06 April 2010

Hepatitis A & B

Hepatitis A

The virus that does not cause chronic liver disease

Hepatitis A
* “Infectious Hepatitis”
* First characterized in 1973
* Detected in human feces
* Hepatovirus genus
* A reportable infectious disease
* U.S. rate of infection 4/100,000
* Highest among children

Risk Factors
* Sexual or household contact
* International travel
* Men who have sex w/ men (MSM)
* Intravenous drug abuse (IVDA)
* Daycare

* Unwitting contact w/ infected person
* Most cases unknown
* Primary route is fecal oral either by person to person contact or ingestion of contaminated food or water

* After ingestion, the HAV survives gastric acid, moves to the small intestine and reaches the liver via the portal vein
* Replicates in hepatocyte cytoplasm
o Not a cytopathic virus
o Immune mediated cell damage more likely
* Once mature the HAV travels through sinusoids and enters bile canaliculi, released into the small intestine and systemic circulation, excreted in feces

Clinical Features
* Incubation is usually 2 to 4 weeks, rarely 6 weeks
* Complete recovery within 2 months for > 50%
* Within 6 months for almost all others
* Low mortality in healthy people
o High mortality when older than age 60
o High in presence of chronic liver disease
* High morbidity
o Around 20% need hospitalization
o Lost work days
o Most become jaundiced
* Asymptomatic < 2 year old * Symptomatic – 5 and older ill about 8 weeks * Cholestatic – jaundice lasts > 10 weeks
* Relapsing w/ 2 or more bouts acute HAV over a 6 to 10 week period
* Acute liver failure – rare in young. When it occurs, is rapid i.e., within 4 weeks

Signs and Symptoms
* Prodrome lasts 1-2 weeks: fatigue, asthenia, anorexia, nausea, vomiting, and abdominal pain
* Less common: fever, cephalgia, arthralgia, myalgia, and diarrhea
* Dark urine is followed by jaundice and hepatomegaly
* Less common: splenomegaly, cervical lymphadenopathy

* During acute infection, anti HAV IgM appears first
* HAV IgG antibody appears early in the course of infection and remains detectable for life, providing lifelong immunity

Prevention Immunization
* All children 12 – 24 months
* Travelers, occupational exposure risk
* All patients w/ hepatitis B or C or those awaiting liver transplantation
* HIV positive patients
* IVD users
* People w/ clotting factor deficiencies
* Lab workers handling live hepatitis A vaccine
* Need for post exposure prophylaxis uncommon. Administration of the vaccine is effective. If needed, administer immune serum globulin within 2 weeks 0.02 ml/Kg IM

Hepatitis A Vaccine
* The vaccine is inactivated HAV
* Schedule for 2 – 18 years depends upon the manufacturer:
o Havirx: 720 EL U/.5mL @ 0, 6-12 mo
o Vaqta: 25 U.5mL @ 0, 6-18 mo
* For those over age 18:
o Havirx: 1440 EL U/1mL @ 0, 6-12 mo
o Vaqta: 50 U/1mL @ 0, 6-18 mo
* Adverse effects: rarely anaphylaxis, injection site induration, erythema, edema, fatigue, mild fever, malaise, anorexia, nausea
* Twinrix:
o 720 El U/1mL 0, 1, 6 mo plus
o 20 mcg HBV

Hepatitis B
The Virus
* The hepatitis B virus is among the smallest genomes of all known animal viruses
* A DNA virus that infects only humans
* Belongs to the family Hepadnaviridae
* Knowledge of the viral proteins that are perceived by the immune system as “antigens” aids understanding of the various tests used to diagnose acute, chronic, and resolved infection and verify response to immunization

HBV Antigens
* Outer envelope contains a surface protein called hepatitis B surface antigen
* HBsAg is a marker of viral replication
* Inner core contains the genome, the DNA polymerase w/ reverse transcriptase activity, hepatitis B core antigen (HBcAg) particles. This antigen is not detectable in serum
* A truncated form of the major core polypeptide known as hepatitis e antigen (HBeAg) is the third antigen generated by virus activity. Marker of high infectivity

Hepatitis B Antibodies
* Hepatitis B surface antibody is the antibody to surface antigen. HBsAb is protective and indicates either resolved infection or immunization
* HBcAb is the antibody to core antigen. This is not a protective antibody. Only those who have been exposed to the virus will have this antibody
* HBcAb is measured in serum as:
o Anti HBc IgM (usually indicates new infection)
o Anti HBc IgG (appears later)
* HBeAb is the antibody to e antigen. Loss of e antigen w/ gain of e antibody is called seroconversion. Not a protective antibody

* Prevalence of HBV varies markedly around the world, w/ > 75% of cases in Asia and the Western Pacific
* Vaccine available > 20 years, but perinatal and early life exposure continue to be a major source of infection in endemic areas
* Most acute HBV cases in the U.S. are seen among young adults, males > females, who use injection drugs and in those who engage in high risk sexual behaviors
* In the U.S., hundreds of people die each year of fulminant HBV
* World wide, chronic HBV and its complications including hepatocellular carcinoma account for > 1 million deaths each year

Risk Factors

* Percutaneous and mucous membrane exposure. The virus is 100 x more infectious than HIV, 10 x more infectious than HCV and is present in all body fluids. Present on horizontal surfaces, eating utensils, personal hygiene items, etc.
* Babies born to infected mother
* Household contact
* Hemodialysis
* Receipt of blood products prior to the early 1970s
* Receipt of previously infected donor liver

Markers of Exposure
* Surface antigen appears as early as 1-2 weeks following exposure, as late as 11-12 weeks
* HBV DNA measurable soon after
* HBeAg appears shortly after HBsAg
* Hepatitis occurs 1 – 7 weeks after appearance of HBsAg

* Governed by interaction between the virus and host immune response
* Following inoculation by the HBV, cytokine release, cell injury and viral clearance follow
* HBsAg disappears by six months and is accompanied by sero conversion to protective HBsAb
* Persistent virus replication after six months ->chronic hepatitis and is the result of a compromised (newborn/HIV) or relatively tolerant immune system status

