Management of chronic pancreatitis: Conservative, endoscopic, surgical

Background

Chronic pancreatitis (CP) is characterized by a progressive inflammatory process, the etiologies of which vary depending on geographic and sociocultural circumstances. Therefore incidence and prevalence of CP differs between the respective regions, which has been shown in studies that include Western and Asian countries as well as India. The reported rates show an incidence of approximately 5 to 15 per 100,000 and prevalence of 40 to 120 per 100,000 inhabitants calculated on the basis of an estimated median survival time of 20 years. Especially in Asian countries, these numbers have increased in recent decades. Etiology of CP includes chronic alcohol consumption as the most common cause with an increasing impact accounting for 70% of all CP cases. ^, A persistent alcohol intake of 70 g/day for a duration of more than 12 months is the threshold for developing CP, and tobacco smoking is a co-risk factor and also an independent factor of CP.

Hereditary CP was recognized as a distinct entity in the 1990s and the underlying genetic mutations were defined in the following years, including mainly mutations in gene loci of cationic trypsinogen (PRSS1), serine protease inhibitor Kazal-type 1 (SPINK1), carboxypeptidase A1 (CPA1), as well as cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC), and carboxyesterlipase (CEL). ^, ^, Today, the proportion of hereditary CP is estimated at 20% to 30% of all CP patients. Especially in previously reported “idiopathic” CP, there may be a considerable number of patients with an unrecognized genetic background, reducing the actual incidence of “idiopathic” CP, which is only accepted as a terminology after exclusion of all other risk factors and may account for approximately 10% of all cases today. Moreover, the term “tropical CP” is now falling into disuse as it has become evident that an aggressive form of idiopathic CP reported from India and other tropical countries in which this term was at first applied is actually strongly associated with genetic mutations/polymorphisms in multiple genes, including SPINK1, CFTR, CTRC, Cathepsin B, and CLDN2/MORC4, with clinical characteristics similar to CP in more temperate countries.

A gallstone etiology of CP remains controversial because this type of CP was exclusively described in Chinese patient cohorts. Besides the fact that no other region in the world observed this type of CP, the pathophysiology of gallstones themselves leading to CP is not explained and it has been assumed that recurrent episodes of gallstone-induced acute pancreatitis (AP) not definitely treated after the first episode finally lead to the picture of CP, rather than this pathophysiology representing a separate etiology of CP itself (see Chapter 33 ).

Autoimmune pancreatitis (AIP) was first described in 1995 and has gained increasing attention since the early 2000s as an important and distinctly different entity of CP in terms of diagnostic measures and therapy. It is found in approximately 5% to 6% of all CP patients. As a presumed systemic IgG4-related sclerosing disease, AIP is addressed in different guidelines and recommendations than CP by most national and international societies today (see Chapters 54 and 60 )

From a pathophysiologic point of view, CP leads to a fibrosclerotic transformation of the pancreatic tissue often associated with calcifications. Local fibro-inflammatory and neuroimmunologic changes lead to a chronic progressive destruction of functional pancreatic tissue. These changes primarily affect exocrine function by acinar cell destruction followed by late symptoms of endocrine failure in most patients when the endocrine cells are affected. The clinical symptoms of exocrine failure include steatorrhea, weight loss, and maldigestion with intolerance of fatty food and malabsorption with vitamin deficiency; endocrine failure leads to symptoms of and eventually complications of diabetes mellitus (DM) ^, (see Chapter 54 ).

In addition, pain is a key feature of CP and clinically the most important symptom in nearly all patients. Pain in CP has been characterized by immunologic and neural modulations, which lead to a reactive change in peripheral nerve diameter, density, and function correlating with pain intensity in the long-term course of CP. ^, After pain generation on a peripheral level, an increasing and stimulus-independent pain sensation develops with characteristics of an autonomous pain caused by neural plasticity and memory function of the peripheral and central nervous system. This neural plasticity finally induces an irreversible change of pain sensation because of cerebral cortical reorganization. Clinically, this cascade is represented by the fact that many CP patients who typically present in a later stage of the disease are already opioid-dependent and highly disabled. ^,

The morphologic macroscopic correlate of CP is characterized by an inflammatory tumorous mass, which is often focused on the head of the gland, pseudocysts, calcifications, and a dilation of the main pancreatic duct with obvious diameter irregularities and stenotic segments. In addition, the bile duct can be obstructed by these changes with a consequent cholestasis. Depending on the enlargement of the inflammatory mass, signs of local compression can be found with a stenosis or occlusion of the portal, superior mesenteric, or splenic vein. This may result in a—mostly left-sided—portal hypertension with collateral circulation via the short gastric veins and can cause a cavernous transformation of the proximal portal vein. Furthermore, the enlarged pancreatic head may result in duodenal and gastric outlet obstruction with subsequent reduction of oral intake, which can further aggravate malnutrition and weight loss.

The major aims of therapy in CP are prevention of acute pain attacks, long-lasting pain relief, prevention of disease progression, correction of metabolic consequences, and restoration of a good quality of life combined with a preservation of endocrine and exocrine function of the pancreas. Furthermore, psychosocial problems should be addressed and managed. Because of the complex pathophysiology of CP, this requires an interdisciplinary management team that includes gastroenterologic, radiologic, pathologic, psychological and surgical expertise.

