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Upon discovery of a liver tumor, the main issue in the workup is to determine whether the tumor is benign or malignant. Many imaging modalities are used to aid in the diagnosis of malignant liver tumors. For the most common of these, hepatocellular carcinoma (HCC), these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.
Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders..
Ultrasonography of liver tumors involves two stages: detection and characterization. Tumor detection is based on the performance of the method and should include morphometric information (three axes dimensions, volume) and topographic information (number, location specifying liver segment and lobe/lobes). The specification of these data is important for staging liver tumors and prognosis. Tumor characterization is a complex process based on a sum of criteria leading towards tumor nature definition. Often, other diagnostic procedures, especially interventional ones are no longer necessary. Tumor characterization using the ultrasound method will be based on the following elements: consistency (solid, liquid, mixed), echogenicity, structure appearance (homogeneous or heterogeneous), delineation from adjacent liver parenchyma (capsular, imprecise), elasticity, posterior acoustic enhancement effect, the relation with neighboring organs or structures (displacement, invasion), vasculature (presence and characteristics on Doppler ultrasonography and contrast-enhanced ultrasound (CEUS).
Ultrasound, CT scan, and MRI may be used to evaluate the liver for HCC. On CT and MRI, HCC can have three distinct patterns of growth:
- A single large tumor
- Multiple tumors
- Poorly defined tumor with an infiltrative growth pattern
A systematic review of CT diagnosis found that the sensitivity was 68 percent (95% CI 55-80%) and specificity was 93 percent (95% CI 89-96%) compared with pathologic examination of an explanted or resected liver as the reference standard. With triple-phase helical CT, the sensitivity 90% or higher, but this data has not been confirmed with autopsy studies.
However, MRI has the advantage of delivering high-resolution images of the liver without ionizing radiation. HCC appears as a high-intensity pattern on T2 weighted images and a low-intensity pattern on T1 weighted images. The advantage of MRI is that is has improved sensitivity and specificity when compared to US and CT in cirrhotic patients with whom it can be difficult to differentiate HCC from regenerative nodules. A systematic review found that the sensitivity was 81 percent (95% CI 70-91%) and specificity was 85 percent (95% CI 77-93%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity is further increased if gadolinium contrast-enhanced and diffusion-weighted imaging are combined.
MRI is more sensitive and specific than CT.
Liver Image Reporting and Data System (LI-RADS) is a classification system for the reporting of liver lesions detected on CT and MRI. Radiologists use this standardized system to report on suspicious lesions and to provide an estimated likelihood of malignancy. Categories range from LI-RADS (LR) 1 to 5, in order of concern for cancer. A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met.
HCC remains associated with a high mortality rate, in part related to initial diagnosis commonly at an advanced stage of disease. As with other cancers, outcomes are significanty improved if treatment is initiated earlier in the disease process. Because the vast majority of HCC occurs in people with certain chronic liver diseases, especially those with cirrhosis, liver screening is commonly advocated in this population. Specific screening guidelines continue to evolve over time as evidence of its clinical impact becomes available. In the United States, the most commonly observed guidelines are those published by the American Association for the Study of Liver Diseases (AASLD). The AASLD recommends screening people with cirrhosis with ultrasound every 6 months, with or without measurement of blood levels of tumor marker AFP. Elevated levels of AFP are associated with active HCC disease, although inconsistently reliable. At levels >20 sensitivity is 41-65% and specificity is 80-94%. However, at levels >200 sensitivity is 31, specificity is 99%.
On US, HCC often appears as a small hypoechoic lesion with poorly defined margins and coarse irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications. This heterogeneity can look similar to cirrhosis and the surrounding liver parenchyma. A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and specificity was 97 percent (95% CI 95-98%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity increases to 79% with AFP correlation.
