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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.
Cholangiocarcinoma, also known as bile duct cancer, is a form of cancer that is composed of mutated epithelial cells (or cells showing characteristics of epithelial differentiation) that originate in the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.
Cholangiocarcinoma is a relatively rare neoplasm that is classified as an adenocarcinoma (a cancer that forms glands or secretes significant amounts of mucins). It has an annual incidence rate of 1–2 cases per 100,000 in the Western world, but rates of cholangiocarcinoma have been rising worldwide over the past few decades.
Prominent signs and symptoms of cholangiocarcinoma include abnormal liver function tests, abdominal pain, jaundice, and weight loss. Other symptoms such as generalized itching, fever, and changes in color of stool or urine may also occur. The disease is diagnosed through a combination of blood tests, imaging, endoscopy, and sometimes surgical exploration, with confirmation obtained after a pathologist examines cells from the tumor under a microscope. Known risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), infection with the parasitic liver flukes "Opisthorchis viverrini" or "Clonorchis sinensis", some congenital liver malformations, and exposure to Thorotrast (thorium dioxide), a chemical formerly used in medical imaging. However, most people with cholangiocarcinoma have no identifiable risk factors.
Cholangiocarcinoma is considered to be an incurable and rapidly lethal cancer unless both the primary tumor and any metastases can be fully removed by surgery. No potentially curative treatment exists except surgery, but most people have advanced stage disease at presentation and are inoperable at the time of diagnosis. People with cholangiocarcinoma are generally managed - though not cured - with chemotherapy, radiation therapy, and other palliative care measures. These are also used as additional therapies after surgery in cases where resection has apparently been successful (or nearly so).
Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present either with worsening of symptoms or may be without symptoms at the time of cancer detection. HCC may directly present with yellow skin, abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.
The most common physical indications of cholangiocarcinoma are abnormal liver function tests, jaundice (yellowing of the eyes and skin occurring when bile ducts are blocked by tumor), abdominal pain (30%–50%), generalized itching (66%), weight loss (30%–50%), fever (up to 20%), and changes in the color of stool or urine. To some extent, the symptoms depend upon the location of the tumor: patients with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with tumors of the bile ducts within the liver more often have pain without jaundice.
Blood tests of liver function in patients with cholangiocarcinoma often reveal a so-called "obstructive picture," with elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase levels, and relatively normal transaminase levels. Such laboratory findings suggest obstruction of the bile ducts, rather than inflammation or infection of the liver parenchyma, as the primary cause of the jaundice.
The prognosis of HCC is affected by the staging of the tumor as well as the liver's function due to the effects of liver cirrhosis.
There are a number of staging classifications for HCC available; however, due to the unique nature of the carcinoma in order to fully encompass all the features that affect the categorization of the HCC, a classification system should incorporate; tumor size and number, presence of vascular invasion and extrahepatic spread, liver function (levels of serum bilirubin and albumin, presence of ascites and portal hypertension) and general health status of the patient (defined by the ECOG classification and the presence of symptoms).
Out of all the staging classification systems available the Barcelona Clinic Liver Cancer (BCLC) staging classification encompasses all of the above characteristics. This staging classification can be used in order to select people for treatment.
Important features that guide treatment include the following:
- 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.
The most common sites of metastasis are the lung, abdominal lymph nodes, and bone.
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.
Children with pancreatoblastoma rarely present with early-stage disease, instead, most present with locally advanced or metastatic disease. Common presenting symptoms include abdominal pain, emesis, and jaundice. A multidisciplinary approach including good clinical history, state of the art imaging, and careful pathology is often needed to establish the correct diagnosis.
Small-cell carcinoma (also known as "small-cell lung cancer", or "oat-cell carcinoma") is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.
Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).
Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.
Initially, nearby lymph nodes are struck early. The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors.
- In lymph nodes, a common symptom is lymphadenopathy
- Lungs: cough, hemoptysis and dyspnea (shortness of breath)
- Liver: hepatomegaly (enlarged liver), nausea and jaundice
- Bones: bone pain, fracture of affected bones
- Brain: neurological symptoms such as headaches, seizures, and vertigo
Although advanced cancer may cause pain, it is often not the first symptom.
Some patients, however, do not show any symptoms.
When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis.
Cancer of unknown primary origin (CUP, "occult cancer") is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a primary tumor.
CUP is found in about 3 to 5% of all people diagnosed with invasive cancer, and carries a poor prognosis in most (80 to 85%) of those circumstances. The other 15 to 20% of patients, however, have a relatively long survival with appropriate treatment.
The signs and symptoms of colorectal cancer depend on the location of the tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, decrease in stool caliber (thickness), loss of appetite, loss of weight, and nausea or vomiting in someone over 50 years old. While rectal bleeding or anemia are high-risk features in those over the age of 50, other commonly described symptoms including weight loss and change in bowel habit are typically only concerning if associated with bleeding.
