Etiology pathophysiology clinical features investigations and surgical management of chronic pancreatitis

1. CHRONIC PANCREATITIS
Dr. S.SIVA SANKAR
1

2. Chronic Pancreatitis
‘a continuing inflammatory disease of the
pancreas, characterized by irreversible
morphological change (ductal distortion
associated with fibrosis) and typically
causing PAIN and/or permanent loss of
function’ (irreversible destruction of
exocrine parenchyma and the destruction of
endocrine parenchyma in the late stages )
2

3. overview
Pancreas
● Anatomy
● Histology
● Exocrine function
● Endocrine function
Chronic Pancreatitis
• Investigations
• Medical management
• Surgical management
• Complications
Chronic Pancreatitis
● Classification
● Etiology
● Pathogenesis
● Clinical features
3

4. 4

5. PANCREAS - Anatomy
● Retroperitoneal organ that
lies in an oblique position,
sloping upward from the C-
loop of the duodenum to the
splenic hilum
● The average gland weighs
between 75 and 125 gm
5

6. 6

7. Development
7

8. Pancreatic duct
● The main pancreatic duct is usually only 2 to 3 mm in diameter and runs closer
to the posterior than to the anterior surface.
● The main pancreatic duct joins with the common bile duct and empties at the
ampulla of Vater or major papilla, which is located on the medial aspect of the
second portion of the duodenum.
● The muscle fibers around the ampulla form the sphincter of Oddi, which
controls the flow of pancreatic and biliary secretions into the duodenum

9. 9
PANCREAS - Histology

10. Pancreatic Stellate Cell : Star in pancreatic Diseases
● Pancreatic stellate cells (PSCs) build
up only about 4–7% of the organ and,
in contrast to the more abundant
acinar cells or islets, neither secrete
digestive enzymes nor hormones
● Normally quiescent, are capable of
remarkable transition into their
activated myofibroblast-like phenotype.
● It is now commonly accepted that
these cells play a pivotal role in the
desmoplastic reaction present in
severe pancreatic disorders.
10

11. Exocrine Pancreas secretes pancreatic juice
approximately 500 to 800 mL per day, colorless, odorless, alkaline,
isosmotic secreted by acinar cells and duct cells.
11

12. Endocrine Pancreas
● ISLET of Langerhans constitute
1% to 2% of the gland
12

13. PANCREAS GENETICS
Intrapancreatic activation of trypsinogen is inhibited by
• Pancreaic secretory trypsin inhibitor (PSTI) or
• Serine protease inhibitor Kazal type 1 (SPINK1)
13

14. Summary
● DUCTULO LOBULAR ANATOMY
● RELATIONS OF PANCREAS
● PANCREATIC HISTOLOGY
● PANCREATIC STELLATE CELL
● PANCREATIC PHYSIOLOGY
● PANCREATIC GENETICS
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15. 15

16. CLASSIFICATION
16

17. TIGAR-O
17

18. SINGER AND CHARI
18

19. PATHOGENESIS
● Inflammatory Fibrosis
● Duct Distortion
19

20. Acute pancreatitis
Chronic pancreatitis
20

21. Hypothesis in pathophysiology
● Oxidative stress hypothesis
● Toxic-metabolic effect
● Stone and duct obstruction theory
● The necrosis-fibrosis sequence
● Sentinal acute pancreatitis event (SAPE)
hypothesis

22. 22

23. Toxic metabolic effect
● Alcohol –direct toxic to the pancreatic acinar cell.
● Causes protein precipitation and plug formation in the
duct .
● Promotes synthesis of lithostathine by acinar cells
● Metabolites of alcohol causes fragility of zymogen
granules and lysosomes leads to autodigestion.
● Ethanol activates PSCs and induces fibrosis.
23

24. Smoking
● Smoking increses the risk of alcohol induced chronic
pancreatitis
● Risk of pancreatic calcification and DM increased among
smokers.
● Hypercalcemia is a stimulant for pancreatic calcium
secretion and calculus formation and obstructive
pancreatopathy.
24