Four Stages of Infection
* Age at time of infection predicts chronicity in most cases. Infants and young children usually become chronically infected. When acquired in adults, the virus is cleared by the healthy immune system in about 95% of cases, leading to natural immunity
* Immune tolerant phase, there is active viral replication. ALT and AST are normal. Immune system does not recognize HBV as “foreign”
* In the immune clearance phase, enzymes rise reflecting immune mediated lysis of infected hepatocytes. This phase can last for years. Seroconversion of HBeAg to HBeAb occurs

Stages of Infection
* Low or non-replicative phase. Also known as inactive carrier (or inappropriately “healthy carrier”). Characterized by resolution of necroinflammation, normalization of enzymes and low levels of HBV DNA. This stage may last for life
* Reactivation. Spontaneous or immunosuppression mediated (cancer chemotherapy or high dose corticosteroid therapy)

Signs and Symptoms
* Incubation period: a few weeks to 6 months
* About 30% develop jaundice
* 10% to 20% of patients develop serum sickness, i.e., fever, arthralgias, rash
* Fulminant hepatitis B occurs in < 1% of cases. 80% mortality without liver transplantation * Enzyme elevations of 1,000-2,000 typical Signs and Symptoms * Fatigue, RUQ discomfort may be the only symptoms * Those in the immune tolerant phase are usually asymptomatic. The phase lasts until late puberty into adulthood Signs of Decompensation * See section on Cirrhosis and Portal Hypertension * Refer to a liver transplantation center * Patient education for people with chronic liver disease should be reinforced * Refer to “Ten Tips for People w/ Chronic Liver Disease” Prevention * Two forms of vaccine now available. * Twinrix – contains both hepatitis A and B vaccines available in an accelerated schedule or standard series * Individual hepatitis B vaccine * Standard schedule is given: o Time 0 o 1 mo o 6 mo Prevention * Educate to avoid IVDU, high risk sexual activity * Prevent peri natal transmission. Serology of pregnant women for HBsAg is standard of practice in U.S. * If pregnant female has high viremia, refer to hepatologist for treatment during the 3rd trimester to reduce risk of transmission to neonate * Babies of HBsAg mothers receive hepatitis B immune globulin with 12 hours of birth and begin the vaccine series immediately Treatment * Six approved medications as of July 2008 o Interferon alpha o Pegylated interferon o Lamivudine o Adefovir Dipivoxil o Entecavir o Telbivudine o Tenofovir approved * Refer to hepatologist The Cholestatic Liver Diseases Adults Cholestatic Liver Disease Etiologies * Immune Mediated: PBC, PSC, autoimmune cholangitis, liver allograft rejection, graft-versus-host disease * Infectious: acute viral hepatitis * Genetic and Developmental: cystic fibrosis, Alagille’s syndrome (syndrome w/ paucity of intrahepatic bile ducts), fibro polycystic liver disease * Neoplastic: Cholangiocarcinoma * Drug-Induced Ductopenia: amoxicillin, amitriptyline, cyproheptadine, erythromycin, tetracycline, thiabendazole * Ischemic * Idiopathic Pathogenesis of Cholestatic Disorders * Immune response (inflammation, auto-antibody) or hepatotoxic injury to bile ducts * Bile duct injury by bile acids - >
* Retention of bile acids in hepatocytes - >
* Liver cell damage, apoptosis, necrosis, fibrosis, cirrhosis - > liver failure

Complications of Chronic Cholestasis
* Pruritis believed to be 2/2 increased opioid receptor tone, or centrally mediated
* Fatigue
* Bone disease: osteopenia, osteoporosis
* Fat soluble vitamin deficiency
* Malabsorption (Sprue, bile salt deficiency, pancreatic insufficiency)

Pruritis in Cholestasis

* Therapy:
o Urso in AICP, PBC (15-30mg/Kg/day)
o Opiate antagonist naltrexone (50mg/day)
o 5-HT3 antagonist odansetron
o SSRI sertaline
o Bile acid sequesterant cholestyramine 4gm t.i.d. to q.i.d.
o Antihistamines rarely effective
o Rifampin 150mg to 300mg b.i.d.

Fatigue in Cholestasis
* High prevalence in Primary Biliary Cirrhosis unrelated to disease severity or duration
* Pathogenesis
o ?decreased hypothalamic cortico-tropin-releasing hormone
o ?CNS accumulation of manganese
* Prognosis worse
* No effective treatment

Bone Disease in Cholestasis
* Clinical manifestations: low bone density, fractures of axial and/or appendicular skeleton
* Pathogenesis: hyperbilirubinemia impairs osteoblast proliferative activity
* Therapy: bisphosphonates, calcium, vitamin D, weight bearing exercise, estrogens appear to be safe

1. Primary Biliary Cirrhosis
A chronic and progressive disease of unknown etiology affecting primarily middle-aged women

Primary Biliary Cirrhosis
* Affects all races
* 9:1 ratio female > male, age 20 – 65
* Characterized by small intrahepatic bile duct destruction and cholestasis
* In the presence of cirrhosis, male > likely than female to develop hepatocellular carcinoma

Laboratory Findings
* Alk Phos 2x to 20x ULN in > 90% of patients
* AST-ALT 1x to 5x ULN > 90%
* Bilirubin – variable. When elevated, may indicate advanced cirrhosis or 2nd condition
* Hypercholesterolemia in 80% of patients

Hypercholesterolemia Unique in PBC
* Hypercholesterolemia
* IgM 1x to 5x ULN > 90%
* Anti mitochondrial antibody > 1:20 titer >90%
* Anti nuclear and/or smooth muscle antibody > 1:80 may be seen in “overlap syndrome”
* Liver biopsy helpful to grade and stage disease, determine if cirrhosis present

