pancreatic diseases

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Pancreatic Diseases

• Dr Ngemera Johannes A
• MD (HKMU), Mmed Int. Medicine (MUHAS)
• July 10th, 2023

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OUTLINE

• Anatomy and Physiology of the Pancreas
• Pancreatic autodigestion
• Pancreatitis (Acute and Chronic )
• Definition
• Etiology
• Pathogenesis
• Types
• Epidemiology
• Clinical manifestation
• Complications
• Severity assessment
• Diagnosis
• Differential diagnosis
• Management
• Pancreatic malignancies

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Pancreas - Anatomy
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Pancreas - Anatomy

• Retroperitoneal organ in the upper abdomen
• Measuring about 15-20cm in length
• Parts
• Head
• Neck
• Body and
• Tail
• Uncinate process
• curves behind the superior mesenteric vessels

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Pancreas Physiology

• Exocrine - (80 of the pancreatic mass) -
  Pancreatic juice
• Digestive enzymes
• Fluid and electrolytes, particularly bicarbonate
• Endocrine - (1 2 of the pancreatic mass)
• Islets of Langerhans
• Insulin (ß cells)
• Glucagon (? cells)
• Somatostatin (d-cell),and
• Gastrin (G-cells)
• Ductal system about 18 of Pancreatic mass

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Exocrine Pancreas

• Pancreas secretes about 20 digestive enzymes
• Amylolytic
• Lipolytic, and
• Proteolytic enzymes.
• Packaged in zymogen granules in inactive
  pro-enzyme forms, except for amylase and lipase.
• Activated in intestinal lumen for digestion of
  proteins, carbohydrates, fat and nucleic acids.
• The pancreas has a great capacity to secrete
  these enzymes,
• At least 90 of the gland has to be destroyed
  before clinically significant mal-digestion is
  observed.

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Pancreatic Enzymes

• Amylolytic enzymes
• Amylase - hydrolyze starch to oligosaccharides
  and to the disaccharide maltose.
• Lipolytic enzymes
• lipase, phospholipase A2 and cholesterol esterase
• Proteolytic enzymes
• Endopeptidases and Exopeptidases -
• secreted as inactive precursors and packaged as
  zymogens.
• Enterokinase, an enzyme found in the duodenal
  mucosa, cleaves the lysine-isoleucine bond of
  trypsinogen to form trypsin.
• Trypsin then activates the other proteolytic
  zymogens in a cascade phenomenon.

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Pancreas - Bicarbonate Secretion

• Neutralize the acidic (pH lt 2) gastric chyme
  entering the duodenum to a pH level (gt 6)
  optimal for enzymatic digestion
• The ductal and centroacinar cells secrete about
  12 L/day of pancreatic juice.
• The pancreatic juice is isotonic (pH of 89).

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Autodigestion of the Pancreas

• Prevented by
• Packaging of pancreatic proteases in precursor
  form and
• Synthesis of protease inhibitor which can bind
  and inactivate about 20 of trypsin activity.
• Pancreatic secretory trypsin inhibitor (PSTI) or
  SPINK1,
• These protease inhibitors are found in
• the acinar cell,
• the pancreatic secretions,
• the a 1 and a 2 globulin fractions of plasma.
• Loss of any of these protective mechanisms leads
  to zymogen activation, autodigestion, and acute
  pancreatitis.

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Acute Pancreatitis

• acute inflammatory process of the pancreas
• Highly variable(mild self limiting to severe with
  risk of death)
• Oedematous pancreatitis -mild and self-limited
  disorder
• Necrotizing pancreatitis - necrosis correlates
  with the severity of the attack and its systemic
  manifestations.

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AETIOLOGY OF ACUTE PANCREATITIS
Remember this ? I GET SMASHED

• Scorpion sting
• Microbiological
• Autoimmune
• Surgery or trauma
• Hyperlipidemia 
• Emboli or ischemia
• Drugs or toxins

• Idiopathic
• Gallstones
• Ethanol
• Tumours

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AETIOLOGY OF ACUTE PANCREATITIS
Remember this ? I GET SMASHED

