What is Gallbladder Cancer?

The gallbladder is a small organ on the right side of the abdomen just below the liver. The primary function of the gallbladder is to store the digestive fluid secreted by the liver called bile. Any cancer originating in this vital organ is referred to as gallbladder cancer. Gallbladder cancer is rare than most malignancies.

According to the American Cancer Society estimates, fewer than 4000 new cases are expected in the year 2017. Also, if detected early, gallbladder cancer patients have a good prognosis for complete recovery. That said, it is often difficult to diagnose gallbladder cancer in its early stages. Only 20% of gallbladder cancers are diagnosed in the early stages.

Few specific symptoms associated with cancer and the location of the organ make it difficult to spot a gallbladder cancer in the early stages. It is one of the reasons for the high mortality rate associated with the condition.

In this article, we will talk in detail about gallbladder cancer and take a closer look at some of the treatment options available.

What is Gallbladder Cancer?

The gallbladder is a pear-shaped organ with the sole purpose of storing and concentrating the secretions from the liver. It is about 3-4 inches in length and rarely wider than an inch. Although the gallbladder has a function, it is not necessary for survival. People who have their gallbladders removed go on to live healthy lives. The wall of the gallbladder consists of three layers of tissue.

The outermost is called the Serosal layer, the middle is called the muscular layer, and the innermost is termed the Mucosal layer. The Mucosal layer of the gallbladder has cells that have gland-like properties.

About 90% of all gallbladder cancers originate in the innermost layer of the gallbladder wall and belong to a group of cancers called Adenocarcinomas. As cancer progresses, it invades the other layers of the organ as well. If remained untreated, cancer can spread to other parts of the body including the liver and intestines.

About 6% of all gallbladder cancers belong to a particular group called papillary adenocarcinomas. The cancer cells of this type of gallbladder cancer are arranged in finger-like projections. It is worth a special mention as this kind of gallbladder cancer has the best prognosis even after a relatively late diagnosis. One of the reasons for this is the fact that papillary adenocarcinomas have less propensity to spread to the liver and lymph nodes. It makes cancer less aggressive and more treatable even after a late diagnosis.

History

Gallbladder cancer was first described in medical literature as early as 1777. It was always considered a deadly disease with a poor prognosis. The difficulty in diagnosing cancer in its early stages made things even bleaker.

However, the outlook improved with modern anti-cancer medications as well as advanced diagnostic tools. Although the incidence of gallbladder cancer in the United States is very low (3 in 100,000 people), it is significantly higher in Central America, India, and Eastern and Central Europe, and Japan.

Among the population of the United States, Native Americans and Hispanic communities are at a significantly higher risk. From a historical perspective, the buildup of gallstones has been attributed to the development of gallbladder cancer. Although gallstones are one of the key risk factors, there are other causes of gallbladder cancer. The prognosis of gallbladder cancer has improved over time.

That said, if cancer is not caught in its early stages, the outlook remains grim. The overall 5-year survival of people suffering from late-stage gallbladder cancer is close to about 3%; which is one of the lowest among most cancers.

Risk Factors

Several factors may increase the possibility of gallbladder cancer. Some of the factors such as lifestyle and diet can be changed, while others can’t.

Let’s take a closer look at some of these key risk factors.

• Gallstones

Gallstones are collections of pebble-like structures inside the gall bladder. They are formed when substances such as cholesterol and salts deposit within the cavity of the gallbladder. The deposition of these gallstones causes severe inflammation in the region that may or may not cause pain and discomfort. Almost 75% of people diagnosed with gallbladder cancer have gallstones in their bladder.

That said, gallstones are relatively common. Only a small fraction of patients suffering from gallstones will have cancer. It is safe to assume that most people suffering from gallstones will never develop gallbladder cancer in their lifetime.

However, the existence of gallstones increases the risk of getting gallbladder cancer nonetheless.

• Porcelain bladder

The excessive deposition of calcium on the inside wall of the gallbladder leads to a condition called the Porcelain bladder. It is often associated with an increased risk of gallbladder cancer. Studies indicate that a long-term inflammation of the gallbladder can stimulate Porcelain bladder. People with this condition stand a higher risk of developing gallbladder cancer.