PBC Treatment
* Slowly progressive, even if asymptomatic
* Ursodeoxycholic acid only effective therapy. May improve natural history
* Transplant curative
* Manage disease specific complications

Effects of Ursodeoxycholate
* Urso is a hydrophilic bile acid having multiple anti-inflammatory and immunomodulatory actions
* Urso administration in the setting of pro-apoptotic stimuli (bile salts, ethanol, TGF-beta, FAS ligand) inhibits in vitro apoptosis (programmed cell death)
* Reduces mitochondrial membrane permeability

Monitor for and Treat PBC Associated Disorders
* Keratoconjunctivitis Sicca
* Scleroderma, CREST syndrome
* Gallstones
* Arthropathies:
o Rheumatoid, psoriatic arthritis, Raynaud’s phenomenon, Hypertrophic osteodystrophy, Avascular necrosis, Chondrocalcinosis
* Thyroid disease, renal tubular acidosis

PBC Associated Disorders
* Malabsorption
* Celiac Sprue
o 6% of PBC patients have Celiac Sprue
o 3% of Sprue patients have PBC
* Bile salt deficiency
* Pancreatic insufficiency

Manage PBC Complications
* Standard liver disease recommendations
* PBC specific symptom management
* Refer for liver transplantation
* Primary Sclerosing Cholangitis
* One of the most important cholestatic liver diseases in the western world
* Chronic, cholestatic liver disease characterized by
o Inflammation
o Obstruction
o Fibrosis of both intrahepatic and extrahepatic bile ducts

Primary Sclerosing Cholangitis
* Many patients will progress to cirrhosis
* Highly variable in and between individuals
* Usually fatal important complication is cholangiocarcinoma
* Etiology largely unknown, though evidence points to immune system involvement

* No specific treatment
* Treatment aimed at management of disease associated conditions
* Prevalence unknown
* Almost half are asymptomatic at diagnosis
* No specific diagnostic marker for PSC

PSC Clinical Features
* Labs:
o Two- fold increase in alk phos, most have increased AST and ALT
o Albumin and protime normal in early disease
o Bilirubin initially normal, but gradually increases and fluctuates widely w/ extrahepatic biliary strictures, infection, obstructing stone sludge or stone
* Imaging
* Magnetic resonance cholangio-pancreatography demonstrates intrahepatic duct changes
* Histology
* Liver biopsy for staging the disease
* Liver biopsy to rule out other potentially treatable causes of cholestasis

PSC Patient Presentation
* Large bile duct PSC may have asymptomatic elevation of LFTs. Can be cirrhotic w/ no symptoms
* Symptomatic patients will have cholestasis-type symptoms plus:
o Abdominal pain
o Weight loss
o Hepatomegaly
o Acute cholangitis

PSC Associated Diseases
* Inflammatory bowel disease, most often ulcerative colitis
* These patients have increased risk for colorectal carcinoma
* 25% have another autoimmune disease

PSC Complications
* Related to cholestasis: pruritis, fatigue, fat soluble vitamin deficiency, osteoporosis
* Related to cirrhosis: liver failure, peristomal varices
* Extra-hepatic disease: IBD, pancreatitis, sprue, diabetes, thyroid disease
* PSC specific

PSC Disease Specific Complications
* Fever
* Abdominal pain
* Dominant stricture
* Gall stones
* Cholangiocarcinoma

PSC Prognosis
* Factors of Importance:
o Older age
o Increasing bilirubin
o Histological advanced stage
o Child-Pugh-Turcotte Class C

PSC Treatment Goal Improve Quality of Life
* Medical support
* Endoscopic treatments
* Surgical interventions
* Liver transplantation – PSC recurrence is more frequent than PSC

Case Study

Hepatitis A & B .ppt


Magnetic Resonance CholangioPancreatography

Magnetic Resonance CholangioPancreatography
By:Falguny Bhavan MS4
Oregon Health & Sciences University
Radiology Clerkship

