Acute Pancreatitis

Genetic Basis of Acute Pancreatitis

Explanation

Gallstones > alcohol > idiopathic

ACUTE BILIARY PANCREATITIS

Explanation:

• Women > Men
• Recurrent biliary pancreatitis = ABCB4 mutation
• Gland is morphologically normal
• Endocrine & Exocrine deficiencies = Compared to Alcoholic Pancreatitis, Biliary pancreatitis has less incidence
• Stones = Increased risk of Biliary pancreatitis by
  • Cholesterol stones
  • Small stones(<5mm) ; numerous (>20 stones)
  • good emptying of Gall Bladder
  • wide cystic duct
• ERCP only in cases of Cholangitis [otherwise no role in Biliary pancreatitis even in severe pancreatitis]
• Moderate or severe pancreatitis = Interval Cholecystectomy
• PONCHO trial = Same admission cholecystectomy can be done in Mild Biliary pancreatitis

Alcoholic Pancreatitis

Explanation

• Transient organ failure +/ - Local or systemic complications = moderately severe

  

Atlanta Classification :Collections in Acute Pancreatitis:

Explanation:

• No air foci on CT = no infection

Determinant based Classification of Acute Pancreatitis

Explanation:

• This patient has no infected necrosis but there is persistent organ failure = Severe
• Mortality Rates
  • severe = 35%
  • Critical = 88%

Explanation:

• 2 phases
  • Early (within 7 days)⇒ Sterile inflammation ⇒ SIRS ⇒ Organ Failure ⇒ death
  • Late (after 2 weeks) ⇒ Necrosis ⇒ Infection of necrosis ⇒ Sepsis ⇒ Organ failure ⇒ death
• The presence of (persistent) organ failure is the key determinant for morbidity and mortality in acute pancreatitis, in particular (early) multiorgan failure is associated with high mortality.
• The International Association of Pancreatology (IAP) / American Pancreatic Association (APA) guidelines recommend using persistent systemic inflammatory response syndrome (SIRS) (>48 hours) as a marker to predict severity of acute pancreatitis." Persistent organ failure is also one of the key determinants of the severity of acute pancreatitis in the Revised Atlanta Classification

PROGNOSTIC SCORING SYSTEMS OF ACUTE PANCREATITIS

Explanation:

• BISAP AND APACHE scores are used within 24 hrs to grade severity of pancreatitis

• BISAP ≥ 3 in first 24 hrs ⇒ Severe acute pancreatitis

  • BUN
  • GCS
  • SIRS
  • Age
  • Pleural Effusion

  

CT SCAN IN ACUTE PANCREATITIS:

Explanation:

• To assess disease severity = we have many prognostic scoring systems as discussed above
• Predictive ability similar to clinical scoring system
• Not routinely performed on admission for assessment of disease severity
• Should be done in patients with
  • persistant organ failure
  • SIRS or sepsis
  • Not improving after 6-10 days of onset of disease

Explanation:

• Here CECT is not advised because there is no doubt in diagnosis of pancreatitis and disease severity is not assessed by CECT

Explanation:

• This question is about CTSI score.
• CTSI Score for this patient is 10 = 17% mortality
• Imaging
  • Non contrast
    • Pancreatic size index
    • Balthazar grade
    • EPIC score (Extrapancreatic inflammation)
    • MOP score (Mesenteric edema and peritoneal fluid)
  • Contrast : ( r/o Necrosis & pseudoaneurysms)
    • CTSI
    • Modified CTSI (Vascular complications and pleural effusion)

Role of ERCP in Biliary Pancreatitis:

Explanation:

• Diagnosis : Moderate Severe Biliary pancreatitis [ No cholangitis because = No fever but only jaundice; Very mild elevation of counts ; No evidence of obstruction] Bilirubin elevated ⇒ Cholestasis
• Jaundice + Fever = cholangitis
• here Pancreatitis with Cholestasis = grey area ⇒ ERCP or Wait and watch ? ? ?
  • Transient obstruction in Gallstone pancreatitis ⇒ wait for 48 hrs for the Ampullary edema to settle down and stone to pass out ⇒ if Bilirubin in persistently elevated after 2 days ⇒ EUS or MRCP to look for stones in Distal CBD
  • But if there is fever / Cholangitis confirmed ⇒ ERCP + stenting
• Role of ERCP:
  • No role of ERCP in pancreatitis irrespective of disease severity(APEC trial)
  • ERCP only in presence of cholangitis (biliary sepsis)
  • In jaundice and pancreatitis without cholangitis — ERCP if SIRS is present
  • Jaundice is present without cholangitis- Wait for 24-48 hours—if peristant rise - EUS to look for stones —