There remains controversy as to the most effective screening protocols. For example, while there is data to support decreased mortality related to screening in people with hepatitis B infection, the AASLD notes that “there are no randomized trials [for screening] in Western populations with cirrhosis secondary to chronic hepatitis C or fatty liver disease, and thus there is some controversy surrounding whether surveillance truly leads to a reduction in mortality in this population of patients with cirrhosis.”
The most common method of testing for hepatoblastoma is a blood test checking the alpha-fetoprotein level. Alpha-fetoprotein (AFP) is used as a biomarker to help determine the presence of liver cancer in children. At birth, infants have relatively high levels of AFP, which fall to normal adult levels by the first year of life. The normal level for AFP in children has been reported as lower than 50 nanograms per milliliter (ng/ml) and 10 ng/ml. An AFP level greater than 500 (ng/ml) is a significant indicator of hepatoblastoma. AFP is also used as an indicator of treatment success. If treatments are successful in removing the cancer, the AFP level is expected to return to normal.
Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.
Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.
There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.
Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice. Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma. Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.
In the United States screening is typically recommended between the age of 50 and 75 years. For those between 76 and 85 years of age the decision to screen should be individualized. A number of screening methods can be used including stool based tests every 3 years, sigmoidoscopy every 5 years and colonoscopy every 10 years. For those at high risk, screenings usually begin at around 40. It is unclear which of these two methods is better. Colonoscopy may find more cancers in the first part of the colon but is associated with greater cost and more complications. For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association does not recommend any type of screening in the 10 years following the colonoscopy. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended. It takes about 10 years after screening for one out of a 1000 people to benefit.
In Canada, among those 50 to 75 at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years. Colonoscopy is less preferred.
Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between age 50 and 60. Examples of countries with organised screening include the United Kingdom, Australia and the Netherlands.
Hepatic adenoma is usually detected by imaging, typically an ultrasound or CT, as a hyperenhancing liver nodule. Given that several liver tumors appear similarly on these imaging modalities, a multi-phase contrast-enhanced imaging study such as CT or MRI may be used to provide more information. The significance of making a specific diagnosis is that, unlike other benign liver tumors such as hemangioma and focal nodular hyperplasia, hepatic adenomas have a small but meaningful risk of progressing into a malignancy. Although imaging provides supportive information, a definitive diagnosis of hepatic adenoma requires biopsy of the tissue.
Surgical removal of the tumor, adjuvant chemotherapy prior to tumor removal, and liver transplantation have been used to treat these cancers. Primary liver transplantation provides high, long term, disease-free survival rate in the range of 80%, in cases of complete tumor removal and adjuvant chemotherapy survival rates approach 100%. The presence of metastases is the strongest predictor of a poor prognosis.
Prevention of cancers can be separated into primary, secondary, and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination against the hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promoting safe injection practices, screening blood donation products, and screening high-risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention to discourage mold, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.
Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.
Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs and antiviral drugs.
Treatment can consist of surgery (hepatectomy), chemotherapy and/or therapies specifically aimed at the liver like radiofrequency ablation, transcatheter arterial chemoembolization, selective internal radiation therapy and irreversible electroporation. For most patients no effective treatment exists because both lobes are usually involved, making surgical resection impossible. Younger patients with metastases from colorectal cancer confined to one lobe of the liver and up to 4 in number may be treated by partial hepatectomy. In selected cases, chemotherapy may be given systemically or via hepatic artery.
In some tumors, notably those arising from the colon and rectum, apparently solitary metastases
or metastases to one or other lobes may be resected. A careful search for other metastases is required, including local recurrence of the original primary tumor (e.g., via colonoscopy) and dissemination elsewhere (e.g., via CT of the thorax). 5 year survival rates of 30-40% have been reported following resection.
CT-scans, MRIs, sonography (ultrasound), and endoscopy (including endoscopic ultrasound) are common diagnostic tools. CT-scans using contrast medium can detect 95 percent of tumors over 3 cm in size, but generally not tumors under 1 cm.