• Idiopathic ??Hypertensive sphincter or
  microlithiasis
• Gallstones (45)
• Ethanol (35)
• Tumors Pancreas, Ampulla, Choledochocele
• Scorpion stings
• Microbiological
• Viral Mumps, Rubella, Varicella, Viral
  hepatitis, CMV, EBV, HIV, Coxsackie virus,
  Adenovirus
• Bacteria Mycoplasma, Campylobacter, TB,
  Leptospirosis
• Parasites Ascariasis, Clonorchiasis,
  Echinococcosis

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AETIOLOGY OF ACUTE PANCREATITIS

• Autoimmune SLE, Crohns diseaseSurgery or
  trauma
• Manipulated sphincter of Oddi (ERCP), Blunt
  trauma to abdomen, Penetrating peptic ulcer
• Hyperlipidemia  (TG gt11.3 mmol/L gt1000mg/dL).
  Hypercalcemia, Hypothermia
• Emboli or ischemiaDrugs or toxins
• Azathioprine, Mercaptopurine, Furosemide,
  Estrogen, Methyldopa, H2blockers, Valproic acid,
  Antibiotics, Acetaminophen, Salicylates,
  Methanol, Organophosphates, Steroids

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Pathophysiology of Acute Pancreatitis
?proteolytic enzymes release and ?antiproteolytic
factors
Premature activation of zymogen granules
Protease enzymes release
Autodigestion of the Pancreas
Involvement of adjacent structures
Acute Pancreatitis
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Pathogenesis of Acute Pancreatitis

• The anatomic changes due to
• Pancreatic Duct obstruction Gallstone, Tumor,
  etc
• Primary acinar cell damage Microbes, Drugs,
  Direct trauma, alcohol
• Defective Intracellular transport of proenzymes
  within acinar cells
• Causes inappropriately activated pancreatic
  enzymes
• Trypsinogen ? trypsin
• Trypsin activates other proenzymes
• Leading to Auto-digestion of the pancreatic
  substance

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Pathogenesis of Acute Pancreatitis

• Pancreatic Duct Obstruction leads to
• ? intra-pancreatic ductal Pressure ? Accumulation
  of an enzyme rich interstitial fluid ? local fat
  necrosis ? lipase released
• Leucocytes ? pro-inflammatory Cytokines ?
  interstial oedema ? ?Local Blood Flow ?Ischaemic
  injury to acinar cells ? Necrosis

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Pathogenesis of Acute Pancreatitis

• The activated enzymes digest the pancreatic
  substances which cause
• Disintegration of fat cells
• Damage elastic fibers of blood vessels
• Trypsin converts Pre-Kallikrein to Kallikrein ?
  Kinin system which activates
• Hageman factor
• The clotting and
• Compliment system

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Pathogenesis of Acute Pancreatitis

• Activated proteolytic enzymes digest cellular
  membranes within pancreas and cause
• edema,
• interstitial hemorrhage,
• vascular damage,
• coagulation and cellular necrosis.
• This can lead to extension of localized process
  into generalized systemic inflammatory response
  leading to shock, ARDS, Multi-organ system
  failure

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Pathogenesis of Acute Pancreatitis

• 5 alcohol abusers develop pancreatitis.
• 75-85 self limited inflammation within days to
  weeks.
• 15-25 severe course with local and systemic
  complications and risk of death.
• Mortality 3-5

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Types of Acute Pancreatitis

• Pathological type
• Acute edematic pancreatitis
• Acute hemorrhgic and necrotic pancreatitis
  (AHNP)
• Clinical type
• Mild Acute pancreatitis (MAP)
• Severe Acute pancreatitis (SAP)
• Fulminant Acute pancreatitis (FAP)
• 
  

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Epidemiology

• Worldwide incidence 5 to 80 per 100,000
  population
• 3 of all causes of hospital abdominal pain
• Age-related demographics
• Alcohol-related - 39 years
• Biliary tractrelated - 69 years
• Trauma-related - 66 years
• Drug-induced etiology - 42 years
• ERCP-related - 58 years
• AIDS-related - 31 years
• Vasculitis-related - 36 years
• Sex-related demographics male gt Female
• In males ? alcohol
• In females ? biliary tract disease

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Clinical features

• Abdominal pain (95)
• mild and tolerable discomfort to severe,
  constant, and incapacitating.
• steady and boring in character,
• located in the epigastrium and periumbilical
  region
• often radiates to the back as well as to the
  chest, flanks, and lower abdomen.
• Worsened by supine position, alcohol or food
• relieved by sitting with the trunk flexed and
  knees drawn up.