25. Necrosis Fibrosis Theory
● A) An episode of acute pancreatitis produces an acute inflammatory
cell infiltrate in the peri-ductal areas.
● (B) The healing phase of acute pancreatitis involves collagen
deposition in the affected periductal areas.
● (C) Extrinsic compression of the ducts by collagen obstructs the acinar
cell complex.
● (D) Worsening obstruction results in acinar cell atrophy, stasis, and
secondary stone formation.
25

26. Oxidative Stress hypothesis
Oxidized by-products are generated
within the hepatocytes and secreted in
the bile.
The bile is refluxed into the pancreatic
ducts and causes oxidative damage at
the level of the acinar and ductile cells.
Chronic exposure to oxidative stress
leads to fibrosis.
26

27. STONE FORMATION
● The stone and duct-obstruction
theory.
● (A) In predisposed individuals,
pancreatic fluid is lithogenic,
leading to protein plug and stone
formation.
● (B) Accumulation of stones within
the acinar cell complex produces
ulceration and inflammation of
the ductules.
● (C) Ductular obstruction from
epithelial inflammation and the
stones themselves leads to
atrophy, exocrine insufficiency,
and fibrosis
• Initial non calcified protein precipitate
(Protein Plug), which serves as a focus for
layered calcium carbonate precipitation
• Calcium carbonate crystals trapped in a
matrix of fibrillar and other material
• PSP-lithostathine- reg protein
• Increased pancreatic juice protein levels in
alcoholic men are reversible by abstinence from
alcohol.
27

28. SAPE Hypothesis
28

29. Activation of PSC
29

30. FIBROSIS
● Perilobular fibrosis that forms
surrounding individual acini, then
propagates to surround small
lobules, and eventually coalesces to
replace larger areas of acinar
tissue
● Activation of PSCs that are found
adjacent to acini and small arteries
● Proliferative factors such as
transforming growth factor beta,
platelet-derived growth factor, and
pro inflammatory cytokines and
synthesize and secrete type I and
III collagen and fibronectin
30

31. DUCT DISTORTION
● Although calculus disease and
duct enlargement appear
together as late stages of
chronic pancreatitis, controversy
persists over whether they are
associated, are independent
events, or are causally related.
● Calcific stone disease is normally a
marker for an advanced stage of
disease, parenchymal and ductular
calcifications do not always correlate
with symptoms.
31

32. CLINICAL FEATURES
32

33. Clinical Features
● PAIN – Most Common
 Left upper quadrant /epigastric pain
 Radiating to back
 Moderate to severe pain
 Recurrent /persistent pain
 Increased by food intake during acute episode
 Associated with nausea &vomiting
● Type A pain - short relapsing episodes lasting days to
weeks, separated by pain-free intervals.
● Type B pain -prolonged, severe, unrelenting pain.
33

34. Causes of Pain
● Primary
 Duct Obstruction
 Tissue Hypertension
 Tissue Ischemia
 Active Inflammation
 Active Nociception
● Secondary
 Local Complication
 Remote Complication
● Treatment-Related
 Surgical
 Medical (opioid induced) 34

35. Strategies to relieve pain
• Reducing secretion /decompress the secretory
component.
• Resecting the focus of chronic inflammatory change.
• Neural ablative procedures.

36. Clinical Features
● Chronic Weight loss
● Malnutrition (Fat ,Vit. A,D,E,K etc. )
● Steatorrhea –classical
 loose/bulky stool
 Greasy, sticky, oily, fowl smelling
36

37. Clinical Features
● Endocrine insufficiency occurs late in the disease.
● Usually after about 90%of the pancreatic parenchyma
has been replaced by fibrosis.
● Diabetes is more common in patients with alcohol
associated chronic calcifying pancreatic.
37

38. Pancreatogenic diabetes/Type 3cDM
● Pancreatogenic diabetes is seen after surgical resection
for benign/malignant disease.
● Frank diabetes in 20%
● Impaired glucose tolerance in 70%
● Loss of functioning pancreatic tissue results in deficiency
of insulin,glucagon and pancreatic polypeptide.

