Pancreas

    .

    See "References / Further Reading"

    Acute Pancreatitis

    Introduction

    • Acute onset of pancreatic and peripancreatic inflammation
    • Rate is rising (10-45 cases / 100,000), 5% mortality rate.
    • Classification:
      • Severity Criteria

        Mild Pancreatitis

        (Most Cases)

        Acute pancreatitis that does not meet

        "severe" criteria".

        Severe Pancreatitis

        - 20% of acute pancreatitis

        - up to 20% mortality

        Organ failure

            - hypoxemia

            - hypotension

            - renal failure

        OR

        Complications:

           - Pancreatic Necrosis

           - Fluid collections

         

    • Premature activation of intracellular pancreatic trypsinogen to trypsin conversion (activation).
      • Triggers inflammatory cascade, causing capillary leak --> Can cause SIRS

    Causes

    • 80% of all acute pancreatitis are from Gall Stones or EtOH
    • Causes of Pancreatitis

      G - Gall Stones (45%) (MOST COMMON)

         - Microlithiasis

      E - Ethanol (35%)  (MOST COMMON)

      T - Tumors (choledochocele)

      S - Steroids

      M - Mumps

      A - Autoimmune Pancreatitis

         - (Other infections: viral [CMV, MUMPS], parasitic [toxoplasma, Ascaris lumbricoides])

      S - Scorpion bite

      H - Hypertriglyceridemia (TG > 5.6) Hypercalcemia

      E - ERCP (post-ERCP), Emboli, Ischemia

      D - Drugs

      • SAND Mnemonic
      • S - Simvastatin
      • A - Azathioprine, 6-MP
      • N - NSAIDS?
      • D - Diuretics (Furosemide, hydrochlorthiazide)
      • Mesalamine, asparaginase, didanosine

       

      Others:

      - Pancreas divisum (two congenital pancreatic ducts)

      - Genetic, Ischemia

     

    Symptoms

    • Sudden onset pain in epigastric region with radiation to the back.
      • (more comfortable seated position than supine).
    • Nausea, vomiting, fever.
    • Pleural Effusions --> dyspnea. (from capillary leak).

     

    Diagnostic Criteria

    • Diagnostic Criteria for Acute Pancreatitis

      Need at least two of:

          1.  Typical clinical symptoms

          2.  Elevated serum amylase and/or lipase level> 3x ULN

          3.  Typical findings on cross-sectional imaging.


       
    • Lipase has a longer half-life, MUCH more specific.
    • Amylase is less specific (can see in salivary glands, fallopian tubes rises sooner.
      • Non-specific, also seen in:
        • Perforated peptic ulcer
        • Intestinal ischemia
        • Acute hepatitis or cholecystitis
        • Rupture ectopic pregnancy
        • Parotidis
        • CKD
      • Macroamylasemia
        • Bening condition - multimers of amylase that are poorly filtered (need to do SPEP to find out). 
      • Gullo Syndrome
        • Rare cause of benign amylase and sometimes even lipase elevations.
    • Contrast CT - only if clinical picture is not clear.
      • Pancreatic or peripancreatic edema (+inflammatory stranding), fluid collections
      • Pancreatic necrosis (but rare on initial imaging). 
      • Splenic vein thrombosis? 

     

    Prognosis

    • Ranson Criteria  (need parameters on admission + 48hrs later).
      • Problem: Complexity, and cannot make initial analysis.
    • Apache Score (MORE COMMON)
      • The Acute Physiology and Chronic Health Evaluation (APACHE) II
      • More accurate than Ranson, but cumbersome. (i.e. need ABG, etc...)
    • Hemoconcentration
      • Potential predictor of morbidity and mortality (marker of capillary leak).
      • **Elevated BUN (serum)** Most important, most reliable, can trend.
      • Elevated Creat
      • Elevated Hematocrit
    • Others:
      • Medical comorbidities
      • >75, 
      • BMI > 30

