1. Dr.Khalid A. Jasim Al-Khazraji
2014
Chronic Pancreatitis
Professor
Dr.Khalid A. Jasim Al-Khazraji
M.B.CH.B , C.A.B.M , FRCP , FACP

2. Definition Prevalence
Chronic pancreatitis Is an inflammatory disease of the pancreas characterized by The presence of permanent and progressive morphologic or and functional damage to the pancreas.
Prevalence
Autopsy reports – % - .

3. Etiology
ALCOHOL: In Western countries, alcohol is the cause of at least 70% of all cases of chronic
pancreatitis, The risk of alcoholic chronic pancreatitis increases logarithmically with rising alcohol
use, but there is no true threshold value below which the disease does not occur.
TOBACCO: smoking is common in patients with alcoholic chronic pancreatitis and is associated
with an increased risk for pancreatic calcifications, and smoking cessation after the clinical onset
of chronic pancreatitis reduces the risk of subsequent calcifications. There is also evidence that
smoking is an independent risk factor for chronic pancreatitis. Smoking is also associated with a
much higher rate of secondary pancreatic cancer and overall mortality in patients with chronic
pancreatitis.
TROPICAL PANCREATITIS: Tropical pancreatitis accounts for about 70% of all cases of
chronic pancreatitis in southern India. The pathophysiology of tropical pancreatitis is unknown.
GENETIC: Only one type of mutation appears sufficient to cause chronic pancreatitis: mutations
in PRSS1 in families with hereditary pancreatitis.
AUTOIMMUNE PANCREATITIS: Autoimmune pancreatitis refers to a distinct chronic
inflammatory and sclerosing disease of the pancreas. The distinct characteristic of the disease is a
dense infiltration of the pancreas, and often other organs, with lymphocytes and plasma cells ,
many of which express IgG4 on their surface.
OBSTRUCTIVE CHRONIC PANCREATITIS: Obstructive chronic pancreatitis refers to a
distinct entity produced by a (generally) single dominant narrowing or stricture of the main
pancreatic duct
MISCELLANEOUS
- Recurrent or Severe Acute Pancreatitis :Recurrent episodes of acute pancreatitis of any etiology
may eventually lead to the development of a chronic inflammatory response within the pancreas,
the activation of pancreatic stellate cells, and chronic pancreatitis.
- Hypertriglyceridemia,Hpercalcemia
IDIOPATHIC CHRONIC PANCREATITIS :accounts for 10% to 30% of all cases of chronic
pancreatitis

4. Pathophysiology of chronic pancreatitis
- The pathophysiologic processes must ultimately account for the features of chronic pancreatitis, including loss of parenchymal cells, self-sustaining chronic inflammation, and fibrosis.
- Alcoholic chronic pancreatitis, being the most common form, has received the most attention.

5. Clinical Features Abdominal pain: is the most common clinical problem.
Severe pain decreases appetite and limits food consumption, contributing to weight
loss and malnutrition. Chronic severe pain leads to a dramatic reduction in quality of
Life, loss of social functioning, and frequent addiction to narcotic
analgesics. Intractable pain is the most common reason for hospitalization and for
surgery in patients with chronic pancreatitis. Pain is most commonly described as
being felt in the epigastrium, often with radiation to the back. Pain is usually
described as boring, deep, and penetrating and is often associated with nausea and
vomiting. Pain may be relieved by sitting forward or leaning forward, by assuming
the knee-chest position on one side, or by squatting and clasping the knees to the
chest. Pain may worsen after a meal and often is nocturnal.
Steatorrhoea: occurs when more than 90% of the exocrine tissue has been
destroyed; protein malabsorption only develops in the most advanced cases.
DIABETES MELLITUS: Like exocrine insufficiency, endocrine insufficiency is a
consequence of long-standing chronic pancreatitis and is especially common after
pancreatic resection and in tropical (fibrocalcific) pancreatitis.

