*2.2.1.1 Secretin stimulation test*

Hormonal stimulation tests are considered to be the most sensitive and specific tests that investigate pancreatic function, including chronic pancreatitis. The test, introduced by Dreiling in 1948, is based on the physiological pancreatic stimulation by secretin with release of water and bicarbonates from the centroacinar and ductal cells. The volume of the duodenum aspiration and bicarbonate concentration are evaluated after double lumen duodenal tube insertion. Standardized ranges, which exclude pancreatic exocrine insufficiency, are: 80–130 mEq/L for peak bicarbonate concentration; 10.1–37.0 mEq/h bicarbonate output, and volume 1.5–5.7 mL/kg for volume/kg. The patient is most likely to suffer from CP if the peak bicarbonate concentration is less than 80 mEq/L. The sensitivity of the test ranges between 60 and 94% and the specificity between 67 and 95%. In a growing number of publications, the use of secretin in the course of other techniques (secretin-enhanced MRCP or endoscopic secretin testing) demonstrates the ability for evaluation of minimal structural changes in the pancreas, in contrast to standard imaging methods which fail to diagnose them [35–38].

### *2.2.1.2 Cholecystokinin stimulation testing*

The classical cholecystokinin stimulation test was developed and first used in the Mayo Clinic. The test measures the enzyme output. Cholecystokinin is given as a continuous infusion of 40 ng/kg/h, but can also be administered as a bolus. Cholecystokinin increases bile secretion in the duodenum during the first 20–40 min after administration, and as a result, the measurement of pancreatic secretion might be affected. The cholecystokinin test disadvantages are as follows: a need for simultaneous gastric and duodenal juices collection during intubation, duodenal perfusion of mannitol and polyethylene glycol solution, delayed stomach emptying, mediation of pain, symptoms of nausea and vomiting most probably due to blood–brain barrier passage [35, 39–43].

## *2.2.1.3 Secretin-cholecystokinin testing*

The combined secretin-cholecystokinin stimulation testing, also called the secretin-pancreozymin test, allows the simultaneous measurement of secretion of

**39**

could be reduced [35, 46–51].

*Up-To-Date View on the Clinical Manifestations and Complications of Chronic Pancreatitis*

both bicarbonate and enzyme by the pancreatic gland. However, cholecystokinin may be administered before or after secretion as long as there is no international standard for test performing and it seems to play insignificant role for diagnostic accuracy. Like the classic cholecystokinin test, it increases the secretion of bile in the

After introducing the idea of obtaining pure pancreatic juice during ERCP in 1982, the technique was adopted and modified by the Japanese pancreatic group and the Cleveland Clinic researchers. The pancreatic fluid collected during ERCP has a higher bicarbonate concentration compared with the classic secretin test (130 mEq/L for healthy subjects and less than 105 mEq/L for CP) and is not contaminated with bile and duodenal content. The drawbacks of the method are the potential ERCP complications, the relatively short time for sample collection—15 min and the need for sedation, which can affect pancreatic secretion. Therefore, the collection of duodenal juice after secretin with or without cholecystokinin stimulation during a standard endoscopic procedure with a tube placed in the endoscope biopsy canal was developed as a comparable alternative. The peak of bicarbonate concentration and the lipolytic activity in the duodenal juice are significantly lower in patients with CP. However, experts find bicarbonate and enzyme output to be more reliable markers for exocrine pancreatic function. Due to its nature—invasiveness, labor intensity, length of procedure (endoscope placement in the duodenum for 1 h) and price, the use of endoscopic tests is limited to some specialized centers, so they are not widely used in every-

