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Dr Julia Epstein Gastroenterology department Hadassah Medical center. Biliary Tract Disease. Biliary disease. Gallstones Congenital anomalies Extrinsic compression of the bile ducts Hepatobiliary parasitism Noncancerous strictures. Biliary tract anatomy. Ampullary anatomy.

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Biliary tract disease

Dr Julia Epstein

Gastroenterology department

Hadassah Medical center

Biliary Tract Disease


Biliary disease
Biliary disease

  • Gallstones

  • Congenital anomalies

  • Extrinsic compression of the bile ducts

  • Hepatobiliary parasitism

  • Noncancerous strictures



Ampullary anatomy
Ampullary anatomy

Biliary duct sphincter

Pancreatic duct sphincter

Papilla of Vater

Sphincter of Oddi


כיס מרה

  • מבנה אגסי 7.5-10 ס"מ

  • • תכולה 30-50 ס"מ

  • • מרה מיוצרת←כבד

  • • מרה נאגרת←כיס מרה

  • CCK• אוכל שומני←תרסריון←הפרשת מרה מתכווץ +

  • ספינקטר ע"ש אודי נפרה ← מעבר מיצי מרה לתריסריון

  • • ספיגה מחדש לוריד הפורטלי←חזרה לכבד Enterohepatic Circulation : כבד←מרה←מעי


מיצי מרה

מכיל: מים, אלקטרוליטיים -

Na, K, Ca, Cl, HCO3

לציטין,חומצות שומן, כולסטרול,

בילירובין ומלחי מרה

מאיפה מגיע בילירובין?

תפקיד:

– ספיגה של השומנים לאחר תהליך אמולסיפיקציה

– שפעול מיצי הלבלב

– המרה (בסיסית) סותרת את מיץ הקיבה החומצי

המגיע לתריסריון.


מבנה מרה

  • מלחי המרה ← מסיסים במים

  • פוספוליפידים + הכולסטרול ← לא מסיסים במים

  • הופכים למסיסים שנוצרות מיצלות

  • היחס בין שלושת המרכיבים עדין

  • כל חריגה מהיחס המסוים ←

  • מרה רוויה + שקיעה של

  • כולסטרול (יצירת אבנים)



Gallstones pathophysiology
Gallstones – Pathophysiology

  • Cholesterol, ordinarily insoluble in water, comes into solution by forming vesicles with phospholipids

  • If ratio of cholesterol, phospholipids, and bile salts altered, cholesterol crystals may form

  • Gallstone formation involves a variety of factors:

    • Cholesterol supersaturation

    • Mucinhypersecretion by the gallbladder mucosa creates a viscoelastic gel that fosters nucleation.

    • Bile stasis



Gallstones
Gallstones

  • Risk factors:

  • Obesity

  • Female gender

  • Parity

  • Maternal family history ( ABCB4 , CYP7A1)

  • Ethnic predilection (Hispanic, Native americans)

  • Increasing age

  • Rapid weight loss


Gallstones1
Gallstones

  • Risk factors:

    Ileal disease

    Lipid abnormalities (high TG, low LDL)

    Medications (contraceptives, postmenopausal

    estrogens, lipid lowering agents

    fibric acid derivated)

  • TPN


5 f s
5F’s

  • Fair

  • Fat

  • Fertile

  • Female

  • Forty


מצבים שכיחים

  • Cholelithiasis

  • Biliary colic

  • Hydrops

  • Empyema

  • Choledocholithiasis

  • Acute Cholecystitis

  • Ascending Cholangitis


Gallstones types
Gallstones – Types

  • Two main types:

    • Cholesterol stones (85%)

    • Pigment stones (15%) occur in 2 subtypes—

      brown and black.

