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Please, silence your pagers
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Yaroslavl, Russia (EST. 1010)
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PancreatitisNew in Diagnosis and Treatment

• Boris V. Vinogradsky, MDDepartment of
  SurgeryMedical College of OhioToledo, Ohio
• March 03, 2001

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Theodor Kocher called the pancreas the mischief
maker of the abdomen. Some surgeons have
stronger language to describe this organ, but
decorum demands that such a language be excluded
from such a syllabus.
J.Patrick OLeary, MD
5
Pancreatitis Classification

• Acute Pancreatitis
• Interstitial edematous pancreatitis
• Sterile necrotizing pancreatitis
• Infected pancreatic necrosis/abscess
  Hemorrhagic pancreatitis
• Chronic Pancreatitis
• Uncomplicated recurrent pancreatitis
• Calcifying chronic pancreatitis
• Obstructive chronic pancreatitis

6
Pancreatitis

• Pancreatitis is a complex disorder of the
  exocrine pancreas with unclear pathogenic
  mechanisms, which is characterized by acute
  acinar cell injury and both regional and systemic
  inflammatory responses.
• Overall mortality 6.0-20.5
• Acute necrotizing pancreatitis 50
• No specific treatment

7
Normal Pancreatic Physiology

• The pancreas secretes 500-800 ml/day of an
  alkaline, colorless, odorless, isosmotic fluid
  containing large quantity of bicarbonate and
  digestive enzymes
• Stimulated by secretin, duodenal pH of less than
  4.0
• Vagal stimulation through acetylcholine
• Inhibited by truncal vagotomy, atropine

8
Normal Release of Pancreatic Enzymes
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
9
Normal Pancreatic Physiology

• Enzymes are NOT secreted at a fixed ratio,
  specific nutrients can cause a relative increase
  of one of the fractions
• CCK is the primary regulator of enzymes secretion
• Ca and diacylglycerol are second messengers

Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
10
Normal Release of Pancreatic Enzymes
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
11
Pancreatic Enzymes

• Pancreatic enzymes
• Amylase Active
• Proteolytic enzymes Inactive
• Lipases Inactive
• Inhibitors
• Alpha1-antitrypsin
• Beta2-macroglobulin
• Pancreatic secretory trypsin inhibitor

12
Normal Pancreatic Physiology

• Proteolytic proenzymes such as trypsinogen
  convert to active form under the influence of
  ENTEROKINASE,
• luminal HCl and spontaneously

13
Causes of Acute Pancreatitis
Most common Ethanol abuse Cholelithiasis Less
common ERCP Trauma Hyperlipidemia (types I, IV
and V) Pancreas divisum Least common Familial Id
iopathic Drugs
Baron TH, Morgan DE. Acute Necrotizing
Pancreatitis, NEJM, 1999
14
Initial triggering event in development of acute
pancreatitis is DUCTAL HYPERTENSION
15

• Ethanol use is the most common cause of acute
  pancreatitis in the United States

16
Alcohol in Acute Pancreatitis

• Acetaldehyde formation
• Microtubular disruption
• Increase in acinar cell membrane permeability
• Elevated triglycerides level
• Formation of cytotoxic free fatty acids
• Increased HCl production stimulates secretin
  release and increases pancreatic ductal flow
• Elevation of pancreatic intraductular pressure

17
Protein Stones Formation
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
18
Gallstones in Acute Pancreatitis

• Simple cholelithiasis 72 of patients
  Choledocholithiasis 20
• Cholecystitis 8
• Stool screening 85-94 patients
• for stones within 10 days of onset of
  disease
• (late Dr.Kelly from
• Akron, OH)

Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
19
Common Channel Concept
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
20
Acute Pancreatitis

• Fundamental pathologic event is injury to acinar
  cell
• Process begins within minutes

21
Acute Pancreatitis Pathogenesis

• Autophagic cytoplasmic vacuoles (zymogen lakes)
  formation
• Elevated levels of TNF-alpha, IL-1, IL-6
• Hypoxia
• Loss of normal cell polarity
• Basolateral disordered discharge

Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
22
Acute Pancreatitis Initiation
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
23
Acute Pancreatitis Pathology
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
24
Acute Pancreatitis Pathogenesis
Microvascular endothelial cell injury in multiple
target organs
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
25
Changes in Lung Alveoli
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
26
Shifting Gears
27
Yaroslavl Medical School Class of 1986
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Russia
Yahoo!Maps - Europe, Russia, 2001
29

• Cardinal symptom of acute pancreatitis is
  epigastric abdominal
• PAIN

30
Symptoms and Signs

• Abdominal pain 85-100
• Nausea and vomiting 55-90
• Anorexia 80
• Tachicardia 65-80
• Fever 12-80
• Ileus 50-80
• Abdominal tenderness/mass 90-99
• All non-specific

Baron TH, Morgan DE. Acute Necrotizing
Pancreatitis, NEJM, 1999
31
Other Signs

• Grey-Turner sign
• Cullen sign
• Fox sign
• All non-specific and present in less than 20 of
  patients

32
Hyperamylasemia

• Salivary gland injury
• Burns
• Small bowel injury
• Cerebral trauma
• Multiple trauma
• Diabetic ketoacidosis
• Macroamylasemia
• Renal failure/transplantation
• Pregnancy
• Dissecting aortic aneurysm

Larvin M, McMahon MJ. APACHE II score for
assessment and monitoring of acute pancreatitis.
Lancet 1989 2 738
33

• CT scanning is the BEST imaging study in
  evaluation of acute pancreatitis

34
Acute Pancreatitis CT Scanning
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
35
Acute Fluid Collection
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
36
Ultrasound of the Pancreas
Staren ED. Ultrasound for the Surgeon, 1997
37
Ransons Criteria

• On admission
• Age 55 years
• WBC 16,000
• Glucose 200
• LDH 350
• AST 250
• After 48 hours
• Drop in Hct 10
• Increase in BUN 5
• Ca
• Arterial PaO2
• Base deficit 4
• Fluid deficit 6 L
• Total Ranson score of 3 or more indicates severe
  acute pancreatitis
• Banks PA, AJG, Vol..92, No.3, 1997

38
APACHE-II

• A Total Acute Physiology Score
• Temperature (Rectal)
• MAP (mmHg)
• Heart rate
• Respiratory Rate
• Oxygenation (PaO2 - mmHg)
• Serum Na, K, Cre, Hct, WBC
• Glasgow Coma Score
• B Age points
• C Chronic health points
• Total APACHE II score of 8 or more indicates
  severe acute pancreatitis
• Banks PA, AJG, Vol..92, No.3, 1997

39
Acute Pancreatitis Complications

• Early
• Systemic Local
• ARDS GI bleeding
• ARF Adjacent bowel necrosis/fistula
  Hypocalcemia formation
• Shock Hydronephrosis
• Coagulopathy Splenic rupture or hematoma
• Hyperglycemia Splenic vein thrombosis Infecte
  d necrosis/abscess

Steinberg et al., Acute Pancreatitis, NEJM, 1994
40
Acute Pancreatitis Complications
Late Pseudocyst (1-4) Duct obstruction Endocrine
insufficiency Diabetes
Steinberg et al., Acute Pancreatitis, NEJM, 1994
41
Acute Pancreatic Necrosis

• Acute necrotizing pancreatitis - process when one
  or more diffuse or focal areas of nonviable
  pancreatic parenchyma are present.
• The International Symposium on Acute
  Pancreatitis, 1992
• Present in 20-30 of the 185,000 new cases of
  acute pancreatitis per year in the United States
• Pancreatic glandular necrosis usually associated
  with necrosis of peripancreatic fat

Beger HG et al. Natural course of acute
pancreatitis. World J Surgery 1997
42
Acute Pancreatic Necrosis

• Acute necrotizing pancreatitis - affected
  portions do not show normal contrast enhancement
• Contrast-enhanced dynamic CT scanning - GOLD
  standard (accuracy 90 if more than 30 of the
  gland is affected)
• Patients with necrosis have 82 morbidity and 23
  mortality
• Patients without 6 and 0

Beger HG et al. Natural course of acute
pancreatitis. World J Surgery 1997
43
Pancreatic Abscess
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
44
Infected Pancreatic Necrosis
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
45
Acute Pancreatic Necrosis

