THE GALLBLADDER

I. Introduction/General Information A. Location: 1. Epigastric region 2. Right hypochondriac region 3. On inferior surface of liver 4. Between quadrate and right lobes B. Pear-shaped, hollow structure

C. Fundus slants inferiorly, to the right Introduction/General Information, con’t. C. Fundus slants inferiorly, to the right D. Attached to liver by loose (areolar) connective tissue E. Peritoneum covers free surfaces

The Gall Bladder and Bile Ducts Fundus

G. Body and neck directed toward porta hepatis Introduction, continued … F. Normal measurements: 7-10 cm long ~ 6 cm diameter 30 – 35 cc volume G. Body and neck directed toward porta hepatis

Introduction, continued … H. Neck is continuous with cystic duct I. Cystic duct: 1. joins common hepatic duct 2. superior and posterior to pylorus of stomach

J. Common Bile Duct 1. 10-15 cm long 2. Courses through lesser omentum Introduction, continued … J. Common Bile Duct 1. 10-15 cm long 2. Courses through lesser omentum 3. Deep to pyloric sphincter 4. Narrow tube, 1-2 mm diameter 5. Should be no more than 6 mm in diameter

6. May be 8-10 mm in post- cholecystectomy patients CBD, continued … 6. May be 8-10 mm in post- cholecystectomy patients 7. Normally has smooth walls 8. Joins with pancreatic duct 9. convergence is seen a. anterior to portal vein b. posterior to head of pancreas

K. Combined duct empties into duodenum @ ampulla of Vater Introduction, continued … K. Combined duct empties into duodenum @ ampulla of Vater L. Sphincter of Oddi guards duct, regulates bile flow Closed: bile goes into gallbladder Open: bile goes into duodenum

II. Detailed Anatomy A. Fundus of GB: 1. may be palpated 2. in angle between lateral border of right rectus abdominis and costal margin 3. At level of elbow 4. Most anterior visceral structure

1. Visceral surface of liver Detailed Anatomy, con’t. B. Body of Gallbladder 1. Visceral surface of liver 2. Deep to transverse colon or hepatic flexure of colon 3. Descending portion of duodenum is medial

Detailed anatomy, continued … G. Cystic Duct 1. 3-4 cm long 2. Extends from neck of gallbladder to common hepatic duct 3. Joins with common hepatic duct inferior to porta hepatis 4. Spiral valve may extend into neck of gallbladder

Biliary tract, continued … L. Blood supply to gallbladder: 1. Cystic artery a. arises (~ 60% of the time) from right hepatic artery b. passes posterior to hepatic duct, then divides

Gallbladder Diseases Cholelithiasis & Cholecystitis 1. Cholecystitis = inflammation of GB 2. Cholelithisis = Stone(s) in GB

Bile Bile Bile salts (primary: cholic, chenodeoxycholic acids; secondary: deoxycholic, lithocholic acids) Phospholipids (90% lecithin) Cholesterol Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and phospholipid

Types of Gallstones Mixed (80%) Pure cholesterol (10%) Pigmented (10%) Black stones (contain Ca bilirubinate, cirrhosis and hemolysis) Brown stones ( biliary tract infection)

Gallstone Pathogenesis Pathogenesis of cholesterol gallstones involves: (1) cholesterol supersaturation in bile, (2) crystal nucleation, (3) gallbladder dysmotility, (4) gallbladder absorption Black pigment stones: contain Ca++ salts, hemolytic conditions or cirrhosis, found in the gallbladder Brown pigment stones: Asians, contain Ca++ palmitate, found in bile ducts, biliary dysmotility and bacterial infection

Gallstone Risk Factors “Female, Fat, Forty, Fertile” Oral contraceptives Obesity Rapid weight loss (gastric bypass pts) Fatty diet DM Prolonged fasting TPN Ileal resection Hemolytic states Cirrhosis Bile duct stasis (biliary stricture, congenital cysts, pancreatitis, sclerosing cholangitis) IBD Vagotomy Hyperlipidemia

Cholecystitis (Acute & Chronic) ESSENTIAL FEATURES • Cholesterol stones form in 20% of women and 10% of men by age 60 • Cholesterol stone risk factors include: –Female gender –Age –Obesity –Estrogen exposure –Fatty diet –Rapid weight loss EPIDEMIOLOGY • Symptoms develop in about 3% of asymptomatic patients each year (20–30% over 20 years) • Acalculous cholecystitis affecting patients with acute, severe systemic illness