      • Black stones result when excess bilirubin enters the bile and polymerizes into calcium bilirubinate (chronic hemolysis)

      • Brown stones are made up of calcium bilirubinate and calcium-soaps. Bacteria involved in formation via secretion of beta glucuronidase and phospholipase


Gallstones natural history
Gallstones – Natural History

  • 80% of patients, gallstones are clinically silent

  • 20% of patients develop symptoms over 15-20 years (1-2% per year)

  • 50-70% continued to have symptoms and complications

  • More than 90% of complications are preceded by biliary colic


Biliary colic
Biliary Colic

  • Intermittent obstruction of the cystic duct, no inflammation of GB

  • Severe epigastric/ RUQ pain growing over 15 min and remaining constant up to 3h

  • Frequency of attacks varies

  • Normal examination

  • Lab tests usually normal

  • DS: US, EUS

  • Natural history: 30% have no further symptoms

    50% continue symptoms in 2y


Acute calculous cholecystitis
Acute Calculous Cholecystitis

  • Impacted stone in the cystic duct

  • 75% are preceded by attacks of biliary colic

  • Visceral epigastric pain – mod to severe, irradiated to RUQ, back, shoulder, chest and lasting > 6 h

  • Fever, Right subcostal tenderness with inspiratory arrest

    ( Murphy’s sign) , palpable GB

  • Leucocytosis, mild elevation of BIL, Amylase

  • 50% resolve spontaneously in 7-10 days without surgery

  • DS: US, EUS, CT

  • 10% are complicated by perforation.


Empyema mucocoele
Empyema / Mucocoele

  • Mucocele refers to an overdistended gallbladder filled with mucoid or clear and watery content.

  • Empyema refers to a gallbladder filled with pus due to acute cholecystitis


Choledocholithiasis
Choledocholithiasis

  • Intermittent obstruction of CBD

  • Often symptomatic – indistinguishable from biliary colic

  • Predisposed to acute cholangitis and pancreatitis

  • Signs : jaundice with pain.

  • Investigations

    • Elevated BIL, transient spike in Tranaaminases / Amylase,

    • US, EUS, CT

  • Treatment

    • ERCP - Endoscopic Retrograde CholangioPancreatography


Ascending cholangitis
Ascending Cholangitis

  • Impacted stone in CBD causing bile stasis

  • Bacterial superinfection

  • Charcot’s triad : pain, jaundice, fever – 70%

  • Mental confusion, hypotension, RUQ tenderness

  • Jaundice (>80%)

  • Peritoneal signs (15%)

  • Elevated WBC, BIL, APH (blood cult usually pos)

  • Emergent decompression of the CBD

    (ERCP, PTC)


Acute biliary pancreatitis
Acute biliary pancreatitis

  • Pancreatic duct obstruction or chemical inflammation

  • Signs - Variable – None to Sepsis

    (Severe pain, fever, tachycardia, low BP),

    Jaundice, acute abdomen

  • Investigations

    • Bloods – U&E, FBC, LFT, Amylase, CRP

    • Ultrasound of abdomen

    • MRCP

    • CT Pancreas

  • Treatment Supportive / ERCP


  • Gallstone ileus
    Gallstone ileus

    • Obstruction of the small bowel by a large gallstone

      • A stone ulcerates through the gallbladder into the duodenum and causes obstruction at the terminal ileum/rt colon

    • Symptoms : SBO - vomiting, abdominal pain, distension, obstructive bowel sounds

    • Investigations: X-ray, US/CT - air in CBD

    • Treatment : Laparotomy and removal of stone from small bowel and cholecystectomy.


    Mirizzi s syndrome
    Mirizzi’s Syndrome

    Inflammatory phenomenon secondary to a pressure ulcer caused by an impacted gallstone at the gallbladder infundibulum

    The impacted gallstone causes first external obstruction of the CBD

    Eventually erodes into the bile duct evolving into a cholecystocholedochal fistula with different degrees of communication between the GB and CBD



    Lemmmel s syndrome
    Lemmmel’s Syndrome

    Duodenal diverticula syndrome

    Secondary to extrinsic compression by periampullarydiverticula in the absence of additional pathology (cholelithiasis, tumor)

    • The hypothesized mechanisms:

    • Alterations of the papillary motility

    • Bacterial contamination

    • Extrinsic compression of the Main biliary tract



    Acute acalculous cholecystitis
    Acute Acalculous Cholecystitis

    • Presence of an inflamed gallbladder in the absence of an obstructed cystic or common bile duct

    • Typically occurs in the setting of a critically ill patient (eg, severe burns, multiple traumas, lengthy postoperative care, prolonged intensive care)

    • Accounts for 5% of cholecystectomies

    • Etiologyis thought to have ischemic basis, and gangrenous gallbladder may result

    • Increased rate of complications and mortality

    • An uncommon subtype known as acute emphysematous cholecystitis generally is caused by infection with clostridial organisms and occlusion of the cystic artery associated with atherosclerotic vascular disease and, often, diabetes.


