Medchrome » Hepato-biliary

Hepatocellular Carcinoma or Liver Cancer

Administrator — Sun, 30 May 2010 15:31:08 +0000

Hepatocellular Carcinoma Or Liver Cancer: Causes, Clinal Features, Diagnosis and Management

• Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte, generally leading to death within 6-20 months.
• Hepatocellular carcinoma frequently arises in the setting of cirrhosis, appearing 20-30 years following the initial insult to the liver.
• 25% of patients have no history or risk factors for the development of cirrhosis.
• currently one of the most common worldwide causes of cancer death

Massive Liver tumor

Epidemiology: worldwide (China, sub-Saharan Africa, Japan)

Pathophysiology
• Tumors are multifocal within the liver 75% of the time. Late in the disease, metastases may develop in the lung, portal vein, periportal nodes, bone, or brain.

Mortality/Morbidity

Cure, usually through surgery, is possible in fewer than 5% of all patients.
Median survival from time of diagnosis is generally 6 months.
portal vein occlusion, which occurs commonly,portends an even shorter survival.
Complications from hepatocellular carcinoma are those of hepatic failure; death occurs from cachexia, variceal bleeding, or (rarely) tumor rupture and bleeding into the peritoneum

Race • Hepatocellular carcinoma is most commonly found among Asian persons, due to childhood infections with hepatitis B.

Sex
• Hepatocellular carcinoma occurs more commonly in men than in women

Age
• Hepatocellular carcinoma is rarely diagnosed in persons younger than 40 years.
• In Africa and Asia, age at diagnosis is substantially younger, occurring in the fourth and fifth decades of life, respectively.

Etiology

1. Cirrhosis
About 80% of patients with newly diagnosed hepatocellular carcinoma have preexisting cirrhosis attributed to alcohol, hepatitis C infection, and hepatitis B infection.

2.Hepatitis B virus
• Global incidence of chronic HBV infection is estimated to be 350 million persons; chronic HBV infection is the most common cause of hepatocellular carcinoma worldwide.
• Chronic infection in the setting of cirrhosis increases the risk of hepatocellular carcinoma 1000-fold.

3.Hepatitis C virus
• HCV is a global pandemic affecting 170 million persons. HCV infection results in a higher rate of chronic infection compared to HBV infection (approximately 80% of
infected subjects).
• It has become the most common cause of hepatocellular carcinoma in Japan and Europe. About 30% progress to cirrhosis, and in these, about 1-2% per year develop
hepatocellular carcinoma.
• Co-infection with HBV further increases the risk

4. Hemochromatosis:.
5. Aflatoxin: This hepatic carcinogen is a byproduct of fungal contamination of foodstuffs in sub-Saharan Africa and East and Southeast Asia. It causes DNA damage and mutations of the p53
gene.
Rare associations:
1. Primary Biliary Cirrhosis
2. Androgenic steroids,
3. Primary Sclerosing Cholangitis
4. 1-antitrypsin deficiency
5. Thorotrast radioactive contrast
6. Oral contraceptives
7. Porphyria cutanea tarda.
8. Obesity and diabetes have been implicated as risk factors for hepatocellular carcinoma ( related to NASH and Non Alcoholic Fatty Liver)

Clinical History
• Patients generally present with symptoms of advancing cirrhosis.
• Pruritis
• Jaundice
• Splenomegaly
• Variceal bleeding
• Cachexia
• Increasing abdominal girth (portal vein occlusion by thrombus with rapid development of ascites)
• Hepatic Encephalopathy
• Right upper quadrant pain (uncommon)Physical
• Jaundice
• Ascites
• Hepatomegaly
• Alcoholic stigmata (Dupuytren contracture, spider angiomata)
• Asterixis
• Pedal edema
• Periumbilical collateral veins
• Enlarged hemorrhoidal veins

Differential Diagnoses
A. Cholangiocarcinoma
B. Cirrhosis
C. Hepatocellular Adenoma
Other Problems to Be Considered
1. Dysplastic nodules in cirrhosis
2. Fibrous nodular hyperplasia
3. Metastatic disease
4. Primary hepatic lymphomaDiagnosis

Laboratory Studies
• Expect total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase, albumin, and prothrombin time to show results consistent with cirrhosis.
• Alpha-fetoprotein (AFP) is elevated in 75% of cases.
• The level of elevation correlates inversely with prognosis.
• An elevation of greater than 400 ng/mL predicts for hepatocellular carcinoma with specificity greater than 95%.