The inflammation associated with calcium deposits in the Porcelain bladder is considered one of the major risk factors for the development of gallbladder cancer.

• Gender

There is a strong correlation between sex and risk of getting gallbladder cancer, at least in the United States. Women in the United States are twice as likely to get gallbladder cancer than men.

Women are also at a higher risk of developing gallstones and inflammation associated with Porcelain bladder compared to men.

• Ethnicity and geographic location

Race is also an important risk factor for developing gallbladder cancer. In the United States, for instance, gallbladder cancer is more common amongst people of Native American and Hispanic ethnicities.

It is not that surprising when you consider that these ethnicities are more prone to gallstones- a known risk factor. African Americans have the lowest risks among all ethnicities in the United States. Geography also plays a role as a risk factor for gallbladder cancer.

People living in India, Pakistan, Japan, Central, and Eastern Europe are at a higher risk. However, the reason for this geographic factor is not completely understood.

• Cysts in the bile ducts

The ducts that connect the liver with the gallbladder are called bile ducts. These ducts sometimes develop bile-filled cysts called Choledochal cysts. If undiagnosed, these cysts can grow to an enormous size sometimes containing as much as 2 quarts of bile. Patients suffering from Choledochal cysts stand at a higher risk of developing gallbladder cancer. The inner lining of these cysts often exhibits pre-cancerous features.

Hence the existence of these cysts is considered a potential risk factor for developing gallbladder cancer.

• Polyps in the gallbladder

Gallbladder polyps are the unwanted growth of the inner lining of the gallbladder that forms a bulge on the inner wall of the bladder. Although there can be several reasons for the polyps to form, cholesterol deposition is the most common. Other reasons may include a small tumor or inflammation. If the size of these polyps increases beyond 1 centimeter, they pose a significant risk of turning cancerous.

Hence, if larger polyps are observed in the gallbladder, the surgeons advise removing the entire gallbladder surgically.

• Malformations in the bile duct

The bile duct carries the bile stored by the gallbladder to the intestine. Usually, the bile duct is joined by a duct coming from the pancreas carrying pancreatic juice. In some people, the pancreatic duct meets the bile duct closer to the gallbladder than normal. It causes the reflux of pancreatic juice into the gallbladder.

The reflux flow also keeps the bile in the gallbladder for more time than usual. People with this anatomical abnormality in their bile duct have a larger risk of developing bladder cancer. The precise reason for the increased risk is not known.

However, the reflux of pancreatic juice combined with the delayed emptying of the gallbladder may be the probable cause.

• Exposure to toxic chemicals

Exposure to certain industrial chemicals may increase the risk of developing gallbladder cancer. That said, as gallbladder cancer is one of the rarest cancers, there is not enough research data on the topic. According to a study, exposure to Nitrosamines can increase the risk of developing gallbladder cancer.

• Salmonella infections

Salmonella is a bacterium that is pathogenic in humans. It causes a disease known as Typhoid. People suffering from typhoid or carrying the disease are at a significantly higher risk of developing gallbladder cancer compared to people who are not infected. The inflammation of the gallbladder due to typhoid is considered the reason for the risk. That said, Typhoid is rare in the United States.

However, it is quite common in Central American and Asian countries.

• Family history

Although the incidences of gallbladder cancer are rare, the risk of getting it increases with a family history of the disease. However, most people will not get gallbladder cancer even if their family member was diagnosed with it.

Gallbladder Cancer Symptoms

One of the reasons that make gallbladder cancer deadly is the lack of definite signs and symptoms, especially in the early stages of the disease. However, the symptoms do appear early in some cases leading to an early diagnosis.

Here is a list of some of the most common symptoms of gallbladder cancer:

• Pain in the belly

One of the most consistent signs of gallbladder cancer is abdominal pain. The pain is usually isolated to the upper-right part of the abdomen. That said, it should be noted that abdominal pain can result from several other issues as well. Hence, abdominal pain, in no way, can be a definitive symptom of gallbladder cancer.

• Nausea and Vomiting

Like the abdominal pain, nausea or vomiting can be due to a myriad of reasons. However, people who have gallbladder cancer may experience nausea and vomiting.

• Jaundice

Jaundice is often a symptom associated with late-stage gallbladder cancer. If cancer has grown large enough to block the bile ducts, the accumulation of bile can cause severe jaundice.