39. Paradoxical combination of
 Enhanced peripheral sensitivity to insulin
 Decreased hepatic sensitivity to insulin .
 Results in Brittle diabetes and requires special attention.

40. ABC grading of CP
A- No Pain
B- Pain without Complications
C- Pain with Complications
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42. Investigations
•Pancreatic Function Tests
•Imaging
42

43. 43

44. Pancreatic function tests
Pancreatic enzymes
1. Lipase (Normal range 0 to 160 U/L)
2. Amylase (Normal range 40 to 140 U/L)
specificity of both serum amylase and lipase for chronic pancreatitis
is 90%–95%, sensitivity is extremely low, around 10%.
As a consequence, serum markers can not be used for establishing
the diagnosis of chronic pancreatitis.
44

45. Pancreatic polypeptide
● correlates most strongly with chronic pancreatitis
● Severe chronic pancreatitis associated with
blunted/absent PP response to feeding.
● Normal PP response does not rule out the presence of
early disease
Nagpal, S. J. S., Bamlet, W. R., Kudva, Y. C., & Chari, S. T. (2018). Comparison
of Fasting Human Pancreatic Polypeptide Levels Among Patients With Pancreatic
Ductal Adenocarcinoma, Chronic Pancreatitis, and Type 2 Diabetes Mellitus.
Pancreas, 1. doi:10.1097/mpa.0000000000001077
45

46. Direct aspiration of
pancreatic juice by
endoscopic cannulation is
done after stimulation.
● Lundh test meal
● Hormonal stimulation (
CCK or secretin )
● Estimation of Trypsin,
Amylase,Lipase,Bicarbon
ate levels
46

47. Indirect tests of pancreatic exocrine function:
● Bentiromide test
urinary excretion of the proteolytic metabolite PABA is
measured after ingestion of N-benzoyl L-tyrosyl P-aminobenzoic
acid.
● Triolene breath test
to assess the presence of metabolites of fat.
47

48. Fecal fat and weight estimation test
● measures the stool content of fat after a nutritional intake
of 100 g of fat per day during 3 days.
● If the stool fat content exceeds 7 g/day, the diagnosis of
steatorrhea is established
48

49. Fecal Elastase
Measurement of the fecal elastase C1 level is the preferred
noninvasive study to diagnose pancreatic exocrine
insufficiency and Screening test for Chronic Pancreatitis
A fecal elastase C1 concentration above 200 μg/g feces is
normal;
between 100 and 200 μg/g --mild to moderate pancreatic
insufficiency;
below 100 μg/g --severe pancreatic exocrine insufficiency.
49

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51. 51
Markers for malnutrition

52. Imaging techniques
Radiologic imaging assists in
Diagnosis
Evaluation of severity of disease
Detection of complications
Assisting in determining treatment options
52

53. PLAIN XRAY
● The finding of diffuse
pancreatic calcifications
on plain abdominal films
is quite specific for
chronic pancreatitis.
Seen in 60% cases.
● Focal calcifications may be
seen in cystic and islet cell
tumours of the pancreas, and
in peripancreatic vascular
calcifications.
53

54. ULTRASOUND
Ultrasonography is used as a screening method for patients with
abdominal symptoms or trauma.
Ultrasonographic findings indicative of chronic pancreatitis include
● dilation of the pancreatic duct,
● pancreatic ductal stones,
● gland atrophy or enlargement,
● irregular gland margins,
● pseudocysts,
● changesin the parenchymal echo texture.
54

55. ERCP
● Gold standard for diagnosis and staging of chronic
pancreatitis.
● “Chain of lakes”
Used for
● Biopsy
● Brushing for cytology
● For stenting to relieve obstruction
● Drain a pseudocyst
55

56. ● ERCP induced pancreatitis -5%
● More risk among patients with
sphincter of oddi dysfunction
h/o post ERCP pancreatitis
ERCP is reserved when diagnosis is unclear despite use of
other imaging methods.
a diagnostic or therapeutic maneuver is indicated.
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58. Cambridge Calssification - ERCP
58