• Infected necrosis develops in 30-70 of patients
  with acute necrotizing pancreatitis and accounts
  for more than 80 of deaths from acute
  pancreatitis
• Deaths occur in two phases
• Early - 1-2 weeks due to multisystem organ
  failure due to release of inflammatory mediators
  and cytokines
• Late - due to systemic infections
• Sterile necrosis mortality - 10

Rau B et al.. Surgical treatment of infected
necrosis. World J Surgery 1997
46
Sterile Pancreatic Necrosis
Lived (n16) Died (n10) Ransons
Score 4.6 /- 0.4 6.3 /- 0.5 APACHE II,
adm. 6.9 /- 0.8 13.0 /- 2.5 APACHE II, 48
hrs 8.9 /- 1.1 16.5 /- 3.0 No. of
complications 2.2 /- 0.2 3.6 /-
0.3 Shock 12.5 90.0 Renal failure
50.0 90.0 BMI 25.2 /- 0.9 28.9 /- 1.0

- Severe disease with systemic complications
Karimgani I et al. Prognostic Factors in Sterile
Pancreatic Necrosis Gastroenterology 1992 103
1636-40
47
Pancreatic Necrosis CTSI
Acute pancreatitis Groups A-E - 0-4
points Necrosis 50 - 6
points

Balthazar EJ et al. Imaging and Intervention in
Acute Pancreatitis Radiology1994 193297-306
48
General Treatment Issues
Patients need to be placed in intensive care
environment with constant monitoring Aggressive
fluid resuscitation Nasogastric suction is
appropriate in patients with ileus and vomiting
for symptomatic relief Administration of
Imipenem-Cilastatin is recommended. Start as
soon as the diagnosis is made and continued for
2-4 weeks.
49
Pancreatic Necrosis Antibiotics

• Foitzik et al.Pathogenesis and prevention of
  early pancreatic infection, Ann Surg, 1995

50
ERCP
Kelly and Wagner randomly assigned patients with
gallstone-induced pancreatitis to early (hours) or late (48 hours) surgery/ERCP - 12
and 48 mortality Neoptolemos (England) showed
lower morbidity 24 vs. 64 in group with ERCP
vs. conventional treatment ERCP within 24 hours
of admission reduced the incidence of biliary
sepsis, but it only benefited severely ill
patients and while reducing morbidity, it did
not change mortality.
Neoptolemos JP et al.,Controlled Trial of Urgent
ERCP, Lancet, 1988 Fan S-T et al.,Early Treatment
of Acute Biliary Pancreatitis, NEJM, 1993
51
Interventions for Pancreatic Necrosis
Aggressive surgical pancreatic debridment
(necrosectomy) is the standard of care if
drainage is undertaken and may require multiple
abdominal operations. Two options for
laparotomy Debridement with wide sump
drainage Debridement with open packing Overall
mortality with closed or open techniques is
approximately 20
Rau B et al.. Surgical treatment of infected
necrosis. World J Surgery 1997
52
Acute Pancreatitis Necrosectomy
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
53
Acute Pancreatic Necrosis
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
54
Acute Pancreatic Necrosis
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
55
Surgical Debridement
I do not know if this those operations extended
life of the patient, but they definitely
shortened mine. Unknown surgeon
56
Alternative Methods of Debridement
Percutaneous Therapy (Interventional
radiology) Endoscopic Therapy Peritoneal lavage
(closed technique) Great technical expertise
required Team approach is necessary Combination
of methods can be used
Rattner DW et al.Early surgical debridement of
symptomatic pancreatic necrosis is beneficial
irrespective of infection. Am J Surgery, 1992
57
Nutritional Support
Total enteral nutrition delivered through a
JEJUNAL feeding tube is preferable in patients
with AP in the absence of substantial ileus and
can be started within first 48 hours of onset of
illness. It is well tolerated, cheaper, less
total risk and a lower risk of developing
infectious complications.
McClave SA et al. Clinical nutrition in
acutepancreatitis. Dig Dis Sci, 1997
58
Chronic Pancreatitis