The lack of bile drainage from the liver causes an increase in the blood levels of bilirubin- a yellow pigment in bile. The increase in bilirubin in the blood causes the skin and white part of the eyes to turn yellow. The accumulation of bile in the liver causes inflammation of the liver as well.

• Swelling of the gallbladder and lumps in the belly

If cancer has grown to a considerable size, it can block the bile ducts resulting in inflammation of the gallbladder. Cancer can also potentially spread into the other parts of the abdomen especially the liver and the intestine. The inflammation of the lumps can be felt on the right side of the belly by palpating the abdomen. Imaging techniques such as ultrasound can also reveal the presence of these lumps in the belly.

• Other symptoms

Apart from the symptoms listed above, there can be other symptoms attributed to gallbladder cancer. Although these symptoms are less common than the ones discussed earlier, they do occur in some patients.

• Loss of appetite
• Swollen belly
• Sudden unexpected weight-loss
• Low-grade fever
• Dark-colored urine
• Greasy and light-colored stools

At this point, it is important to reiterate that gallbladder cancer is not common. Most of the symptoms described above can also occur in the case of gallstones. Some symptoms such as abdominal pain can be explained by far simpler causes such as gas or indigestion. However, if the symptoms persist, it is important to consult with the doctor. Early detection is the best chance to beat gallbladder cancer.

Screening

As we discussed earlier, gallbladder cancer is one of the most difficult to diagnose. The gallbladder is situated deep in the abdomen, and there are no specific early signs and symptoms of gallbladder cancer. Hence, a regular medical examination often unable to diagnose gallbladder cancer, especially in the early stages.

Unfortunately, there are no blood tests to screen for gallbladder cancer in healthy individuals either. Most gallbladder cancers are diagnosed when the gallbladder is surgically removed after a diagnosis of gallstones. A biopsy (microscopic examination) of the tissue of the removed gallbladder is always performed to screen for cancer. If the patient presents with some of the symptoms, the doctor can try to diagnose gallbladder cancer using a variety of tests and exams.

• Physical exam

If a patient exhibits early signs and symptoms of gallbladder cancer, the doctor will conduct a medical history and physical exam. The medical history helps the doctor to identify some of the risk factors that we previously discussed. The physical exam focuses on the identification of any lumps or swelling in the abdomen, especially around the liver. Fluid buildup or tenderness can indicate cysts or blocked bile ducts.

The doctor also examines the skin and the white part of the eye (Sclera), to identify signs of jaundice. If cancer has spread to the lymph nodes, it may swell. The doctor will examine the lymph nodes especially above the collar bone and in the armpit. Any swelling or tenderness may indicate the spread of cancer.

If the preliminary physical exam suggests the possibility of gallbladder cancer, the doctor will recommend further tests.

• Liver and gallbladder function tests

Blood tests to detect the level of bilirubin in the blood are done to determine the functioning efficiency of the liver and the gallbladder. Gallbladder cancer can cause the bile ducts to clog leading to the accumulation of bile in the liver. Bile accumulation may result in a spike in the blood level of bilirubin. Lab tests can identify these increased levels quite quickly. If the tests reveal an increased level of bilirubin in the blood, it may indicate a problem with the liver or gallbladder.

The doctor may also order other blood tests including albumin, serum phosphates, AST (Aspartate Transaminase) to ALT (Alanine Transaminase) ratio. These tests assess the function of the liver and are called ‘Liver function tests.’

• Tests for tumor markers

The presence of certain proteins in the blood can indicate cancer. Proteins such as CEA (Carcinoembryonic Antigen) and CA 19-9 are elevated in the blood of patients with gallbladder cancer. A lab test can determine the presence of these proteins in the blood.

However, the presence of these proteins in the blood is an indication of an advanced stage of gallbladder cancer.

• Ultrasound imaging

Imaging techniques are very helpful in positively identifying gallbladder tumors. Ultrasound imaging is one of the first imaging techniques used if there is a suspicion of gallbladder cancer. During an ultrasound scan, sound waves are transmitted into the abdomen using an ultrasound machine. The waves reflected from the various organs are captured and converted to simulate an image of the organs. The imaging is a simple procedure and does not require any special preparation. There is no radiation involved either. The doctor can identify any abnormalities such as swelling, tumor, or cysts using this technique.

