Biliary Neoplasm

Biliary neoplasms are tumors that develop in the bile ducts or gallbladder, affecting the system responsible for carrying digestive fluid from the liver to the small intestine. While most of these tumors are cancerous, understanding their characteristics and treatment options is essential for patients facing this diagnosis.

Table of contents

• What Is Biliary Neoplasm?
• Types of Biliary Tumors
• The Biliary System
• How Common Is This Condition?
• Risk Factors
• Signs and Symptoms
• Diagnosis
• Treatment Options
• Outlook and Survival
• Living with Biliary Neoplasm

What Is Biliary Neoplasm?

Biliary neoplasm refers to abnormal growths that develop in the biliary system, which includes the bile ducts and gallbladder. Most biliary tract neoplasms are malignant (cancerous), though some benign (non-cancerous) tumors can also occur^[1][9]. These tumors have been traditionally divided into cancers of the gallbladder, the bile ducts outside the liver (extrahepatic bile ducts), and the ampulla of Vater^[1].

When cancer develops in the bile ducts, it is called cholangiocarcinoma^[2]. The biliary system is part of the digestive system and is responsible for storing, concentrating, and transporting bile from the liver to the small intestine to help digest fats^[7].

cholangiocarcinoma, bile duct cancer, gallbladder cancer, biliary tract cancer

Types of Biliary Tumors

Biliary neoplasms can be classified based on where they develop in the biliary system. There are three main categories of bile duct cancer and a separate category for gallbladder cancer^[2][5].

Intrahepatic cholangiocarcinoma develops in the bile ducts inside the liver. Only a small number of bile duct cancers are intrahepatic, and these are sometimes classified as a type of liver cancer^[2][3].

Extrahepatic cholangiocarcinoma forms in the bile ducts outside the liver. This type is further divided into two categories. Perihilar bile duct cancer, also called a Klatskin tumor, is found in the area where the right and left bile ducts exit the liver and join to form the common hepatic duct^[2][3]. Distal bile duct cancer is found in the area where the ducts from the liver and gallbladder join to form the common bile duct, which passes through the pancreas and ends in the small intestine^[2].

Gallbladder cancer is the fifth most common malignancy of the gastrointestinal tract and is found incidentally in 1 to 3 percent of cholecystectomy specimens^[1]. Approximately 50 percent of cholangiocarcinomas arise in the bile ducts of the perihilar region, 40 percent in the distal region, and 10 percent in the intrahepatic region^[15].

The most common type of biliary tract cancer is adenocarcinoma, which makes up about 90 percent of all biliary tract cancers. This type starts in the epithelial cells of the inner walls of the gallbladder or bile duct^[7].

The Biliary System

• Liver
• Gallbladder
• Bile ducts (intrahepatic and extrahepatic)
• Small intestine
• Pancreas

The biliary tract is made up of a series of thin tubes called bile ducts that span from the liver to the small intestine. These ducts transport bile to the small intestine where it helps digest the fats in food^[5].

The liver produces bile, a yellow-green fluid that helps break down fats during digestion. The bile ducts located within the liver are called intrahepatic bile ducts. The smallest ducts come together to form the right and left hepatic ducts, which lead out of the liver^[2].

The two ducts join outside the liver and form the common hepatic duct. The gallbladder, a small pear-shaped pouch in the upper abdomen, stores bile. The cystic duct connects the gallbladder to the common hepatic duct. Bile from the liver passes through these ducts and is stored in the gallbladder^[2][3].

When food is being digested, bile stored in the gallbladder is released and passes through the cystic duct to the common bile duct and into the small intestine. The common bile duct passes through the pancreas before entering the small intestine^[2].

How Common Is This Condition?

Although infrequent, bile duct carcinomas and cancer of the gallbladder are not rare. In the United States, an estimated 6,000 to 7,000 new cases of carcinoma of the gallbladder and 3,000 to 4,000 new cases of carcinoma of the bile ducts are diagnosed annually^[1].

Biliary tract cancer is a rare disease. Roughly 10,000 Americans are diagnosed with cancer of the biliary tract each year^[6]. Approximately 8,000 patients per year are diagnosed with biliary tract cancer in the United States^[5].

The true incidence of bile duct cancer is unknown because establishing an accurate diagnosis is difficult^[15].

Risk Factors

Several factors may increase the risk of developing biliary tract cancer. Age is an important factor, as the risk increases with age, particularly in individuals over 65, though these cancers are being diagnosed at increasingly younger ages^[24].

Gallbladder carcinoma has a peak incidence in the sixth and seventh decades of life and is three to five times more predominant in females^[1]. Women are more prone to gallbladder cancer, while bile duct cancer affects both men and women equally^[24].

