“Acute pancreatitis is the most terrible of all calamities that occur in connection with the abdominal viscera. The suddenness of its onset, the illimitable agony which accompanies it, and the mortality attendant upon it, all render it the most formidable of catastrophes.” -Sir Berkeley Moynihan, Ann Surg 1925; 81:132-8.
Acute Pancreatitis
Etiology: 80% Gallstones or ETOH, 10% Other, 10% Idiopathic
Course: 80% Benign, 20% Severe
General Pathophysiology
Prevention of zymogen granules being exported from pancreatic acinar cells --> fusion of granules with intracellular lysosomes --> intracellular activation of trypsinogen to trypsin --> intracellular cascade of enzymes ---> pancreatic and surrounding autodigestion -->
- fat necrosis
- vasculitis--> thrombosis --> necrosis
- inflammatory response --> sirs
Gallstone Pancreatitis
Passage of gallstone --> reflux into pancreatic duct --> relative pancreatic obstruction/oversecretion --> inappropriate activation of pancreatic enzymes --> pancreatic inflammation
Opie “Common Channel Theory” correct for different reason than he thought
Common Channel in 90% of Acute Gallstone AP cases VS 20% of controls*
Seen in 3-8% of sxic cholelithiasis cases
Seen in 30% of sxic microlithiasis* cases
35-60% chance of recurrence after initial case at an average of 108 days after d/c
Alcoholic Pancreatitis
Mechanism poorly understood
Appears to involve: hypersecretion; obstruction from protein plugging; toxic effects (transient hyper triglycerides, free radical formation)
10 years of heavy drinking = 10% risk of acute pancreatitis
People usually get cirrhosis (daily drinkers) or pancreatitis (binge drinkers)
Other causes (the other 10%)
HyperTGs
Hyper Ca++
Med Side Effect
Tumor
Trauma/Ischemia/Post ERCP
Hypertriglyceridemia
Increased triglycerides --> more liberated free fatty acids in pancreatic microcirculation --> toxic effect
Seen c TGs > 1000 (extremely high)
Usually seem to have more severe course
Need to include TG reduction in treatment (may need plasmapheresis)
Hypercalcemia
See in 1-2% of HPT cases
? Mechanism: calcium induced trypsinogen activation, pancreatic duct stone formation, hypersecretion
Treatment is supportive and involves correction of HPT or other etiology of increased Ca++
Medications
Usually Mild, Less Acute
Different Mechanisms: hypersecretion, toxic accumulation, many unknown,
Can happen after being on the drug for awhile
Clearly linked: azathioprine, 6-mercaptopurine, trimethoprim-sulfamethoxazole, pentamidine, 2,3-dideoxyinosine, asparaginase, methyl-dopa
Weaker association: sulfasalazine, captopril, Alfa-interferon, estrogen, aminosalicylic acid, corticosteroids, corticotropin, acetaminophen, sulindac, tetracycline, metronidazole, thiazides diuretics, furosemide, isotretinoin, valproic acid
Questionable association: acetaminophen, cyclosporin, cytarabine, erythromycin, roxithromycin, ketoprofen, metolazone, octreotide
ERCP
~30-40% have enzyme elevations (don't run straight to surgery)
~5% have clinically significant pancreatitis
Diagnostic Approach to Evaluation for “Other Causes”
TG level
Ca++ level
Review Meds
MRCP/CT/EUS to eval. for Tumor
Idiopathic Pancreatitis
Etiology: Microlithiasis (80%), anatomic abnormalities (20%), sphincter of oddi dysfunction (30%), gene mutations (<5%)
Microlithiasis -
? Argument for Lap. Cholecystectomy;
? Role of Duodenal Crystal Study - duodenal fluid sent to lab to study
EUS is best study for stones
Diagnostic Algorithm
US -->CT -->ERCP/EUS --> observation vs. cholecystectomy vs. sphincter of oddi manometry
2007 AGA Recommendations
CT or EUS in idiopathic pancreatitis cases > 40 yo
Observe pts with single, uncomplicated case
EUS, ERCP, or Lap Chole for recurrent cases
Etiology: Pancreas Divisum
Failure of the greater + lesser pancreatic ducts to fuse = majority of bile drained by dominant dorsal duct of santorini, minority from ventral duct of wirsung
Causes a problem when another abnormality (like a duodenal diverticula) obstructs the duct of santorini
See in ~5% of pop.