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Biliary colic but becoming unremitting and steady in epigastrium or right upper quadrant • Fever • Nausea • Vomiting • Right upper quadrant pain to palpation with peritoneal signs • Murphy sign • Anorexia

LABORATORY FINDINGS • Leukocytosis IMAGING FINDINGS • Right upper quadrant US showing gallstones, gallbladder wall thickening (> 4 mm), or pericholecystic fluid (no stones if acalculous cholecystitis) • HIDA scan showing failure of filling of gallbladder (> 95% sensitive) • CT showing gallbladder wall thickening (> 4 mm), pericholecystic fluid (for patients with suspected acalculous cholecystitis) as sensitive as US

DIAGNOSTIC CONSIDERATIONS • Other causes of acute abdominal pain Gallbladder: cholecystitis, choledocholithiasis, cholangitis Duodenal ulcer Hepatitis Appendicitis (atypical presentation) Pancreatitis RULE OUT • Choledocholithiasis • Pancreatitis

WORK-UP • History and physical exam • CBC • Amylase and lipase • Liver function tests • ALP, GGT • Right upper quadrant US • HIDA scan for difficult cases • CT if abdominal US not technically possible (patients with suspected acalculous cholecystitis, large wounds etc)

HIDA scan (Hepatobiliary Imino-Diacetic Acid scan) - radionuclide IV, extracted from blood, excreted into bile Uptake by liver, GB, CBD, duodenum w/in 1hr = normal Slow uptake = hepatic parenchymal disease Filling of GB/CBD w/delayed or absent filling of intestine = obstruction of ampulla Non-visualization of GB w/ filling of the CBD and duodenum = cystic duct obstruction and acute cholecystitis (95% sensitivity & specificity)

TREATMENT AND MANAGEMENT MEDICAL • All patients require IV fluids and antibiotics • Management then can include either early cholecystectomy (generally preferred) or cholecystectomy after about 6 weeks SURGERY • Laparoscopic cholecystectomy • Open cholecystectomy • Cholecystostomy tube (if cholecystectomy too hazardous) Indications • Suspected acute cholecystitis • Suspected acalculous cholecystitis • Failure to resolve cholecystitis on antibiotics

Complications • Bile duct injury or leak • Empyema –Suppurative cholecystitis occurs with frank pus in the gallbladder, high fever, chills and systemic toxicity –Percutaneous drainage or cholecystectomy is necessary • Pericholecystic abscess –Localized perforation at the gallbladder can result in a pericholecystic abscess –Treatment requires drainage with or without initial cholecystectomy • Free perforation –Rare but causes generalized peritonitis –This occurs when a gangrenous portion of the wall necroses prior to local adhesion formation –The diagnosis is rarely made before urgent laparotomy –Treatment is cholecystectomy • Cholecystoenteric fistula –Perforation at the gallbladder into an adjacent viscous generally resolves the acute episode –Symptomatic fistula and/or patients with continued gallstone symptoms should have cholecystectomy and closure at the fistula

a. Intraluminal echogenic projections Gallbladder Diseases, continued … Polyps of GB a. Intraluminal echogenic projections b. do not change position with patient c. Must be differentiated from septations, mucosal folds 1. septations extend across lumen 2. folds change configuration upon inspiration

Cholelithiasis ESSENTIAL FEATURES • Divided into symptomatic and asymptomatic • Caused by cholesterol (most common), black pigment, or brown pigment stones • Cholesterol stones form in 20% of women and 10% of men by age 60 • Cholesterol stone risk factors include: –Female gender –Age –Obesity –Estrogen exposure –Fatty diet –Rapid weight loss • Black pigment stone risk factors include: –Hemolytic disorders –Living in Asia • Brown pigment stone risk factors include: –Biliary stasis –Biliary infections EPIDEMIOLOGY • 20 million affected in United States • Symptoms develop in about 3% of asymptomatic patients each year (20–30% over 20 years) • Each year, complicated gallstone disease affects 3–5% of patients who are symptomatic

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Asymptomatic • Biliary colic –Right upper quadrant or epigastric –Episodic, often after meals or at night, lasting as long as 2–4 hours • Nausea • Vomiting • Diarrhea • Mild right upper quadrant tenderness to palpation