Management of Acute Pancreatitis

• Pain - WHO step ladder, morphine can be used
• Goal directed fluid therapy, crystalloids> colloids [RL>NS]
• No role of prophylactic antibiotics
• No role of probiotics (PROPATRIA trial)
• Nutrition in severe pancreatitis (PYTHON trial) ⇒ even in cases of Severe pancreatitis we should start on Enteral feeding if they can tolerate
  • Oral > Nasoenteric (If not tolerating oral during first 3-5 days)
  • Nasogastric > > Nasojejunal

Explanation:

• at admission = Interstitial edematous pancreatitis with no necrosis
• current diagnosis = Pancreatic necrosis with peripancreatic fat stranding ⇒ now look for Infection [ any air foci + clinical signs of infection ] ⇒ no signs of infection here for this patient ⇒ Sterile Necrosis
• Management :
  • irrespective of necrosis we give supportive care unless there is signs of infection
  • if there is infected necosis only then we go for STEP UP Approach by starting with PCD ⇒ VARD / Endoscopic Necrosectomy ⇒ Open / lap Necrosectomy

Explanation:

Management of NECROSIS:

• Sterile necrosis :
  • No intervention is required
  • Supportive care
  • Intervention if compressive symptoms (GOO, jaundice, compartment syndrome)
• Infected necrosis : STEP UP APPROACH (PANTER trial)
  • Antibiotics +PCD
  • VARD(video assisted retroperitoneal debridement/Endoscopic necrosectomy
  • Open necrosectomy
  • Mortality 20-30%
• Diagnosis of infected pancreatic necrosis -
  • Air foci (can be present in enteric fistula also)
  • SEPSIS, fever, tachycardia SIRS
  • FNA of collection is not required
  • Clinical + Radiological

Explanation:

• VARD = we use a laparoscope
• Minimally Invasive Percutaneous Necrosectomy = we use a operating nephroscope

• Minimally Invasive Pancreatic Necrosectomy (MIPN)

  • Catheter exchanged for a radiologic guidewire
  • Low-compliance balloon dilator to dilate to 30 FG
  • Amplatz sheath for access
  • Operating nephroscope for debridement under direct vision
  • High-flow lavage for rapid evacuation of pus and necrotic material
  • Continuous postoperative lavage with 0.9% normal saline

• Video-Assisted Retroperitoneal Debridement (VARD)

  • Performed in supine position with left side elevated
  • Subcostal incision of 5 cm in the left flank
  • Uses in situ percutaneous drain as a guide
  • Standard suction device clears purulent material
  • Long grasping forceps for visible necrosis removal
  • 0-degree laparoscope for deeper access
  • Two large-bore single lumen drains for closed continuous postoperative lavage

Explanation:

• PANTER TRIAL = Step Up approach VS Open Necrosectomy
• Step Up approach has 2 ways to go up after PCD + antibiotics
  1. Surgical: VARD or MIPN ⇒ Open Necrosectomy
  2. Endoscopic: Through stomach ⇒ Metallic Stents = Endoscopic Transluminal drainage/ necrosectomy
• PENGUIN trial : VARD with endoscopic transluminal necrosectomy
• TENSION trial : Surgical step up with endoscopic step up

Explanation:

Management of Late Walled-Off Pancreatic Necrosis

Indications for Intervention for WOPN:

• Infection, either suspected radiologically or clinical picture
• Nutritional failure
• Persistent abdominal pain

Choice of Intervention:

• Guided by the clinical picture, anatomic position of the collection, and local expertise
• Increasingly, the choice lies between:
  • Endoscopic drainage
  • Laparoscopic drainage

Notes:

• There is some degree of overlap between the early and late patient populations
• Most studies in the literature include heterogeneous groups

AutoImmune Pancreatitis

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ACUTE PANCREATITIS ( Live class Notes)

July 15, 2024

Acute Pancreatitis

• Inflammatory condition of pancreas
• Interstitial edematous and necrotizing pancreatitis
• Mortality: 1% in mild cases to 30% in severe cases with organ failure
• Gallstones and alcohol: 60-80% of cases

Natural History

• 70-80% have mild self-limiting disease
• Mortality: 1% in mild disease
• 10-20% have severe disease
  • Mortality: 40-50%
• Two phases:
  • Early (14 days): SIRS ⇒ Organ failure due to SIRS = Most common cause of death
  • Late (after two weeks): Sepsis, Organ failure due to Infected necrosis