Secretin-enhanced MRCP becomes more and more interesting as a method of visualization and morphological assessment of the pancreatic structure, as well as for quantitative assessment of various aspects of pancreatic exocrine function. The magnetic resonance technique has a number of advantages: lack of invasiveness, safety, possibility of three-dimensional reconstruction. The method is costly and is currently limited to large centers, where it is often used in combination with other tests. Its sensitivity is about 90% and is a reliable method for diagnosis of CP in an early stage. In CP, fibrous tissue gradually replaces the glandular elements in the pancreas. This process is reflected in the s-MRCP through characteristic changes in the major pancreatic duct (presence or absence of dilated main pancreatic duct >1 mm), peripheral branches (the presence or absence of dilated peripheral branches) and the volume of pancreatic secretion. The method enables the diagnosis of pancreatic divisum, pseudocysts, ductal disruption resulting from pancreatic necrosis or trauma. For the pancreatic functional evaluation a semiquantitative assessment of the duodenal filling with pancreatic juice at 10th min after secretin application is performed by the following criteria: grade 0-missing duodenal filling; grade 1-only bulbus duodeni filling; grade 2-filling up to genu inferior duodeni; grade 3-fluid filling after genu inferior duodeni. Grade 0–2 is assumed to demonstrate reduced exocrine function. During S-MRCP volume of pancreatic output is predominantly measured. That is why sphincter of Oddi spasm or obstructive lesions may lead to false CP diagnosis. Because of the technique performance and duration the sensitivity

*DOI: http://dx.doi.org/10.5772/intechopen.84738*

duodenum [24, 35, 44].

*2.2.1.4 Endoscopic testing*

day practice [24, 39, 45].

*2.2.1.5 Secretin-enhanced MRCP (s-MRCP)*

#### *Up-To-Date View on the Clinical Manifestations and Complications of Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.84738*

both bicarbonate and enzyme by the pancreatic gland. However, cholecystokinin may be administered before or after secretion as long as there is no international standard for test performing and it seems to play insignificant role for diagnostic accuracy. Like the classic cholecystokinin test, it increases the secretion of bile in the duodenum [24, 35, 44].

### *2.2.1.4 Endoscopic testing*

*Pancreatitis*

psychological therapies [8, 9].

*2.2.1.1 Secretin stimulation test*

fail to diagnose them [35–38].

*2.2.1.2 Cholecystokinin stimulation testing*

to blood–brain barrier passage [35, 39–43].

*2.2.1.3 Secretin-cholecystokinin testing*

**2.2 Pancreatic exocrine insufficiency**

analgesics (Paracetamol, NSAIDs, Aspirin) are first-line drugs with Paracetamol being the preferable one. If no pain relief is achieved, weak opioids (Tramadol), strong opioids (Morphine, Oxycodone), gabapentinoids (Pregabalin), antidepressants or *N*-methyl-d-aspartate receptor antagonists (Ketamine) could be used. Endoscopic treatment with or without Extracorporeal Shock Wave Lithotripsy has a beneficial role in cases with duct obstruction (see below). If endoscopic treatment is ineffective, surgery procedures (drainage, partial or total resection) are indicated. Better results are observed, when applied in early stages of CP and in patients with no opioids requirements. Other non-pharmacological options in selected patients include bilateral thoracoscopic splanchnicectomy, celiac plexus blocks and splanchnic nerve ablation, spinal cord stimulation, transcranial magnetic stimulation,

*2.2.1 Pancreatic exocrine insufficiency assessment by direct functional tests*

Hormonal stimulation tests are considered to be the most sensitive and specific tests that investigate pancreatic function, including chronic pancreatitis. The test, introduced by Dreiling in 1948, is based on the physiological pancreatic stimulation by secretin with release of water and bicarbonates from the centroacinar and ductal cells. The volume of the duodenum aspiration and bicarbonate concentration are evaluated after double lumen duodenal tube insertion. Standardized ranges, which exclude pancreatic exocrine insufficiency, are: 80–130 mEq/L for peak bicarbonate concentration; 10.1–37.0 mEq/h bicarbonate output, and volume 1.5–5.7 mL/kg for volume/kg. The patient is most likely to suffer from CP if the peak bicarbonate concentration is less than 80 mEq/L. The sensitivity of the test ranges between 60 and 94% and the specificity between 67 and 95%. In a growing number of publications, the use of secretin in the course of other techniques (secretin-enhanced MRCP or endoscopic secretin testing) demonstrates the ability for evaluation of minimal structural changes in the pancreas, in contrast to standard imaging methods which

The classical cholecystokinin stimulation test was developed and first used in the Mayo Clinic. The test measures the enzyme output. Cholecystokinin is given as a continuous infusion of 40 ng/kg/h, but can also be administered as a bolus. Cholecystokinin increases bile secretion in the duodenum during the first 20–40 min after administration, and as a result, the measurement of pancreatic secretion might be affected. The cholecystokinin test disadvantages are as follows: a need for simultaneous gastric and duodenal juices collection during intubation, duodenal perfusion of mannitol and polyethylene glycol solution, delayed stomach emptying, mediation of pain, symptoms of nausea and vomiting most probably due