    Cholecystectomy
    Cholecystectomy

    • Laparoscopic cholecystectomy standard of care

    • Timing

      • Early vs interval operation

    • Patient consent

      • Conversion to open procedure 10%

      • Bleeding

      • Bile duct injury

      • Damage to other organs


    Biliary disease1
    Biliary disease

    • Gallstones

    • Congenital anomalies

    • Extrinsic compression of the bile ducts

    • Hepatobiliary parasitism

    • Noncancerous strictures


    Biliary tract cysts
    Biliary Tract Cysts

    • Choledochal cysts

    • Consist of cystic dilatations of the extra-hepatic biliary tree

    • Uncommon abnormality and 90% diagnosed before age 30

    • Infantile form presentation identical to biliary atresia

    • 50% present with combination of jaundice, abdominal pain, and an abdominal mass


    Choledochal cysts
    Choledochal cysts

    • Classified into 5 types

    • Can occur in the presence of pancreatico-biliary maljunction (PBM)

    • Treatment for choledochal cysts is surgical excision of the cyst with construction

    • Most ominous complication is malignancy


    Choledochal cysts1
    Choledochal cysts

    PBM

    Caroli disease


    Biliary ductopenic disorders
    Biliary ductopenic disorders

    • Paucity of interlobular bile ducts - 2 types: syndromic and non syndromic

      Syndromic ( Alagille’s syn)

      ADD d/t JAG1 gene

      Intrahepatic cholestasis and biliary hypoplasia

      Pruritus and hepatomegaly

      Extrahepatic manifeatations - congenital heart

      defects, eye defects, triangular face


    Biliary ductopenic disorders1
    Biliary ductopenic disorders

    • interlobular ductopenia as result of inflammatory condition:

    • PSC

    • PBC

    • GVHD

    • Liver allograft resection

    • Drug induced liver disease

    • idiopathic


    Biliary disease2
    Biliary disease

    • Gallstones

    • Congenital anomalies

    • Extrinsic compression of the bile ducts

    • Hepatobiliary parasitism

    • Noncancerous strictures


    Extrinsic compression of the bile ducts
    Extrinsic compression of the bile ducts

    • Biliary tract tumor

    • Carcinoma of the head of pancreas

    • Acute and chronic pancreatitis

    • Lymph nodes – lymphoma or metastasis

    • Benign stricture of biliary ducts


    Biliary tract tumor cholangiocarcinoma cancer of the gall bladder
    Biliary Tract TumorCholangiocarcinoma Cancer of the Gall Bladder


    Cholangiocarcinoma
    Cholangiocarcinoma

    • Slow growing malignancy of biliary tract which tend to infiltrate locally and metastasize late

    • 90% adenocarcinoma

    • 60-70% at the bifurcation ofhepatic ducts

    • 20-30% - in the distal CBD

    • 5-10% - arise within the liver (peripheral)


    Biliary tree neoplasms
    Biliary Tree Neoplasms

    • Clinical symptoms:

      • Weight loss (77%)

      • Nausea (60%)

      • Anorexia (56%)

      • Abdominal pain (56%)

      • Fatigue (63%)

      • Pruritus (51%)

    • Symptomatic patients usually have advanced disease, with spread to hilar lymph nodes before obstructive jaundice occurs

    • Associated with a poor prognosis

    • Fever (21%)

    • Malaise (19%)

    • Diarrheoa (19%)

    • Constipation (16%)

    • Abdominal fullness (16%).


