Diagnosis and Management of Gallbladder Disease

Resident Version

Created by Dr. Brian Johnson

Objectives:

1) Understand the clinical presentation of gallbladder disease 2) Understand the work up of gallbladder disease 3) Identify common medical treatments 4) Know when to seek surgical consultation

References: 1. Nakeeb et al. “Gallstones: genetics versus environment.” Ann Surg 2002;235:842-9. 2. Shea JA, et al. “Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.” Arch Intern Med 1994;154:2573-81. 3. Cushieri A, Croce E, Faggioni A, Jakimowicz J, Lacy A, Lezoche E, et al. “EAES ductal stone study. Preliminary findings of multi-center prospective randomized trial comparing two-stage vs single-stage management.” Surg Endosc 1996;10:1130-5. 4. Papi C, et al. “Timing of cholecystectomy for acute calculous cholecystitis: a meta- analysis.” Am J Gastroenterol 2004;99:147-55. 5. Uhl W, et al. “IAP guidelines for surgical management of acute pancreatitis.” Pancreatology 2002;2:565-73.

Further Reading: Bellows C, Berger D, Crass R. Management of Gallstones. Am Fam Physician 2005;72:637-42

Trowbridge RL, Rutkowski NK, Shojania KG. Does this person have acute cholecystitis? JAMA. 2003 Jan 1;289(1):80-6. Case Presentation

48 yo obese male with a history of HTN presents to the ED with right sided abdominal pain for two days and one day of nausea and vomiting. The patient reports he has had similar pain in the past, but never this severe, nor for this long. The pain came on shortly after eating breakfast out with friends. He denies any changes in bowel habits, no weight loss and no hematemesis.

PMH: Obesity HTN Diabetes

PSH: Appendectomy age 18

Family History: MI in father at age 72 Mother with gallstones

Exam: Temp 37.3 HR 116 BP: 156/88 RR: 20 96% RA Gen: Mild distress Cardiac: Tachy, no m/r/g Chest: Clear to auscultation Abdomen: Diminished bowel sounds, pain to palpation of the RUQ and epigastrium with guarding. No rebound. Ext: No edema, clubbing or cyanosis Rectal: Guaiac negative

WBC 12.8 CBC 42 Platelets 322 Chemistry: Na 138 K 3.8 Cl 111 CO2 16 BUN 22 Cr 1.2 Calcium 8.2 AST: 98 ALT: 90 Alk Phos: 114 T bili: 2.3 Lipase 1120

CXR: Hypoinflated, no opacities RUQ U/S: Murphy sign negative, no gallbladder wall thickening

What is on your differential?

What might have caused the increase in lipase?

What labs or further studies would you order?

What treatment options might be appropriate in this patient? Overview/Outline for Discussion

Gallstone disease affects 12% of US population

Gallstones are classified by composition: Cholesterol (90% in US), black pigment (assoc. w/ hemolysis) or brown pigment (assoc. w/ bacterial and helminthic infections). Most have a mixed composition.

Risk Factors for Gallbladder Disease:  Body habitus: Obesity, rapid wt. loss, cyclic wt. loss  Childbearing  Drugs: Ceftriaxone, postmenopausal estrogens, total perenteral nutrition  Ethnicity: Native American, Scandinavian  Female gender  Heredity: first degree relative  Ileal disease  Increasing age

Obesity and family history are strong risk factors conferring a 2.2 relative risk symptomatic gallbladder disease.(1)

Diffrerential of Right Upper Quadrant Pain Biliary colic Steady, non-paroxysmal, lasts for four to six hours, occas. radiation to right subscapular area Acute cholecystitis Longer lasting (>6 hrs), tenderness, fever and leukocytosis Dyspepsia Bloating, nausea, belching Duodenal ulcer Pain after meals, may be relieved by eating food and antacids Hepatic abscess Pain w/ fever and chills, palpable liver Acute MI Right upper quadrant or epigastric pain

Evaluation: The initial evaluation of gallstone disease still remains a gestalt diagnosis as no clinical signs, nor laboratory findings are sufficiently sensitive and specific to preclude the need for imaging.