The combined secretin-cholecystokinin stimulation testing, also called the secretin-pancreozymin test, allows the simultaneous measurement of secretion of

**38**

After introducing the idea of obtaining pure pancreatic juice during ERCP in 1982, the technique was adopted and modified by the Japanese pancreatic group and the Cleveland Clinic researchers. The pancreatic fluid collected during ERCP has a higher bicarbonate concentration compared with the classic secretin test (130 mEq/L for healthy subjects and less than 105 mEq/L for CP) and is not contaminated with bile and duodenal content. The drawbacks of the method are the potential ERCP complications, the relatively short time for sample collection—15 min and the need for sedation, which can affect pancreatic secretion. Therefore, the collection of duodenal juice after secretin with or without cholecystokinin stimulation during a standard endoscopic procedure with a tube placed in the endoscope biopsy canal was developed as a comparable alternative. The peak of bicarbonate concentration and the lipolytic activity in the duodenal juice are significantly lower in patients with CP. However, experts find bicarbonate and enzyme output to be more reliable markers for exocrine pancreatic function. Due to its nature—invasiveness, labor intensity, length of procedure (endoscope placement in the duodenum for 1 h) and price, the use of endoscopic tests is limited to some specialized centers, so they are not widely used in everyday practice [24, 39, 45].

#### *2.2.1.5 Secretin-enhanced MRCP (s-MRCP)*

Secretin-enhanced MRCP becomes more and more interesting as a method of visualization and morphological assessment of the pancreatic structure, as well as for quantitative assessment of various aspects of pancreatic exocrine function. The magnetic resonance technique has a number of advantages: lack of invasiveness, safety, possibility of three-dimensional reconstruction. The method is costly and is currently limited to large centers, where it is often used in combination with other tests. Its sensitivity is about 90% and is a reliable method for diagnosis of CP in an early stage. In CP, fibrous tissue gradually replaces the glandular elements in the pancreas. This process is reflected in the s-MRCP through characteristic changes in the major pancreatic duct (presence or absence of dilated main pancreatic duct >1 mm), peripheral branches (the presence or absence of dilated peripheral branches) and the volume of pancreatic secretion. The method enables the diagnosis of pancreatic divisum, pseudocysts, ductal disruption resulting from pancreatic necrosis or trauma. For the pancreatic functional evaluation a semiquantitative assessment of the duodenal filling with pancreatic juice at 10th min after secretin application is performed by the following criteria: grade 0-missing duodenal filling; grade 1-only bulbus duodeni filling; grade 2-filling up to genu inferior duodeni; grade 3-fluid filling after genu inferior duodeni. Grade 0–2 is assumed to demonstrate reduced exocrine function. During S-MRCP volume of pancreatic output is predominantly measured. That is why sphincter of Oddi spasm or obstructive lesions may lead to false CP diagnosis. Because of the technique performance and duration the sensitivity could be reduced [35, 46–51].

### *2.2.2 Pancreatic exocrine insufficiency assessment by indirect functional tests*

Indirect pancreatic tests are available in clinical practice and are therefore more common. Indirect tests assess pancreatic exocrine function by quantifying pancreatic digestive ability or pancreatic enzyme levels in feces. The sensitivity and specificity of these indirect tests are variable and lower than the direct ones especially in mild and moderate PEI. From a methodological point of view, tests can be classified as oral and fecal tests.

In the oral tests, the substrate is given per os along with test meal. Pancreatic enzymes hydrolyze the substrate in the duodenum, and released metabolites are absorbed from the intestine, metabolized in the liver and therefore they can be measured in serum, urine or exhaled air. Various extrapancreatic causes could limit the accuracy of oral pancreatic tests, mainly by interfering with normal digestion: reduced gastric emptying, biliary secretion and/or intestinal absorption due to intestinal disease. Impaired gastric emptying may be affected by the administration of metoclopramide or another prokinetic (cisapride, domperidone etc.) [24, 35].