* Introduction
* Technique
* Advantages
* Limitations
* Clinical applications

Anatomy of the Hepato-Biliary and Pancreatic system

* Basic principle: body fluids (bile and pancreatic secretions) have high signal intensity on heavily T2-weighted MR sequences therefore, appear white
o Background tissues generate little signal appear dark
* Stationary or slow-flowing fluid within the bile and pancreatic ducts appears bright relative to low signal intensity produced by adjacent solid tissues
* New MR advancements allow faster imaging in which imaging is performed during single breath-holding session to reduce motion artifact due to respiration
* New variants such as rapid acquisition with relaxation enhancement (RARE) and half-Fourier acquisition single-shot turbo spin-echo (HASTE) can be performed in a breath-hold period with a scan time of <20 seconds provide superior images Advantages * Does not require intravenous or oral contrast material to be administered into the ductal system * Avoids complications of ERCP such as pancreatitis (3-5%), sepsis, perforation, hemorrhage, sedation * Can be completed in 10 minutes, easily performed as outpatient examination * Passive procedure; displays the ducts in the resting state and more accurately displays native caliber of the duct than ERCP. o In ERCP, segments may be overdistended because of attempt to visualize the duct upstream from a stricture, or segments may be underdistended because of the operator's fear of inducing cholangitis or pancreatitis. Limitations * Purely diagnostic, does not provide access for therapeutic intervention (e.g. stone extraction, stent insertion, or biopsy) * Image artifact due to other structures in abdomen with high fluid content * Lack of patient compliance; claustrophobia, inability to breath-hold * Dropout of signal can be caused by metallic clips, crossing defects induced by the right hepatic artery, or from severely narrowed ducts, such as occurs with primary sclerosing cholangitis * Lower resolution than direct cholangiography o Can miss small stones (<4 mm), small ampullary lesions, primary sclerosing cholangitis, and strictures of the ducts Clinical applications: Diseases Diagnosed by MRCP Biliary Disease * Screening examination in patients with low or intermediate probability of choledocholithiasis * Cholangiocarcinoma * Anatomic variants (low or medial duct insertion, aberrant right hepatic duct) * Failed or incomplete ERCP * Post-operative anatomy or screening for biliary complications * Primary sclerosing cholangitis * Cystic disease of bile duct (choledochal cyst, choledochocele, Caroli’s disease) Pancreatic Disease * Anatomic variants (pancreas divisum) * Chronic pancreatitis * Pancreatic cancer Clinical Applications: General guidelines for selection of MRCP or ERCP Obstruction of the Common Bile Duct * MRCP can visualize the normal or dilated common bile duct in 96 to 100 percent of patients. * Strictures typically appear as focal areas of ductal narrowing or signal void with proximal dilatation. * Cause of biliary strictures may be more difficult to determine on the basis of MRCP alone. o lacks specificity o differentiation between benign and malignant causes is based on a combination of clinical, radiographic, and pathological data * Obstruction 2° to calculi, pancreatic adenocarcinoma, or pancreatitis is usually obvious with MRCP, and with aid of conventional MRI or CT Obstruction Combined Biliary-Duct Obstruction and Pancreatic-Duct Obstruction Due to a Small Mass in the Pancreatic Head. The biliary-duct obstruction is indicated by the curved arrow, and the pancreatic-duct obstruction by the straight arrow. The mass was identified on axial, contrast-enhanced, T1-weighted images (not shown) obtained by routine MRI during the same examination. Arrowheads indicate the pancreatic duct. * ERCP is more beneficial in pts with dilatation of the common bile duct who have obstruction at the ampulla, since it permits direct visualization of the ampulla, biopsy of lesions, manometry, or endoscopic sonography. * MRCP Study of 79 cases of biliary obstruction found 14 due to malignant cause; 6 cases due to ampullary carcinoma. o 2 of 6 cases were misdiagnosed as benign obstructions, and 2 cases of benign obstruction were thought to be ampullary cancers. (This study used an early form of the technique, and results may be more accurate with the currently available technology.) * MRCP performed after pharmacologic stimulation with secretin has been shown to be helpful in evaluating ampullary obstruction Secretin-enhanced MRCP * Visualization of the pancreatic duct can be improved with imaging after administration of IV secretin * Secretin frequently used when pancreatic duct is not apparent on MRCP * Reduces the incidence of false positive findings of strictures Secretin-enhanced MRCP Dynamic MRCP with Intravenous Injection of Secretin in Patient with Abdominal Pain after a Whipple Procedure. (ERCP was not attempted because the patient had a pancreaticoenteric anastomosis.) In Panel A, the pancreatic duct (arrowheads) is incompletely visualized on MRCP before the administration of secretin. In Panel B, an MRCP obtained 15 minutes after the administration of secretin shows prominent and prolonged dilatation of the pancreatic duct upstream of a stricture (arrow) at the pancreaticoenteric anastomosis. Common duct stones * Displayed by MRCP as a signal void within bright signal arising from bile * MRCP is a useful means of determining presence or absence of CBD stones, as well as number, size, and location * MRCP is as accurate as ERCP for detecting choledocholithiasis o Sensitivity = 95-100% o Specificity = 85-100% * Increased sensitivity in pts with suspected gallstone pancreatitis, and pts with non-specific abdominal pain and normal LFTs * Stones larger than 4 mm are readily seen but difficult to differentiate from filling defects such as blood clots, tumor, sludge, or parasites o Other mimickers include flow artifacts, biliary air, and a pseudostone at the ampulla * In the presence of a dilated CBD, MRCP has a 90 to 95 percent concordance with ERCP in diagnosing CBD stones over 4 mm in diameter * ERCP is preferred in pts with cholangitis because it allows therapeutic drainage Cholangiocarcinoma * Role of MRCP in the diagnosis and management of bile duct malignancy is not yet defined * Useful noninvasive adjunct * Capability to evaluate the bile ducts both above and below a stricture while also identifying any intrahepatic mass lesions * Study of 126 patients with suspected bile duct obstruction showed that MRCP alone has limited specificity in the diagnosis of malignant strictures o Malignant obstruction dx by MRCP in 12 out of 14 pts o Positive predictive value = 86% o Negative predictive value = 98% Pancreatitis * Acute pancreatitis o MRCP is useful for evaluating bile ducts and cystic duct remnants for stones, for evaluating the pancreatic ducts, and for documenting the presence of cysts in or around the pancreas. o ERCP is often preferred in patients with gallstone pancreatitis since endoscopic papillotomy can be performed in pts with obstructive jaundice or biliary sepsis. * Chronic pancreatitis o MRCP is useful in demonstrating complications such as, ductal dilatation, strictures, intraductal calculi, fistulas, and pseudocysts o Defines ductal anatomy and extent of ductal disease prior to surgical drainage * MRCP is as accurate as ERCP for distinguishing pancreatic cancer from chronic pancreatitis. o In study of 124 patients who were suspected of having pancreatic cancer, pts underwent a number of diagnostic studies, including ERCP and MRCP. The correct diagnosis was confirmed histologically and clinically. 37 patients (30 percent) dx with pancreatic cancer; others had chronic pancreatitis (46 percent) or other causes. o MRCP sensitivity (84%) and specificity (97%) for diagnosis of pancreatic cancer o ERCP sensitivity (70%) and specificity (94%) * Secretin-enhanced MRCP is being increasingly studied for evaluation of pancreatic exocrine function and in the early diagnosis of chronic pancreatitis Variant ductal anatomy * MRCP is also useful in demonstrating variant anatomy and congenital anomalies of the biliary tract and pancreatic duct o Pancreas divisum o Choledochal cyst o Annular pancreas o Abnormal pancreaticobiliary junctions o Aberrant bile ducts * And in evaluation of pts prior to laparoscopic cholecystectomy Normal Extrahepatic Bile Duct and Incidental Pancreas Divisum. Magnetic resonance cholangio-pancreatography is an accurate method of diagnosing pancreas divisum because it shows the dominant dorsal pancreatic duct (arrowheads) continuously from the tail to the head of the pancreas, crossing the common bile duct (curved arrows) and draining at the minor papilla (straight arrow) superiorly and separately from the common bile duct. GB denotes gallbladder. Failed or incomplete ERCP * ERCP is technically challenging o Associated with 10-20% failed cannulation rate o Anatomic variants can contribute to failed ERCP attempts * MRCP is useful in demonstrating variant anatomy o MRCP may have advantages compared to ERCP in specific settings such as pts who have gastric outlet or duodenal stenosis or who have had surgical rearrangement (eg, Billroth II) or ductal disruption, resulting in ducts that can’t be assessed by ERCP * MRCP also allows evaluation of ducts in pts with contraindications for ERCP: o Cervical spine fractures, head and neck tumors, sleep apnea, other diseases/ injuries that preclude placement of endoscope or positioning Post-surgical anatomy Normal Results of Magnetic Resonance Cholangiopancreatograpy in a Patient after Cholecystectomy. Imaging was performed in two seconds with the thick, single-slice technique. The normal common bile duct (arrow) and pancreatic duct (arrowheads) are clearly visible. Du denotes duodenal bulb. References Magnetic Resonance CholangioPancreatography.ppt