No real increased incidence of AP
Exception = Obstruction of duct of Santorini (eg tic)
Treatment: Lesser sphincterotomy, distal pancreatectomy
Etiology: Sphincter of Oddi Dysfunction
Presentation - Hx
Epigastric Pain
Gradual or acute onset
Typically post-prandial or EtOH
Severe in intensity
“Piercing” through to back
+/- N/V (“Reflexive Vomiting”)
Presentation - PE
Epigastric Peritoneal Signs
SIRS picture in severe cases
Retroperitoneal hemorrhage - Grey-Turner’s (bruising of the flanks), Cullen’s (peri-umbilical ecchymosis), &/or Fox’s Signs (bruising over the inguinal ligament)
Diagnosis
Hx/PE
Amylase
- Not specific (perforated DU, salivary disorders, etc... also cause)
- Peaks earlier (within 24 hr with return to normal over 1 week)
- Relative depletion with chronic EtOH and bound by triglycerides
- 90% sensitivity
Lipase
- Solely of pancreatic origin (but can be up with perforated duodenal ulcer, perforated bowel)
- Remains elevated longer
- More sensitive and specific
- NOT PROGNOSTIC
Prognosis: Scoring Systems
Ranson’s Criteria
- On admission: Age >55, WBC > 16,000, LDH > 350, Glucose > 200, AST > 250
- Within 48 hrs: Hematocrit decrease by >10%, urea nitrogen increase > 5 mg/dL, serum calcium < 8 mg/dL, arterial PO2 < 60 mmHg, base deficit > 4mEq/L, estimated fluid sequestration > 6 L
Score = 1 point for each of the above = mortality: <3 = 1%; 3-4 = 15%; 5-6 = 50%; >6 = 100%;
Modified scoring for non-EtOH cases
APACHE II Score = (acute physiology score) + (age points) + (chronic health points)
CT Severity Index
Based on 2 aspects of CT appearance: extent of inflammation and extent of necrosis
Inflammatory Process Score:
Normal Pancreas – 0; Pancreatic Inflamation – 1; Peripancreatic Inflamation – 2; Single Fluid Collection – 3; Multiple Fluid Collections or gas present – 4
Pancreatic Necrosis Score:
None – 0; < 30% - 2; 30-50% - 4; > 50% - 6
CTSI = IP severity score + necrosis severity score
CTSI is better prognostic tool than clinical scores
CTSI 0-3 – f/u CT & ICU care not necessary
Score - morbidity; mortality
0-3 - 42%; 2%
4-6 - 81%; 19%
7-10 - 100%; 33%
May be better to delay CT to avoid kidney injury, resuscitate then scan
Prognosis
Mortality: all cases 5% (2-9%); interstitial pancreatitis 3% (1-7%); Necrotizing 17% (8-39%); infected necrosis 30% (14-62%); sterile necrosis 12% (2-44%)
Treatment
What works:
NPO
Aggressive Resuscitation for SIRS
Analgesia (avoid Morphine - sphincter of oddi constriction)
What doesn't work:
Immune Modulators - too late
ENZ Inhibitors - too late
Peritoneal Lavage
Enteral Nutrition
Minimizes bacterial translocation (+/- additional benefit of adding lactobacillus)
Avoids hyperglycemia and line complications
Jejunal placement (doesn't stimulate pancreatic secretion)
Use high protein, low fat, elemental formula (eg Peptamen 1.5)
Ileus can be problematic
Abx Prophylaxis
Less benefit than previously thought
No benefit in the absence of necrosis
Some evidence of prophylactic benefit with necrosis > 30%
SIRS mandates empiric antibiotics until infectious focus ruled out
DOCs = meropenem/imipenem x 14days
Antifungal prophylaxis not routinely indicated
Possible benefit from selective decontamination
ERCP
Indicated c cholangitis picture
No indication in mild cases
? Role in severe cases without cholangitis with retained stone
~5% incidence of causing pancreatitis
Treatment of Gallstone Pancreatitis