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Clinical features

• Nausea
• vomiting and
• abdominal distention
• due to gastric and intestinal hypomotility and
  chemical peritonitis are also frequent
  complaints.

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Clinical features

• Distressed and anxious, Low-grade fever, ?PR, and
  ? BP
• Shock may result from
• hypovolemia secondary to exudation of blood and
  plasma proteins into the retroperitoneal space
• increased formation and release of kinin
  peptides, which cause vasodilatation and
  increased vascular permeability and
• systemic effects of proteolytic and lipolytic
  enzymes released into the circulation.

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Clinical features

• Jaundice occurs infrequently due to edema of the
  head of pancreas with compression of the
  intra-pancreatic portion of the common bile duct.
• Erythematous skin nodules due to subcutaneous fat
  necrosis may occur.
• In 10 to 20 - basilar rales, atelectasis, and
  pleural effusion(frequently left-sided).
• Abdominal tenderness, rebound tenderness and
  muscle rigidity are present to a variable degree
• ? or absent Bowel sounds

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Clinical features

• A pancreatic pseudocyst may be palpable in the
  upper abdomen.
• Cullen's sign - Periumbilical ecchymoses
• Faint blue discoloration around the umbilicus as
  the result of hemoperitoneum
• Grey-Turner's sign - Flank ecchymoses
• Blue-red-purple or green-brown discoloration of
  the flanks reflects tissue catabolism of
  hemoglobin.

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Blue-red-purple or green-brown discoloration of
the flanks reflects tissue catabolism of
hemoglobin
Faint blue discoloration around the umbilicus as
the result of hemoperitoneum
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Complications - Local

• Necrosis Sterile or infected
• Pancreatic abscess
• Pancreatic pseudocyst
• Pain
• Rupture ?Hemorrhage ? infection
• Obstruction of GIT
• stomach, duodenum, colon
• Pancreatic ascites
• Disruption of main pancreatic duct
• Leaking pseudocyst

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Complications - Local

• Involvement of contiguous organs by necrotizing
  pancreatitis
• Massive intraperitoneal hemorrhage
• Thrombosis of blood vessels
• Splenic vein
• Portal vein
• Bowel infarction
• Obstructive jaundice

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Complications - Systemic

• Pulmonary
• Pleural effusion, Atelectasis, ARDS
• Cardiovascular
• ?BP, Hypovolemia, Pericardial effusion,
• Hematologic DIC
• GI hemorrhage
• PUD, Erosive gastritis,
• Hemorrhagic pancreatic necrosis with erosion into
  major blood vessels,
• Portal vein thrombosis,
• variceal hemorrhage

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Complications - Systemic

• Renal
• Oliguria, azotemia, acute tubular necrosis
• Metabolic
• Hyperglycemia, Hypertriglyceridemia, ?Ca2
• CNS
• Encephalopathy, Sudden blindness (Purtscher's
  retinopathy), Fat emboli
• Fat necrosis
• Subcutaneous tissues (erythematous nodules)
• Septicemia
• due to pancreatic necrosis and abscess

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Assessing severity

• Based on age and laboratory parameters computed
  48hrs post admission.
• The higher the risk profile the more prolonged,
  complicated, clinical course.
• Ransons criteria
• Modified Glasgow
• APACHE II(Acute Physiologic and Chronic Health
  Evaluation)
• Atlanta criteria

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Ransons criteria

• During initial 48 h

• At admission or diagnosis

• Age gt55 years
• Leukocytosis gt16,000/ L
• Hyperglycemia gt11 mmol/L (gt200 mg/dL)
• Serum LDH gt 350 IU/L
• Serum AST gt 250 IU/L

• ?hematocrit by gt10 percent
• Fluid deficit of gt 4000 mL
• ?Ca2 lt 1.9 mmol/L (lt8.0 mg/dL)
• Hypoxemia (pO2 lt60 mmHg)
• ?BUN to gt1.8 mmol/L (gt5 mg/dL) after IV fluid
  administration
• Hypoalbuminemia albumin level lt32 g/L (lt3.2
  g/dL)

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Ranson's criteria 

• Ranson's criteria consist of 11 parameters.
• 5 factors are assessed at admission and 6 during
  the next 48 hours
• Mortality increases with an increasing score.
• Using the 11 component score
• Score lt3 ? mortality 0 to 3
• Score 3 ? mortality 11 15
• Score 6 ? mortality 40
• a meta-analysis of 110 studies found the Ranson's
  score to be a poor predictor of severity (De
  Bernardinis M, et al)