• Alpha-fetoprotein (AFP) is inadequate for screening purposes because of the high rate of false positives in active hepatitis; it only begins to rise when vascular invasion occurs

Imaging Studies

Ultrasonography
An advantage is that Doppler imaging can be performed at the same time to determine the patency of the portal vein.
CT scanning -Triphasic technique (ie, without contrast, then with early [arterial] and late [portal] imaging).CT scanning has the added benefit of detecting extrahepatic disease, especially lymphadenopathy.
MRI-detect smaller lesions and can also be used to determine flow in the portal vein. The overall sensitivity of MRI is thought to be similar to that of triphasic CT scanning.
Angiography-Shows characteristic tumor blush in hepatocellular carcinoma
Chest radiography may demonstrate pulmonary metastases
Bone scanning and head CT scanning are of low yield in the absence of specific symptoms.
PET scan: Under experiment
Biopsy-Frequently necessary for diagnosis.Core biopsy is favored over fine needle biopsy since larger amounts of tissue, often with normal surrounding parenchyma, can be obtained.

Biopsy may be omitted in a clinical setting of a growing mass in a cirrhotic liver (>2 cm) noted on 2 coincident imaging techniques with at least one imaging showing contrast enhancement.
Likewise, a growing mass in a cirrhotic liver on one imaging modality with an associated AFP level greater than 500-1000 ng/mL is clinically diagnostic of hepatocellular carcinoma . Biopsy is generally obtained percutaneously under ultrasonographic or CT guidance.
Using laparoscopic guidance may make obtaining a percutaneous biopsy easier. Obtaining a biopsy may be unnecessary in patients who will undergo resection regardless of diagnosis.

• One system is the CLIP (Cancer of the Liver Italian Program) scoring system, which assigns a cumulative prognostic score ranging from 0-6 based upon

1. Child-Pugh stage,
2. tumor morphology,
3. alpha-fetoprotein level,
4. and portal vein thrombosis,
5. can predict median survivalTNM staging criteria for hepatocellular carcinoma

• T1 – Solitary tumor without vascular invasion
• T2 – Solitary tumor with vascular invasion or multiple tumors none more than 5 cm
• T3 – Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)
• T4 – Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
• N0 – Indicates no nodal involvement
• N1 – Indicates regional nodal involvement
• M0 – Indicates no distant metastasis
• M1 – Indicates metastasis presence beyond the liverStage grouping
• Stage I = T1 + N0 + M0
• Stage II = T2 + N0 + M0
• Stage IIIA = T3 + N0 + M0
• Stage IIIB = T4 + N0 + M0
• Stage IIIC = TX + N1 + M0
• Stage IVB = TX + NX + M1CLIP scoring system: Score of 0-2 is assigned for each of the 4 features listed below; cumulative score ranging from 0-6 is the CLIP score.

Child-Pugh stage Stage A = 0 Stage B = 1 Stage C = 2

Tumor morphology
Uninodular and extension less than 50% = 0
Multinodular and extension less than 50% = 1
Massive and extension greater than 50% = 2
Alpha-fetoprotein Less than 400 = 0, Greater than 400 = 1
Portal vein thrombosis Absent = 0 Present = 1

:Estimated survival based on CLIP score
• score of 0 – about 31 months;
• score of 1- about 27 months;
• score of 2- about 13 months;
• score of 3- 8 months;
• scores 4-6-approximately 2 months.Medical Care

Treatment:

1.Available treatment options depend on the size, number, and location of tumors; presence or absence of cirrhosis; operative risk based on extent of cirrhosis and comorbid diseases; overall performance status; patency of portal vein; and presence of metastatic disease.
2.Before instituting definitive therapy
• treat the complications of cirrhosis with diuretics,
• paracentesis for ascites, l
• actulose for encephalopathy,
• ursodiol for pruritus,
• sclerosis or banding for variceal bleeding, and
• antibiotics for spontaneous bacterial peritonitis.
• Surgical resection and liver transplantation are the only chances of cure but have limited applicability. Other local therapies are chemoembolization, ethanol ablation, radiofrequency ablation, cryoablation, and radiotherapy. Patients whose disease is downstaged following chemoembolization may be eligible for transplantation. Systemic treatment with chemotherapy may be used for advanced disease.