6. COMPLICATIONS
- PSEUDOCYST : occur in about 25% of patients with chronic pancreatitis and are
most common in alcoholic chronic pancreatitis. The most common symptom associated
with a pseudocyst is abdominal pain. Less common manifestations are a palpable mass, nausea
and vomiting (due to compression of the stomach or duodenum), jaundice (due to compression
of the bile duct), and bleeding. Some patients are asymptomatic. Elevations in serum lipase
and amylase values are found in at least one half of patients, and a persistent elevation in
serum lipase or amylase can be a clue to the presence of a pseudocyst.
The diagnosis of pseudocyst is generally easily made through imaging studies US, CT, MRI,
and EUS. .
ERCP is associated with an approximately 15% chance of infection of a previously uninfected
pseudocyst, so this procedure should be undertaken only after antibiotics have been
administered and therapy is imminent.
Treatment is not necessary in all patients. Patients who have mature pseudocysts smaller than 6
cm, minimal or no symptoms, no complications, and are reliable may be managed
conservatively. Even larger pseudocysts that remain asymptomatic can be managed
expectantly. Very large pseudocysts, an enlarging pseudocyst, and symptomatic or
complicated pseudocysts require therapy. Also unlike the acute fluid collections associated
with acute pancreatitis, pseudocysts occurring in the setting of chronic pancreatitis are
generally mature at the time of their diagnosis and a delay in therapy is not needed to allow the
pseudocyst capsule to mature. Therapy for symptomatic, complicated, or enlarging
pseudocysts can be surgical, percutaneous, or endoscopic.
- GASTROINTESTINAL BLEEDING: May develop from a variety of causes. Some are not
related to chronic pancreatitis, such as bleeding from a Mallory-Weiss tear, esophagitis, peptic
ulcer disease, and varices from concomitant alcoholic cirrhosis. Others occur as a direct result
of the pancreatitis, most notably bleeding from a pancreatic pseudocyst, pseudoaneurysm, and
portal or splenic vein thrombosis.
- BILE DUCT OBSTRUCTION
- DUODENAL OBSTRUCTION
- PANCREATIC FISTULA

7. Diagnosis Tests of function Tests of structure
1-Direct hormonal stimulation (with pancreatic stimulation by secretin or cholecystokinin or both):
Using oroduodenal tube.
Using endoscopy.
2-Magnetic resonance cholangiopancreatography with secretin stimulation.
3- Fecal elastase
4- Fecal chymotrypsin
5- Serum trypsinogen (trypsin)
6- Fecal fat
7- Blood glucose level.
Tests of structure
1- Endoscopic ultrasonography.
2-Endoscopic retrograde cholangiopancreatography.
3-Magnetic resonance imaging with magnetic resonance
cholangiopancreatography.
4-Computed tomography
5-Abdominal ultrasonography
6- Plain abdominal film

8. TESTS OF PANCREATIC FUNCTION
Tests of pancreatic function can be divided into those that directly measure
pancreatic function by measuring the output of enzymes or bicarbonate from
the pancreas and those that measure the released enzymes indirectly (through
its action on a substrate or its level in blood or stool).
Direct Tests: Direct hormonal stimulation tests are believed to be the most
sensitive function test for chronic pancreatitis.
Indirect Tests: can generally measure pancreatic enzymes in blood or stool. Tests that
measure the effect of pancreatic enzymes on an orally administered substrate with
collection of metabolites in blood, breath, or urine are of historical interest only.
Serum Trypsinogen: (often called serum trypsin) can be measured in blood and provides a
rough estimation of pancreatic function. Very low levels of serum trypsinogen (<20 ng/mL)
can be seen in patients with advanced chronic pancreatitis with steatorrhea. Serum
trypsin is not decreased in patients with other forms of steatorrhea, .
Pancreatic Enzymes in Stool: Low concentrations of chymotrypsin or elastase in stool can
reflect inadequate delivery of these pancreatic enzymes to the duodenum. Both can be
measured on random samples of stool. Fecal chymotrypsin is low in most patients with
chronic pancreatitis and steatorrhea. . False-positive results have been reported in other malabsorptive conditions
(celiac disease, Crohn's disease), . Because the test is usually normal in patients without steatorrhea, it is
reliably positive only in advanced chronic pancreatitis.
Fecal elastase has significant advantages over fecal chymotrypsin in that it is much more
stable in passage through stool and is easier to measure. Levels less than 200 mg per gram
stool are considered abnormal. The test is reasonably accurate in more advanced chronic
pancreatitis. Fecal elastase can be low in other diseases causing diarrhea, such as
short bowel syndrome and small bowel bacterial overgrowth.
Fecal Fat Excretion: Maldigestion of fat occurs after 90% of pancreatic lipase secretory
capacity is lost. The simplest evaluation of pancreatic lipase action is the measurement of
fecal fat excretion during a 72-hour collection of stool. Although theoretically quite simple,
the test is difficult to perform in practice. The patient must follow a diet containing 100
g/day fat for at least three days before the test, and complete collection of the sample is
difficult to achieve. In health, less than 7 g of fat (7% of the ingested dose) should be
present in stool..