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Adverse prognostic factors in acute pancreatitis
(Glasgow criteria)

• Age gt 55 years
• PO2 lt 60 mmHg
• WBC gt 15 109/L
• Albumin lt 32 g/L
• Serum calcium lt 2 mmol/L (8 mg/dL) (corrected)
• Glucose gt 10 mmol/L (180 mg/dL)
• Urea gt 16 mmol/L (45 mg/dL) (after rehydration)
• Alanine aminotransferase (ALT) gt 200 U/L
• Lactate dehydrogenase (LDH) gt 600 U/L
• Severity and prognosis worsen as the number
  of these factors increases.
• More than three implies severe disease.

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Acute physiology and chronic health evaluation
(APACHE II) score

• Hemorrhagic peritoneal fluid
• Obesity BMI gt 29.9
• Key indicators of organ failure
• BP lt90 mmHg, pulse gt130 beats per minute,
• pO2 lt60 mmHg
• Oliguria (lt50 mL/h) or ?BUN and creatinine
• Serum calcium lt1.9 mmol/L (lt8.0 mg/dL)
• serum albumin lt33 g/L (lt 3.2 g/dL)
• Score 0 2 ?2 mortality Score 3 4 ? 15
  mortality
• Score 5 6 ? 40 mortality Score 7 8 ? 100
  mortality

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Diagnosis

• Pancreatic enzymes Amylase and lipase
• Values 3x Upper normal limit is diagnostic if
  other causes are excluded.
• Serum amylase
• ?within 6 to 12 hours of onset, t1/2 10 hrs).
• usually elevated for 3 5 days
• Non specific can be elevated in other conditions
• E.g. Parotitis, Trauma, Surgery, Radiation,
  Intestinal obstruction, Infarction, Renal failure
  , Malignancy with ectopic amylase production
• Urine Amylase

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Diagnosis

• Serum lipase
• may remain elevated for 714 days.
• The sensitivity 85 to 100 (Agarwal N, et al)
• more specific than serum amylase and urinary
  total amylase in diagnostic accuracy

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Other Laboratory Investigations

• FBP
• Serum electrolytes Ca2
• RBG
• Lipid Profile, Renal profile
• Liver Function Test
• ALP, total bilirubin, AST, ALT ? gallstone
  pancreatitis.
• ALT gt 150 U/L ? gallstone pancreatitis and a more
  fulminant disease course.
• Diagnostic paracentesis

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Radiology

• Done to find the causes and exclude other causes
  of Acute abdomen
• Abdominal Ultrasound
• Plain Abdominal X-ray
• Abdominal CT Scan or MRI

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Differential diagnosis

• Perforated viscus especially peptic ulcer
• acute cholecystitis and biliary colic
• acute intestinal obstruction
• mesenteric vascular occlusion
• renal colic
• myocardial infarction
• dissecting aortic aneurysm
• pneumonia and
• diabetic ketoacidosis.

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Guidelines

• Atlanta
• British Society of Gastroenterology
• American College of Gastroenterology
• International Association of Pancreas
• Santorini Conference
• World Congress of Gastroenterology

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Risk Stratification

• Mild cases general ward
• Severe cases Always in ICU setting
• Strategy tailoring according to
• Severity
• Risk factors (e.g age, obesity)
• Presence of SIRS
• Routine lab values(Hct, Ser.creatinine )
• NONOPERATIVE MANAGEMENT IS THE MAINSTAY

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Principles of Management

• Fluid resuscitation
• Nutritional Support
• Symptomatic Treatment
• Management of Metabolic Complications
• Prophylactic Antibiotic Coverage
• Monitoring and Reassessment
• Role of ERCP
• Role of surgery

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Fluid resuscitation

• Approach
• Aggressive fluid resuscitation
• Amount of fluid required
• (250-500) ml/hr acc. to AGC guidelines or
• (5-10) ml/kg/hr acc. to IAP guidelines
• In severe volume depletion
• 20ml/kg over 30 min followed by 3ml/kg/hr for
  (8-12) hrs
• Ideal fluid Isotonic crystalloids RINGER
  LACTATE