• E. CT scanning

A CT (Computerized Tomography) scan uses X-rays to image a particular area of the body at various angles. The images are then merged by a computer to create a 3-dimensional image revealing the structure of the organs. A dye may be injected into the blood to improve the resolution, although, it is not always necessary. A CT scan can reveal the presence of tumors, swelling, or cysts. It is a more precise method of imaging compared to ultrasound.

The CT scan images can help the doctor to identify the tumor in the gallbladder positively.

• MRI (Magnetic Resonance Imaging) scan

An MRI scan is like a CT scan but uses radio waves instead of X-rays. The radio waves transmitted back are utilized by the machine to create a picture of the inner organs of the body. A dye is usually injected into the bile duct to create an image of the gallbladder. Sometimes, a dye may be injected into a vein near the gallbladder to get a detailed picture of blood vessels supplying blood to the organ. These images can help the doctors to identify the size and extent of the tumor spreading positively.

• Laparoscopy

The technique is an invasive procedure in which a small incision is made in the abdomen, and the organs are checked for cancer. Laparoscopy allows the doctors to identify the tumor, remove the organ, or collect samples for examination in the lab.

• Bioscopy

A small sample of the tissue removed during the Laparoscopy can be used to check for cancer. This technique is called a biopsy, and it enables the identification of tumor cells. The technology can reveal the extent of cancer and help in staging cancer as well.

Diagnosis and Stages

It is important to know the extent of the gallbladder cancer progression to design therapy. It is usually done by assigning different stages to gallbladder cancer depending on the progress and organs involved. Gallbladder cancer is staged as follows.

Stage 0 (Carcinoma in-situ)

It is the most preliminary stages of gallbladder cancer and has the best prognosis. Cancer in this stage is represented by a few abnormal cells in the innermost layer of the gallbladder wall. There are no tumors and no invasion into other organs.

Stage I

Stage I is designated if the cancer is already formed.

It is further divided into the following two sub-stages.

• Stage IA: If cancer has spread beyond the innermost layer and has infiltrated into the muscular layer of the gallbladder, it is designated Stage IA.
• Stage IB: This level is designated for cancers that have spread beyond the muscular layer into the connective tissue layer.

Stage II

Stage II is further divided into two sub-stages.

• Stage IIA: In this stage, the gallbladder cancer has already spread outside the organ into the liver and adjoining region including the stomach and intestine.
• Stage IIB: If the cancer is spread to the lymph nodes, muscle layers, and adjacent tissues.

Stage III

In this stage, cancer has already spread into one of the major blood vessels supplying the liver or nearby organs.

Stage IV

It is the most invasive stage of gallbladder cancer. In this stage, cancer has already spread to lymph nodes that are distant from the gallbladder. At this point, cancer has spread to many other tissues as far as the lungs. It is the most advanced stage of gallbladder cancer with the poorest prognosis.

Sometimes, gallbladder cancer stages are grouped together according to the location of treatment.

• Localized (Stage I)

As the name suggests, cancer in this group is localized in the wall of the gallbladder, and the treatment involves complete surgical removal of the gallbladder.

• Unresectable (Stage II through IV)

In stages II through IV, the gallbladder cancer has spread to lymph nodes and the nearby organs. Hence, complete removal of the organ can’t eliminate cancer.

Treatments and Drugs

The treatment options for gallbladder cancer depend on the progression of cancer. Both surgical and non-surgical treatments are available for treating gallbladder cancer.

However, if cancer has progressed to an advanced stage, surgery may not be the preferred method.

• Surgery

If the gallbladder cancer is localized and not spread in the nearby areas, it can be treated by completely removing the gallbladder. The surgery, called Cholecystectomy, is undertaken only if the cancer is identified as Stage ) or Stage I. A laparoscope is used to make an incision in the abdomen, and the gallbladder is surgically removed. Sometimes, the adjacent lymph nodes may also need to be removed to limit the spread of the cancer post-surgery. If cancer has spread to the adjacent tissues, palliative surgeries can be done to restrict further spreading.

Some of these palliative surgeries include the following:

Biliary bypass: This operation is performed if a part of the bile duct is blocked by the tumor and the bile is backing up in the gallbladder. A new path for the bile to reach the small intestine is created during this surgery.