Systemic chemotherapy
The most active single agent drugs tested have been
• doxorubicin,
• cisplatin, and
• fluorouracil.
• Response rates are about 10%, and treatment shows no clear impact on overall survival.
• More recently, gemcitabine and capecitabine have been evaluated in clinical trialscisplatin-based combination regimens, such as gemcitabine and oxaliplatin, have shown improved response rates around 20%,

Chemoimmunotherapy uses a combination of chemotherapy and immunomodulatory agents,

• such as interferon-alpha.
• Antiangiogenesis agents (ie,bevacizumab), which work by disrupting the formation of blood vessels that feed tumors, are a new class of drugs that may prove to be of benefit in the treatment of hepatocellular carcinoma.
• Sorafenib, a multitargeted oral kinase inhibitor, has recently been shown in a phase III trial to prolong survival in patients with hepatocellular carcinoma.
Sunitinib
Erlotinib

• Embolizing agents such as cellulose, microspheres, lipoidal, and gelatin foam particles are used to deliver intra-arterial chemotherapy (mitomycin, doxorubicin, cisplatin) to the tumor via the hepatic artery.

• Partial hepatectomy

• Orthotopic liver transplantation can be considered for patients.

• Local tumor ablation

• Intratumoral injections of ethanol or acetic acid, heat (via radiofrequency, microwave, or laser
ablation), or cold (cryoablation with liquid nitrogen) may be used to locally control tumors smaller
than 4-5 cm. These techniques are frequently performed percutaneously as outpatient
procedures. In general, these procedures are reserved for patients who do not meet criteria for
surgical resection yet are candidates for a liver-directed procedure based on the presence of
limited liver-only disease.
• Radiofrequency ablation (RFA) is the delivery of radiofrequency thermal energy to the
hepatocellular carcinoma lesion causing necrosis of the tumor.
• Percutaneous ethanol or acetic acid ablation is reserved for patients with small tumors; however,
in many areas, the ease and efficacy of RFA has now replaced these older techniques.
Radiation therapy is limited by dose-related radiation hepatitis, which precludes the
administration of external beam radiation in doses effective for tumor eradication. Doses of 2500
cGy may be used for palliative measures.
• CyberKnife system is a new technology that uses a combination of robotics and image guidance
to deliver concentrated and highly focused beams of radiation to the tumor while minimizing
radiation exposure to the surrounding healthy liver tissue.

Summarized- Source Medscape.com, Bailey and Love’s manual of surgery, wikipedia, Manipal book of Surgery

Pyogenic Liver Abscess

Administrator — Tue, 18 May 2010 16:30:55 +0000

Liver Blood supply:

Anatomy of liver

The liver derives blood from the hepatic artery (20%) and the portal vein (80%).

The hepatic artery usually arises from the aorta at the coeliac axis and divides into the right and left branches at the hilus.
The venous drainage from the liver is by three large hepatic veins right, middle and left into the inferior vena cava (IVC), just below the diaphragm.

The 3 major forms of liver abscess,

classified by etiology, are as follows:

1. Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases in the United States.
2. Amebic abscess due to Entamoeba histolytica accounts for 10% of cases.
3. Fungal abscess, most often due to Candida species, accounts for less than 10% of cases.

Risk factors : DM, underlying hepatobiliary or pancreatic malignancy, and liver transplant. Geographic factors may also play a role. mortality rate : 2 ~ 12% (mortality appears to be related to underlying comorbidities rather than to the abscess itself.)

Pathophysiology:

The liver receives blood from both systemic and portal circulations. Increased susceptibility to infections would be expected given the increased exposure to bacteria. However, Kupffer cells lining the hepatic sinusoids clear bacteria so efficiently that infection rarely occurs. Multiple processes have been associated with the development of hepatic abscesses

Causes:

Infection through portal vein:

acute appendicitis, diverticulitis, amoebic colitis, UC

Infection through the CBD:

stricture, periampullary Ca, rec. cholangitis, ERCP

Infection through hepatic artery:

septicemia, pyaemia

Extension abscess:

sudiaphragmatic abscess, empyema thoracis, injuries

Infection through umbilicus:

neonatal umbilical sepsis giving rise to pyaemia

Pyogenic liver abscess has been reported as a secondary infection of

1.amebic abscess
2.hydatid cystic cavities and metastatic and primary hepatic tumors.
3.complication of liver transplantation
4.hepatic artery embolization in the treatment of hepatocellular carcinoma
5.ingestion of foreign bodies, which penetrate the liver parenchyma.