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Fluid resuscitation

• Goal  
• Reduction in BUN
• IAP suggested resuscitation goals
• HR lt 120 bpm
• MAP ( 65-85 )mm of Hg
• Urine output gt ( 0.5-1) ml/kg/hr
• Hematocrit ( 35-44 ) ( one of the best
  indicators of survival )
• EXCEPTIONS Pre-existing CARDIOVASCULAR and
  RENAL comorbidities
• Importance
• Prevention of acute pancreatitis induced
  hypovolaemic shock Inadequate resuscitation
  increased chance of necrosis Most beneficial
  over first 12-24 hrs

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Nutritional Support

• Different  school of thoughts
• Continue oral feeding
• Nil per oral
• Nasojejunal tube feeding
• Nasogastric tube feeding
• Total parenteral nutrition

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1. Oral feeding

• continuation of oral feeding may not be possible
  due to
• Aggravasion of pain after oral intake
• Nausea and recurrent vomiting
• Preexisting abdominal distension caused by ileus
• In mild AP, oral feedings can be started
  immediately if
• There is no nausea and vomiting, and Abdominal
  pain has resolved
• In mild AP, initiation of feeding with a low-fat
  solid diet appears as safe as a clear liquid diet
  (Level II evidence)

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2. Nil per oral

• The traditional school of thought
• Rationale for
• Avoidance of oral intake prevents stimulation of
  exocrine pancreatic functions, hence Pancreatic
  rest
• Patient often unable to retain oral feed.
• Ileus resulting from pancreatitis.
• Rationale against
• Acute pancreatitis inflammatory stress
• Prolonged avoidance of enteral feeding ? altered
  gut mucosal integrity ? increased chance of
  infection.

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3. Total Parenteral Nutrition

• Rationale for
• Maintenance of proper nutrition avoiding
  gastrointestinal complications
• Rationale against
• Increased chance of altered gut mucosal integrity
  
• Acts as a portal for introduction of additional
  infection
• Increased expenses

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4. Nasogastric and 5. Nasojejunal Tube Feeding

• Maintenance of Nutrition Enterally avoiding the
  gastrointestinal complications Of both NPM and
  TPN
• Low expenses
• Rationale against
• Not applicable in patients with Ileus

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Latest Recommendations

• Strict limitation of enteral nutrition is
  unnecessary
• Nasojejunal tube feeding not better than
  Nasogastric tube feeding
• Jejunal tube feeding only in patients unable to
  resume enteral feed early
• TPN not required unless severely debilitated
  patient
• In case TPN or tube feeding required , resume
  oral feed as soon as pain disappears and patient
  is able to retain feed ( generally 3-7 days in
  mild disease)
• Suggested addition of Lactobacillus sp.
  Preparations to enteral feed may reduce infective
  complications of acute pancreatitis

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Management

• Goals
• Provide supportive care
• Decrease pancreatic inflammation
• Prevent/identify/treat complications

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Management of mild Acute Pancreatitis

• Self limiting course - 85 to 90
• Subsides spontaneously, usually within 3 to 7
  days after treatment
• Bed rest
• Analgesics with meperidine/pethidine
• Nil orally, NGT
• IV rehydration and electrolyte replacement

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Management of Severe Acute Pancreatitis

• Aggressive hydration 250 500ml/hr Ringers
  Lactate preferred (ACG guideline 2013)
• Feeding TNP, enteral feeding
• Analgesics
• Anti-inflammatory corticosteroids and
  indomethacin
• suppress inflammatory cytokines under trial
• Lexipafant Platelet-activating factor
  antagonist
• Prophylactic antibiotics e.g. ciprofloxacin and
  metronidazole ( ? Not recommended? - ACG
  guideline 2013)
• For infected pancreatic necrosis iv antibiotics -
  imipenem

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Management post AP

• Identify and treat cause/association of AP to
  prevent recurrence
• Cholecystectomy for Gallstones
• Endoscopic sphincterotomy in some patients
• Bile stone dissolving therapies.
• Lipid lowering drugs
• Avoid causative drugs
• Identify cases of idiopathic AP Sphincter of Odd
  malfunction.
• Advice abstention from alcohol

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Chronic pancreatitis
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Chronic Pancreatitis
Progressive chronic inflammatory process of the
Pancreas
Permanent Pancreatic structural damage
Fibrosis and Atrophy of the Pancreas
Impaired Exocrine and Endocrine Pancreatic
function
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Pathophysiology

