The gallbladder, gallstones, and beyond….

Leslie Kobayashi, MDJanuary 31, 2012

Anatomy

Liver Bile ducts Pancreas Duodenum Transverse colon

Anatomy

FundusBodyInfundibulum/NeckCystic duct

Spiral Valves of Heister

AnatomyTriangle of calot

Borders: CHD, cystic duct, liver edge

Contents: Cystic artery, node of Calot

Ductal Anatomy

Right and Left Hepatic ductsCommon Hepatic ductCystic ductCommon bile duct

Aberrant anatomy

Vascular Normally (>90%)

cystic a. arises from RHA

Replaced right hepatic a.

Replaced left hepatic a.

Bile500-1500mL produced daily

Composition: water, electrolytes, bile salts, proteins, lipids

Ductal epithelium products▪ Alkaline phosphatase▪ HCO3

Hepatocyte products▪ Bile in conjugated soluble form synthesized from

cholesterol▪ Primarily cholate and chenodeoxycholate

Bile

95% of bile re-absorbed into the liver via portal vein (enterohepatic circulation) 85-90% in terminal ileum via active transport 10-15% deconjugated in colon, absorbed

passively 5% excreted in stool Cycles 6-10x daily

80% of bile stored in GB in fasting state

GB

Function store and concentrate bile Absorption: NaCL, H2O occurs rapidly Secretion: mucus, H+

GB average capacity 30-50mL Can increase to 300mL with obstruction

Normal ejection 50-70% in 30-40min

Significance

Do gallbladder problems create a significant healthcare burden?

YES!

Health burden 6.2 Billion$ in US 1.8 million ambulatory care visits Increased 20% since 1980’s Cholecystectomy most common

elective abdominal procedure in the US▪ 750,000 annually

Why does that happen?

Stones

Types of stones

Cholesterol stones (75%) Female fat fertile

Black stones (20%) Hemolytic diseases (Sickle cell disease) Cirrhosis

Brown stones (5%) Infection PSC

*primarily form in the ducts

Cholesterol stones

Low calcium, radiolucentCreated when fractional cholesterol

content of bile increased, and with incomplete emptying of GB

Associated with obesity, rapid weight loss, Native American/Hispanic heritage, ↑TG’s, ↓HDL, Spinal cord injury

Cholesterol stones

Hormonal influence Estrogen increases lithogenicity of bile

▪ Increased risk for females▪ Increased risk in obesity

Progesterone increases SM relaxation and bile stasis, decrease bile salt secretion▪ Increased risk in pregnancy

Cholesterol stones

Increase risk of stone formation TPN Octreotide Ceftriaxone

Decrease risk of stone formation Statins ?ursodiol

Pigmented stones

Often radiopaque due to calcium bilirubinate, calcium fatty acid soaps and inorganic calcium salts

Two types Black Brown

Pigmented stones

Black Form in GB Bile sterile Associated with age, hemolytic DO’s,

alcoholism, cirrhosis, Gilbert’s syndrome, Cystic fibrosis, pancreatitis and TPN

Cholecystectomy curative

Pigmented stones

Brown Form in ducts as well as GB Always infected 1O with enteric organisms,

often associated with cholangitis Associated with parasitic infection (liver

fluke) Associated with IBD, duodenal

diverticulae Will often recur after LC/OC

Stones: Where do they go?

And what do they do?