Cholangitis & Management of Choledocholithiasis

Cholangitis & Management of Choledocholithiasis
By: Ruby Wang MS 3

* Cholangitis
o Clinical manifestations
o Diagnosis
o Treatment
* Diagnosis and management of choledocholithiasis
o Pre-operative
o Intra-operative
o Post-operative

* HPI:
o 86 yo lady p/w 3-4 episodes of RUQ/mid-epigastric abdominal pain over the last year, lasting generally several hours, accompanied by occasional emesis, anorexia, and sensation of shaking chills.
o ROS: negative otherwise
* PE:
o VS: T 36.2, P98 , RR 18, BP 124/64
o Abdominal exam significant for RUQ TTP
* Labs
o AST 553, ALT 418. Alk Phos 466. Bilirubin 2.7
o WBC 30.3
* Imaging
o Abdominal US: multiple gallstones, no pericholecystic fluid, no extrahepatic/intrahepatic/CBD dilatation
* Cholangitis is bacterial infection superimposed on biliary obstruction
* First described by Jean-Martin Charcot in 1850s as a serious and life-threatening illness
* Causes
o Choledocholithiasis
o Obstructive tumors
+ Pancreatic cancer
+ Cholangiocarcinoma
+ Ampullary cancer
+ Porta hepatis
o Others
+ Strictures/stenosis
+ Sclerosing cholangitis
+ Ascaris lumbricoides
Clinical Manifestations
* RUQ pain (65%)
* Fever (90%)
o May be absent in elderly patients
* Jaundice (60%)
* Hypotension (30%)
* Altered mental status (10%)
Additional History
Additional Physical
Diagnosis: lab values
o 79% of patients have WBC > 10,000, with mean of 13,600
o Septic patients may be neutropenic
* Metabolic panel
o Low calcium if pancreatitis
o 88-100% have hyperbilirubinemia
o 78% have increased alkaline phosphatase
o AST and ALT are mildly elevated
+ Aminotransferase can reach 1000U/L- microabscess formation in the liver
o GGT most sensitive marker of choledocholithiasis
* Amylase/Lipase
o Involvement of lower CBD may cause 3-4x elevated amylase
* Blood cultures
o 20-30% of blood cultures are positive
Diagnosis: first-line imaging
o Advantage:
+ Sensitive for intrahepatic/extrahepatic/CBD dilatation
# CBD diameter > 6 mm on US associated with high prevalence of choledocholithaisis
# Of cholangitis patients, dilated CBD found in 64%,
+ Rapid at bedside
+ Can image aorta, pancreas, liver
+ Identify complications: perforation, empyema, abscess
o Disadvantage
+ Not useful for choledocholithiasis:
# Of cholangitis patients, CBD stones observed in 13%
+ 10-20% falsely negative - normal U/S does not r/o cholangitis
# acute obstruction when there is no time to dilate
# Small stones in bile duct in 10-20% of cases

o Advantages
+ CT cholangiograhy enhances CBD stones and increases detection of biliary pathology
# Sensitivity for CBD stones is 95%
+ Can image other pathologies: ampullary tumors, pericholecystic fluid, liver abscess
+ Can visualize other pathologies- cholangitis: diverticuliits, pyelonephritis, mesenteric ischemia, ruptured appendix
o Disadvantages
+ Sensitivity to contrast
+ Poor imaging of gallstones
Diagnostic: MRCP and ERCP
Magnetic resonance cholangiopancreatography (MRCP)
o Advantage
o Disadvantage:
Endoscopic retrograde cholangiopancreatography (ERCP)

Medical Treatment
* Resucitate, Monitor, Stabilize if patient unstable
o Consider cholangitis in all patients with sepsis
* Antibiotics
o Empiric broad-spectrum Abx after blood cultures drawn
Surgical treatment
* Endoscopic biliary drainage
o Endoscopic sphincterotomy with stone extraction and stent insertion
* Surgery
o Emergency surgery replaced by non-operative biliary drainage
o Once acute cholangitis controlled, surgical exploration of CBD for difficult stone removal
o Elective surgery: low M & M compared with emergency survey
o If emergent surgery, choledochotomy carries lower M&M compared with cholecystectomy with CBD exploration
Our case…
* Condition:
* ERCP attempted
* Laparoscopic cholecystectomy planned
o Dissection of triangle of Calot
o Cystic duct and artery visualized and dissected
o Cystic duct ductotomy
o Insertion of cholangiogram catheter advanced and contrast bolused into cystic duct for IOC
* Intraoperative cholangiogram
o Several common duct filling defects consistent with stones
o Decision to proceed with CBD exploration

* Choledocholithiasis develops in 10-20% of patients with gallbladder disease
* At least 3-10% of patients undergoing cholecystectomy will have CBD stones