    Risk factors
    Risk factors

    • Liver flukes (Opistorchis viverrini, Chlonorchis sinensis)

    • Chemial exposition (Asbestosis)

    • Congenital predisposition (PBM, Choledochal cysts)

    • Intrahepatic biliary stones

    • PSC


    Cholangiocarcinoma diagnosis and initial workup
    CholangiocarcinomaDiagnosis and Initial Workup

    • Jaundice

    • Weight loss, anorexia, abdominal pain, fever

    • US – bile duct dilatation

    • 3-phase CT

    • MRCP/MRI

    • ERCP with Brush biopsy

    • PercutaneousCholangiography with Internal Stent and Brush Biopsy


    MRCP: Cholangiocarcinoma at the Bifurcation

    Klatskin tumour - Cholangiocarcinoma of junction of right & left hepatic ducts



    Surgical removal only 25 resectable at the time of diagnosis
    Surgical Removal – only 25%resectable at the time of diagnosis

    • Node Dissection in Bile Duct Excision

    • Roux-en-Y Hepaticojejunostomy


    Cholangiocarcinoma1
    Cholangiocarcinoma

    Palliative therapy :

    • Stent

    • Chemotherapy +/- Radiation Therapy

    • Survival with surgery and chemo/radiation is 24 to 36 months

    • With chemotherapy / radiation alone survival is 12 to 18 months

    • Liver transplantation – 80% 5-y survival rate

    • In selected patients who complete chemo-radiation protocol


    Gallbladder cancer
    Gallbladder Cancer

    • 6th decade

    • 1:3, Male:Female

    • Highest prevalence in Israel, Mexico, Chile, Japan, and Native American women.

    • Risk Factors: gallstones, porcelain gallbladder, polyps, Salmonella typhi carrier state, some drugs


    Gall bladder cancer
    Gall Bladder Cancer

    • Uncommonly diagnosed preoperatively

    • >80% with gallstones

    • Clinical manifestation from abdominal pain to unexplained weight loss and jaundice

    • Palpable RUQ mass

    • Jaundice suggests local extention with ductal obstruction

    • DS: US, EUS, CT


    Gall bladder cancer1
    Gall Bladder Cancer

    • Discovered on pathology after a routine cholecystectomy (1-2%)

    • If negative for metastasis:

      • Radical cholecystectomy with nodal dissection, central hepatectomy, w or w/o bile duct excision

      • Excise port sites

      • Followed by Chemo/Radiation

    • 5 year survival = 60%


    Gallbladder cancer1
    Gallbladder Cancer

    • Cholecystectomy should not be offered for all patients with stones for fear of cancer

    • Cholecystectomy should be considered for calcified GB and for growths (adenomyoma, polyps > 15 mm)


    Pancreatic cancer
    Pancreatic cancer

    • Pancreatic cancer is the most common malignant cause, followed by cancers of the gallbladder, bile duct, liver, and large intestine.


    Metastasis
    Metastasis

    • 1st category involves local extension into the hilum by a tumor arising in an adjacent structure, such as the gallbladder, cholangio CA

    • The 2nd - includes metastases from a distant primary site, most often from solid tumors, such as carcinoma of the breast, colon, ovaries or lymphoma, melanoma

    • Mechanical cholestasis caused by the stricture,

      mostly of the common hepatic or common bile duct

      Patients have severe jaundice and associated symptoms such as pruritis, recurrent cholangitis and malaise.



    Biliary disease3
    Biliary disease

    • Gallstones

    • Congenital anomalies

    • Extrinsic compression of the bile ducts

    • Hepatobiliary parasitism

    • Noncancerous strictures


    Hepatobiliary parasitism
    Hepatobiliary parasitism

    • Pyogenic cholangitis &hepatic abscess, ductal stones, biliary obstruction

    • Clonorchis sinensis, Opisthorchis viverrini, O. felineus, Fasciola hepatica

    • Ascaris lumbricoides, Echinococcus spp.


