Hepatocellular carcinoma (HCC, also called hepatoma) is a primary malignancy (cancer) of the liver. Most cases of HCC are secondary to either a viral hepatitide infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).[1] 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. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography (it should be stated, however, that the sensitivity of this technique remains, even with current state-of-the-art technology, below 50%).
The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months.[2] This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. This is a rare tumor in the United States.
Epidemiology
HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, central and Southeast Asia, and the Amazon basin. Males are affected more than females usually and it is more common between the 3rd and 5th decades of life[1] Hepatocellular carcinoma causes 662,000 deaths worldwide per year.[3]
Non-Western Countries
In some parts of the world, such as sub-Saharan Africa and Southeast Asia, HCC is the most common cancer, generally affecting men more than women, and with an age of onset between late teens and 30s. This variability is in part due to the different patterns of hepatitis B transmission in different populations - infection at or around birth 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.[1] 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.
Pathogenesis
Main article: Carcinogenesis
Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of Hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to Hepatitis C. In Hepatitis B, however, the integration of the viral genome into infected cells is the most consistently associated factor in malignancy. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. The toxin aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in countries like China and western Africa has led to relatively high rates of heptatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection and thus are not related to 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 and des-gamma carboxyprothrombin 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
Once imaged, diagnosis is confirmed by percutaneous biopsy and histopathologic analysis.
The key characteristics on CT are hypervascularity in the arterial phase scans, washout or de-enhancement in the portal and delayed phase studies, a pseudocapsule and a mosaic pattern. Both calcifications and intralesional fat may be appreciated.
CT scans use contrast agents, which are typically iodine or barium based. Some patients are allergic to one or both of these contrast agents, most often iodine. Usually the allergic reaction is manageable and not life threatening.
An alternative to a CT imaging study would be the MRI. MRI's are more expensive and not as available because fewer facilities have MRI machines. More important MRI are just beginning to be used in tumor detection and fewer radiologists are skilled at finding tumors with MRI studies when it is used as a screening device. Mostly the radiologists are using MRIs to do a secondary study to look at an area where a tumor has already been detected. MRI's also use contrast agents. One of the best for showing details of liver tumors is very new: iron oxide nano-particles appears to give better results. The latter are absorbed by normal liver tissue, but not tumors or scar tissue.
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.[4]
Staging and prognosis
Important features that guide treatment 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.
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-suppressant post-transplant drugs decrease the chance of survival.
* 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.
* Percutaneous ethanol injection (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 performed in the treatment of large tumors (larger than 3 cm and less than 4 cm in diameter), most frequently 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.
* Sealed source radiotherapy can be used to destroy the tumor from within (thus minimizing exposure to healthy tissue). TheraSphere is an FDA approved treatment which has been shown in clinical trials to increase survival rate of low-risk patients. This method uses a catheter (inserted by a radiologist) to deposit radioactive particles to the area of interest.
* 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 be 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.
* Adjuvant chemotherapy: 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.[5]
* 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 center 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.
There is a new drug Sorafenib which was originally used for Renal Cell Cancer that has shown promising results when used with Hepatocellular Cancer
* 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.
Awareness
The Jade Ribbon Campaign is used for awareness of liver cancer and hepatitis B in the Pacific Islands, where such illnesses are more widespread than elsewhere.
Future directions
Current research includes the search for the genes that are disregulated in HCC,[6] protein markers,[7] and other predictive biomarkers.[8][9] 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.
Showing posts with label liver. Show all posts
Showing posts with label liver. Show all posts
Saturday, July 12, 2008
Liver disease reference
Liver disease is a broad term describing any number of diseases affecting the liver. Many are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
* Haemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
* Wilson's disease, a hereditary disease which causes the body to retain copper.
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, likely autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts.
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Gilbert's syndrome, a genetic disorder of bilirubin metabolism, found in about 5% of the population.
* Glycogen storage disease type II,The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
There are also many pediatric liver disease, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, and progressive familial intrahepatic cholestasis, to name but a few.
A number of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products.
Symptoms of a diseased liver
The external signs include a coated tongue, bad breath, skin rashes, itchy skin, excessive sweating, offensive body odour, dark circles under the eyes, red swollen and itchy eyes, acne rosacea, brownish spots and blemishes on the skin, flushed facial appearance or excessive facial blood vessels.[1]
Other symptoms include jaundice, dark urine, pale stool, bone loss, easy bleeding, itching, small, spider-like blood vessels visible in the skin, enlarged spleen, fluid in the abdominal cavity, chills, pain from the biliary tract or pancrea, and an enlarged gallbladder.[2]
The symptoms related to liver dysfunction include both physical signs and a variety of symptoms related to digestive problems, blood sugar problems, immune disorders, abnormal absorption of fats, and metabolism problems.[3]
The malabsorption of fats may lead to symptoms that include indigestion, reflux, hemorhoids, gall stones, intolerance to fatty foods, intolerance to alcohol, nausea and vomiting attacks, abdominal bloating, and constipation.