StonesAsymptomatic Symptomatic

Uncomplicated

Complicated

No obstruction

+ Infection/inflammation

+ Obstructio

n

CBD

- Infection

+infection

Ampulla

GSP

Choledocho Cholangitis

Biliary colic

Cholecystitis

In the gallbladder

Incidence: 10-30% of the population Asymptomatic (80%) Symptomatic (1-3% per year)

No inflammation: Biliary colic +inflammation: acute cholecystitis +obstruction : choledocholithiasis, GSP +obstruction+inflammation: cholangitis

Biliary colic

History Transient abdominal pain Occurs after fatty meals

Exam Benign

Labs Normal

Ultrasound GS

Hyperechoic masses, dependent in location

Acoustic shadowing

Cholecystitis

History Prolonged pain Fevers Nausea/emesis

Exam Fever, tachycardia RUQ TTP,

Murphy’s sign

Labs Leukocytosis Mild ↑ LFT’s

Imaging Ultrasound HIDA

Cholecystitis

Gallstones Obstruction of gallbladder

Obstruction causes inflammation Inflamed wall is thickened Edema or emphysema of GBW

Cholecystitis

Inflammation may or may not be associated with infection 50-70% of bile cultures are positive

E. coli, Klebsiella, Streptococcus, Enterobacter

Ultrasound

95% sensitivity/specificitySigns of cholecystitis

Gallstones GBW >3mm Pericholecystic fluid GBW striations or air within GBW Sonographic Murphy’s sign

GS with GBW thickeningNormal GBW <3mm

Pericholecystic fluid

HIDA

Cholescintigraphy: Injection of Tc99 labeled hydroxyl iminodiacetic acid

HIDA→hepatocytes→secreted into bile Normal visualization of GB, CBD

and SB within 30-60 min +scan if no visualization of GB

within 1hr and +uptake in CBD or SB

HIDA

Rim sign*Sphincter, ↙CBD

Normal HIDAPositive

HIDA

HIDA

False positives common in fasting patients Up to 40-60% in critically ill

Can decrease false+ rate with morphine ↑sphincter of Oddi pressure causing

preferential filling of the GB

Cholecystitis: Complications

↑Tension in GBW =↓perfusion →Necrosis of GBW Gangrenous/emphysematous cholecystitis

▪ 1% of cases, 3:1 M>F▪ Conversion rate 30-50%

GB Perforation▪ Assoc with ↑mortality (~20%)▪ Gallstone ileus

Gallstone ileus

Complications

Cystic duct obstruction→ Hydrops

Bile is absorbed but GB mucosa continues to secrete mucus

GB tense, filled with mucinous fluid

ComplicationsMirrizi’s syndrome

Impacted stone in infundibulum or CD →External compression of the CBD

0.7-1.4% of patients Assc with ↑risk of CBD injury, GB cancer

What if the stones escape the GB?

Stones in the CBD

Stone in CBD

No obstruction

Symptomatic

Asymptomatic

+ obstruction

No infection

+Infection

Choledocholithiasis

History: jaundice, icterus, pruritis, dark urine, steatorrhea, acholic stools, bleeding

Exam: jaundice, icterus, RUQ pain, Murphy’s sign

Labs Elevated LFT’s, INR Elevated bilirubin highest PPV 25-50% May be normal in up to 30% of patients

Choledocholithiasis

Imaging Dilated CBD on UTZ

▪ CBD <5mm risk of stone ~1%▪ CBD >5mm risk of stone 58%

MRCP Sensitivity 95% Specificity 89%

CBD dilation

Stones within the bile duct

Cholangitis

History/Exam: similar to choledocholithiasis with sepsis, septic shock

Labs/Imaging: similar to choledocholithiasis with leukocytosis, bactermia, ±MSOF

Charcot’s triad Reynolds pentad

RUQ pain, fevers, jaundiceTriad + ΔMS, shock

Beyond the CBD

Gallstone pancreatitis History: epigastric pain,

nausea/emesis Exam: RUQ/epigastric TTP, SIRS Labs: amylase/lipase ↑3x nl,

±↑LFT’s, leukocytosis Imaging: ±CBD dilation, pancreatic

edema, necrosis, fluid collection

Ranson’s criteria-AlcoholicFirst 24hours:

Glucose >200 Age >55 LDH>350 AST>250 WBC>16k

48 hours Ca <8 Hct↓>10 PaO2 <60 BUN↑>5 Base Deficit >4 Sequestration >6L

Ranson’s criteria-Non-Alcoholic

First 24hours: Glucose >220 Age >70 LDH>400 AST>440 WBC>18k

48 hours Ca <8 Hct↓>10 PaO2 <60 BUN↑>2 Base Deficit >5 Sequestration >6L

Ranson’s criteria

Each category 0 or 1Add up total pointsMortality

0-2 <5% 3-4 15% 5-6 40% 7-8 ~100%

Treatments

Treatment

MedicalSurgical

Lap Open CBDE

ERCP sphincterotom

y, stent

Percutaneous Cholecystosto

my tube

Treating the gallbladder

Gallstone “Cleanse”

PreparationEat a diet high in alkaline-forming foods and low in fats for at least 3-5 days before the cleanse.Help to gently prepare the liver by having a glass of fresh apple juice every day for 1 week prior to the cleanse. Apple juice helps to dissolve the stones

Ingredients

•Epsom salts (Magnesium Sulfate): 4 tablespoons•Olive oil: 1/2 cup or 125 ml•Fresh pink grapefruit: squeeze 1/2 cup (125 ml) juice•Or use 7-8 fresh lemons/limes: squeezed into 1/2 cup juice•1 liter jar with lid

Medical

Or you could try:

IVF hydrationAntibioticsBowel rest

Medical

Ursodiol: used as Mechanism: supplemental bile acid

decreases lithogenicity of bile, dissolve existing stones

Indications: bridge to LC/OC, too sick for OR, cirrhotics, PSC, TPN

Efficacy: may ↓LFT’s in PSC/cirrhotics, may ↓stones/sludge on UTZ, does not ↓symptoms, prevent need for OR, stones recur after cessation of medication

Medical

Diet: Cholesterol/Fatty acids

Carbohydrates

Legumes

Unsaturated fats

Coffee, FiberVitamin C, Alcohol

Treatment

Failure of medical management in acute cholecystitis 32%

Recurrence rate of GSP 29-63% Surgical management results in

reduced HLOS

Treatment

Timing of surgery for acute cholecystitis Within 48hrs vs >72hrs no difference in

conversion rates, OR time, LOS Comparing first hospitalization (<7d) vs

delayed (>6wks)▪ 17.5% rqr emergent cholecystectomy for

recurrent/unresolving sx’s▪ No difference in conversion rates or CBD

injury

Treatment

Timing of surgery for GSP Early operation safe with mild pancreatitis Rason’s criteria <3

Increased conversion rate, HLOS, and operative complications in early operation in severe pancreatitis Ranson’s criteria ≥3

Surgical approaches

Laparoscopic

Port placement Umbilicus Subxiphoid just to the right of the

falciform at the level of the inferior liver edge

2-3cm below costal margin in midclavicular line

Anterior axillary line, below the fundus of gallbladder

Laparoscopic

Retraction and dissection of Triangle of Calot prior to Gallbladder removal from fossa

CD may be clipped, sutured, tied, stapled

Remove gallbladder in fundus→dome direction

Open

Right subcostal incision Mini-cholecystectomy (5-8cm)

incision associated with equivalent outcomes/complications and less post-op pain, decreased LOS

Dome down dissection technique Isolate cystic artery/duct and suture

ligate

Lap vs. open

Conversion rate: 0.18-35% ave 4.7% CBD injury rates

Lap 0.2-0.6% Open 0-0.3%

Complication rate Lap ~1.2% Open (bile leak 1%)

LOS: shorter for Lap

Difficult Cholecystectomy RF’s for conversion

Male sex Obesity ↑age Wide short cystic duct Low surgeon case load

Gangrenous or emphysematous chole ↑risk of conversion RR 3.2 (CI 2.5-4.2) No ↑risk of local complications or CBD injury

Other options

Cholecystostomy tube

Can be transhepatic or transperitoneal no difference in outcomes

Technical success 96-98% Resolution of symptoms 68-96% Mortality 3-14% Complications