Pathophysiology

• MC cause: Gall stones, Ethanol
• Fusion of zymogen and lysosomes
• Activation of cathepsin B
• Premature activation of trypsin
• Pancreatic injury:
  • Inflammatory mediator
  • SIRS
  • MODS
  • Death

Biliary Pancreatitis

• Most common cause: Gallstones
• Incidence: 3-8%
• Gender: F>M
  • 4-8% of gallstones develop biliary pancreatitis
• Clinical Features:
  • Less incidence of endocrine and exocrine insufficiency
  • Histologically normal gland
  • Bile reflux into the pancreas due to spasm or obstruction at the ampulla (Opie)
• Risk Factors:
  • Small stone (< 5mm)
  • Wide cystic duct (> 5mm)
  • High stone load (> 20 gallstones)
  • Mulberry stone
  • Irregular surface
  • Excess cholesterol
  • Good emptying of the gall bladder
• Genetic Factors:
  • SPINK 1 and ABCB4 genes involved in trypsin activation
• Timing of Cholecystectomy:
  • Mild: In same admission (PONCHO trial)
  • Moderate to severe: After 6 weeks
• Role of ERCP: Only in cholangitis

Alcoholic Pancreatitis

• 2nd most common cause
• Gender: M>F
• Incidence: 5-10% (with 100 g/day alcohol consumption for 5 years)
• Pathophysiology:
  • Increases secretion of GP2 and lithostathine (stones)
  • Increases trypsinogen and cathepsin B
  • Associated with ROS, FAEE, smoking, and bacterial endotoxemia

ERCP Pancreatitis

• Most common complication: Pancreatitis
  • 90% is mild
  • Incidence: 1-3% (diagnostic ERCP), 2-5% (therapeutic ERCP)
• Clinical Features:
  • New onset abdominal pain within 24 hours
  • Increased amylase/lipase (common for everyone, but prolonged hospitalization of 2 nights or more is considered ERCP pancreatitis)
• Risk Factors:
  • Young age
  • Female gender
  • Sphincter of Oddi Dysfunction (SOD)
  • Intraductal Papillary Mucinous Neoplasm (IPMN)
  • Previous pancreatitis
  • Therapeutic procedures (e.g., sphincterotomy)
  • Abnormal visualization of secondary pancreatic duct
• Prevention: Rectal indomethacin reduces the incidence

Autoimmune Pancreatitis (AIP)

• General Characteristics:
  • Segmental, diffuse narrowing of the main pancreatic duct (MPD)
  • Diffuse enlargement of the pancreas
  • Elevated IgG4 levels
  • Lymphoplasmacytic inflammation and storiform fibrosis
  • Sausage-shaped pancreas

Type 1 AIP (Lymphoplasmacytic Sclerosing Pancreatitis - LPSP):

• Without GEL (Granulocytic Epithelial Lesion)
• Gender: Male predominance, 75% in males
• Serum IgG4 Level: Often elevated (~66%)
• Extra-pancreatic Involvement: Proximal bile duct, salivary gland, kidney, retroperitoneum (~50%)
• Recurrence: High (20%-60%)
• Associated with IgG4-Related Disease: Yes

Type 2 AIP (Idiopathic Duct-Centric Pancreatitis - IDCP):

• With GEL (Granulocytic Epithelial Lesion)
• Gender: Equal, 50% in males
• Inflammatory Bowel Disease Association: Common (~10%-20%)

Clinical Differential Diagnosis:

• Painless obstructive jaundice as a differential diagnosis of pancreatic malignancy

CT Imaging Features:

• Segmental and diffuse narrowing of MPD
• Diffuse pancreatic enlargement

• Sausage-shaped appearance of the pancreas

  

Drugs Causing Pancreatitis

• Antibiotics:
  • Sulfonamides
  • Metronidazole
  • Erythromycin
  • Tetracycline
• Antiretrovirals:
  • Didanosine
  • HAART (Highly Active Antiretroviral Therapy)
• Diuretics:
  • Thiazides
  • Furosemide
• Others:
  • 6-Mercaptopurine
  • Valproic Acid

Metabolic Factors Causing Pancreatitis

• Hypertriglyceridemia:
  • Types I, IV, V hyperlipidemia
  • Triglyceride level > 10000 mg/dl
• Hypercalcemia
• Structural Abnormalities:
  • Trauma
  • Tumor (IPMN is the most common cause)
  • Pancreas divisum
  • Annular pancreas