    Management

    • ADMIT ALL
      • ICU if hemodynamically unstable or breathing challenges
    • Require:
      • Narcotic analgesia
      • Bowel rest (NPO)
      • Aggressive early fluids (Pancreas can sequester a lot of fluid) --> decrease ECV --> AKI + other organs.
        • High risk of necrotizing pancreatitis (contrast CT often demonstrates inflammation and hypoperfusion).
        • Monitor hypovolemia signs (tachycardia, hypotension, dry MM, hematocrit).
        • Rehydration helps prevent organ failure.
    • Other therapies:
    1. NG Tube  --> NOT INDICATED
    • Usually not needed, unless have ileus as a result from pancreatitis
    1. ERCP --> USUALLY NOT
    • ERCP: AVOID, can worsen: in gall stones or worsening sympsoms + rising liver chemistry
    • ONLY in two scenarios:
      • 1.  Concominant ascending cholangitis (fever, RUQ pain, and jaundice)
      • 2.  Gallstone pancreatitis who is not improving clinically and has worsening liver chemistry tests.
    1. Starting: Naso-Jejunal feeding
    • Criteria: Start as soon as feasible NJ feeding, especially if no signs of improvement in first 72-92hrs.
    • Avoid IV nutrition (high risk fungemia, bacteremia).
    1. Surgery
    • Cholecystectomy indicated prior to discharge if pt has gall stone pancreatitis, and no other complications.  (previously done as O/P once pancreas "cools off")
    • Also done if pancreas is necrotic, due to high risk of mortality.  But usually need repeat OR to keep removing necrotic tissue.  Various drains are currently investigated.
    1. Antibiotics --> NOT INDICATED
    • In the past used carbapenems, but now not indicated, even if necrosis is present.
    • Studies: NO BENEFIT on mortality (predisposis to intra-abdominal fungal infections)
    • If significant pancreatic necrosis --> can consider percutaneous fine-needle aspiration (culture + Gram stain).
      • Abx only for culture-proven infected necrosis of the pancreas.
      • If documented necrotizing pancreatitis and develop clinical instability (Fever, Hypotension)
        • Must sample pancreatic bed (endoscopically, percutaneously, or surgical).
        • May need drainage, if infected.
    1. Probiotics --> worsen outcomes

     

    Complications

    • Pseudocysts (Most Common)
      • Fluid collection without solid degree (no epithelial layer)  - Most common complication
        • Often walled off pancreatic necrosis
      • Pancreatic fluid collections due to destruction of main pancreatic duct or branches.
      • Often have continued abdominal pain, failure to thrive, hospitalization etc..
        • Can have mass effect on stomach
      • Pseudocysts typically resolve spontaneously, and do not need treatment.
      • If persist or have mass effect: surgical decompression, percutaneously, endoscopically.
    • Leaking Pancreatic Ducts (30%)
      • If untreated, can develop fistulas.
      • Treated with:
        • Endoscopic stenting.
        • Can use octreotide to decrease secretions. 
        • Pancreatic enzymes to replace what is lost.
        • Bowel rest.
    • Splenic Vein Thrombosis
      • Anticoagulation not recommended.
      • Secondary to inflammation around that vein in pancreas.
      • Can cause gastric varices.
    • Diabetes
      • If lost a lot of pancreas.

     

    Treatment

    1. IV HYDRATION -> Aggressive!!!
      • High risk of necrotizing pancreatitis (contrast CT often demonstrates inflammation and hypoperfusion).
      • Monitor hypovolemia signs (tachycardia, hypotension, dry MM, hematocrit).
      • Rehydration helps prevent organ failure.
    2. Notes On Other Therapies
      1. Antibiotics? --> NOT INDICATED in acute pancreatitis, even if necrosis is present.  In the past used carbapenems.
        • Studies show no benefit of prophylactic abx in severe necrotic pancreatitis.  (abx raise risk of abdominal fungal infections)
        • If significant pancreatic necrosis --> can consider percutaneous fine-needle aspiration (culture + Gram stain).
        • Treat only if culture-proven infected necrosis of the pancreas.
      2. ERCP ?
        • ->  Can worsen pancreatitis.  Only indicated if gallstone pancreatitis and worsening liver chemistry + instability (or if concerning for ascending cholangitis).
      3. NG suction? --> NOT INDICATED
        • Early feeding decreases hospital stay, mortality.  No need to NG suction.
      4. Probiotics contraindicated: increases mortality.
      5. Surgery:
        • If necrotic, high mortality.
        • However have to repeat OR many times, keep taking out necrotic tissue.
        • Investigated various drains.

