have become overinfected, can be drained by echoendoscopy. Drainage usually involves the placement of soft silicone stents through the wall of the stomach or duodenum, which promote the emptying of the collector.  In addition, in selected cases, echendoscopy may be combined with "ablation" of nerve plexuses near the pancreas to reduce chronic pain.

In case of chronic symptomatic pancreatitis and/or with a tendency to develop complications, such as biliary or duodenal obstruction that cannot be definitively resolved endoscopically, or in all cases in which there is a doubt of neoplasia, surgery is the treatment of choice and can include both resective surgery (in "mass-forming" forms that infiltrate the biliary tract or duodenum) and derivative surgery (decompression of the pancreatic duct). 

Sometimes total pancreasectomy is necessary to achieve resolution of pain and complications, associated, when possible, with autologous transplantation of pancreatic insulae to reduce the risk of diabetes.

The complexity of the clinical presentation therefore requires that treatment be carried out after multidisciplinary discussion in facilities with specific expertise of gastroenterologists/endoscopists, surgeons, radiologists, nutritionists, pain therapists, immunologists, geneticists, diabetologists, anatomopathologists. Within the Pancreas Center of San Raffaele, there are outpatient clinics dedicated to chronic pancreatitis run by gastroenterologists and surgeons, and cases are discussed by all the specialists involved.

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