    Clinical manifestation of hydatid cyst
    Clinical manifestation of hydatid cyst

    • Most patients with hepaticuncomplicatedhydatid cyst are asymptomatic

    • Possible symptoms and signs are: RUQ pain , epigastric pain , fever , fatigue , nausea and dyspepsia ,hepatomegaly and abdominal mass

    • Complications:

    • Superinfection of hydatid cysts

    • Rupture to adjacent structures (peritoneal spillage,

    • cholangitis, pancreatitis, anaphylaxis)

    • Rare – portal HTN, hepatic vein thrombosis,

      secondary biliary cirrhosis


    Diagnosis
    Diagnosis

    • History of exposure

    • Chest and abdominal X-ray

    • Ultrasound (diagnostic method of choice)

    • CT (better information about location, depth , mandatory

      before planning operation)

    • MRI (for NS, venous system and biliary complications )

    • Serology (positive – confirms infection, negative test

      does not exclude)


    Gharbi s us classification
    Gharbi’s US classification

    • Type I - Pure fluid collection

    • Type II - Fluid collection with a detached membrane

    • Type III - Fluid collection with multiple septa and or daughter cysts

    • Type IV - Hyperechoic with high internal echoes

    • Type V - Cysts with reflecting, calcified walls





    Treatment of hepatic hydatid cyst
    Treatment of hepatic hydatid cyst

    • The treatment of hepatic hydatid cysts is strongly indicated in order to prevent cyst complications

    • The therapeutic options are:

      1. Surgical intervention – remains thecornerstone of radical treatment

      2. Percutaneous drainage

      3. Drug therapy


    Surgical options
    Surgical options

    • Open surgical techniques

    • Radical removal of pericystic membrane and parasitic content

    • Marsupialization(partial cysto-pericystectomy)

      Contraindications: severe comorbidity

      Complications: biliary fistula, cyst infection, pleural effusion, peritonitis, abscess, anaphylactic shock

    • Laparoscopic surgery

      Contraindications: Deep intraparenchimal cysts

      > 3 cysts, with thick calcified wall

      Complications: intra-abdominal seeding due to pneumoperitoneum


    Paliative procedures
    Paliative procedures

    • PAIR - puncture-aspiration-injection-reaspiration

      Indicated for type I , II and III cysts

      Inoperable patients, pregnant women

      Multiple disseminated cysts

    • Contraindications:

      IV, V types of cysts,

      ruptured cysts into biliary tree or peritoneum

    • ERCP – Naso-biliary drainage – biliaryendoprosthesis

    • Combined therapy with albendazole is an effective and safe alternative to surgery for uncomplicated hydatid cysts

      (Khuroo et al, 1998)


    Indications for drug therapy who guidelines 1996
    Indications for drug therapy:WHO Guidelines 1996

    • Inoperable primary liver or lung echinococcosis

    • Multiple echinococcalmultiorgan and peritoneal cysts

    • Preoperative or pre-drainage (at least 4 days before surgery and 1 m (ABZ) or 3 m (MBZ) after)

    • Poor patient status

      Contraindications:

    • Large cysts that are at risk of rupture

    • Pregnancy ,chronic liver disease or depressed BM


    Biliary disease4
    Biliary disease

    • Gallstones

    • Congenital anomalies

    • Extrinsic compression of the bile ducts

    • Hepatobiliary parasitism

    • Noncancerous strictures


    Biliary stricture non cancerous cause s
    Biliary Stricture – Non Cancerous Causes

    Noncancerous causes of bile duct stricture include:

    • Injury to the bile ducts during surgery for gallbladder removal

    • Pancreatitis (inflammation of the pancreas)

    • Primary sclerosingcholangitis

    • Gallstones (benign CBD stricture, papillary

      stenosis

    • Blunt trauma to the abdomen


    Primary sclerosing cholangitis
    Primary Sclerosing Cholangitis

    • Chronic cholestatic biliary disease characterized by non-suppurativeinflammation and fibrosis of the biliary ductalsystem

    • Cause is unknown but is associated with autoimmune inflammatory diseases, such as chronic ulcerative colitis and Crohn’s colitis, and rare conditions, such as Riedel thyroiditis and retroperitoneal fibrosis

    • Most patients present with fatigue and pruritus and, occasionally, jaundice


    PSC

    • Natural history is variable but involves progressive destruction of the bile ducts, leading to cirrhosis and liver failure

    • Clinical features of cholangitis (ie, fever, right upper quadrant pain, jaundice) are uncommon unless the biliary system has been instrumented.