• Irreversible damage to the pancreas as distinct
  from the reversible changes noted in acute
  pancreatitis.
• The presence of histologic abnormalities
• chronic inflammation,
• fibrosis,
• progressive destruction of both exocrine and
  eventually endocrine tissue

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Tigar-O Classification System

• Toxic/metabolic
• Idiopathic
• Genetic
• Autoimmune
• Recurrent and Severe Acute Pancreatitis
• Obstructive

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Tigar-O Classification System

• Toxic-metabolic
• Alcoholic
• Tobacco smoking
• Hypercalcemia
• Hyperlipidemia
• Chronic renal failure
• Medicationsphenacetin abuse
• Toxinsorganotin compounds (e.g., DBTC)
• Idiopathic
• Early onset
• Late onset
• Tropical

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Tigar-O Classification System

• Genetic
• Hereditary pancreatitis
• Cationic trypsinogen
• PRSS1
• PRSS2
• CFTR mutations
• SPINK1 mutations
• Autoimmune
• Isolated autoimmune chronic pancreatitis
• Autoimmune chronic pancreatitis associated with
  Sjögren's syndrome
• Inflammatory bowel disease
• Primary biliary cirrhosis

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Tigar-O Classification System

• Recurrent and Severe Acute Pancreatitis
• Postnecrotic (severe acute pancreatitis)
• Recurrent acute pancreatitis
• Vascular diseases/ischemia
• Postirradiation
• Obstructive
• Pancreas divisum
• Sphincter of Oddi disorders (controversial)
• Duct obstruction (e.g., tumor)
• Preampullary duodenal wall cysts
• Posttraumatic pancreatic duct scars

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Tigar-O Classification System

• Cigarette smoke leads to an increased
  susceptibility to pancreatic self-digestion and
  predisposes to dysregulation of duct cell CFTR
  function.
• It has become increasingly apparent that smoking
  is an independent, dose-dependent risk factor.

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Major causes of CP

• Alcohol abuse ? direct toxic effect on the
  pancreas
• 70 80 of cases of chronic pancreatitis
• Chronic (gt 6-12yrs) alcohol abuse-150-175gm/day
• genetic predisposition
• only 5 - 10 of alcoholics develop chronic
  pancreatitis
• Prolonged consumption of socially acceptable
  amounts of alcohol is compatible with the
  development of chronic pancreatitis
• Autoimmune pancreatitis
• SLE, Sjögren's syndrome

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Major causes of CP

• Genetic causes
• mutations in the cystic fibrosis gene, (CFTR
  gene)
• hereditary pancreatitis ? pancreatic
  adenocarcinoma
• Gene encoding for trypsinogen.
• The defect prevents the destruction of
  trypsinogen and allows it to be resistant to the
  effect of trypsin inhibitor, become spontaneously
  activated, and to remain activated.

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Major causes of CP

• Ductal obstruction
• Trauma,
• pseudocysts,
• Calcific stones,
• tumors,
• ampulla stenosis
• possibly pancreas divisum (Dorsal and ventral
  ducts)
• Systemic disease e.g. hypertriglyceridemia,
  possibly hyperparathyroidism

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Major causes of CP

• Tropical pancreatitis -Nutritional
• Observed in India, Africa, Indonesia
• Children are commonly affected, and often die in
  early adulthood from endocrine and exocrine
  dysfunction.
• The cassava fruit had been implicated as an
  etiologic factor in this disorder, although it is
  no longer thought to be related .
• Mutations in the serine protease inhibitor SPINK1
  have been identified in some patients
• Idiopathic pancreatitis 10-30

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Pathogenesis of chronic pancreatitis

• incompletely understood
• Proteinaceous ductal plugs theory
• ? secretion of pancreatic proteins ?
  proteinaceous plugs formation in inter and intra
  lobular ducts? act as a nidus for calcification,
  leading to stone formation within the duct
  system? ductal epithelial lesions which scar and
  obstruct the ducts? inflammatory changes and cell
  loss.