Diagnosis of Pancreatitis

• Clinical Presentation:
  • Characteristic abdominal pain
• Laboratory Tests:
  • Raised amylase/lipase levels
  • Amylase:
    • Non-specific
    • Not raised after 5 days
  • Lipase:
    • Specific
    • Prolonged elevation
  • Trypsinogen activation peptide, trypsinogen-2 levels (more specific)
  • Imaging Evidence:
  • Confirmatory imaging evidence of pancreatitis

Severity Classification

Atlanta 2012 classification

Determinant Based = Necrosis & Organ Failure

Scoring Systems for Pancreatitis

• Ranson Score:
  • 11 prognostic factors
  • Completed after 48 hours
• APACHE-II Score:
  • 12 variables
• Imrie Score:
  • 9 variables
• SIRS Criteria
• BISAP (Bedside Index for Severity in Acute Pancreatitis)
• CRP (C-Reactive Protein)
• JSS (Japanese Severity Score)

Organ Failure Scores

• SOFA (Sequential Organ Failure Assessment)
• Goris Score
• Marshall Score

New Scoring Systems

• BISAP:
  • Bedside Index for Severity in Acute Pancreatitis
• PASS (Pancreatitis Activity Scoring System):
  • SIRS
  • Pain
  • Opiates
  • Ability to tolerate oral liquids

Laboratory Assessment

• CRP: > 150 mg/L
• Hematocrit
• Procalcitonin: > 1.8
• Cytokines:
  • IL-6
  • IL-8
• Trypsinogen Activation Peptide
• Urinary TAP (Trypsinogen Activation Peptide)

Imaging

• Modality of Choice:
  • CECT (Contrast-Enhanced Computed Tomography)
  • Detects necrosis
  • Should be performed after 72 hours
• CT Scoring Systems:
  • Unenhanced CT:
    • Balthazar Score
    • PSI (Pancreatitis Severity Index)
    • MOP (Mesenteric edema and peritoneal fluid, extrapancreatic necrosis, extrapancreatic inflammation - EPIC score)
  • CECT:
    • CT Severity Index
    • Modified CT Severity Index

Timing of CT Scan in Acute Pancreatitis

• Study Findings:
  • Analysis of 159 episodes of Acute Pancreatitis (AP) in 150 patients
  • Compared accuracy of seven CT scoring systems (CTSI, MCTSI, PSI, EP, EPIC, MOP, and Balthazar) with two clinical scoring systems (APACHE II and BISAP)
  • Predictive accuracy of CT scoring systems is similar to clinical scoring systems
  • Conclusion: CT scan should not be routinely performed on admission for assessing disease severity
• Recommendations:
  • CT scan is not recommended early in the course of pancreatitis due to low utility
  • CT scan should be performed in the following cases:
    • Persistent organ failure
    • Presence of SIRS (Systemic Inflammatory Response Syndrome) or sepsis
    • Lack of improvement within 6 to 10 days into the disease course
    • Probable infected pancreatic necrosis
• Evidence-Based Medicine Recommendation:
  • Grade B recommendation for the use of CT in the specified conditions above

Management of Acute Pancreatitis

• Analgesia:
  • WHO pain ladder
  • Opiate and morphine
  • Epidural analgesia
  • Patient-controlled analgesia
• Fluid Therapy:
  • Cornerstone within 12-24 hours
  • Decreases SIRS and organ failure
  • Crystalloid > Colloid (SAFE trial)
  • NS = RL
  • Hydroxyl ethyl starch (?)
  • 5-10 ml/kg/hour
  • Goal-directed fluid therapy
• Intra-abdominal Hypertension:
  • IAP > 12 mm Hg
  • ACS: IAP > 20 mm Hg with organ failure
  • 15% of AP patients; 50% mortality
• Nutrition:
  • Oral/EN within 24-72 hours
  • Enteral > Parenteral
  • NG > NJ
  • Role of Glutamine supplementation
  • No evidence for PERT/probiotics
• Antibiotics:
  • No evidence for routine prophylaxis
  • Indicated for cholangitis
  • Indicated for infected necrosis
• ERCP:
  • Only for cholangitis
  • APEC trial: Early ERCP not associated with better outcomes
• Management of Necrosis:
  • Step-up approach
  • Indications for intervention:
    • Sepsis (Radiological/Clinical)
    • Nutritional failure
    • Persistent abdominal pain
    • Management of complications
  • Surgery avoided in first 2 weeks except for bleeding/ischemia
  • Gas in necrosis indicates infection/internal fistula
  • Procedures:
    • Percutaneous drainage (Percutaneous necrosectomy)
    • Video-assisted retroperitoneal debridement
    • Endoscopic cystogastrostomy
• Pancreatic Necrosis:
  • Contrast-enhanced CT is the investigation of choice
  • Low attenuation area after IV contrast
  • 20% of AP develop ANC
  • Infection is the most common cause of death in AP
  • Infection signs: Fever, increased WBC count, CT air foci
  • Organ failure
  • Sterile necrosis requires no treatment unless compressive symptoms
• Clinical Trials:
  • PANTER trial:
    • Management of infected pancreatic necrosis
    • 35% managed with percutaneous drainage alone
  • TENSION trial:
    • Endoscopic step/VARD-based surgical approach
  • MISER trial:
    • Endoscopic step-up vs. laparoscopic cystogastrostomy (CG)