LABORATORY FINDINGS • Normal liver function tests, normal amylase and lipase, normal WBC count IMAGING FINDINGS • Right upper quadrant US showing acoustically dense stones in gallbladder with acoustic shadowing without evidence of gallbladder wall thickening or pericholecystic fluid (> 90% sensitive for gallstones)

DIAGNOSTIC CONSIDERATIONS • Other causes of abdominal pain RULE OUT • Cholecystitis • Choledocholithiasis • Pancreatitis

WORK-UP • History and physical exam • CBC • Liver function tests • Amylase and lipase • Right upper quadrant US

TREATMENT AND MANAGEMENT SURGERY • Laparoscopic cholecystectomy • Open cholecystectomy Indications • Symptomatic cholelithiasis • Porcelain gallbladder (25% risk of carcinoma) Contraindications • First or third trimester of pregnancy (relative) • Previous upper abdominal surgeries (laparoscopic) Complications • Bile duct injury or leak

Cholelithiasis, Rare Complications ESSENTIAL FEATURES Gallstone Ileus • Small bowel obstruction secondary to 1 or more large gallstones entering via cholecystoduodenal fistula Mirizzi Syndrome • Biliary stricture secondary to direct compression by chronically impacted cystic duct gallstone or chronic inflammation secondary to chronically inflamed gallbladder EPIDEMIOLOGY • Both gallstone ileus and Mirizzi syndrome are rare complications mainly affecting patients older than 60 years

LABORATORY FINDINGS Gallstone Ileus • Hypokalemia • Prerenal azotemia • Hypernatremia • Leukocytosis Mirizzi Syndrome • Hyperbilirubinemia • Elevated alkaline phosphatase

IMAGING FINDINGS Gallstone Ileus • Abdominal x-ray –Air-fluid levels –Dilated loops of small bowel –Possible pneumobilia • US –Cholelithiasis and pneumobilia • Hypaque swallow –Fistula between duodenum and gallbladder Mirizzi Syndrome –Biliary dilatation (> 6 mm) –Cholelithiasis –Possible thickened wall of gallbladder • ERCP or percutaneous transhepatic cholangiogram (PTC) –Stricture of common bile duct

WORK-UP Gallstone Ileus • History and physical exam • CBC • Electrolytes • Blood urea nitrogen, creatinine • Plain abdominal x-ray • Right upper quadrant US • Small bowel contrast study if partial small bowel obstruction Mirizzi Syndrome • Liver function tests

TREATMENT AND MANAGEMENT SURGERY Gallstone Ileus • Removal of retained small bowel gallstone(s) via enterostomy or partial resection if bowel damaged • Cholecystectomy and resection of fistula and duodenal closure at same operation or as staged procedure Mirizzi Syndrome • Cholecystectomy and resection and/or bypass of stricture via hepaticojejunostomy Contraindications • Clinical status of patient during laparotomy for gallstone ileus

Complications Gallstone Ileus • Missed enteral gallstone and recurrent obstruction • Duodenal leak • Bile duct injury or leak Mirizzi Syndrome • Anastomotic leak or stricture • Cholangitis

Choledocholithiasis & Gallstone Pancreatitis ESSENTIAL FEATURES • Cholesterol stone risk factors include: –Female gender –Age –Obesity –Estrogen exposure –Fatty diet –Rapid weight loss • Complicated gallstone disease affects < 0.5% annually of patients who are asymptomatic EPIDEMIOLOGY • Average age generally 10 years older than those affected by cholelithiasis (eg, 40–50 years of age)

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Right upper quadrant pain • Painless jaundice • Both pain and jaundice • Fever • Asymptomatic • Nausea • Vomiting • Anorexia

LABORATORY FINDINGS • Conjugated hyperbilirubinemia (for choledocholithiasis) • Elevated alkaline phosphatase (for choledocholithiasis) • Leukocytosis (for pancreatitis or cholangitis) IMAGING FINDINGS • Right upper quadrant US showing presence of gallstones, dilated common bile duct (CBD) (> 6 mm) and CBD stone in only 20–30% of patients with choledocholithiasis • ERCP showing dilated CBD and presence of single or multiple CBD stones in patients with choledocholithiasis • ERCP showing impacted ampullary gallstone in < 10 % of patients with gallstone pancreatitis