9. TESTS OF PANCREATIC STRUCTURE (IMAGING)
Plain Abdominal Radiography: The finding of diffuse (but not focal)
pancreatic calcifications in abdominal films is quite specific for chronic
pancreatitis. Focal calcifications may be seen in cystic and islet cell tumors of
the pancreas, and in peripancreatic vascular calcifications. Calcifications occur
late in the natural history of chronic pancreatitis and may take from 5 to 25
years to develop. Calcifications are most common in alcoholic, late-onset
idiopathic, hereditary, and tropical pancreatitis and far less common in early
onset idiopathic pancreatitis. Acceleration of the clinical course of chronic
pancreatitis and subsequent calcifications are particularly common in patients
who smoke. Calcifications are not static once they develop and may in fact
wax and wane over time.

10. Abdominal Ultrasonography: has been widely studied as a diagnostic tool
for chronic pancreatitis. This modality is limited in that the pancreas (and
particularly the pancreatic head) cannot be adequately visualized in some
patients owing to overlying bowel gas or body habitus. Ultrasonographic
findings indicative of chronic pancreatitis include dilation of the pancreatic
duct, shadowing pancreatic ductal stones, gland atrophy or enlargement,
irregular gland margins, pseudocysts, and changes in the parenchymal
echotexture.
Most studies suggest a sensitivity of 50% to 80% with a specificity of 80% -
90%. The true sensitivity and specificity may be different because most of
these studies are older and did not use modern state-of-the-art equipment.
Grading of Chronic Pancreatitis by Ultrasonography (US) or Computed
Tomography (CT):
Normal: No abnormal findings on a good-quality study visualizing the entire
Gland.
Equivocal: One of the following:
Mild dilatation of the pancreatic duct (2-4 mm) in the body of the gland
Gland enlargement ≤2-fold normal
Mild-moderate: One of the preceding findings plus at least one of the
following:
Pancreatic duct dilatation (>4 mm)
Pancreatic duct irregularity
Cavities <10 mm
Paranchymal heterogeneity
Increased echogenicity of duct wall
Irregular contour of the head or body
Focal necrosis of parenchyma
Severe: Mild/moderate features plus one or more of the following:
Cavity >10 mm
Intraductal filling defects
Calculi/pancreatic calcification
Ductal obstruction (stricture)
Severe duct dilatation or irregularity
Contiguous organ invasion

11. Computed Tomography:
The overall sensitivity of CT for chronic pancreatitis is between 75% and 90%,
with a specificity of 85% or more.
CT is able to image the pancreas in essentially all patients and hence has a
substantial advantage over U/S.
Contrast-enhanced CT scan demonstrating multiple calcific densities (arrow) along the line of the main pancreatic duct in a patient with chronic pancreatitis.

12. Magnetic Resonance Imaging:
MRI, coupled with MRCP is as accurate, and probably more so, than
CT in patients with chronic pancreatitis. MRCP results agree with
ERCP results in about 90% of cases.
Endoscopic Retrograde Cholangiopancreatography:
Pancreatography has been considered the most specific and sensitive
test of pancreatic structure, and many consider it the gold
standard. It also has the advantage over all previously discussed tests
in that therapy (e.g., pancreatic duct stenting or stone extraction)
may be administered during its performance. The disadvantage,
however, is that ERCP is the risky diagnostic test, with
complications occurring in at least 5% of patients and a mortality
rate of 0.1% to 0.5%. In most studies in patients with chronic
pancreatitis, the sensitivity of ERCP is between 70% and 90%, with
a specificity of 80% to 100%.Thus, chronic pancreatitis can exist in
the absence of any visible changes within the pancreatic duct.

