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Hepatocellular carcinoma

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Hepatocellular carcinoma
   Classifications and external resources

     ICD- 10   C 22.0
     ICD- 9    155
     ICD-O:    8170/3
   MedlinePlus 000280
    eMedicine  med/787

   Hepatocellular carcinoma (HCC, also called hepatoma) is a primary
   malignancy (cancer) of the liver. Most cases of HCC are secondary to
   either hepatitis infection (usually hepatitis B or C) or cirrhosis (
   alcoholism being the most common cause of hepatic cirrhosis). In
   countries where hepatitis is not endemic, most malignant cancers in the
   liver are not primary HCC but metastasis (spread) of cancer from
   elsewhere in the body, e.g. the colon. Treatment options of HCC and
   prognosis are dependent on many factors but especially on tumor size
   and staging.

   Outside of the West, the commonly accepted prognosis is a median
   survival of 3 months from diagnosis. This is partially due to late
   presentation with large tumours, but also the lack of medical expertise
   and facilities.

Epidemiology

   The epidemiology of HCC exhibits two main patterns, one in North
   America and Western Europe and another in Non-Western Countries
   (regions such as sub-Saharan Africa, central Asia, Southeast Asia, and
   the Amazon basin).

Non-Western Countries

   In some parts of the world, such as Sub-Saharan Africa and Southeast
   Asia (and especially Taiwan and China) HCC is the most common cancer,
   generally affecting men more than women, and with an age of onset
   between late teens and 30's. This variability is in part due to the
   different patterns of Hepatitis B transmission in different populations
   - infection at or around birth (as in Taiwan) predispose to earlier
   cancers than if people are infected later. The time between hepatitis B
   infection and development into HCC can be years even decades, but from
   diagnosis of HCC to death the average survival period is only 5.9
   months, according to one Chinese study during the 1970-80s, or 3 months
   ( median survival time) in Sub-Saharan Africa according to Manson's
   textbook of tropical diseases. HCC is one of the deadliest cancers in
   China. Food infected with Aspergillus flavus (especially peanuts and
   corns stored during prolonged wet seasons) which produces aflatoxin,
   poses another risk factor for HCC.

North America and Western Europe

   Most malignant tumors of the liver discovered in Western patients are
   metastases (spread) from tumors elsewhere. In the West, HCC is
   generally seen as rare cancer, normally of those with pre-existing
   liver disease. It is often detected by ultrasound screening, and so can
   be discovered by health-care facilities much earlier than in developing
   regions such as Sub-Saharan Africa.

   Acute and chronic hepatic porphyrias (acute intermittent porphyria,
   porphyria cutanea tarda, hereditary coproporphyria, variegate
   porphyria) and tyrosinemia type I are risk factors for hepatocellular
   carcinoma. The diagnosis of an acute hepatic porphyria (AIP, HCP, VP)
   should be sought in patients with hepatocellular carcinoma without
   typical risk factors of hepatitis B or C, alcoholic liver cirrhosis or
   hemochromatosis. Both active and latent genetic carriers of acute
   hepatic porphyrias are at risk for this cancer, although latent genetic
   carriers have developed the cancer at a later age than those with
   classic symptoms. Patients with acute hepatic porphyrias should be
   monitored for hepatocellular carcinoma.

Diagnosis, screening and monitoring

   Hepatocellular carcinoma (HCC) most commonly appears in a patient with
   chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or with
   cirrhosis (about 80%). These patients commonly undergo surveillance
   with ultrasound due to the cost-effectiveness.

   In patients with a higher suspicion of HCC (such as rising
   alpha-fetoprotein levels), the best method of diagnosis involves a CT
   scan of the abdomen using intravenous contrast agent and three-phase
   scanning (before contrast administration, immediately after contrast
   administration, and again after a delay) to increase the ability of the
   radiologist to detect small or subtle tumors. It is important to
   optimize the parameters of the CT examination, because the underlying
   liver disease that most HCC patients have can make the findings more
   difficult to appreciate.

   On CT, HCC can have three distinct patterns of growth:
     * A single large tumor
     * Multiple tumors
     * Poorly defined tumor with an infiltrative growth pattern

   Both calcifications and intralesional fat may be appreciated.

   In patients who have a contrast agent allergy or poor renal function,
   an MRI scan of the abdomen is a more costly but effective substitute.

   Once imaged, diagnosis is confirmed by percutaneous biopsy and
   histopathologic analysis.

Pathology

   Macroscopically, liver cancer appears as a nodular or infiltrative
   tumor. The nodular type may be solitary (large mass) or multiple (when
   developed as a complication of cirrhosis). Tumor nodules are round to
   oval, grey or green (if the tumor produces bile), well circumscribed
   but not encapsulated. The diffuse type is poorly circumscribed and
   infiltrates the portal veins, or the hepatic veins (rarely).