Appendicitis was traditionally the major cause of liver abscess. Biliary tract disease is now the most common source of pyogenic liver abscess.
Abscesses usually are multiple, unless they are associated with surgical interventions or indwelling biliary stents. In these instances, solitary lesions can be seen.
The right hepatic lobe is affected more often than the left hepatic lobe by a factor of 2:1. Bilateral involvement is seen in 5% of cases. The predilection for the right hepatic lobe can be attributed to anatomic considerations. The right hepatic lobe receives blood from both the superior mesenteric and portal veins, whereas the left hepatic lobe receives inferior mesenteric and splenic drainage. It also contains a denser network of biliary canaliculi and, overall, accounts for more hepatic mass. Studies have suggested that a streaming effect in the portal circulation is causative.

Symptoms:

The most frequent symptoms of hepatic abscess include the following:

Fever (either continuous or spiking)
Chills
Right upper quadrant pain
Anorexia
Malaise

Cough or hiccoughs due to diaphragmatic irritation may be reported.
Referred pain to the right shoulder may be present.
Individuals with solitary lesions usually have a more insidious course with weight loss and anemia of chronic disease. With such symptoms, malignancy often is the initial consideration.
Fever of unknown origin (FUO) frequently can be an initial diagnosis in indolent cases.
Afebrile presentations have been documented.

Physical Signs:

Fever and tender hepatomegaly -the most common signs.
A palpable mass need not be present.
Mid epigastric tenderness, with or without a palpable mass, is suggestive of left hepatic lobe involvement.
Decreased breath sounds in the right basilar lung zones, with signs of atelectasis and effusion on examination or radiologically, may be present.
A pleural or hepatic friction rub can be associated with diaphragmatic irritation or inflammation of Glisson capsule.
Jaundice may be present in as many as 25% of cases and usually is associated with biliary tract disease or the presence of multiple abscesses

Differential Diagnosis of Hepatic Abscess:

1.Biliary Disease 2. Hydatid Cysts 3.Cholecystitis 4. Pneumonia, Bacterial 5.Empyema, Pleuropulmonary 6.Gastritis, Acute 7.Hepatocellular Carcinoma

Lab Investigations:

CBC count with differential ¡Anemia of chronic disease
Neutrophilic leukocytosis Liver function studies
Hypoalbuminemia and elevation of alkaline phosphatase (most common abnormalities)
Elevations of transaminase and bilirubin levels (variable) Blood cultures are positive in roughly 50% of cases.
Culture of abscess fluid should be the goal in establishing microbiologic diagnosis. ELISA for E. histolytica
CT and ultrasound – modalities of choice Abscesses must be distinguished from tumors and cysts. CT or ultrasound-guided aspiration should be sent for gram stain and culture. Blood cultures should always be performed when liver abscess is suspected; they are positive in up to 50 percent of cases

Complications:

Sepsis Empyema resulting from contiguous spread or intrapleural rupture of abscess Rupture of abscess with resulting peritonitis Endophthalmitis when an abscess is associated with K pneumoniae bacteremia

MANAGEMENT of LIVER ABSCESS:

Percutaneous needle aspiration Under CT scan or ultrasound guidance, needle aspiration of cavity material can be performed. Diagnostic + therapeutic.

Percutaneous drainage has become the standard of care and should be the first intervention considered for small cysts. Seldinger or trochar technique.

For single abscesses with diameter ≤5 cm : percutaneous catheter drainage or needle aspiration is acceptable. For single abscesses with diameter >5 cm :percutaneous management : catheter drainage is preferred over needle aspiration. ¡surgical intervention is preferred over percutaneous drainage

Medical Therapy

Empiric broad-spectrum antibiotics should be administered pending abscess gram stain and culture results.
A third generation cephalosporin such as ceftriaxone PLUS metronidazole.(Flumarin)
fluoroquinolone (eg, ciprofloxacin PLUS metronidazole
Monotherapy with a carbapenem

follow imaging, WBC count and serum CRP If good response – 2~4 weeks of therapy, no or incomplete drainage- 4~6 weeks of therapy. Drainage catheters should remain in place until drainage is minimal (usually up to seven days).

Open surgery can be performed by 2 approaches.

Abscess cavity was later packed with betadine gauge

A transperitoneal approach allows for abscess drainage and abdominal exploration to identify previously undetected abscesses and the location of an etiologic source.
For high posterior lesions, a posterior transpleural approach can be used.
A laparoscopic approach is also commonly used in select cases.

( Source Medscape-emedicine, Manipal, Bailey and Love and various sites).