Pre-op diagnosis & management
o Diagnosis: Clinical history and exam, LFTs, Abdominal U/S, CT, MRCP
+ High risk (>50%) of choledocholithiasis:
# clinical jaundice, cholangitis,
# CBD dilation or choledocholithiasis on ultrasound
# Tbili > 3 mg/dL correlates to 50-70% of CBD stone
+ Moderate risk (10-50%):
# h/o pancreatitis, jaundice correlates to CBD stone in 15%
# elevated preop bili and AP,
# multiple small gallstones on U/S
+ Low risk (<5%): # large gallstones on U/S # no h/o jaundice or pancreatitis, # normal LFTs o Treatment: + ERCP + Surgery Intra-op diagnosis and management * Diagnosis: intraoperative cholangiography (IOC) o Cannulation of cystic duct, filling of L and R hepatic ducts, CBD and common hepatic duct diameter, presence or absence of filling defects. o Detect CBD stones o Potentially identify bile duct abnormalities, including iatrogenic injuries o Sensitivity 98%, specificity 94% o Morbidity and mortality low * Treatment o Open CBD exploration + Most surgeons prefer less invasive techniques o Laparoscopic CBD exploration + via choledochotomy: CBD dilatation > 6mm
+ via cystic duct (66-82.5%)
+ CBD clearance rate 97%
+ Morbidity rate 9.5%
+ Stones impacted at Sphincter of Oddi most difficult to extract
o Intraoperative ERCP

Early years: Open CBD exploration & Introduction of endoscopic sphincterotomy
* 1889, 1st CBD exploration by Ludwig Courvoisier, a Swiss surgeon
o Kocherization of duodenum and short longitudinal choledochotomy
o Stones removed with palpation, irrigation with flexible catheters, forceps,
o Completion with T-tube drainage
o For many years, this was the standard treatment for cholecystocholedocholithiasis
* 1970s, endoscopic sphincterotomy (ES)
o Gained wide acceptance as good, less invasive, effective alternative
o In patients with CBD stones who have previously undergone cholecystectomy, ES is the method of choice

Open surgery vs Endoscopic sphincterotomy
* In patients with intact gallbladders, ES or open choledochotomy?
o Design: 237 patients with CBD stone and intact gallbladders, 66% managed with ES and rest with open choledochotomy
o Results: No significant difference in morbidity and mortality rates
+ Lower incidence of retained stones after open choledochotomy
o Conclusion: open surgery superior to ES in those with intact gallbladders
* Is ES followed by open CCY superior to open CCY+ CBDE?
o Results: Initial stone clearance higher with open surgery
* Cochraine database of systematic reviews
* In patients with severe cholangitis, open or ES?

Laparoscopic CBD Exploration
* In 1989, laparoscopic removal of gallbladder replaced open surgery
o In the past decade, laparoscopic CBD exploration (LCBDE) developed
* Techniques
o IOC define biliary anatomy: size and length of cystic duct, size of bile duct stones
o Choledochotomy
o Transcystic approach
* Results
Post-op Diagnosis and Management
* T-tube cholangiography
In summary
* Non-surgical care first line
* Surgical Care if endoscopy and IR drainage fail
* Open procedure
* Cholecystectomy
* CBD exploration

Cholangitis & Management of Choledocholithiasis.ppt


Biliary Tumors Cholangiocarcinoma and Cancer of the Gall Bladder

Biliary Tumors Cholangiocarcinoma and Cancer of the Gall Bladder
By: Larry Pennington, MD

Ulcerative Colitis
Thorotrast Exposure
Sclerosing Cholangitis
Typhoid Carrier
Choledochal Cysts
Adult Polycystic Kidney Disease
Liver Flukes

Papillomatosis of Bile Ducts
Extra-hepatic: Distribution
Diagnosis and Initial Workup
Intra and Extra-hepatic Cholangiocarcinoma
Cholangiocarcinoma Intra-hepatic Disease
* Suspicious mass on CT. Quadruple phase CT with 0.5 cm cuts through the liver and portal hepatitis. Consider CTA reconstruction.
* Bx
* If adenoncarcinoma: look for primary with a chest CT and upper/lower endoscopy.
* Colon, pancreas, and stomach are common primary sites.

Cholangiocarcinoma Intra-hepatic Disease-Surgery/Ablation
* Extent of surgical therapy is determined by the location, hepatic function, and underlying cirrhosis.
* Anatomic resections have lowest recurrence rates. However nonanatomic resection increases potential surgical candidates and improves survival.
* Hepatic devascularization prior to resection is preferred
* Ablative therapy gives good local control.

Child’s Classification
Intra-hepatic Disease: Extent of Resection
Intra-hepatic Disease
Representative Case
MRCP of Extra-hepatic Cholangiocarcinoma at the Bifurcation
Klatskin tumor
Cholangiocarcinoma Extra-hepatic
Cholangiocarcinoma Pathology
Extra-hepatic Disease: Surgical Therapy
ERCP: Distal CBD Cancer
Ca of CBD Bifurcation
Node Dissection in Bile Duct Excision
Roux-en-Y Hepaticojejunostomy
Extra-hepatic Disease: Positive Margins or Unresectable
Extra-hepatic Disease: Unstentable
* Bypass if possible
* If not use proximal decompression and feeding jejunostomy
* Chemotherapy/Radiation Therapy/Brachy therapy as tolerated or clinical trial.
Cholangiocarcinoma Prognosis
* Best Result are with distal CBD tumors completely excised. Cure = 40%
* Incomplete resection plus radiation gives a median survival of 30 m.
* Stenting plus chemo/radiation gives a median survival of 17 to 27m
* Those stented alone live only a few months

Cancer of the Gall Bladder
Gall Bladder Cancer
Presentation (1)
Presentation 2
PET Scan and Cholangiocarcinoma
Sclerosing type of Cholangiocarcinoma
Cytological Brushing of Cholangiocarcinoma