13. Cambridge Grading of Chronic Pancreatitis on Endoscopic Retrograde Pancreatography
GRADE MAIN PANCREATIC DUCT SIDE BRANCHES
Normal Normal Normal
Equivocal Normal <3 Abnormal
Mild Normal ≥3 Abnormal
Moderate Abnormal ≥3 Abnormal
Severe Abnormal with at least 1 of the following: ≥3 Abnormal
Large cavity (>10 mm)
Obstruction
  Filling defects
Severe dilatation or irregularity
ERCP image shows subtle dilatation of the terminal ends of the secondary branches (open arrow) and a mild stricture in the pancreatic body (arrow).

14. Endoscopic Ultrasonography.
Diagnosis of Chronic Pancreatitis on Endoscopic Ultrasonography
Parenchymal abnormalities
Hyperechoic foci
Hyperechoic strands
Lobularity of contour
Cysts
Ductal abnormalities
Main duct dilatation
Main duct irregularity
Hyperechoic ductal walls
Visible side branches
Calcification

15. Examples of endoscopic ultrasound (EUS) chronic pancreatitis (CP) criteria. A: Hyperechoic duct wall (arrow); B: Cyst (arrow); C: Hyperechoic strands (arrows); D: Visible side-branch (arrow); E: Dilated and irregular main pancreatic duct with visible side-branches (arrow); F: Hyperechoic foci (arrows).

16. TREATMENT
ABDOMINAL PAIN : is the most common and most debilitating symptom of chronic pancreatitis as well as the one most often requiring medical care.
Medical Therapy : Several modalities are available to help control pain.
Analgesics
The majority of patients with chronic pancreatitis require some form of analgesia. Some patients’ pain may be managed with acetaminophen or aspirin, but most require more potent narcotic agents. There is a risk of addiction to narcotics with the use of these agents.
Cessation of Alcohol and Tobacco
Continued alcohol abuse hastens the development of pancreatic dysfunction,
also continued alcohol abuse, along with smoking, increases mortality.
Antioxidants
Damage by free radicals has been proposed as one mechanism for pancreatic damage in alcoholic and other forms of chronic pancreatitis. Patients with chronic pancreatitis (particularly alcoholic) have evidence of oxidant stress and reduced antioxidant capacity. Oxidant stress is a strong activator of pancreatic stellate cells. There are now several small randomized trials of a mixture of antioxidants (selenium, beta-carotene, vitamin C, vitamin E, and methionine) that indicate that this therapy reduces the pain of chronic pancreatitis. The overall effect of antioxidants is very modest but the data now support their use in these patients and the therapy is risk-free.
Octreotide
Octreotide, the synthetic analog of the native hormone somatostatin, decreases pancreatic secretion and reduces circulating CCK levels. This agent therefore might reduce pain via the same mechanisms invoked for the use of enzymes for pain. In addition, octreotide has some direct antinociceptive effect separate from any effect on pancreatic enzyme secretion.

17. Pancreatic Enzyme Therapy
Pancreatic secretion is under feedback control. The use of pancreatic enzymes to reduce pain is based on the ability of these agents to activate this feedback control system in a way to reduce pancreatic secretion. Delivering proteases to the duodenum or very proximal jejunum can suppress pancreatic secretion. This action is due to the ability of the proteases in this segment of small bowel to reduce CCK release, by destroying an intestinal CCK-releasing factor, which is one of the primary stimulants of CCK release.
In patients with chronic pancreatitis, the lack of delivery of serine proteases to the duodenum could allow more CCK-releasing factor to escape denaturing. As a result, one would expect higher levels of CCK-releasing factor within the duodenum and higher serum levels of CCK. Higher levels of circulating CCK would stimulate the pancreas to secrete, with this strong stimulation leading to pancreatic pain by raising pancreatic duct or tissue pressure or by forcing digestive enzymes into the interstitium if secretion is occurring against pancreatic ductal obstruction.
The oral administration of pancreatic enzymes could restore normal feedback suppression of pancreatic secretion by providing active serine proteases in the duodenum, which could again denature the CCK-releasing factor, thereby reducing the hyperstimulation and relieving pain.