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Clinical Features

• Abdominal pain
• Epigastric, dull and often radiates to the back,
  
• Constant or intermittent with frequent pain-free
  intervals
• associated with nausea and vomiting
• partially relieved by sitting upright or leaning
  forward.
• worse 15 to 30 minutes after eating especially
  fatty meal ? fear of eating ? Weight loss
• Also aggravated by alcohol
• mild to quite severe pain , with narcotic
  dependence as a frequent consequence

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Clinical Features

• Pancreatic insufficiency  
• When over 90 of pancreatic function is lost
• Maldigestion is manifested as
• Chronic diarrhea,
• steatorrhea (Fat malabsorption in 30 50)
• weight loss
• Pancreatic diabetes ( 50) in  patients with
  chronic calcifying disease than those with
  chronic non-calcifying disease

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Clinical Features

• Classic triad for diagnosis of Chronic
  pancreatitis
• Pancreatic calcifications
• Steatorrhea
• Diabetes mellitus

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Complications

• Pseudocyst - 10 pts
• Pancreatic ascites or pleural effusion
• Bile duct or duodenal obstruction
• Obstructive jaundice
• Splenic vein thrombosis
• Pancreatic cancer - increased risk

78
Investigations

• A 72-hour fecal fat gt7 g of fat/day is diagnostic
  of malabsorption (gold standard)
• Fecal elastase ? 200 mcg/g is suggestive of
  pancreatic insufficiency (sensitivity and
  specificity of 93)
• Amylase and Lipase - are non-diagnostic
• Testing exocrine function
• secretin stimulation test.
• RBG ?FBG and Impaired Glucose tolerance

79
Imaging studies

• Plain Abdominal Xray
• Diffuse Pancreatic calcifications indicate
  significant damage
• Abdominal ultrasound
• ductal dilatation, Gallstones
• Abdominal CT Scan
• may show calcification, dilated ducts, or an
  atrophic pancreas, fluid collections
  (pseudocyst) and pancreatic cancer.
• MRCP
• direct view of the pancreatic duct and is now the
  diagnostic procedure of choice.

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Gall stone Pancreatitis by ERCP
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Investigations

• ?bilirubin and ALP ? bile duct obstruction
• Markers of autoimmune
• ?ESR, IgG4,
• rheumatoid factor,
• Anti-Nuclear Antibodies (ANA), and
• anti-smooth muscle antibody titer.
• Tumor markers
• CA 19-9, carcinoembryonic antigen (CEA)
• Genetic testing  

84
Management

• The goals of treatment include
• pain management,
• correction of pancreatic insufficiency
• management of complications
• Pain
• stop alcohol and
• Stop cigarette smoking
• Analgesic narcotics
• Pancreatic enzyme supplements to suppress
  pancreatic exocrine secretion relieve pain in
  some patients

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Management.

• Malabsorption
• for significant steatorhoea give pancreatic
  enzyme supplements with meals.
• Endoscopic treatment
• Surgical Rx

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• Carcinoma of the Pancreas /
• Pancreatic cancer

87
Introduction - Pancreatic cancer

• Malignant neoplasm of the pancreas.
• Much feared disease due to
• its notoriously late presentation
• early metastases and
• poor survival rates.
• Poor prognosis with fewer than 5 of those
  diagnosed still alive five years after diagnosis.
  
• Complete remission is still rare.

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Introduction - Pancreatic cancer

• About 95 of exocrine pancreatic cancers are
  adenocarcinomas
• The majority arise in the head or neck.
• The remaining 5 include
• adenosquamous carcinomas
• signet ring cell carcinomas
• hepatoid carcinomas
• colloid carcinomas
• undifferentiated carcinomas

89
Pathogenesis - Risk factors

• Increased risk associated with
• Age
• rare lt 40years,
• median age at presentation is 70-75 years.
• Smoking
• Increased BMI
• association shown particularly with obesity.
• Chronic and hereditary pancreatitis
• chronic pancreatitis is associated with a 5-15
  fold increase in risk and
• hereditary pancreatitis with a 50-70 fold
  increase.

90
Pathogenesis - Risk factors

• Family history
• in up to 10 patients, there is a family history
  of pancreatic cancer.
• Risk is also increased in other cancer syndromes
  
• Hereditary non-polyposis
• Colorectal carcinoma,
• Familial adenomatous polyposis (strongly
  associated with periampullary tumours).
• High frequency genetic changes associated with
  pancreatic adenocarcinoma include
• mutations of k-ras oncogene,
• inactivation of p53, p16 and
• smad4/TGF-ß tumour suppressor genes

91
Pathogenesis - Risk factors

• Dietary factors fat, coffee and alcohol
• have not been proven to increase risk (Robbins
  associates these!!).
• It is controversial whether alcohol consumption
  is a risk factor for pancreatic cancer.
• Drinking alcohol excessively is a major cause of
  chronic pancreatitis, which in turn predisposes
  to pancreatic cancer.
• However, chronic pancreatitis associated with
  alcohol consumption does not increase risk of
  pancreatic cancer as much as other types of
  chronic pancreatitis.
• Overall, the association is consistently weak and
  the majority of studies have found no
  association.