59. CT findings
 dilated pancreatic duct (68%), 5mm to 7mm at body
 parenchymal atrophy (54%),
 pancreatic calcifications (50%) .
Other findings include
 peripancreatic fluid,
 focal pancreatic enlargement,
 biliary duct dilation, and irregular pancreatic parenchyma
contour.
59

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61. 61

62. CT is particularly useful to assess complications, such as
● pancreatic duct disruption,
● pseudocysts,
● portal and splenic vein thrombosis, and
● splenic and pancreaticoduodenal artery
pseudoaneurysms.
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63. 63

64. MAGNETICRESONANCE CHOLANGIO PANCREATOGRAPHY(MRCP)
● Non invasive
● It can assess both pancreatic parenchyma andducts.
● It can detect pancreatic duct dilatation,ductal
narrowing and filling defects.
MRCP with secretin injection is particularly useful to evaluate
intraductal strictures and pancreatic duct disruption and to
confirm the need for interventional procedures.
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66. 66

67. Map of Chain of lakes
67

68. Endoscopic Ultrasound
● EUS has emerged as the most accurate technique to
diagnose chronic pancreatitis in patients with minimal
change disease or in the early stages.
● EUS is highly reliable in ruling out pancreatic carcinoma
when CT findings are normal or equivocal
● EUS is now frequently used as a preliminary step in the
evaluation of patients with pancreatic disease.
68

69. EUS can recognize
● Small intraductal lesions
● Intraductal mucus
● Cystic lesions
● Subtle ductular abnormalities
● EUS is more sensitive than ERCP in detecting mild
disease
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70. Rosemont Criteria for EUS
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72. 72

73. Clinical approach-critical qns
1. Is it a large duct disease ?
2. Is it a small duct disease ?
3. Is there a mass ?
4. If there is a mass,is it mass forming pancreatitis or
neoplastic ?
5. What complications are present ?
6. Is there acute inflammation or overt sepsis ?
7. Does the pt have functional deciciency ?
8. Is the patient malnourished ?
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74. MANAGEMENT
● Medical therapy
 Analgesia
 Enzyme therapy
 Antisecretory therapy
● Neurolytic therapy
● Endoscopic management
● Surgical management
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75. Medical Management
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76. Izbiki Pain Score
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77. 77

78. Pancreatic enzyme replacement (PERT)
● Pancreatic enzyme replacement is beneficial in patients
with exocrine insufficiency
● Its benefit in controlling chronic pain is controversial.
● Uncoated pancreatic enzymes should be given with PPI
for acid suppression.
78

79. .
• Conventional enzymes are the treatment of choice for pain
relief
• Enteric-coated pancreatic enzyme preparations are treatment
of choice for steatorrhea.
• Acid-suppressive therapy should not be given with enteric-
coated preparations
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80. PERT
80

81. Anti secretary therapy
• Octreotide acetate used for pain relief in obstructive
pancreatopathy.
• Octreotide therapy and TPN for severe pain
exacerbations
Neurolytic therapy
Celiac plexus neurolysis with alcohol injection
EUS guided celiac plexus block.

82. Endoscopic
management
●Pancreatic duct stenting
●Decompression of a pancreatic duct leak,
● Drainage of pancreatic pseudocysts that can be
catheterized through the main pancreatic duct
● Pancreatic duct sphincterotomy
● Endoscopic stone removal
● Extracorporeal shock wave lithotripsy (ESWL)
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83. SURGICAL MANAGEMENT
83

84. Surgical management
Indications
● Intractable pain (most common indication)
● Multiple strictures in pancreatic duct unsuitable for
endotherapy.
● Biliary or duodenal obstruction,
● pseudocyst or pseudoaneurysm formation,
● Suspicious of malignancy
84

85. Objectives of surgical management
• Pain relief
• Control of complications
• Preservation of exocrine and endocrine functions
• Social and occupational rehabilitation
85