18. Endoscopic Therapy
the general goal of endoscopic therapy is to improve drainage of the pancreatic duct by relieving ductal obstruction.
Pancreatic Duct Sphincterotomy
Pancreatic duct sphincterotomy is generally required for larger-caliber pancreatic stent placement and for pancreatic duct stone extraction.
Stent Placement
Stent placement in the pancreatic duct is most often performed to dilate and bypass an obstructing stricture.
Pancreatic Duct Stone Removal
Combined Endoscopic Therapy
Surgical Therapy
Surgical therapy in chronic pancreatitis is most commonly considered for intractable abdominal pain for which medical therapy has failed. Other indications for surgery in these patients are complications involving adjacent organs or structures (duodenal, splenic venous, or biliary complications), failure of endoscopic or radiologic management for pseudocysts, internal pancreatic fistulas, and exclusion of malignancy despite an extensive evaluation. Surgical options for pain are pancreatic ductal drainage, resection of all or part of the pancreas, and both. The choice of surgical procedure depends in large part on the ductal anatomy, presumed pathogenesis of pain, and associated complications as well as local surgical preferences and expertise.

19. Nerve Blocks and Neurolysis
Attempts to block the transmission of nociceptive stimuli have met with limited success. Celiac plexus block is used rarely in patients with chronic pancreatitis owing to the short duration of action. Celiac plexus block (usually using a combination of a glucocorticoid and a long-acting local anesthetic like bupivacaine) and celiac plexus neurolysis (using an injection of absolute alcohol) can be administered by CT- or EUS-guided techniques.
Celiac plexus block under EUS guidance is safer, more effective, and more long-lasting than that delivered under CT guidance, but the effect of even EUS-guided celiac plexus block appears to be too transitory for long-term management.
Celiac plexus neurolysis has generally been used only in pancreatic carcinoma, although better methods of identifying the celiac ganglia on EUS may allow better targeted injections.
MALDIGESTION AND STEATORRHEA
As noted, although patients with chronic pancreatitis may maldigest fat, protein, and carbohydrates, it is the fat maldigestion that is the principal clinical problem. It has been estimated that 30,000 IU (or about 90,000 USP units) of lipase delivered to the intestine with each meal should be sufficient to eliminate steatorrhea. This corresponds to approximately 10% of the normal pancreatic output of lipase. Lower dosages of enzymes can improve but not completely correct steatorrhea. It would seem relatively straightforward to achieve this goal with the use of enzyme supplements, but a number of factors limit the effectiveness of commercially available enzyme supplements.

20. DIABETES MELLITUS
Diabetes mellitus is an independent predictor of mortality in patients with chronic pancreatitis. Morbidity and mortality due to diabetes mellitus may occur from progressive microangiopathic complications or from more dramatic complications, such as treatment-induced hypoglycemia (in those with inadequate glucagon reserve).
Ketoacidosis is distinctly unusual. Given the risk of treatment-induced hypoglycemia and the difficulty of close follow-up in patients who continue to abuse alcohol, therapy is usually directed at controlling urinary losses of glucose rather than on tight control of blood glucose value. Some patients show response to the use of an oral hypoglycemic, such as a sulfonylurea, a thiazolidinedione, or metformin. Insulin is often needed, however, and patients with chronic pancreatitis tend to have lower insulin requirements than patients with type 1 diabetes mellitus. Overvigorous attempts at tight control of blood glucose value are often associated with disastrous complications of treatment-induced hypoglycemia.
Attempts at tight control of blood glucose value are indicated in one subgroup, however—patients with hyperlipidemic pancreatitis—in whom the diabetes is usually a primary illness and tight control of blood glucose makes control of serum lipids possible. In long-standing diabetes, appropriate monitoring for nephropathy, retinopathy, and neuropathy is indicated.

21. The End
Thank you…..
2014