Nervous system disorders include depression, mood changes, especially anger and irritability, poor concentration and "foggy brain", overheating of the body, especially the face and torso, and recurrent headaches (including migraine) associated with nausea.
The blood sugar problems include a craving for sugar, hypoglycaemia and unstable blood sugar levels, and the onset of diabetes (Type 2).
Abnormalities in the level of fats in the blood stream include elevated LDL cholesterol, reduced HDL cholesterol, elevated triglycerides, clogged arteries leading to high blood pressure heart attacks and strokes, build up of fat in other body organs (fatty degeneration of organs), lumps of fat in the skin (lipomas and other fatty tumors), excessive weight gain (which may lead to obesity), inability to lose weight even while dieting, sluggish metabolism, protuberant abdomen (pot belly), cellulite, fatty liver, and a roll of fat around the upper abdomen (liver roll).[4]
The College of Holistic Medicine lists other symptoms of a diseased liver that include tired eyes, a tendency to have accidents, weak sexual vitality, impotence and prostate problems, a psychologically that you are irritable and get angry easily, devoting far too much attention to trivial details, overeating, stubbornness, prone to anger, highly emotional and hypersensitive, heaviness in the head, poor digestion, hemorrhoids, ovarian problems and cysts, PMS, flatulence and petrifaction of tissues, and possible headaches and migraines.
* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
* Haemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
* Wilson's disease, a hereditary disease which causes the body to retain copper.
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, likely autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts.
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Gilbert's syndrome, a genetic disorder of bilirubin metabolism, found in about 5% of the population.
* Glycogen storage disease type II,The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
There are also many pediatric liver disease, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, and progressive familial intrahepatic cholestasis, to name but a few.
A number of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products.
Symptoms of a diseased liver
The external signs include a coated tongue, bad breath, skin rashes, itchy skin, excessive sweating, offensive body odour, dark circles under the eyes, red swollen and itchy eyes, acne rosacea, brownish spots and blemishes on the skin, flushed facial appearance or excessive facial blood vessels.[1]
Other symptoms include jaundice, dark urine, pale stool, bone loss, easy bleeding, itching, small, spider-like blood vessels visible in the skin, enlarged spleen, fluid in the abdominal cavity, chills, pain from the biliary tract or pancrea, and an enlarged gallbladder.[2]
The symptoms related to liver dysfunction include both physical signs and a variety of symptoms related to digestive problems, blood sugar problems, immune disorders, abnormal absorption of fats, and metabolism problems.[3]
The malabsorption of fats may lead to symptoms that include indigestion, reflux, hemorhoids, gall stones, intolerance to fatty foods, intolerance to alcohol, nausea and vomiting attacks, abdominal bloating, and constipation.
Nervous system disorders include depression, mood changes, especially anger and irritability, poor concentration and "foggy brain", overheating of the body, especially the face and torso, and recurrent headaches (including migraine) associated with nausea.
The blood sugar problems include a craving for sugar, hypoglycaemia and unstable blood sugar levels, and the onset of diabetes (Type 2).
Abnormalities in the level of fats in the blood stream include elevated LDL cholesterol, reduced HDL cholesterol, elevated triglycerides, clogged arteries leading to high blood pressure heart attacks and strokes, build up of fat in other body organs (fatty degeneration of organs), lumps of fat in the skin (lipomas and other fatty tumors), excessive weight gain (which may lead to obesity), inability to lose weight even while dieting, sluggish metabolism, protuberant abdomen (pot belly), cellulite, fatty liver, and a roll of fat around the upper abdomen (liver roll).[4]
The College of Holistic Medicine lists other symptoms of a diseased liver that include tired eyes, a tendency to have accidents, weak sexual vitality, impotence and prostate problems, a psychologically that you are irritable and get angry easily, devoting far too much attention to trivial details, overeating, stubbornness, prone to anger, highly emotional and hypersensitive, heaviness in the head, poor digestion, hemorrhoids, ovarian problems and cysts, PMS, flatulence and petrifaction of tissues, and possible headaches and migraines.
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