86. Pain relief in surgical management
● Mechanism of pain in chronic pancreatitis
 intra ductal hypertension
 interstitial hypertension
Pancreatic head is considered as “pacemaker of pain” in
chronic pancreatitis.
Surgical decompression ,adequate drainage and resection
procedures reduces pain.
86

87. Surgical management
● Sphincteroplasty
● Drainage procedures
● Resection procedures
● Hybrid procedures
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88. Transduodenal Sphincteroplasty
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89. Surgical procedures
89

90. Resection procedures
– Indications
• Focal disease, confined to head of pancreas (except
in distal pancreatectomy)
• Suspicious malignant lesion
• Obstructive complication developed by fibrosis
• Non dilated duct
– Disadvantages
• Endocrine insufficiency
• Exocrine insufficiency
90

91. Drainage procedures
Indication
• Isolated dilatation of the pancreatic duct >7mm or
“chain of lakes” appearance without an inflammatory
mass in the head
• Generalized parenchymal involvement (no
focal involvement)
• Recurrent or progressive segmental stenosis of
the pancreatic duct
91

92. Pre op assessment
● Confirmation of the diagnosis of chronic pancreatitis.
● Establish the benign nature of the head mass if present
● Define the anatomy of pancreatic duct,head mass and
parenchyma.
● Evaluation for biliary and duodenal obstruction.
● Ascertain the patency of spleno-porto-mesenteric axis.
● Assessment of exocrine and endocrine function.
● Pain assessment in terms of severity and opioid
dependence.
● Assessment of nutritional,medical and psycho-social
comorbidities. 92

93. Resection Procedures
1. Whipples pancreaticoduodenectomy
2. Pylorus preserving pancreaticoduodenectomy
(Traverso Longmire)
3. Duodenum preserving pancreatic head resection
(Beger procedure)
4. Distal pancreatectomy
5.Total pancreatectomy with islet cell autotransplantation
93

94. WHIPPLES PANCREATICO DUODENECTOMY
Whipples pancreatico Duodenectomy involves
resection of pancreatic head along with
 entire duodenum
 distal third of stomach
 bile duct
 proximal jejunum
• Benefit of resection of unrecognized adenocarcinoma in
pancreatic head mass
• Address the patients with duodenal and distal bile duct
stricture
94

95. Whipple’s
95

96. Classical PD associated with
 nutritional sequelae
 new onset diabetis mellitus
 exocrine insufficiency
96

97. PYLORUS PRESERVING PANCREATICO
DUODENECTOMY
● PPPD does not requires removal of the stomach
● Preferred procedure over classical PD
97

98. BEGER’S DUODENUM PRESERVING PANCREATIC HEAD
RESECTION
– Division of the neck overlying the confluence of the
splenic and superior mesenteric veins + Removal of the
head of the pancreas,
– leaving a small rim of pancreatic tissue along the
duodenum
– Reconstruction with pancreatic duct and bileduct
anastomosis
– Maintain GI and biliary continuity
– Better long term outcomes
98

99. 99

100. Distal pancreatectomy
– Isolated involvement of body and tail
– With or without splenectomy
– Stump closure by sutures or stapler application or by
creating a Roux-en-Y pancreatojejunostomy
– Post-operative outcome is similar in both groups
– Drainage procedure should be reserved for patients with a
dilated duct and/or a stricture in the pancreatic head
Major portion of parenchyma remains untreated
High risk of recurrence
Requirement of completion pancreatectomy in 13%
100

101. Distal pancreatectomy
101

102. Total pancreatectomy
• Leaving thin rim of tissue over the duodenum to maintain
entero duodenal axis ,preserve intrapancreatic portion of
bile duct
– For persistence or recurrent pain
– Extended hospitalisation due to poor diabetes control
– Profound metabolic consequences in absence of islet
transplantation
– Outcomes identical with Whipple’s pancreaticoduodenectomy
102

103. Total pancreatectomy
103

104. TP + Islet cell auto transplantation
104

105. Drainage procedures
1. Duval’s procedure
2. Puestow-Gillesby procedure
3. Modified Puestow or Partington-Rochelle Lateral
Pancreatico Jejunostomy
105