Risk factors for gallbladder cancer include gallstones and a history of chronic cholecystitis (inflammation of the gallbladder). An estimated 22 percent of patients with porcelain gallbladder will develop carcinoma^[1]. Gallbladder cancer is associated with gallstones in more than two thirds of patients^[6]. The presence of gallstones, especially larger ones, raises the risk^[24].

Other risk factors include choledochal cysts, anomalous pancreatico-biliary duct junctions, and gallbladder polyps greater than 1 centimeter in size^[1]. Bile duct cancer can be associated with conditions such as Caroli’s disease, ulcerative colitis, and cysts of the bile duct^[6].

Chronic inflammation conditions such as primary sclerosing cholangitis or chronic gallbladder inflammation can contribute to cancer development. With primary sclerosing cholangitis, the bile ducts inside and outside of the liver become inflamed and scarred, which can cause the bile ducts to become blocked^[24].

Certain congenital conditions affecting the gallbladder and biliary system may increase the risk. Cirrhosis of the liver is also a contributing factor^[24]. Patients experiencing metabolic syndrome, which includes obesity, diabetes, hypertension, and elevated lipid levels, are more prone to these cancers^[24].

Israelis, Japanese, Native Americans, Spanish Americans in the southwest United States, and Eskimos have an increased risk for developing gallbladder cancer^[1].

Signs and Symptoms

Early diagnosis of biliary neoplasm is difficult because most patients present with non-specific findings^[1]. These cancers are tricky because the symptoms frequently only appear when the cancer is at a later stage. Often, gallbladder cancer is incidentally discovered during surgical removal of an infected or inflamed gallbladder^[24].

The most common symptoms include jaundice, which is yellowing of the skin or whites of the eyes. This occurs when bile cannot flow properly through blocked bile ducts^[2][3].

Patients often experience abdominal pain and discomfort, particularly in the right upper quadrant. This presentation is often confused with symptomatic cholelithiasis or chronic cholecystitis^[1][5].

Other symptoms include dark urine and clay-colored stool, which are related to bile flow problems^[2]. Unexplained weight loss, loss of appetite, malaise, anorexia, nausea, and vomiting are common^[1][2].

Patients may also experience fever, extreme itching of the skin (pruritis), and fatigue^[2][5].

Diagnosis

Diagnosing biliary neoplasm involves a combination of medical history review, physical examination, and diagnostic tests^[24]. There are no routine screening tests to check for bile duct cancer before signs and symptoms occur^[2].

Blood tests to measure liver function can give doctors clues about what is causing symptoms. Checking the level of carbohydrate antigen (CA) 19-9 in the blood may provide additional clues. A high level of CA 19-9 in the blood does not necessarily mean bile duct cancer, as this result can also occur in other bile duct diseases^[12]. Blood tests may also show elevated levels of certain enzymes and tumor markers that indicate liver, gallbladder, or bile duct problems^[24].

Imaging tests help visualize the organs and detect abnormalities. These include CT scans (computed tomography), MRIs (magnetic resonance imaging), and ultrasounds^[24]. Ultrasound uses sound waves to create a real-time picture of the inside of the body.

Special procedures may be needed. During endoscopic retrograde cholangiopancreatography (ERCP), a thin, flexible tube equipped with a camera is passed through the throat and into the abdomen. Dye is injected into the bile ducts to highlight them on X-ray images. Tiny tools passed through the tube can also be used to remove gallstones or obtain tissue samples^[12].

Endoscopic ultrasound uses a long, flexible tube with an ultrasound device at the end that is inserted down the throat and into the abdomen. The device emits sound waves that generate images of nearby tissues^[12].

A tissue sample called a biopsy examined by a pathologist under a microscope is needed to confirm the presence of cancer cells^[24]. Familiarity with the imaging characteristics of gallbladder and bile duct neoplasms is important to expedite the diagnosis and appropriate treatment^[1].

Treatment Options

The treatment of biliary neoplasm depends on the type of cancer, where it is located, if it has spread, and the patient’s general health^[13]. Treatment may include surgery, chemotherapy, radiotherapy, targeted medicines, and immunotherapy^[13].

Surgery

Surgery is the only curative modality for biliary tract cancers. Surgical resectability of disease should be established by care teams who are experts in the field^[18]. Many bile duct cancers are multifocal. In most patients, the tumor cannot be completely removed by surgery and is incurable^[15].

If bile duct cancer is found early and has not spread, surgery to remove it should be possible. This will usually involve removing all or parts of the bile duct, as well as parts of other organs or lymph nodes around it. Lymph nodes are part of the body’s immune system^[13].

Surgical resection includes cholecystectomy (removal of the gallbladder), en bloc hepatic resection (removal of part of the liver), and lymphadenectomy with or without bile duct excision, depending on the location of the tumor^[18].

If the cancer has spread too far and cannot be removed, surgery may help control some symptoms. This can include surgery to unblock the bile duct or stop it from getting blocked, which helps with jaundice, or to bypass a blockage in the bile duct or small intestine^[13].