Biliary Tumors Cholangiocarcinoma and Cancer of the Gall Bladder.ppt


04 April 2010

OKAP Glaucoma Review

OKAP Glaucoma Review
By:Yara Catoira-Boyle MD

Introduction to Glaucoma

* What is the definition of glaucoma?
* Group of diseases that have in common a characteristic optic neuropathy associated with visual field loss for which elevated IOP is the primary risk factor
* What are the 3 factors that determine IOP?
* Rate of aqueous production by the CB, resistance to aqueous flow (Juxtacanalicular TM) and the level of EVP
* Of those factors, what is the most common cause of increased IOP?
* Increased resistance to outflow
* What is the prevalence of glaucoma in the general population?
* 1.5-2%
* What the percentage of 1st degree relatives of POAG patients will develop the disease?
* 10-15%
* How many people over 45 y/o are estimated to have glaucoma in the US? What % is bilaterally blind?
* 2.25 million / 4%
* 10 million /2%
* 1 million / 5%
* 5 million /4%
* What is the most common cause of nonreversible blindness in AA in the US?
* Glaucoma (prevalence 3-4X higher than whites)
* What are the leading causes of blindness worldwide?
* Trachoma Cataract glaucoma
* Which one is NOT a risk factor for glaucoma?
* Increased IOP and AA race
* Positive family history
* Advanced age
* Thin central cornea
* Male gender
* DM, myopia, HTN, ischemic vascular disease, arteriosclerosis are all inconclusive
* Which one is correct about the prevalence of Chronic angle closure glaucoma?
* Inuit from Arctic Asians Whites
* Men women
* Myopes hyperopes
* Younger older
* Which one is correct about heredity of glaucoma?
* Prevalence among siblings of pts is 20%
* Lifetime absolute risk at age 89 is 10 x higher for relatives of glaucoma patients
* A single gene is likely to be discovered as the culprit
* The gene responsible for mutations of the TIGR (myocilin) protein is located on chromos 5

A little genetics of glaucoma
* TIGR protein produced by TM cells was id’d in Juvenile glaucoma, and later found to affect up to 3% of OAG
* GLC1A, the gene responsible for TIGR mutations is on chromosome 1
* It seems to be an autossomal dominant inheritance of the polygenic type with late or variable age of onset, incomplete penetrance and substantial environmental influence

IOP and Aqueous Dynamics
* What is correct about the aqueous composition?
* Has less hydrogen and chloride than plasma
* Has deficit of ascorbate
* Has excess bicarbonate
* Contains lysozyme, cAMP, steroid hormones and hyaluronic acid
* Which one is true of rate of aqueous production?
* It has a turnover of 1% per minute
* It increases during sleep
* It increases with age
* It increases during ocular inflammation
* What are the 2 major outflow pathways?
* Pressure-dependent/ TM/ conventional
* Pressure-indepdt/ Uveoscleral/ nonconventio
* What is true about facility of outflow?
* Increases with age
* Not affected by surgery, trauma, medications
* Varies widely in normal eyes, mean 0.22 to 0.28 microL/min/mmHg
* What are the 3 parts of the TM?
* Uveal, corneoscleral and juxtacanalicular
* What is false of the TM anatomy?
* TM is composed of many layers of colagenous tissue covered with endothelium
* TM has pressure-dependent flow
* TM functions as a one way valve
* The aqueous leaves the eye by bulk flow
* Laser trabeculoplasty causes apoptosis of Trabecular cells
* What is false about Schlemm’s canal?
* It is lined by endothelium and transversed by tubules
* It is a multiple channel
* Its average diameter is 370 microns
* The inner wall contains giant vacuoles that have direct communication with the intertrabecular spaces
* When IOP is low, blood may reflux into the canal
* The venous path of aqueous includes episcleral veins, anterior cyliary and superior ophthalmic veins and the cavernous sinus
* What is false about the uveoscleral outflow?
* It refers to any nontrabecular outflow
* Aqueous passes from the AC into the CBM and then into the supraciliary and suprachoroidal spaces
* It is decreased by cycloplegia, adrenergic agents, PG analogs and cyclodyalisis surgery
* It is also decreased by miotics
* It accounts for at least 5-15% of outflow

IOP and Aqueous
* What effect the following medications have on uveoscleral outflow?
* Cycloplegics
* Miotics
* Epinephrine
* Xalatan
* Brimonidine
* Timoptic ....

Clinical Evaluation
* Associate the external adnexae finding with a diagnosis associated with glaucoma
* “ash-leaf” sign
* Plexiform neuroma of upper lid
* Nevus of Ota
* Microdontia or hypodontia
* Port-wine stain (facial cutaneous angioma)
* Yellow or orange papules of skin of head/neck
* EOM restriction, proptosis, pulsating exophthalmos
* What is the type of glaucoma associated with the following corneal signs?
* Krukenberg spindle
* Exfoliating material on anterior chamber
* Keratic precipitates
* “stelate” KP’s
* “beaten bronze” appearance or corneal edema with iris changes
* What is not a possible cause of blood in Schlemm’s canal on gonioscopy
* Compression of episcleral veins with lip of goniolens
* Hypotony
* CC fistula
* Sturge-Weber syndrome
* Dilation of the pupil
* What is false about gonioscopy:
* Normal angle vessels are usually radial along the iris or circumferential on the CB
* Abnormal vessels cross the SS to reach the TM
* The nonpigmented TM is posterior to the pigmented TM
* A C angle indicates that SS is visible
* List potential causes for increased TM pigmentation:
* Malignant melanoma
* Trauma
* Surgery
* Hyphema

* It is false about gonioscopy
* It is necessary to see the angle due to total internal reflection at the tear-air interface (critical angle approximat 46’)
* Koeppe and Barkan lenses are examples of direct gonioscopy, most used in the OR
* Goldmann, Zeiss and Sussman lenses are used for indirect gonioscopy in the office
* Dynamic gonioscopy is done by asking the patient to move his eye
* It is false about gonioscopy
* The order of structures from anterior to posterior is: Schwalbe’s line-nonpigm TM-pigment TM-scleral spur-ciliary body-iris root
* Multiple methods of classification exist
* A Shaffer grade 4 angle is the narrowest
* Spaeth’s classification C40R indicates a normal and open angle