Advances in nuclear medicine imaging, also known as molecular imaging, has improved diagnostic and treatment paradigms in patients with neuroendocrine tumors. This is because of its ability to not only identify sites of disease but also characterize them. Neuronedocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modifications of somatostatin with a longer half-life. OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide.
Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging. Gallium-68 receptor PET-CT is much more accurate than an OctreoScan.
Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some neuroendocrine tumors. This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be assessed.
The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively. The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. This is enabling better selection of the most appropriate therapy for an individual patient.
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer. It is not recommended in those at average risk. There is tentative evidence for calcium supplementation, but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer.
Hepatic adenomas are related to glycogen storage diseases, type 1, as well as anabolic steroid use.
Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.
In the general population, screening of large groups is not currently considered effective, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.
This disease is often discovered during surgery for other conditions, e.g., hernia repair, following which an experienced pathologist can confirm the diagnosis. Advanced stages may present as tumors palpable on the abdomen or distention of the belly ("jelly belly" is sometimes used as a slang term for the condition). Due to the rarity of this disease, it is important to obtain an accurate diagnosis so that appropriate treatment may be obtained from a surgical oncologist who specializes in appendix cancer. Diagnostic tests may include CT scans, examination of tissue samples obtained through laparoscopy, and the evaluation of tumor markers. In most cases a colonoscopy is unsuitable as a diagnostic tool because in most cases appendix cancer invades the abdominal cavity but not the colon (however, spread inside the colon is occasionally reported). PET scans may be used to evaluate high-grade mucinous adenocarcinoma, but this test is not reliable for detecting low-grade tumors because those do not take up the dye which shows up on scans. New MRI procedures are being developed for disease monitoring, but standard MRIs are not typically used as a diagnostic tool. Diagnosis is confirmed through pathology.
The 2010 WHO classification of tumors of the digestive system grades all the pancreatic neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society.
In FHCC, plasma neurotensin and serum vitamin B12 binding globulin are commonly increased and are useful in monitoring the disease and detecting recurrence.
FHCC has a high resectability rate, i.e. it can often be surgically removed. Liver resection is the optimal treatment and may need to be performed more than once, since this disease has a very high recurrence rate. Due to such recurrence, periodic follow-up medical imaging (CT or MRI) is necessary.
As the tumor is quite rare, there is no standard chemotherapy regimen. Radiotherapy has been used but data is limited concerning its use.
The survival rate for fibrolamellar HCC largely depends on whether (and to what degree) the cancer has metastasized, i.e. spread to the lymph nodes or other organs. Distant spread (metastases), significantly reduces the median survival rate. Five year survival rates vary between 40-90%.
FHCC accounts for 1-10% of primary liver cancers. It typically has a young age at presentation (20–40 years: mean age ~27 years) when compared to conventional HCC. Unlike the more common HCC, patients most often do not have coexistent liver disease such as cirrhosis.
For surface epithelial-stromal tumors, the most common sites of metastasis are the pleural cavity (33%), the liver (26%), and the lungs (3%).
While the increased serum concentration of calcitonin is not harmful, it is useful as a marker which can be tested in blood.
A second marker, carcinoembryonic antigen (CEA), also produced by medullary thyroid carcinoma, is released into the blood and it is useful as a serum or blood tumor marker. In general, measurement of serum CEA is less sensitive than serum calcitonin for detecting the presence of a tumor, but has less minute to minute variability and is therefore useful as an indicator of tumor mass.
A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. The liver is a common site for metastatic disease because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein). Metastatic tumors in the liver are 20 times more common than primary tumors. In 50% of all cases the primary tumor is of the gastrointestinal tract, other common sites include the breast, ovaries, bronchus and kidney.
Tumor emboli entering the sinusoids through the liver blood supply appear to be physically obstructed by the Kupffer cells, but if tumor emboli are larger, they tend to become lodged in the portal venous branches.
Diagnosis is primarily performed via fine needle aspiration of the lesion of the thyroid to distinguish it from other types of thyroid lesions. Microscopic examination will show amyloid and hyperplasia of parafollicular C cells.