Drugs that cause acute pancreatitis

"DEFEATS"

D: didanosine (anti-HIV drug)
E: erthyromycin
F: furosemide
E: estrogens
A: azithromycin (Imuran)
T: tetracycline
S: sulfa

Drugs Associated with Pancreatitis:

Definite Cause
·       5-Aminosalicylate ·       6-Mercaptopurine ·       Azathioprine ·       Cytosine arabinoside ·       Dideoxyinosine ·       Diuretics ·       Estrogens ·       Furosemide	·       Metronidazole ·       Pentamidine ·       Tetracycline ·       Thiazide ·       Trimethoprim-sulfamethoxide ·       Valproic acid
Probable Cause
·       Acetaminophen ·       α-Methyl-DOPA ·       Isoniazid ·       L-Asparaginase	·       Phenformin ·       Procainamide ·       Sulindac

Etiology - Acute Pancreatitis

"IT HURTS BADLY"

80-90% due to EtOH and gallstones

I: infection
T: trauma
H: hypercalcemia
U: ulcer (penetrating)
R: renal disease
T: tumor (pancreatic, biliary, duodenal)
S: structural (annular pancreas, pancreas divisum)
B: biliary gallstones
A: alcohol
D: drugs ("DEFEATS")
L: lipids
Y: "y"atrogenic

MELD score

MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43

In interpreting the MELD Score in hospitalized patients, the 3 month mortality is:

• 40 or more — 71.3% mortality
• 30–39 — 52.6% mortality
• 20–29 — 19.6% mortality
• 10–19 — 6.0% mortality
• <9 — 1.9% mortality

Hepatic Abscess

Potential routes for hepatic seeding are:
1) Biliary tree (currently most common)
2) Portal vein (usually GI source)
3) Hepatic artery (can be from any distant infection site/sepsis)
4) Direct extension (usually from abscess in vicinity of liver)
5) Trauma
Cryptogenic abscesses are very common and often a source is not identified

Microbiology:
most common organisms: E coli, Klebsiella pneumoniae

Antibiotic therapy and percutaneous drainage are currently the mainstays of treatment.
However, when this fails or the pt has a concomitant disease process that requires operative management, surgical drainage is indicated:
- use imaging to help guide site of drainage
- needle aspirate to confirm location and to get C&S sample (aerobic, anaerobic and gram stain - for ameobae too)
- abscess drained and finger dissection to break loculations
- biopsy wall of abscess cavity to rule out amebic trophozoites and presence of necrotic tumor
- biopsy normal liver --> presence of micro-abscesses will warrant a longer course of IV antibiotics
- closed suction drains in abscess cavity

Management of Asymptomatic Gallstones

Few predictive factors for symptomatic progression of gallstone disease:
- Bariatric surgery - 30% develop gallstones
- post-colectomy - 20% will develop symptoms within 5 years
- prolonged TPN use

Despite these risk factors, there are few indications for prophylactic cholecystectomy:
- Expectant Management of Cholelithiasis is the accepted treatment despite low morbidity of lap chole
- Diabetes is not an indication for prophylactic chole.  Diabetics do not have any significant difference in prevalence, presentation or complications compared to nondiabetics

Post-Transplantation:
- Cyclosporine leads to gallstone formation.
- Need for prophylactic chole has been shown to be of benefit in cardiac transplant patients if screening u/s shows stones (Milas et al, Mayo clinic)
- in renal transplant patients, majority (~90%) remain asymptomatic

Hemoglobinopathies:
- at risk of developing pigmented stones.
- sickle cell: 70% of pts
- hereditary spherocytosis: 85%
- thalassemia: 24%
- Gallstones in sickle cell patients can pose a problem. ~50% will become symptomatic within 3-5 years. Presence of gallstones can be diagnostically challenging due to possibility of abdominal sickling crisis.
- Hemoglobinopathies are an indication to perform prophylactic lap chole, lap chole should also be performed if doing a lap splenectomy

Bariatric Surgery:
- incidence of gallstone formation after rapid weight loss:
- general population: 10-20%
- bariatric surgery population: 30-40%
- if gallstones documented at time of bariatric surgery - lap chole recommended
- Ursodiol - can decrease incidence if patient compliant (prevents cholesterol absorption, expensive (~$1.50/d), BID). Suggested for patients undergoing bariatric surgery without prior evidence of stones.

Incidental Cholecystectomy - Controversial:
- During AAA: controversial due to the presence of graft material.  Review of incidental chole - shown to be safe as long as performed after retroperitoneum is closed
- Other abdominal surgeries: One study (Watemberg et al) showed that in pts >70 yo with cholelithiasis, M&M was higher if you DO NOT do incidental chole during laparotomy for other reasons.... yet we do not routinely do this in practice - why?
- most were small studies - only Watemberg was larger study

CBD injuries

Strasberg classification CBD injuries

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Gallbladder Polyps

Prevalence GB Polyps: 3-10%

Differential:
- Cholesterol polyps (50-70%)
- inflammatory
- hyperplastic
- adenoma
- malignant (8%)

Predictive factors for malignancy:
- size >1cm
- broad based sessile polyps
- age >50

Treatment:
- suspicion for GB cancer low: lap chole
- suspicious for GB cancer: open chole with intraop frozen section
- small polypoid lesion: U/S q6 mo for 2 yrs to ensure stable lesion

Gallbladder Cancer

T1a GB Ca: usually early stage

- usually found incidentally after routine lap chole

- incidence after routine lap chole for cholelithiasis - 1-2%

- 5 year survival for T1a GB ca confined to the mucosa - 85-100%

Symptomatic patients: usually advanced stage

- U/S only 50% sensitive for GB ca

- if suspicion of GB cancer pt should have a CT scan or MRI to look for invasion into adjacent structures, LN or encasement of portal vein or hepatic artery.

- Other investigations to consider: PET, MRCP, ERCP

Treatment is based T-stage of the tumor

- contraindications to surgical resection: liver mets, malignant ascites, peritoneal mets, distant disease, extensive involvement of hepatoduodenal ligament, encasement or occlusion of major vessels, poor performance status.

Lap Chole:

Tis or T1a

Radical Cholecystectomy:

-T1b (15% subserosal LN involvement) or T2 (40-80% subserosal LN involvement)

- radical cholecystectomy involves resection of GB with a 2cm hepatic parenchymal margin and LN dissection within the porta hepatis, gastroduodenal ligament, gastrohepatic ligament and Kocher for LN dissection behind duodenum
- can be done at time of initial lap chole or can be delayed - survival the same

Radical Cholecystectomy +/- en bloc resection of locally invaded organs:

- advised for T3/T4 tumors only if there is no evidence of metastatic spread

- 25-44% 5 year survival rate

Palliation:
- survival in locally unresectable or metastative disease often <1 yr
- no effective adjuvant treatment - all part of clinical trials