• Treatment of Complications
• Pain
• Abstinence
• Enzyme replacement
• Endoscopic therapy
• Analgesics
• Surgical treatment
• Puestow procedure
• Pancreatic resection
• Malabsorption
• Biliary complications

59
Chronic Pancreatitis
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
60
Chronic Pancreatitis

• Intractable pain is the most frequent indication
  for operation in patients with chronic
  pancreatitis

61
Chronic Pancreatitis Imaging
Sensitivity Specificity Ultrasound 60 80-90
CT scan 75-90 85 ERCP 90 90 KUB -
the simplest confirmatory test for chronic
pancreatitis
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
62
Pancreatic Calcifications
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
63
Pancreatic Calcifications
Chronic Pancreatitis, University of Illinois at
C-U Pathology Library, 2000
64
Pancreatic Calcifications
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
65
Main Duct Dilation
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
66
Main Duct Disruption
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
67
Distal Stricture of the CBD
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
68
Pancreatic Pseudocyst
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
69
Compression of the CBD
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
70
Duodenal Compression
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
71
Chronic Pancreatitis Inhibition
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
72
Enzymes Replacement

• Lipase Content
• Pancreatine 8000
• Liozyme 3600
• Ku-Zyme HP 2300
• Cotazyme-S 2000
• Pancrease 4500
• Viocase 3800

Physicians Desk Reference, 2001
73
Indications for Surgical Treatment

• Substantial interference with quality of life
• Interruption of employment
• Nutritional incapacitation
• Narcotic addiction

74
Puestow Procedure
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
75
Puestow Procedure
Zollinger RM. Atlas of Surgical Operations, 1993
76
Pseudocyst Drainage
Zollinger RM. Atlas of Surgical Operations, 1993
77
Pancreaticoduodenostomy
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
78
Main Duct Disruption - Ascitis
Lillemoe KD, Yeo CJ Management of Complications
of Pancreatitis, 1998
79
Pain Relief After Surgical Treatment

• Immediate Long-term
• Puestow Procedure 80 65-70
• Distal pancreatectomy 80
• Whipple operation 70-90 80

Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
80
Chronic Pancreatitis Pain Relief
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
81
Biliary Duct Stenosis
Operative indications Persistent
jaundice Cholangitis Evidence of developing
cyrrhosis on biopsy Inability to exclude
pancreatic cancer Progressive strictures of
biliary ducts Persistent elevation of alkaline
phosphatase
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
82
Biliary Duct Stenosis
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
83
Chronic Pancreatitis Survival
Greenfield LJ. Surgery Scientific Principles and
Practice, 1997
84
Conclusions
1. Aggressive critical care with antibiotics,
pain control, fluid resuscitation and nutrition
is the mainstay of management of acute
necrotizing pancreatitis, with surgery or other
types of debridement limited to patients with
infected necrosis. 2. Hyperamylasemia, if
present, probably, indicates acute
pancreatitis, if absent it proves nothing. 3.
Ultrasound should be used within first 24 hours
of admission. Look for gallstones. 4. ERCP is
neither required for diagnosis, nor provides
prognostic information. It is needed urgently
in patients with gallstones.
85
Conclusions
5. Pseudocysts. Asymptomatic require no
treatment. Symptomatic can be decompressed by
surgical (open or endoscopic) and radiologic
methods. Consider timing. 6. 7. 8. DO NOT
DRINK !!!
86
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87
(No Transcript)
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  17 173-80.
• 59. Kingsnorth AN, Galloway SW, Formela LJ.
  Randomized, double-blind phase II trial of
  Lexipafant, a platelet-activating factor
  antagonist, in human acute pancreatitis. Br J
  Surgery 1995 82 1414-20.
• 60. Kingsnorth AN. Early treatment with
  Lexipafant, a platelet-activating factor
  antagonist, reduces mortality in acute
  pancreatitis a double-blind, randomized,
  placebo-controlled study. Gastroenterology 1997
  112 .