DIAGNOSTIC CONSIDERATIONS • Presence of signs or symptoms suggestive of cholangitis RULE OUT • Biliary stricture

WORK-UP • History and physical exam • CBC • Liver function tests • Amylase and lipase • Right upper quadrant US • ERCP or laparoscopic cholangiogram

TREATMENT AND MANAGEMENT SURGERY • ERCP with sphincterotomy and stone extraction followed by laparoscopic cholecystectomy (preferred when cholangitis present or if pancreatitis does not resolve) • Laparoscopic cholecystectomy with CBD exploration • Laparoscopic cholecystectomy and cholangiogram followed by ERCP and stone extraction (preferred stone extraction technique is center specific for stones noted on screening cholangiogram following resolution of gallstone pancreatitis) • Percutaneous transhepatic cholangiography and stone extraction if ERCP unsuccessful and cholangitis present Indications • Choledocholithiasis noted to be symptomatic or asymptomatic • Gallstone pancreatitis MEDICATIONS • Antibiotics to cover GI flora for cases of cholangitis Complications • Pancreatitis (for ERCP) • Bile duct injury or leak Prognosis • Gallstone pancreatitis resolves in > 90% of cases Prevention • Treatment of symptomatic cholelithiasis

Choledochal Cyst ESSENTIAL FEATURES • Type I cysts (fusiform dilation of common bile duct [CBD]) account for 85–90% • Type II (true diverticula of CBD) 1–2% of cases • Type III (choledochocele–-dilation of distal/intramural portion of CBD) < 2% of cases • Type IV (multiple cysts involving intrahepatic and extrahepatic ducts) as high as 15% of cases in some series • Type V (cystic malformation of intrahepatic ducts) rare • 3–5% incidence of carcinoma EPIDEMIOLOGY • Onset of symptoms usually in infancy or childhood

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Jaundice • Fever • Pain • Palpable right upper quadrant mass • Hepatomegaly • Bleeding varices • Asymptomatic

LABORATORY FINDINGS • Hyperbilirubinemia • Elevated alkaline phosphatase • Leukocytosis • Elevated amylase and lipase IMAGING FINDINGS • US showing characteristic cystic dilation of biliary tree corresponding to type as well as proximal dilation in presence of obstruction • ERCP or magnetic resonance cholangiopancreatography (MRCP) showing cystic dilation corresponding to type and proximal obstruction in presence of obstruction

WORK-UP • History and physical exam • Liver function tests • CBC • Amylase and lipase • Abdominal US • ERCP or MRCP (adults) • HIDA scan or MRCP (children)

TREATMENT AND MANAGEMENT SURGERY • Cyst excision and biliary reconstruction (types I–III) • Types IV and V individualized and may require partial hepatectomy if unilobar involvement TREATMENT MONITORING • Surveillance for carcinoma since patients still at increased risk for remainder of biliary tree Complications • Biliary stricture or leak • Cholangitis

Cholangiocarcinoma ESSENTIAL FEATURES • Arises from biliary epithelium • Risk factors –Primary sclerosing cholangitis –Choledochal cysts –Clonorchis infection EPIDEMIOLOGY • < 4500 patients per year • Average age, 50–70 years • Evenly distributed among men and women

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Painless jaundice • Right upper quadrant pain • Pruritus • Anorexia • Malaise • Weight loss • Cholangitis • Asymptomatic

LABORATORY and IMAGING FINDINGS LABORATORY FINDINGS • Hyperbilirubinemia • Elevated alkaline phosphatase • Elevated CA 19-9 IMAGING FINDINGS • US showing dilated extrahepatic and intrahepatic biliary ducts (depending on level of tumor) • CT or MRI with biliary dilatation and occasional visible hepatic tumor • Percutaneous transhepatic cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP) visualizing proximal and distal extent of tumor –PTC provides opportunity for brushings for cytologic studies of tumor • Mesenteric angiography for question of portal vasculature involvement

DIAGNOSTIC CONSIDERATIONS • History of pancreatitis (possible benign stricture) • History of ulcerative colitis (possible primary sclerosing cholangitis) • Choledocholithiasis RULE OUT • Extrahepatic disease or bilobar involvement

WORK-UP • History and physical exam • Liver function tests • CA 19-9 • US to screen for anatomic causes of hyperbilirubinemia • Abdominal CT • PTC or MRCP (PTC if brushings needed) • Angiography if portal vessel involvement suspected