    PSC

    Medical Care

    • Chronic progressive disease with no curative medical therapy

    • Goals of medical management are to treat the symptoms and to prevent or treat the known complications

    • Liver transplantation is the only effective therapy and is indicated in end-stage liver disease.

      Surgical Care

    • Indications for liver transplantation include variceal bleed or portal gastropathy, intractable ascites, recurrent cholangitis, progressive muscle wasting, and hepatic encephalopathy.

    • Recurs in 15-20% of patients after transplantation.


    Primary biliary cirrhosis
    Primary Biliary Cirrhosis

    • Progressive cholestatic biliary disease that presents with fatigue and itching or asymptomatic elevation of the alkaline phosphatase.

    • Jaundice develops with progressive destruction of bile ductules that eventually leads to liver cirrhosis and hepatic failure.

    • Autoimmune illness has a familial predisposition


    PBC

    Antimitochondrial antibodies (AMA) are present in 95% of patients

    Goals of treatment are to slow the progression rate of the disease and to alleviate the symptoms (eg, pruritus, osteoporosis, sicca syndrome)

    Liver transplantation appears to be the only life-saving procedure.


    ERCP

    Endoscopic retrograde

    cholangiopancreatography (ERCP)

    • Endoscopictube is placed into the patient’s mouth, through the stomach, and into the duodenal portion of the small intestine.

    • Contrast is introduced into the biliary tract through the endoscope, in a retrograde manner.

    • X-rays taken


    ERCP

    • ספינקטרוטומיה

    • הוצאת אבנים (בלון, בסקט), ריסוק אבנים

    • הכנסת סטנטם


    PTC

    הזרקת חומר ניגוד דרך עור לדרכי מרה

    התוך כבדיים תחת סונר והדמיה ברנטגן


    PCC

    • PerCutaneous Cholecystostomy

    • במקרים קשים בהם ניתוח עלול לסכן את החולה – ניקוז מרה בשיטה מלעורית


    Indications for biliary stenting
    Indications For BiliaryStenting

    Indications for stent insertion include:

    • AmpullaryStenosis

    • Bile duct injury

    • Benign or malignant biliary obstruction

    • Prevention of obstruction where stone extraction is not possible at that time

    • Pancreatic duct strictures, stones and sphincter of Oddi dysfunction


    Stent placement endoscopic approach
    Stent Placement -Endoscopic Approach

    • A catheter is inserted through the endoscope into the ostium of the common bile duct.

    • While maintaining the endoscope position in the duodenum, a wire is inserted through the catheter into the bile duct.

    • The stent delivery system is then inserted over the wire to the site of obstruction, where the stent is deployed.


    Stent placement endoscopic approach1
    Stent Placement – Endoscopic Approach

    Success rate of ERCP 90-95%

    Complication rate of approximately 3-5%.

    Complications:

    • Pancreatitis

    • Bleeding

    • Perforation

    • Infection

    • Cardiopulmonary depression from conscious sedation.


    Biliary stent percutaneous transhepatic a pproach ptc
    Biliary Stent - Percutaneoustranshepatic approach PTC

    For biliary stent placement using a percutaneous approach:

    • A fine needle is inserted between the 4th and 5th rib on the patient’s right side

    • The puncture is through the liver

    • The needle is inserted into an intrahepatic duct under image guidance.

    Photo on file at Medtronic


    Biliary stent percutaneous approach
    Biliary Stent - Percutaneous Approach

    Success rate 95% when ducts are dilated

    • 5-10% rate of major complications which include:

    • Sepsis

    • Bile leak

    • Intraperitoneal haemorrhage, Haemobilia

    • Hepatic and perihepatic abscess, Pneumothorax

    • Skin infection and granuloma at the catheter entry site

    • Contraindicated in patients with bleeding diatheses and significant ascites.


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