Clinical evaluation: The classic Murphy’s sign, while helpful, is not adequately sensitive nor specific to rule in or rule out biliary disease. Studies indicate Murphy’s sign is 70% sensitive and 87% specific.(4)

Laboratory evaluation: Elevated LFTs including AST, ALT, Alk Phos and Total bili all may be suggestive of biliary disease, but none is adequately sensitive nor specific to rule in or out disease. Imaging: Ultrasound of liver: Murphy’s sign, pericholecystic fluid, and gallbladder wall thickening point to acute cholecystitis (US is less sensitive for acute cholecystitis than HIDA (88%sens, 80%spec.), but more sensitive than HIDA for choledocolithiasis (84%sens, 99%spec)(2). Common bile duct dilatation >8mm indicates choledocolithiasis.

HIDA Scan: Functional test measuring patency of cystic and common bile ducts. Nonvisualization of gallbladder indicates the cystic duct is occluded. May be helpful in both acute cholecystitis and choledocolithiasis. Higher sensitivity (97%sens, 90%spec.) than US for acute cholecystitis, but not as readily available.(2)

CT Scan: Useful for determination of complications from biliary disease, but not as sensitive as US for acute biliary disease.

Medical Management of Gallbladder Stones:

The role of medical management of gallbladder disease has decreased with the advent of laproscopic cholecystectomy. However, in selected patients, namely those who are not good surgical candidates and at high risk of developing symptomatic disease, three modalities are still commonly used:

1) Oral Bile Salt Therapy  Primarily ursodeoxycholic acid (UDCA) used  Short-term results are poor w/ therapy lasting two or more years  Efficacy best with: (37% dissolution rate w/ one meta-analysis) a) small stones (<1cm) b) mild symptoms c) good gallbladder function (normal emptying needed to clear stones) d) minimal calcification and low density on CT (<75 Hounsfield units) (high calcification indicates mixed stone with less cholesterol content)

2) Contact Dissolution  Same characteristics as with bile salt therapy improve effectiveness of contact dissolution  Transhepatic approach with direct needle puncture of gallbladder and injection of methyl tertbutyl ether (MTBE) which dissolves cholesterol  Risks include bleeding, bile leak and recurrent gallstones

3) Extracorporeal shock wave lithotripsy  Most effective in pts w/ single large stone  Access is a major limitation Role of ERCP:

Generally recognized that ERCP is beneficial in patients with obstructive jaundice or biliary sepsis.

Role of ERCP in reducing gallstone pancreatitis is diminished. Multicenter Study showed no difference in primary endpoints between single stage lap chole vs two stage preop ERCP followed by lap chole. Single stage reduced hospital stays by three days.(3)

When to Call Surgery: Traditionally, acute cholecystitis was treated with a “cooling off” period for several weeks before proceeding to surgery. More recent data has shifted this toward early cholecystectomy. In a patient with biliary disease and an intact gallbladder, consultation with your surgical colleagues will almost always be warranted.

Current recommendations regarding surgical intervention for biliary disease include: Biliary cholic: Data has begun to indicate patients with uncomplicated biliary pain should have lap chole on first open operative date. Uncomplicated acute cholecystitis: A recent meta-analysis indicated patients with acute cholecystitis who receive a lap chole early in their disease have shorter hospital stays and no difference in rates of complication when compared to delayed surgery.(4) Gallstone pancreatitis: Current recommendation from the International Association of Pancreatology is cholecystectomy during the same hospitalization for patients with gallstone pancreatitis.(5)

Review Questions:

1) Which of the following is a common, severe complication of acute cholecystitis? a) emphysematous cholecystitis b) cholecystenteric fistula c) gangrenous cholecystitis d) Mirrizi’s syndrome e) porcelain gallbladder

2) Acalculous cholecystitis is NOT associated with which of the following: a) critically ill patients b) patients on TPN c) patients with poor oral intake d) major surgical procedures e) ischemia-related chronic gallbladder distention Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).

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Attending Resident (R2/R3) Intern Medical student