TREATMENT AND MANAGEMENT SURGERY • Biliary resection followed by biliary-enteric resection • Extended right or left lobectomy if proximal disease noted (isolated to 1 side) above secondary radicals or if unilateral portal vein or hepatic artery involvement • Pancreaticoduodenectomy (Whipple) for distal common bile duct (CBD) tumors • Biliary-enteric bypass for PTC-placed wall stent for palliation Indications • Resectable cholangiocarcinoma or diagnosis of benign stricture can be difficult to distinguish • Presence of choledochal cyst Contraindications • Bilobar involvement or second order biliary radicals bilaterally • Extrahepatic disease • Main portal vein, bilateral portal vein, or bilateral hepatic artery involvement

Complications • Anastomotic leak or stricture • Cholangitis • Recurrent disease • Liver failure • Hemorrhage Prognosis • 10–30% 5-year survival with curative resection of proximal biliary tumor • 30–50% 5-year survival with distal CBD tumor

Cholangitis, Primary Sclerosing ESSENTIAL FEATURES • Associated with ulcerative colitis 40–60%, pancreatitis 12–25%, diabetes mellitus 5–10%, and rarely other autoimmune disorders • Onset during fourth or fifth decade of life • Increased risk for cholangiocarcinoma

CLINICAL FINDINGS SYMPTOMS AND SIGNS • Intermittent jaundice • Fever • Right upper quadrant pain • Pruritus LABORATORY FINDINGS • Elevated alkaline phosphatase • Hyperbilirubinemia • Leukocytosis IMAGING FINDINGS • Right upper quadrant US, ERCP, and magnetic resonance cholangiopancreatography (MRCP) may show multiple dilatations and strictures of extrahepatic biliary ducts

DIAGNOSTIC CONSIDERATIONS • Cholangiocarcinoma • Presence of cirrhosis RULE OUT

WORK-UP • History and physical exam • Liver function tests • Abdominal US • ERCP • Liver biopsy if question of cirrhosis • Brushings by percutaneous transhepatic cholangiography (PTC) or ERCP if question of malignancy

TREATMENT AND MANAGEMENT SURGERY • Balloon dilatation of multiple strictures • Resection of dominant stricture followed by biliary reconstruction • Liver transplantation (preferably before onset of cirrhosis) Contraindications • Cirrhosis MEDICATIONS • Ursodiol, also known as ursodeoxycholic acid and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. (improves liver function and histology but no difference in 5-year clinical outcome) TREATMENT MONITORING • Alkaline phosphatase levels

Complications and Prognosis Complications • Cholangitis • Recurrent strictures • Primary nonfunction • Allograft rejection • Recurrent stricture post-transplant Prognosis • 85% survival rate 5 years post transplant • 71% actuarial survival at 5 years for resection of dominant stricture (only 20% if cirrhosis present) • 43% long-term success with balloon therapy for multiple strictures

Gallbladder Cancer

Epidemiology 5th most common GI malignancy Women > men High incidence in S America (Chile) pt’s undergoing cholecystectomy for symptomatic gallstones

Risk Factors Gallstones Gallbladder Polyps Chronic Salmonella infection Abnormal Pancreaticobiliary duct junction * Porcelain gallbladder * Age

Presentation/Diagnostic Imaging Presentation is non-specific Diagnositic Imaging Sono CT MR/MRCP EUS

Histology / Pathology * Progression to Ca may take up to 15 yrs Adenocarcinoma 80-90% Anaplastic 7% Squamus 6% Lymphoma, Sarcoma

Staging

Surgical Management Only 10-30% resectable @ time of diagnosis Three Presentations: GB CA discovered during or after lap/open chole for assumed benign dz GB CA suspected after diagnostic evaluation GB CA advanced stage at presentation

Surgical Options Simple cholecystectomy Radical cholecystectomy Radical chole + anatomic liver resection Radical chole + Whipple

What to do during elective lap chole if GB Ca is suspected intraoperatively ? cases found to have GB CA in lap chole Convert to OPEN Resect PORTS No place for laparoscopic resection

Management of locally unresectable (major vascular encasement) NO DEBULKING Chemoradiotherapy No identified impact on survival & remains investigational Systemic chemotherapy – no optimal regimen defined (5-FU based)