92
Clinical features - Pancreatic cancer

• Sometimes called a "silent killer" because early
  pancreatic cancer often does not cause symptoms,
  and the later symptoms are usually nonspecific
  and varied
• Common symptoms include
• Upper abdominal pain radiates to the back
• Painless jaundice when a cancer of the head of
  the pancreas (about 60 of cases) obstructs the
  common bile duct.
• Loss of appetite and/or nausea and vomiting
• Significant weight loss

93
Clinical features - Pancreatic cancer

• Trousseau sign (migratory thrombophlebitis)
• Diabetes mellitus
• Many patients with pancreatic cancer develop
  diabetes months to even years before they are
  diagnosed with pancreatic cancer, suggesting new
  onset diabetes in an elderly individual may be an
  early warning sign of pancreatic cancer.

94
Clinical features

• Patients with pancreatic cancer commonly present
  with advanced disease
• Symptoms are nonspecific
• Vague discomfort, dyspepsia, bloating
• Jaundice
• Weight loss, back pain usually a sign of advance
  disease
• Significant back pain 9 resectability vs minimal
  back pain 31 resectability
• New onset diabetes in patients over 60 should
  raise suspicion.

95
Diagnosis

• Clinically
• History and
• Physical examination
• Laboratory
• Percutaneous needle biopsy
• Liver function tests can show a combination of
  results indicative of bile duct obstruction
  (raised conjugated bilirubin, ?-glutamyl
  transpeptidase and alkaline phosphatase levels).
• CA19-9 (carbohydrate antigen 19.9) is a tumor
  marker that is frequently elevated in pancreatic
  cancer.
• Radiological
• CT SCAN

96
Treatment Options

• Tissue diagnosis NOT NECESSARY Unless surgery
  is not planned
• Potentially resectable tumors
• Laparoscopy to rule out metastatic disease
• Head tumors pancreaticoduodenectomy
• Pancreaticogastrostomy or jejunostomy,
  hepaticojejunostomy, gastrojejunostomy
• Body or Tail tumors distal pancreatectomy with
  splenectomy

97

• PANCREATIC ENDOCRINE NEOPLASMS

98
Insulinomas

• Most common of the pancreatic endocrine neoplasms
  involving the ß cells.
• Responsible for the elaboration of the sufficient
  insulin to induce clinically significant
  hypoglycemia.
• The attacks are precipitated by fasting or
  exercise and are promptly relieved by feeding or
  parenteral administration of glucose.

99
Morphology

• Are generally benign
• Most are solitary lesions (often lt2 cm O).
• Encapsulated, pale to red-brown nodules located
  anywhere in the pancreas.
• Histologically, benigns look remarkably like
  giant islets.

100
Gastrinomas

• Gastrin-producing tumors
• Marked hypersecretion of gastrin.
• May arise in the pancreas, peripancreatic region
  or the wall of the duodenum.
• Over half of the gastrin-producing tumors are
  locally invasive or have already metastasized at
  the time of Dx.
• In 25 of patients, gastrinomas arise in
  conjunction with other endocrine tumors.
• Rarely exhibit marked anaplasia.

101
Summary - Pancreatic tumors

• A variety of benign and malignant tumors may
  arise in the exocrine and endocrine pancreas.
• Exocrine pancreatic tumors are far more common
  than pancreatic endocrine tumors.
• Most exocrine pancreas tumors ? Carcinoma of the
  Pancreas
• Pancreatic cancer is a deadly disease
  characterized by late diagnosis and resistance to
  therapy.

102
THANK YOU FOR YOUR ATTENTION !!!
103
Reference

• Harrisons Principles of Internal Medicine 19th
  ED
• Agarwal N, et al Evaluating tests for acute
  pancreatitis. Am J Gastroenterol 1990 85 356
• Robbins and Cotran 8th ed