Management of Pancreatic Necrosis: Percutaneous vs. Endoscopic Drainage

• Selection Criteria:
  • Position of Collection:
    • Relative to stomach, colon, liver, spleen, and kidney
  • Trial Findings:
    • Results favored endoscopic intervention
    • Endoscopic intervention is the primary choice where available
  • EUS-Guided Puncture:
    • Can be performed within an ICU setting
    • Avoids moving the patient to the radiology department for CT-guided drainage
    • Useful for patients in extremis
• Practice Guidelines:
  • Lateral Collections and Those Extending Behind the Colon:
    • Approach from the left or right flank percutaneously
  • Medial Collections:
    • Prefer endoscopic drainage
    • Avoid percutaneous route if compromised by overlying bowel, spleen, or liver
  • Percutaneous Drainage Route:
    • Consider probability of subsequent "step-up" escalation
    • Site drain as lateral and inferior as possible
    • Avoid the costal margin
    • Initial priority is sepsis control

Management of Necrosis, Pseudocysts, Pancreatic Ascites, and Vascular Complications

Retroperitoneal Step-Up Approach

• Drain Placement: A left-sided percutaneous drain is placed under CT guidance.
• Patient Positioning: Patient is placed supine with the left side up.
• Incision: A subcostal incision is made in the left flank.
• Procedure:
  • The collection is entered.
  • Visible necrosis is carefully removed.
  • Drain and lavage are performed.
  • Complete necrosectomy is not done.

Management of Infected Necrosis

• PANTER Trial:
  • Introduced the step-up approach.
• Initial Management:
  • Antibiotics and Percutaneous Catheter Drainage (PCD) of the collection.
• VARD (Video-Assisted Retroperitoneal Debridement):
  • An alternative to open necrosectomy.
• Surgery: Performed after 4 weeks if necessary.

Endoscopic Step-Up Approach

• Initial Management:
  • Antibiotics and Percutaneous Catheter Drainage (PCD).
• Procedures:
  • Endoscopic Transluminal Necrosectomy.
  • Laparoscopic Cystogastrostomy.
  • EUS-guided necrosectomy.

Endoscopic Cystogastrostomy Stents

• Types of Stents:
  • NAGI stent.
  • AXIOS stent.
  • Lumen-apposing metal stent.
• Adjunct: Use of hydrogen peroxide during the procedure.

Open Surgical Necrosectomy

• Techniques:
  • Open necrosectomy with open or closed packing.
  • Open necrosectomy with continuous closed lavage.
  • Programmed open necrosectomy.

Pseudocyst

• Most Common Cause: Chronic pancreatitis.
• Asymptomatic Pseudocysts: Observation is recommended, regardless of size.
• Symptomatic or Large Pseudocysts:
  • Internal drainage (surgical or endoscopic):
    • Cystogastrostomy.
    • Cystoduodenostomy.
    • Cystojejunostomy.

Pancreatic Ascites

• Cause: Rupture of the pancreatic duct.
• Lab Findings: High amylase and lipase levels in the ascitic fluid.
• Management:
  • Drainage of fluid.
  • Total Parenteral Nutrition (TPN).
  • Octreotide.
  • Pancreatic duct stenting.

Vascular Complications

• Most Common Artery: Splenic artery.
• Pseudoaneurysm: Can lead to bleeding.
  • Managed by angiographic embolization and control of sepsis.
• Most Common Vein: Splenic vein thrombosis, leading to left-sided portal hypertension with gastric varices.
  • Managed by splenectomy.
  • Angiographic embolization and control of sepsis are crucial.