Conservative therapy

Exposition to nutritional and toxic risk factors

In alcoholic CP, stopping alcohol intake and nicotine use with sustained abstinence are principal steps in management. These steps require a high level of patient compliance, and the cessation of both risk factors that usually coincide may be challenging and require accompanying psychological therapy. If not achieved synchronously, the preferable sequence may be smoking cessation before alcohol abstinence which, however, should also be achieved to improve pain frequency, intensity, and therapy response and to maintain the remaining pancreatic function. ^, Abstaining from the mentioned toxic risk factors may not only reduce symptoms and deterioration of pancreatic function but also contribute to a reduction of disease-associated mortality. ^,

Psychological symptoms

Social re-integration and professional rehabilitation are important therapy aims in the typically young (35–60 years old) cohort of CP patients. A psychological therapy approach in CP should address the complex mechanisms of pain-associated disability in social and professional function, dependency on alcohol and smoking, self-blaming, and the patient’s personal economic deterioration. Interventions to address these issues should start as early as possible in the disease course to prevent or reverse the vicious cycle of one factor enhancing the other and can be performed by educational programs and continuous psychological support, as well as self-conducted supportive measures. ^, Despite such approaches, CP patients seem to be at a higher risk of attempted and completed suicide, which underlines the importance of accompanying CP therapy with psychological support.

Exocrine dysfunction

Exocrine dysfunction, characterized by steatorrhea, malabsorption, maldigestion, lack of fat-soluble vitamins and weight loss, must be addressed by adequate oral substitution of pancreatic enzyme preparations (PEPs). PEPs containing high lipase activity must be resistant to gastric acid provided by enteric coating and should homogenously mix with the nutritional components. This provides coordinated gastric emptying with nutrients and an early activation in the duodenum. Different compositions and galenic forms, including capsules and powders, have been developed and tested with variable results. Especially after pancreatic resections for CP, gastric acid blockade is important to facilitate PEP activity and prevent ulcer development. A fat restricting diet to treat steatorrhea is no longer recommended. CP patients often suffer from a reduced body mass index (BMI) because of maldigestion and reduced food intake to avoid abdominal pain. Therefore a sufficient calorie intake is required and must be adjusted to individual patient needs. The dose of PEPs follows fat intake, with approximately 2000 international units (IU) of lipase per gram of fat ingested resulting in dose ranges from 25,000 to 75,000 units of lipase, depending on the fat content of the meal, that must be provided during the meal to achieve an optimal treatment effect. ^, In case of therapy failure, the first step in treatment recommendations is to increase PEP dosage. Even in countries with high-standard healthcare, many patients with CP-related exocrine pancreatic failure are insufficiently treated. The supportive prescription of proton pump inhibitors in addition to an enteric-coated PEP is often necessary in surgical CP patients if PEP alone is not effective and a dose augmentation of PEP does not lead to a satisfying improvement of symptoms. ^, The success of PEP therapy should primarily be judged by the improvement of clinical symptoms (weight gain, improvement of abdominal symptoms). Besides the improvement of digestive and absorptive function, PEPs themselves may lead to pain reduction and—more importantly—contribute to a normalization of intestinal motility and reduction of dyspepsia. ^,

Deficiency in fat-soluble vitamins, especially vitamin A, D and E, is observed in up to 75% of all CP patients, which may lead to clinically manifest osteoporosis, as observed in approximately 25% of CP patients. Fat-soluble vitamin monitoring and replacement should be performed according to current guidelines and supplemented by vitamin B ₁ , B ₂ , and B ₆ therapy in case of persistent alcohol abuse.

Endocrine dysfunction

CP-related endocrine pancreatic insufficiency is defined as DM type 3c, which is characterized by deficiency of insulin and glucagon as well as pancreatic polypeptide. The treatment primarily follows the recommendations of DM type 1 with absolute insulin deficiency. ^, Three main criteria for the diagnosis of DM type 3c are mandatory: exocrine pancreatic insufficiency (tested by monoclonal fecal elastase-1 testing or direct function tests), consistent morphologic pancreatic abnormalities on imaging (endoscopic ultrasound, magnetic resonance imaging [MRI], or computed tomography [CT] scan), and absence of related autoimmune markers of DM type 1. In addition, minor criteria include impaired β-cell function (i.e., measured by C-peptide or glucose concentrations), absence of insulin resistance (defined by homoeostatic model assessment for insulin resistance), impaired incretin secretion (glucagon-like peptide-1 [GLP-1] or pancreatic polypeptide, or both), and low serum concentrations of fat-soluble vitamins (A, D, E, and K). In addition to CP, DM type 3c is found in pancreatic cancer patients, patients after pancreatic surgery, and genetic and metabolic disorders affecting the pancreas (i.e., hemochromatosis or cystic fibrosis) and accounts for 5% to 10% off all DM patients worldwide.

Metformin is recommended as first-line therapy of DM type 3c for CP patients but in most patients an additional therapy with insulin is unavoidable. CP patients show a high risk of hypoglycemia, which can be explained by a lack of compliance, persisting alcohol consumption, and a co-existing autonomous neuropathy. Especially in alcoholic CP, this is associated with a high risk of mortality. Consequently, the avoidance of hypoglycemia must be a major goal that can often be achieved by simple insulin regimens that increase compliance and reduce therapy-associated severe complications.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here