           

    References / Further Reading

    • Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379-2400. PMID: 17032204
    • MKSAP 16

     

    Chronic Pancreatitis

    • Defined as:
      • Irreversible descrution of pancreatic parenchyma causing variable degrees of endocrine and exocrine dysfunction.
      • Heterogenous disorder, huge variation.
    • Most patients:
      • Constant severe abdominal pain radiating to the back.
      • Signs of exocrine dysfunction: weight loss, diarrhea
      • Signs of endocrine dysfunction: IDDM (lose function)
      • Vitamin D/A/E/K deficient.
    • Causes:
      • Toxic:
        • **Habitual alcohol** (>10y of 50g/day of EtOH, any drink glass of wine, can of beer, or shot is 10g)
          • 5 drinks/day raises risk significantly.
        • Tobacco use (also raises risk).
      • Genetic (Cystic Fibrosis, Serine protease inhibitor, Kazal type I, Pancreatic secretory trypsin inhibitor)
      • Obstructive (Pancreatic solid tumor, Intraductal papillary mucinous neoplasm, Pancreas divisum, Trauma)
      • Other (Recurrent acute pancreatitis, Autoimmune)
      • NOTE: 2015 Meta-Analysis identified three risk factors of progression from acute-to-chronic pancreatitis:
        • male sex, alcohol consumption, and smoking.
    • Classified:
      • Large Duct - 
      • Small Duct - hard to diagnose, often hard to see changes on imaging.
    • Diagnosis:
      • No gold standard, typically based on clinical symptoms.  
      • Cross section imaging helpful (pancreatic calcifications, ductal dilatation, parenchymal atrophy and/or focal inflammatory masses)
      • Often times amylase/lipase are normal (no parenchyma to produce). 
      • Endoscopic Ultrasound
      • MRCP (ECRP can make it worse)
      • Direct stimulation of function: (hard to perform, often not available)
        • cholecystokinin or secretin stimulation --> looking for minimal change disease.
        • Early exocrine changes. 
    • Management:
      • Prevent further damage, treat symptoms.
      • Counsel to avoid exposures (alcohol, tobacco)
      • Treat reversible causes (strictures, stones, etc..), endoscopically stent or remove stone.
      • Enteric-coated pancreatic enzymes
        • For exocrine insufficiency (take with meals, at least 30,000u of lipase daily - 10,000/meal + snacks).
        • Ensure replacing fat-soluble vitamins. (ADEK)
      • Non-Enteric-coated pancreatic enzymes
        • Used for pain control 
        • Theoretical: limits stimulation of pancreas by inhibiting cholecystekinin feedback loop.
        • Must be on PPI (enzymes denatured by low pH)
      • Endocrine insufficiency
        • Hard to manage, patients lose glucagon production.
        • Very labile plasma glucose. 
        • Treat with INSULIN.
      • Pain management:
        • Avoid opioids as long as possible.
        • Often opioid dependence. 
        • Can use Vitamin A/E, selenium (antioxidant)
      • Other:
        • Transcranial Magnetic Stimulation (Preliminary studies improved pain, but not yet available).
        • Celiac plexus blockade (corticosteroids or neurolysis [ethanol], either percutaneously or endoscopic U/S).  Usually short-lived benefit.
      • Surgery
        • Last resort, if all medical mgmt exhausted.
        • Operative resection or lateral pancreaticojejunostomy (if obstruction).
        • Total resection rare, makes pts insulin dependent and may not improve pain.

    Pancreatic Adenocarcinoma

    Insulinoma

    • Presenting with neuroglycopenic symptoms and recurrent hypoglycemic episodes.
    • First test: 8h fasting glucose (will be low!), and can directly measure insulin (will be inappropriately high)
    • Imaging:
      • Start with CT (r/o large tumors and metastasis)
      • if CT negative, (can miss small <2cm lesions) do endoscopic ultrasound (90% detection).