Clinical Evaluation
* What is angle recession and how is it different from cyclodyalisis on gonio:
* Angle recession is a tear between the longitudinal and circular muscles of CB= widened CB band
* Cyclodyalisis is a separation of the CB from the SS= gap between CB and sclera
* What is false of the Optic Nerve:
* Consists of about 1.2-1.5 million RGS axons
* The RGC cell body is in the ganglion cell layer of the retina
* The diameter of the intraocular ONH is about 2.5 mm
* There are 2 types of RGC’s: Magnocellular and Parvocellular...
* What percentage of patients with OAG have a screening IOP below 22?
* 30-50%
* What is the average corneal thickness by optical and ultrasound measurements?
* 534 optical and 544 ultrasound
* In the AGIS, patients had significantly better outcomes if their IOP was:
* Below 18 at all visits
* Below 18 50% of visits
* Below 14 at all visits
* Below 14 50% of visits....
Secondary OAG
* What is false about PXF?
* The odds of exfoliation glaucoma are 40% in 10 years
* The angle is often narrow with a +4 pigmented TM and a Sampaolesi line inferior
* The hyaline material is found on the lens, pupil margin, CB epithelium, iris PE, iris stroma, iris blood vessels and subconjunctiva
* SLE features include iris TI at pupil margin and iridodonesis or phacodonesis....
Traumatic OAG
* About hyphemas, is false:
* Sicke cell patients may have severe glaucoma from small hyphemas
* Acute IOP elevations may lead to AION or CRAO in patients with sickle cell
* Treatment consists of corticosteroids, cycloplegics, eye shield, limited activity, head elevation
* Aminocaproic acid is advocated since it has very few side effects and decreases rebleed
* Which drug is the best choice to control IOP in a hyphema patient with sickle cell diz?
* IV Diamox
* Iopidine
* Manitol
* Pilocarpine
* Timolol
* Regarding secondary glaucomas, which one is false?
* UGH syndrome can happen secondary to erosion of IOL haptic into the iris or CB
* UGH presents with chronic inflammation, iris NV, recurrent hyphemas
* Schwartz-Matsuo syndrome refers to elevated IOP after RD due to photoreceptor outer segmemts blocking of TM
* PKP related glaucomas can be of open or closed angle mechanism
* About 50% of people will have some elevation of IOP with the use of topical steroids
* About ACG epidemiology, what is incorrect?
* 10% of the 67 million cases of glaucoma worldwide are of ACG
* Predominant form of glaucoma in East Asia
* PACG is responsible for 91% of the bilateral blindness in China
* About the mechanisms of ACG, the incorrect is:
* Pupillary block is the most common cause of angle closure, including primary AC
* NVG is a type of ACG without pupillary block
* Marfan’s synd and Homocystinuria can lead to pupillary block by lens dislocation
* In Aniridia, Glaucoma is of open type since pupillary block can’t happen due to lack of iris
Primary ACG
* About the risk factors for ACG, the wrong one is:
* The prevalence varies with race: AA whites Japanese East asians Inuits
* White pts tend to have acute AC, while AA and asians have chronic asymptomatic diz
* Shallow AC, thick lens, short AL, small corneal diameter and radius increase risk
* Ages 30-50 are the highest risk
* More common in women and hyperopes

Acute PACG
* What is false about Acute PACG?
* Mild attacks can be broken with Pilocarpine 1-2%, but should avoid stronger miotics
* At IOP 40-50 the pupillary sphincter is too ischemic to respond to miotics and should use aqueous supressants, diamox or manitol
* The chance of acute attack in the fellow eye is 40-80% in 1 year
* High IOP during an acute attack may lead to ischemic nerve damage or retinal vascular occlusion

* What is false of iris and ACG?
* Both mydriasis and miosis can cause acute angle closure in a predisposed eye with shallow AC
* Miotics relax the lens zonules allowing it to sit forward in the AC, decreasing irido-lenticular touch
* Systemic medications including allergy, cold medicines, antidepressants, anticholinergics and topamax carry warning against glaucoma
* Peripheral iridectomy is indicated in patients with critically narrow angles, PAS, h/o previous attack, AC depth 2.0mm, +family history, +provocative test...
Childhood Glaucoma
* Mark the false :
* Primary congenital is the same as infantile glaucoma
* Glaucoma recognized after age 3 is termed Juvenile Glaucoma
* Glaucoma may present with buphthalmos if the IOP elevation starts after age 3
* Developmental glaucoma refers also to secondary glaucomas associated with inflammatory, neoplastic, hamartomatous, metabolic or congenital ocular or systemic anomalies
* Mark the false
* Congenital glaucoma is usually primary(50-70%)
* It is a rare disease (1:10,000 births)
* 60% are diagnosed in the first 6 months, 80% by one year
* 65% are female and bilateral in 70%
* Axenfeld-Rieger syndrome and aniridia are conditions associated with infantile glaucoma...
Medical therapy of glaucoma
* About beta blockers, which one is false:
* Betaxolol is selective for Beta 1 receptors
* They reduce aqueous production by 20-50%
* Are very additive to epinephrine
* Metipranolol was reported to cause iritis
* Effect starts within one hour and may last 4 weeks
* Tachyphylaxis and short term scape are seen
* Are contra-indicated in myasthenia gravis
Surgical Therapy
* What is false about surgical therapy of OAG?
* Usually undertaken when medical therapy fails
* LTP may be considered as a initial step in therapy since it decreases IOP by 20-25%
* The GLT showed that LTP patients did better than medication patients
* LTP is particularly effective in XFG and PG....

OKAP Glaucoma Review.ppt

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