Endoscopic stents: This surgery is also done if the tumor is blocking the bile duct. A stent (thin, flexible tube) is surgically placed in the bile duct during this procedure. Doing this allows the proper drainage of the bile from the gallbladder into the intestine.

If the gallbladder cancer has progressed to late stages, it may not be possible to remove it using surgery. In such cases, radiation and chemotherapy are used as front-line therapies.

• Radiation therapy

It uses high-energy X-rays to kill cancer cells. For the treatment of gallbladder cancer, an X-ray machine is used to generate X-rays to kill the cancerous cells. As the technique uses X-rays to target the gallbladder from outside the body, it has significant collateral damage. Some healthy cells and tissues are also exposed to X-ray radiation during the treatment. That said, newer machines allow for a more targeted approach to treating gallbladder cancer.

Radiation therapy has many uses in treating gallbladder cancer. As radiation therapy uses high-power radiation, it is not without any side effects. The common side effects of radiation therapy include sunburns like skin, nausea, vomiting, and fatigue.

It is often used after the surgical removal of the gallbladder to kill any remaining cancer cells. Radiation therapy after surgery ensures that the stray cancer cells that may have been left behind are also killed to eliminate recurring cancer.

Also, radiation therapy can be used as palliative therapy – if the cancer is too advanced, radiation therapy can be used to alleviate some symptoms such as pain to shrink the tumors.

The side effects of radiation therapy can be worse if it is used in conjunction with chemotherapy.

• Chemotherapy

It involves the use of high potency drugs to kill cancer cells. As these drugs are not very good at differentiating between the cancer cells and healthy cells, they destroy a bunch of healthy cells as well. Hence, there are many side effects of chemotherapy. Chemotherapy can be used as a mainstay therapy or can be combined with other treatments including radiation and surgery. The treatment is given in cycles with breaks between cycles. Chemo cycles to treat gallbladder cancer last for 3-4 weeks.

As a contrast to chemo used in some other forms of cancers, chemo is not administered through a vein in gallbladder cancer. For gallbladder cancer, chemo is usually given as a hepatic artery infusion. Since the hepatic artery supplies blood to the gallbladder tumors, high concentrations of drugs can be achieved using this method. Some of the most common drugs used in chemotherapy for gallbladder cancer include the following.

In many cases, a combination of these drugs is given to reduce side effects and maximize efficacy. Chemotherapy drugs are very powerful and attack the cancer cells rapidly.

As they can’t differentiate between normal and cancer cells all that well, they cause some serious side effects. Some of the side effects of drugs used to treat gallbladder cancer include the following. Although there are severe side effects of chemotherapy, most of these symptoms will go away after the treatment. Additional drugs are often used to mitigate these side effects or at least to make them bearable for the patients.

Coping and Support

Some people will be completely cancer-free post-treatment. In that scenario, completing the treatment can often result in a sigh of relief. However, there is always the worry of cancer coming back. Although the fears are legitimate for most people, they do subside with time. It is crucial to follow-up with doctors on a regular basis even after successful competition of the treatment. During these visits, the doctors will perform regular medical exams and ask for any symptoms.

Learning about the disease and talking with people who successfully defeated gallbladder cancer helps the patients to cope with the post-treatment fall out. If you have any questions regarding your condition, feel free to ask your doctor. It is an excellent idea to write down all the questions you may be having and asking your doctor detailed answers. It is also important that you know about all the treatment options you have. You may not have the same options as others, but asking your doctor will help you to expect realistic results.

Like many other cancers, gallbladder cancer is a major illness. It is natural for patients to feel scared and worried. Reaching out to friends and family can help to cope with the situation better. Talking to friends and relatives is a good way of rejuvenating and recharging your batteries. Talking to your doctor can help you set realistic expectations from your treatments.

Although the physician may not have a clear answer to all your questions, asking them will help you to understand your condition better. Also, ask your doctor for tips to reduce the side effects of chemo. Make sure that you have your medical wishes written down in case you are not able to communicate them.

Seek the support of councilors, medical social workers, or a support group. Talking to people will help you to look at things in a positive light. Support groups are an excellent way to meet individuals who have gone through the same phase as yourself and understood what to expect.