Dislodged catheter 16-33% Bleeding 1.5-1.8% Recurrent cholecystitis 7-41%

Clearing the duct

Natural history of CBD stones

Choledocholithiasis Stones in CBD in 10-15% of symptomatic

pt’s 55-70% pass spontaneously

GSP20-30% of patients have CBD stones 85-90% pass spontaneously

Symptomatic cholecystitis 4.6% +IOC at the time of LC 97.8% pass spontaneously

Surgical approaches

CBDE Can be

performed lap or open

Transcystic or via choledochotomy

Surgical approaches

CBDE Imaging duct

▪ Fluorscopic guidance▪ Choledochoscopy

Clearing duct▪ Basket, snare, flush▪ +/- glucagon to relax sphincter

Surgical approaches

CBDE Completion cholangiogram Clip, tie or staple cystic duct stump Close choledochotomy over T-tube +/-drain external Success rate of duct clearance 75-95%

ERCP

Efficacy 1 procedure: 71-75% Multiple procedures: 84-95%

Mortality 0.2-0.5%Complication rate 5-8%

Perforation Bleeding Pancreatitis Cholangitis

Complications

Complications

1-2% of patients will represent with CBD stone following cholecystectomy Dx <2yrs post-op = retained stone

Dx > 2yrs post-op =recurrent stone

Other Complications

Ileus Incisional/port site herniaWound infectionAbscess

Biloma/bile leak

CBD Injury

Strasberg-Bismuth classification A-CD stump, fossa B/C-aberrant RHD D-lateral injury E-circumferential injury to major duct

Special circumstances

PregnancyIncreased risk of stones

2-12% have stones 0.05-1.2% symptomatic during

pregnancyRisk of stones increased in:

Hispanic Pre-pregnancy obesity (4x) Decreased by EtOH consumption

PregnancyBiliary disease the most common

non-obstetrical cause of maternal hospitalization

Cholecystitis most common 40% GSP 30% CBD stone 20% Biliary colic 10%

Pregnancy

If symptomatic risk of recurrence high 40%-70% recur prior to delivery

If symptomatic risk of fetal loss high 10-20%

Pregnancy

Treatment goals Treat infection Maintain nutrition Prevent contractions/preterm labor Prevent fetal loss Prevent maternal morbidity/mortality

PregnancySurgical management associated

with fewer complications than medical management Contractions equivalent (~30%) Decreased preterm delivery, need

for c-section, and recurrent symptoms

Fetal loss with LC 0-5%

Pregnancy

Ideal timing LC/OC 2nd trimester ↓preterm labor (0% vs. 40%) ↓ fetal loss ↓ risk of fetal malformation Technically easier

1st delay to 2nd, 3rd delay to postpartum

Pregnancy

ERCP can be performed safely with: Low radiation exposure

▪ Fluoro time 14sec-3.2min▪ Radiation exposure 40-310 mrad

Few complications ~7%

Pregnancy

Operative considerations Port placement to accommodate uterus

Hassan vs. Veress likely equivalent

↓insufflation pressure 10-12

CirrhoticsStones more common in cirrhotics

(2x)Diagnosis difficult

Pain nonspecific Elevated LFT’s nonspecific Leukocytosis nonspecific GBW thickening nonspecific

▪ HIDA may be helpful

CirrhoticsManagement differences

Increased operative risk ▪ Morbidity 3x▪ Conversion 2x▪ Bleeding 8x

Increased risk with cholecystostomy▪ Bleeding▪ Ascites/Leak

CirrhoticsMortality

Overall acceptable 0.6-0.8% Significantly increased in Child’s C patients

(17%)LC safer than OC

Less bleeding Shorter OR time Shorter HLOS Possibly lower mortality (open mortality 8-25%)

Other pathology

Acalculous cholecystitis M>F 1.5:1 4-8% of all cholecystitis Dx with UTZ/HIDA

Gallbladder polypsGallbladder cancer

Thank You