Mild Case – lap chole c cholangiogram same admission ~36-60% recurrence
Severe case - interval cholecystectomy
Complications
Early – Hemodynamic related to SIRS
Late - Infectious related to infectious necrosis
Pancreatic Necrosis
Result of microvascular thrombosis
Marker of severe attack
Potential nidus for severe infection - 33% infection rate
Sterile – continue support/Abx
Infected dx by - OR, CT guided FNA, or air on CT
Options in Infective Pancreatic Necrosis
Conservative Management
CT-guided catheter drainage
Endoscopic Drainage
Minimally Invasive Retroperitoneal Necrosectomy
Laproscopic Necrosectomy
Open Necrosectomy - Necrosectomy with Open Packing; Necrosectomy with Post-Op Lavage/Drainage; Necrosectomy with Post-Op Drainage
Pancreatic Necrosectomy - Not before 2 weeks; Debridement not resection; Postop lavage
Video Assisted Retroperitoneal Debridement (VARD)
Hybrid of Laparoscopic & Open Trans-Lumbar Approach
Begins with CT-guided drainage of ? Infected necrosis present after 4 weeks of disease
Reimage in 72 hr c ? Second drain
If SIRS or Necrosis persists to OR
Position supine with “bump” under L
~ 5cm subcostal incision in L mid-axillary line
Follow drain in
Initial debridement under direct visualization
Liberal irrigation
Insufflate CO2 via drain
Laparoscopic or Nephroscopic Debridement
Closure over drains
Post-op lavage - 10L warmed NS Q 24hrs, continue until clear
VARD Hemorrhage - Bleeding --> pack --> angio
VARD in the “Step Up” Approach article
Conclusion of Dutch VADER study - our results indicate that the preferred treatment strategy for patients with necrotizing pancreatitis and secondary infection, from both a clinical and an economic point of view, is a minimally invasive step-up approach consisting of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy
Complications: Pseudocysts
75% of pancreatic cystic lesions
No epithelial lining
Walled-off secretions from duct disruption
+/- ongoing communication
Presentation
Fluid collection > 4 weeks after Hx of AP (if < 4 wks = acute fluid collection or pseudo-pseudocyst)
Complicates 10% of acute EtOH pancreatitis (less common with gallstone pancreatitis)
Ongoing sxs &/or ENZ elevation
+/- GOO
Dx: CT
Management
Complex algorithm, Observe (if asymptomatic), eus/ercp, angiogram/embolization, surgery, percutaneous drainage all options
“Complex Pseudocysts”
Wall > 1 cm
Hypervascular Wall (ie c gastric varices)
Presence of Necrosis (increased risk with parenchymal pseudocysts)
Loculated/Multiple Pseudocysts
Usually need open procedure or extensive laparoscopic
Pseudocyst Management: Perc. Drainage
Reserve for acutely infected cysts
Aspiration for non-communicating, non-infected cysts
Pseudocyst Management: ERCP CystGastrostomy
Option for simple, sxic pseudocysts
Pseudocyst Management: ERCP Stenting
Option for simple, communicating cysts along with drainage
Pseudocyst Management: Operative Internal Drainage
Gold Standard
Allows for debridement
Complications: Pancreatic Ascites
Non-walled off leakage from duct disruption
Rare but difficult problem
Treatment: Stenting VS OR
Complications: Splenic Vein Thrombosis
Complicates 4-45% of pancreatitis cases
Anticoag not indicated - exception: extension into portal vein or SMV with hepatic or bowel complications
Predispose to Isolated Gastric Varices
Treatment:
Asymptomatic - observation (unless OR for other reasons than splenectomy)
Symptomatic - splenectomy
In-extremis - splenic artery embolization