   Microscopically, there are four architectural and cytological types
   (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular
   (adenoid), pleomorphic (giant cell) and clear cell. In well
   differentiated forms, tumor cells resemble hepatocytes, form
   trabeculae, cords and nests, and may contain bile pigment in cytoplasm.
   In poorly differentiated forms, malignant epithelial cells are
   discohesive, pleomorphic, anaplastic, giant. The tumor has a scant
   stroma and central necrosis because of the poor vascularization. 1

Staging and prognosis

   Important features that guide treament include: -
     * size
     * spread ( stage)
     * involvement of liver vessels
     * presence of a tumor capsule
     * presence of extrahepatic metastases
     * presence of daughter nodules
     * vascularity of the tumor

   MRI is the best imaging method to detect the presence of a tumor
   capsule. xx

Treatment

     * Liver transplantation to replace the liver with a cadaver liver or
       a live donor lobe. Historically low survival rates (20%-36%) recent
       improvement (61.1%; 1996-2001), likely related to adoption of Milan
       criteria at US transplantation centers. If the tumor disease has
       metastasized, the immuno-suppresent post-transplant drugs decrease
       the chance of survival. NIH

     * Surgical resection to remove a tumor to treat small or slow-growing
       tumors if they are diagnosed early. This treatment offers the best
       prognosis for long-term survival but unfortunately is possible in
       only 10-15% of cases. Resection in cirrhotic patients carries high
       morbidity and mortality. Medicinenet

     * Percutaneous ethanol injection (PEI)PEI well tolerated, high RR in
       small (< 3 cm) solitary tumors; as of 2005, no randomized trial
       comparing resection to percutaneous treatments; recurrence rates
       similar to those for postresection.

     * Transcatheter arterial chemoembolization (TACE) is usually perform
       in the treatment of large tumors (larger than 3 cm and less than 4
       cm in diameter) most frequently performed by intraarterially
       injecting an infusion of antineoplastic agents mixed with iodized
       oil (such as Lipiodol). As of 2005, multiple trials show objective
       tumor responses and slowed tumor progression but questionable
       survival benefit compared to supportive care; greatest benefit seen
       in patients with preserved liver function, absence of vascular
       invasion, and smallest tumors.

     * Radiofrequency ablation (RFA) uses high frequency radio-waves to
       ablate the tumour.

     * Intra-arterial iodine-131–lipiodol administration Efficacy
       demonstrated in unresectable patients, those with portal vein
       thrombus. This treatment is also used as adjuvant therapy in
       resected patients (Lau at et, 1999). It is believed to raise the
       3-year survival rate from 46 to 86%. This adjuvant therapy is in
       phase III clinical trials in Singapore and is available as a
       standard medical treatment to qualified patients in Hong Kong.

     * Combined PEI and TACE can used for tumors larger than 4 cm in
       diameter, although some Italian groups have had success with larger
       tumours using TACE alone.

     * High intensity focused ultrasound (HIFU) (not to be confused with
       normal diagnostic ultrasound) is a new technique which uses much
       more powerful ultrasound to treat the tumour. Still at a very
       experimental stage. Most of the work has been done in China. Some
       early work is being done in Oxford and London in the UK.

     * Hormonal therapy Antiestrogen therapy with tamoxifen studied in
       several trials, mixed results across studies, but generally
       considered ineffective Octreotide (somatostatin analogue) showed
       13-month MS v 4-month MS in untreated patients in a small
       randomized study; results not reproduced

     * Chemotherapy adjuvant: No randomized trials showing benefit of
       neoadjuvant or adjuvant systemic therapy in HCC; single trial
       showed decrease in new tumors in patients receiving oral synthetic
       retinoid for 12 months after resection/ ablation; results not
       reproduced. Clinical trials have varying results..

     * Palliative: Regimens that included doxorubicin, cisplatin,
       fluorouracil, interferon, epirubicin, or taxol, as single agents or
       in combination, have not shown any survival benefit (RR, 0%-25%); a
       few isolated major responses allowed patients to undergo partial
       hepatectomy; no published results from any randomized trial of
       systemic chemotherapy

     * Cryosurgery: Cryosurgery is a new technique that can destroy tumors
       in a variety of sites (brain, breast, kidney, prostate, liver).
       Cryosurgery is the destruction of abnormal tissue using sub-zero
       temperatures. The tumor is not removed and the destroyed cancer is
       left to be reabsorbed by the body. Initial results in properly
       selected patients with unresectable liver tumors are equivalent to
       those of resection. Cryosurgery involves the placement of a
       stainless steel probe into the centre of the tumor. Liquid nitrogen
       is circulated through the end of this device. The tumor and a half
       inch margin of normal liver are frozen to -190°C for 15 minutes,
       which is lethal to all tissues. The area is thawed for 10 minutes
       and then re-frozen to -190°C for another 15 minutes. After the
       tumor has thawed, the probe is removed, bleeding is controlled, and
       the procedure is complete. The patient will spend the first
       post-operative night in the intensive care unit and typically is
       discharged in 3 - 5 days. Proper selection of patients and
       attention to detail in performing the cryosurgical procedure are
       mandatory in order to achieve good results and outcomes.
       Frequently, cryosurgery is used in conjunction with liver resection
       as some of the tumors are removed while others are treated with
       cryosurgery. Patients may also have insertion of a hepatic
       intra-arterial artery catheter for post-operative chemotherapy. As
       with liver resection, your surgeon should have experience with
       cryosurgical techniques in order to provide the best treatment
       possible.

     * Interventional radiology

   Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial
   embolization/chemoembolization; PFS, progression-free survival; PS,
   performance status; HBV, hepatitis B virus; PEI, percutaneous ethanol
   injection; RR, response rate; MS, median survival.

Future directions

   Current research includes the search for the genes that are
   disregulated in HCC, protein markers, and other predictive biomarkers.
   . As similar research is yielding results in various other malignant
   diseases, it is hoped that identifying the aberrant genes and the
   resultant proteins could lead to the identification of pharmacological
   interventions for HCC.
   Retrieved from " http://en.wikipedia.org/wiki/Hepatocellular_carcinoma"
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   with only minor checks and changes (see www.wikipedia.org for details
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