106. Drainage procedures
Duval’s caudal pancreaticojejunostomy
– Drainage of the tail with a Roux-
en-Y limb of jejunum
– Not effective for disease in the
proximal pancreas
106

107. PUESTOW AND GILLESBY'S LONGITUDINAL
PANCREATICOJEJUNOSTOMY
– Longitudinal decompression
of the body and tail of the
pancreas into a Roux en Y
limb of jejunum
– Provides lager drainage of the
ducts in body and tail .
– Initially described in
conjunction with splenectomy
and the distal pancreatectomy
107

108. PARTINGTON’S LATERAL
PANCREATICOJEJUNOSTOMY (LPJ)
 Duct exposed by longitudinal incision
over anterior surface.
 Side to side anastomosis with jejunum
 No distal pancreatectomy and
splenectomy
Advantage of decompressing pancreatic
duct in the head.
108

109. HYBRID PROCEDURES
1. Frey’s procedure ( Head coring and drainage )
2. Hamburg modification ( IZBICKI procedure )
3. Berne modification
109

110. Frey’s Procedure
● The whole duct is laid widely
open
● Tissue anterior to the duct is
removed to ‘saucerize’the
head of the gland.
● Roux loop of jejunum is laid on
the exposed pancreas
● No neck dissection
110

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112. 112

113. 113

114. Hamburg Modification of Frey’s
/IZBICKI procedure
114

115. BERN’S MODIFICATION
• Bern Modification of DPPHR
– Pancreas is not divided at level
of portal vein
– Useful in significant
inflammation and PHTN
– Less intra-operative bleeding
– Equal outcome compare to Beger’s
procedure
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117. Denervation procedures
Thoracoscopic splanchnicectomy
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119. 119

120. RECAP OF
SURGICAL
PROCEDURES
120

121. Intrapancreatic complications
Pseudocysts
Duodenal or gastric obstruction
Thrombosis of splenic vein
Abscess
Perforation
Erosion into visceral artery
Inflammatory mass
Bile duct stenosis
Portal vein thrombosis
Duodenal obstruction
Duct strictures and/or stones
Ductal hypertension and dilatation
Pancreatic carcinoma
121

122. Extrapancreatic complications
Pancreatic duct leak with ascites or fistula
Pseudocyst extension beyond lesser sac into
mediastinum, retroperitoneum, lateral pericolic spaces,
pelvis, or adjacent viscera
122

123. complications
Formation of mass in the head of pancreas (30 -50%)
Biliary obstruction (30%)
Duodenal obstruction (5-7%)
Porto mesenteric compression (8 -10%)
Splenic vein thrombosis ( 3 -5%)
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124. 124

125. Conclusion
– Pain relief and quality of life - main concern in
treatment of chronic pancreatitis
– Surgery is indicated for relief of intractable pain
and complications associated with CP
– Timing of surgery should be individualized on a
patient to patient basis. Mostly, earlier the
better.
125

126. SUMMARY
● TIGAR-0 , CHIARI CLASSIFICATION
● Pancreatic Stellate Cells Activation
● Fibrosis- Pain- Exocrine And Endocrine insufficiency-
Complications
● ABC grading of Clinical Symptoms
● “Chain of Lakes”
● Izbicki Pain Score -Pain Management
● PERT
● Resection Procedures - PANCREATECTOMIES,
WHIPPLE , BEGAR ,FREY , BERN,, IZBICKI
● Decompression Procedures – DUVAL, PUESTOW,
PARTINGTON ROCHELLE
126

127. REFERENCES
● SABISTON 21ST edition,
● SCHWARTZ 10TH edition,
● MAINGOT 13TH edition,
● FISCHER’S MASTERY IN SURGERY 6TH edition,
● MASTER TECHNIQUES IN SURGERY:
HEPATOBILIARY AND PANCREATIC SURGERY
● BLUMGART 5th edition,
● SHACKELFORD 8th edition,
● THE PANCREAS An Integrated Textbook of Basic
Science, Medicine, and Surgery 3rd edition,
● Various journals.
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