95
Pancreatic Anatomy and Physiology

• Anatomy
• Ventral and dorsal appendages
• Tail of the pancreas - spleen, lienorenal
  ligament and left colic flexure
• Pancreas divisum
• Duodenum and the head of the pancreas share
  vascular supply - must be resected together
• All venous blood drains in to the portal vein
• Safe dissection - anterior to the portal vein
• Predominant lymphatic drainage
• Absence of peritoneal barrier posteriorly

96
Acute Pancreatitis

• Incidence 0.14-1.3
• Patients age and gender
• Alcohol-induced 30-40 (younger)
• Men Women
• Gallstone-induced 40-60 (older)
• Women Men

97
Acute Pancreatitis

• Pathology
• Pathophysiology
• Clinical features
• Incidence and demographics
• Etiology and clinical associations
• Biliary tract stone disease
• Ethanol
• Postprocedural pancreatitis
• Trauma
• Hyperlipoproteinemia
• Hyperparathyroidism
• Drugs
• Infections
• Vascular disease
• Immunologic factors
• Obstruction of the duodenum or pancreatic duct

98
Acute Pancreatitis

• Management
• Medical treatment
• Surgery

99
Acute Pancreatitis

• Pancreatic pseudocysts
• Abscess

100
Chronic Pancreatitis

• Classification
• Incidence
• Causes
• Alcohol consumption
• Heredity
• Hyperparathyroidism
• Tropical pancreatitis
• Duct obstruction
• Idiopathic

101
Chronic Pancreatitis

• Pathogenesis
• Clinical presentation
• Pain
• Malabsorption and weight loss
• Endocrine Insufficiency

102
Chronic Pancreatitis

• Diagnosis
• Routine laboratory tests
• Tests of Pancreatic Exocrine Function
• Imaging studies

103
Bile
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
104
Bile
Howard JM Surgical Diseases of the Pancreas, 3rd
Edition, 1998
105
Drugs in Acute Pancreatitis

• Steroids
• Diuretics
• Calcium
• Coumadin
• Quinidine

• Cimetidine
• Imuran
• Acetaminophen
• Sulfonamides
• Tetracycline
• Clonidine

106
Management of Infection
MORTALITY 96 HOURS AFTER INDUCTION OF ACUTE
NECROTIZING PANCREATITIS AND TREATMENT
WITH DIFFERENT REGIMENS OF ORAL AND/OR
INTRAVENOUS ANTIBIOTICS Group No Mortality
I Control 24 42 II PTA 21 33 III
CEF 22 36 IV PTACEF 20 30 V
IMI 21 33
At the present time administration of
Imipenem-Cilastatin is recommended. Start as
soon as the diagnosis is made and continue for
2-4 weeks.
Foitzik et al.,Pathogenesis and Prevention of
Early Pancreatic Infection, 1995
107
Pancreatic Necrosis Aspiration
Gerzof CG et al, Early Diagnosis of Infection by
CT-guided aspiration, 1987
108
Results of Controlled Trials of Therapies for
Acute Pancreatitis
TREATMENT PROPOSED MECHANISM STUDIES
REFERENCE Nasogastric suction Decreases
pancreatic secretion 0/3
Levant, Naeije H2 blocker 0/3 Loiudice,
Broe Atropine 0/1
Cameron Fluorouracil Decreases pancreatic
secretion 0/1 Sai Somatostatin
0/2
Usadel, Choi Calcitonin
0/1 Goebell
Indomethacin Reduces
prostagiandin levels 0/1
Foulis Ampicillin
Prevent infection 0/3 Finch, Craig
lmipenem 1/1
Pederzoli Aprotinin
Inhibits proteases 1/6 Innic,
Trapnell Fresh-frozen plasma
0/1 Leese Parenteral nutrition
Decreases pancreatic secretion
Provides nutritional requirements
0/1 Sax Peritoneal lavage Removes
toxic factors 1/4 Ranson
Gallstone surgery Removes
obstructing gallstone 0/2
Kelly and Wagner ERCP
2/2 Fan,
Neoptolemos Pancreatic resection Removes
necrotic tissue 0/2
Kivilaakso, Schroeder
Steinberg et al., Acute Pancreatitis, NEJM, 1994
109
Interventions for Pancreatic Necrosis
110
Future Medical Therapies
111
Shifting Gears
112
Long-Term Sequelae