     

    Autoimmune Pancreatitis

    • Chronic inflammatory disease characterized by IgG4 lymphoplasmacytic infiltrate causing chronic autoimmune pancreatitis (AIP).
    • Types:
      • Systemic fibroinflammatory disease that can affect pancreas, bile duct, salivary glands, retroperitoneum, lymph nodes.
      • Most cases described in Japan (0.82/100,000 ppl).
      • Type 2 Autoimmune Pancreatitis:
        • Idiopathic duct-centric chronic AIP.
        • Patients typically younger, male, and have ass'd IBD.
    • Associated
      • Sjögren syndrome, retroperitoneal fibrosis, and primary sclerosing cholangitis.
      • Can have biliary involvement --> Looks like cholangiocarcinoma.
    • Presentation:
      • Painless obstructive jaundice.
      • Rare to present with acute pancreatitis features.
      • Can present with pancreatic mass found incidentally on imaging. (MUST exclude pancreatic adenocarcinoma!!!)
        • Requires tissue diagnosis.
    • Extra-Pancreatic Involvement:
      • Biliary tree (Distal), mimics pancreatic cancer stricture.
    • Diagnosis:
      • Imaging: Cross-sectional imaging --> diffusely enlarged pancreatic parenchyma ("Sausage-shaped" gland) with featureless borders.
      • Lab: Increased circulating Ig (esp. IgG4) are hallmark.
      • Pathology required: Histology (≥ 10 IgG4-positive cells / HPF on immunostain of lymphoplasmacytic infiltrate with storiform fibrosis).
      • Definitive Dx: Combination of labs, pathology, ang imaging.
    • Treatment:
      • Corticosteroids is primary treatment--> rapid response!
        • 30-40% will have relapses, may require longer courses.
        • If 2nd relapse --> chronic prednisone or steroid sparing agent (6MP or azathioprine).

     

    Cystic Neoplasms of Pancreas

    • Incidence is increasing b/c incidentally detecting on imaging.
    • Prevalence is 20% in pop'n, but only 1% are malignant.
    • Generally do endoscopic ultrasound (EUS) to sample cystic fluid.

     

     

    Lesion

    Carcinoem-bryonic

    Antigen

    Amylase

    CA 19-9

    NOTES:

    Pseudocyst

    Low

    High

    Low

     

    Intraductal papillary mucinous neoplasm

     

    (IPMN)

     

    (Most Common)

    High

    Low

    Low

    Typically involve main pancreatic duct, sometimes side branches.

    Surgical indication:

    • Main- and combined main+side branches IPMNs have the highest malignant potential and should be resected. 
    • Side-branch IPMNs = no resection as long as: <3 cm in diameter, Do not connect with the main duct, Do not cause symptoms such as pancreatitis, Do not have worrisome features on imaging such as nodularity or a thickened cyst wall.

    Mucinous cystadenoma

    High

    Variable

    Variable

    • Defined: histologically by presence of ovarian stroma.
    • Rate of transformation is very low, but operative resection still recommended if candidate.
    • Sampling on EUS + fluid analysis.

    Serous cystadenoma

    Low

    Low

    Variable

    • Benign lesions, can grow large enough to cause obstruction.
    • Low (if any!) malignant potential. 
    • Multiple microcysts within lesion + central scar = pathognomonic
    • Manage conservatively

     

    Neuroendocrine Tumors

    • Associated with MEN1 and Hippel-Lindau disease.
    • Endoscopic ultrasound has 90% detection rate (for insulinomas)

    Clinical Characteristics of Pancreatic Neuroendocrine Tumors

    Tumor Type

    Hormone

    Symptoms

    Criteria for Diagnosis

    Gastrinoma

    (MOST COMMON)

    Gastrin

    Peptic ulcers, diarrhea, esophagitis (Zollinger-Ellison syndrome)

    Elevated serum gastrin >1000 pg/mL (1000 ng/L), secretin stimulation test

    Tx: ALL SHOULD BE RESECTED

    Insulinoma

    Insulin

    Hypoglycemia; associated with MEN-1

    Inappropriately high insulin level during hypoglycemia

    VIPoma

    (RARE)

    Vasoactive intestinal peptide

    Watery diarrhea, hypokalemia, hypochlorhydria (Verner-Morrison syndrome)

    Elevated serum VIP level >75 pg/mL (75 ng/L)

    Glucagonoma

    (RARE)

    Glucagon

    Dermatitis (necrolytic migratory erythema), diabetes mellitus

    Elevated serum glucagon >1000 pg/mL (1000 ng/L)

    MEN-1 = multiple endocrine neoplasia type 1; VIP = vasoactive intestinal peptide.

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