The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:
- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.
- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.
- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting
- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.
- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
Most cancers typically present as a single primary tumor. Over the course of time—particularly if the primary tumor is left untreated—smaller "satellite" tumors will appear at other places in the body, a phenomenon known as metastasis. Less commonly, a metastatic tumor is found first; but in most such cases, the primary tumor can then be located via examination and testing. Rarely (3-5% of the time), the primary tumor cannot be found because it is too small, or because it has regressed due to immune system activity or other factors. In such situations a diagnosis of cancer of unknown primary origin (CUP) is made.
CUP usually comes to attention because of masses or swellings found somewhere in the body, either by physical examination or on medical imaging performed for another indication. The disease typically develops rapidly, and metastases may occur in places in the body that are otherwise unusual. Comprehensive physical examination is part of the process to identify a possible primary source of cancer; this should include the breasts, lymph nodes, the skin, external genitals, as well as an internal examination of the rectum and of the pelvic organs.
The location of metastases may be a clue as to the underlying source, even if this cannot be found on investigations. For instance, a woman in whom there is axillary lymphadenopathy (swelling in the lymph nodes of the armpit) it is likely that the cancer originated in the breast, and men with lymph node deposits in the mediastinum of the chest and/or retroperitoneal space of the abdomen may have a germ cell tumor.
A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.
Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine). A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.
Most colorectal cancers are due to old age and lifestyle factors with only a small number of cases due to underlying genetic disorders. Some risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red and processed meat as well as alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.
Bowel cancer may be diagnosed by obtaining a sample of the colon during a sigmoidoscopy or colonoscopy. This is then followed by medical imaging to determine if the disease has spread. Screening is effective for preventing and decreasing deaths from colorectal cancer. Screening, by one of a number of methods, is recommended starting from the age of 50 to 75. During colonoscopy, small polyps may be removed if found. If a large polyp or tumor is found, a biopsy may be performed to check if it is cancerous. Aspirin and other non-steroidal anti-inflammatory drugs decrease the risk. Their general use is not recommended for this purpose, however, due to side effects.
Treatments used for colorectal cancer may include some combination of surgery, radiation therapy, chemotherapy and targeted therapy. Cancers that are confined within the wall of the colon may be curable with surgery while cancer that has spread widely are usually not curable, with management being directed towards improving quality of life and symptoms. Five year survival rates in the United States are around 65%. This, however, depends on how advanced the cancer is, whether or not all the cancer can be removed with surgery, and the person's overall health. Globally, colorectal cancer is the third most common type of cancer, making up about 10% of all cases. In 2012, there were 1.4 million new cases and 694,000 deaths from the disease. It is more common in developed countries, where more than 65% of cases are found. It is less common in women than men.
Pancreatoblastoma is a rare type of pancreatic cancer.
It occurs mainly in childhood and has a relatively good prognosis.
Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose. Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis. About 40% of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated. In total, 85% of PanNETs have an elevated blood marker.
Functional tumors are often classified by the hormone most strongly secreted, for example:
- gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea
- insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide
- glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels
- VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)
- somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea
- less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumor
In these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available.
Many of the symptoms of NSCLC can be signs of other diseases, but having chronic or overlapping symptoms may be a signal of the presence of the disease. Some symptoms are indicators of less advanced cases while some may signal that the cancer has spread. Some of the symptoms of less advanced cancer include chronic cough, coughing up blood, chest pain, hoarseness, shortness of breath, wheezing, chest pain, weight loss, and loss of appetite. A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections like bronchitis or pneumonia. Signs of more advanced cases include bone pain, nervous system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast Syndrome, and nausea, vomiting and constipation brought on by hypercalcemia. Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness.
Signs and symptoms of TCC are entirely dependent on the location and extent of the cancer.
Transitional cell carcinoma (TCC) also urothelial carcinoma (UCC), is a type of cancer that typically occurs in the urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. It is the second most common type of kidney cancer, but accounts for only five to 10 percent of all primary renal malignant tumors.
TCC arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs.
When the term "urothelial" is used, it specifically refers to a carcinoma of the urothelium, meaning a TCC of the urinary system.
Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications. The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm).
Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body. Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Five percent of the population can have thyroid nodules, and the majority will be benign.
Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon).
Pancreatic neuroendocrine tumors (PanNETs, PETs, or PNETs), often referred to as "islet cell tumors", or "pancreatic endocrine tumors" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within the pancreas.
PanNETs are a type of neuroendocrine tumor, representing about one third of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Many PanNETs are benign, while some are malignant. Aggressive PanNET tumors have traditionally been termed "islet cell carcinoma".
PanNETs are quite distinct from the usual form of pancreatic cancer, the majority of which are adenocarcinomas, which arises in the exocrine pancreas. Only 1 or 2% of clinically significant pancreas neoplasms are PanNETs.
Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.