Palliative surgery may be done to relieve symptoms caused by a blocked bile duct and improve quality of life. During a biliary bypass operation, the doctor will cut the gallbladder or bile duct in the area before the blockage and sew it to the part past the blockage or to the small intestine^[10].

If the tumor is blocking the bile duct, surgery may be done to put in a stent (a thin, flexible tube) to drain bile that has built up in the area^[10][13].

Chemotherapy

Chemotherapy uses medicines to kill cancer cells. Patients may have chemotherapy after surgery to get rid of any remaining cancer and help stop the cancer coming back, or to help make the cancer smaller and control and improve the symptoms if surgery is not possible^[13][16].

Chemotherapy may be given with radiotherapy (chemoradiotherapy) or with targeted medicines or immunotherapy^[13].

Targeted Medicines and Immunotherapy

Targeted medicines kill cancer cells. Immunotherapy uses medicines to help the immune system kill cancer. Patients may have immunotherapy if the cancer has spread to another part of the body. These treatments may be given either on their own or with chemotherapy^[13].

Which targeted or immunotherapy drug a patient receives may depend on gene changes in the cancer cells. Biomarker testing tells doctors how to target their treatments^[25].

Radiotherapy

Radiotherapy uses high-energy rays of radiation to kill cancer cells. It is not often used to treat bile duct cancer, but patients may have radiotherapy after surgery to help stop the cancer coming back, to help control and improve the symptoms of advanced cancer, or with chemotherapy^[13][16].

External radiation therapy uses a machine outside the body to send radiation toward the area with cancer. Radiation is given in a series of treatments to allow healthy cells to recover and to make radiation more effective^[10].

Outlook and Survival

At the time of diagnosis, most patients with gallbladder carcinoma are considered unresectable because of direct extension into adjacent organs, local lymph node metastases, or distant metastatic disease. The 5-year survival rate for this tumor is less than 5 percent^[1].

Cholangiocarcinoma is often diagnosed when it is advanced, making successful treatment difficult to achieve^[3]. Unfortunately, most patients with bile duct cancer are not diagnosed until the cancer has advanced to the point where it has spread^[6].

Advanced bile duct cancer is cancer that has spread outside the bile ducts. It can also mean bile duct cancer that has come back some time after first treatment. Unfortunately, advanced bile duct cancer is unlikely to be cured^[20].

Treatment for advanced or late-stage biliary tract cancers is focused on relieving symptoms, controlling the cancer, and improving quality of life^[23].

Living with Biliary Neoplasm

Living with biliary neoplasm can be difficult. Patients may have a number of different feelings, including feeling shocked, upset, numb, frightened, confused, angry, guilty, or sad. Everyone reacts in their own way^[22].

Nutrition and Diet

It is common for people with biliary tract cancer to have problems eating and digesting food after treatment. These problems are caused by the total or partial loss of the gallbladder and other organs involved in digestion. Nutritional problems may include difficulty digesting fatty foods (called fat intolerance), abdominal pain after eating, loss of appetite, nausea and vomiting, diarrhea, increased gas, or bloating^[23].

Good nutrition can help manage the side effects of treatment, speed up recovery, heal wounds and rebuild damaged tissues, and improve the body’s immune system. Patients may need more energy (calories). It helps to eat small, frequent meals or snacks rather than three large meals a day. It is important to relax dietary restrictions, for example choosing full-cream rather than low-fat milk^[21].

A healthcare team, including a registered dietitian, can help maintain nutrition during and after treatment as well as deal with any side effects^[23].

Managing Side Effects

Patients may experience fatigue, weight loss, nausea, and diarrhea during treatment. Exercise and medication can help manage these side effects^[25].

People with advanced biliary tract cancer are often in poor health because their biliary tract and surrounding organs are no longer working properly. Healthcare teams can help manage symptoms including pain, jaundice and extreme itching, loss of appetite, and nausea and vomiting^[23].

Emotional and Mental Health Support

Thoughts and feelings can change over time. Relaxation, self-care, and support groups can help patients care for their mental health during treatment^[25].

Specialist nurses can help if patients are finding it difficult to cope or if they have any problems. They can provide information and signpost patients to support in their local area^[22].

Some people find it helpful to talk to other people about how they are feeling. Talking to friends and relatives about the cancer can help and support patients. Some may prefer to see a counselor or talk to a spiritual leader^[22].

Body Image and Self-Esteem

Biliary tract cancer and its treatments can affect self-esteem and body image. Treatment can change the body in different ways, including scars, hair loss, skin problems, changes in body weight, loss of body parts, and yellowing of the skin. Some of these changes can be temporary, while others can last for a long time or be permanent^[23].

Follow-up Care

Patients have regular tests and follow-ups if they have bile duct cancer, or after surgery to remove the cancer. How often they have the appointments depends on their situation^[16].