Holly Stachler Stachler1

Professor Kretzer

English 1201

18 November 2021

What is Cholangiocarcinoma?

My family recently received the devastating news that my cousin, Robbie, was diagnosed

with Cholangiocarcinoma, a rare form of cancer in the bile ducts of the liver. Robbie is 28 years

old, an engineer, and has dreams of starting a family with his girlfriend. He was diagnosed with

this disease at the end of August this year. Robbie has been so strong and positive during this

difficult time, but the rest of his loved ones are struggling to see him in this position. With this

overwhelming news comes confusion and denial for the people who are close to Robbie. After

hearing about Robbie’s condition, I felt the need to know what was happening inside his body.

From researching this disease, I have found that Cholangiocarcinoma is one of the most

aggressive forms of cancer that is continually being researched by medical professionals due to

the short survival duration of the patients.

Cholangiocarcinoma, commonly known as bile duct cancer, is a kind of cancer that starts

in the bile ducts. MedlinePlus, a service of the National Library of Medicine, explains what bile

ducts are. Bile ducts are the small tubes connecting the liver and gallbladder with the small

intestine. These tubes transport bile, a fluid that aids in the digestion of fats in diet

(“Cholangiocarcinoma: Medlineplus Genetics”, 2020). Extrahepatic bile ducts carry bile outside

of the liver, made up of the common hepatic duct and the common bile duct (National Cancer

Institute). Intrahepatic bile ducts carry bile inside of the liver. Bile is produced in the liver and

then transported to the gallbladder via the common hepatic and cystic ducts (National Cancer

Institute). The bile is released from the gallbladder during digestion (National Cancer Institute).
Holly Stachler Stachler2

Professor Kretzer

English 1201

18 November 2021

The National Cancer Institute, the center for cancer research, explains how common

Cholangiocarcinoma is. Cholangiocarcinoma is rare, affecting less than 6 in 100,000 people

around the world (National Cancer Institute). This disease affects around 8,000 people per year

in the United States (National Cancer Institute). In areas of the world such as northeast Thailand,

cholangiocarcinoma is more common (National Cancer Institute). Cholangiocarcinoma is more

common in adults over 65 years old, and it affects men more than women for unknown reasons

(National Cancer Institute).

Cancers occur when there is a mutation buildup in critical genes. Mutations are mistakes

in the DNA sequence that cause cells to grow and divide uncontrollably, forming a tumor

(Cholangiocarcinoma: Medlineplus Genetics, 2020). Somatic mutations are mistakes in DNA

that occur after conception, and cannot be passed to offspring (National Cancer Institute).

Somatic mutations can occur in tumor suppressors which are genes that help control the growth

and division of cells (National Cancer Institute). Cholangiocarcinoma can be caused by

oncogenes, which are altered versions of genes important in normal cell growth (National Cancer

Institute). Oncogenes can be activated irregularly and cause normal cells to be cancerous

(“Cholangiocarcinoma: Medlineplus Genetics”, 2020). Germline mutations, variations in genes

that have been inherited, have not been found to be a risk factor for this disease.

(“Cholangiocarcinoma: Medlineplus Genetics”, 2020). In the case of cholangiocarcinoma, the

cancer-causing genetic abnormalities are acquired during a person's lifetime and are only found

in the bile ducts (Cholangiocarcinoma: Medlineplus Genetics, 2020).

Holly Stachler Stachler3

Professor Kretzer

English 1201

18 November 2021

There are three ways cancer can spread through your body. Cancer can spread through

the tissues in your body by growing into nearby areas (National Cancer Institute). It can also

spread through the lymph system. Cancer will spread to other parts of the body via lymph veins

and cause a tumor there (National Cancer Institute). The last way cancer can spread is through

your blood. Cancer will spread through your blood vessels to other places of your body, where it

will create tumors (National Cancer Institute). The term "metastasis" refers to the spread of

cancer. The metastatic tumor is always the same type of cancer as the primary tumor (National

Cancer Institute).

The position of cholangiocarcinoma in relation to the liver distinguishes the various kinds

(“Cholangiocarcinoma: Medlineplus Genetics”, 2020). Intrahepatic cholangiocarcinoma begins

in the bile ducts within the liver, this is the least common form of this disease (National Cancer

Institute). Only about 10 percent of all cholangiocarcinoma cases have the intrahepatic type

(National Cancer Institute). Hilar cholangiocarcinoma is a type of cholangiocarcinoma that

develops in the bile ducts just outside the liver. This is the most common form of this disease

(National Cancer Institute). The remaining types of bile duct cancer are called distal

cholangiocarcinomas. The distal forms begin in the parts of the bile ducts near the small intestine

(National Cancer Institute). Extrahepatic cholangiocarcinomas is a term used to describe the

group of cholangiocarcinomas that include both hilar and distal cholangiocarcinomas (National

Cancer Institute). The extrahepatic bile duct anatomy is pictured below (National Cancer

Institute).
Holly Stachler Stachler4

Professor Kretzer

English 1201

18 November 2021

There are many risk factors for developing cholangiocarcinoma. Some risk factors

include primary sclerosing cholangitis, chronic ulcerative colitis, cysts in the bile ducts, cirrhosis

of the liver, Hepatitis B or C virus, diabetes, obesity, genetic factors, and past infection with liver

flukes (Veterans Health Administration, 2017). Other factors that influence the development of

cholangiocarcinoma are inflammatory bowel disease, exposure to certain chemical toxins used in

manufacturing, and lifestyle factors such as smoking, and alcohol use (“Cholangiocarcinoma:

Medlineplus Genetics”, 2020). People in Southeast Asia can be infected with parasitic worms

that live in the bile ducts, increasing the risk of cholangiocarcinoma (“Cholangiocarcinoma:

Medlineplus Genetics”, 2020). Persons who develop cholangiocarcinoma usually have no family

history of the disease, although some studies have found that blood relatives of people who have

the condition have a higher risk of having it than other people (National Cancer Institute).
Holly Stachler Stachler5

Professor Kretzer

English 1201

18 November 2021

Cholangiocarcinoma does not cause symptoms in the early stages, so it is not usually

recognized until it has spread to other bodily tissues (“Cholangiocarcinoma: Medlineplus

Genetics”, 2020). Because the signs of this disease may not be specific to cholangiocarcinoma,

it is difficult to diagnose (Patel, 2011). Symptoms will only be recognized when the bile ducts

get blocked by the tumor. A common symptom of cholangiocarcinoma is jaundice, which is

yellowing of the skin and the whites of the eyes (“Cholangiocarcinoma: Medlineplus Genetics”,

2020). Other symptoms include fatigue, itching, dark-colored urine, loss of appetite, weight loss,

and stomach pain (“Cholangiocarcinoma: Medlineplus Genetics”).

An article written by Tushar Patel, “Cholangiocarcinoma-- Controversies and

Challenges,” for the U.S. National Library of Medicine, explains the challenges when battling

this form of cancer. This article illustrates how cholangiocarcinoma diagnosis can be difficult

and may require the assistance of experienced interventional endoscopists, radiologists, and

cytopathologists (Patel, 2011). An article from the U.S. Department of Veterans Affairs explains

how people in the military are exposed to bile duct cancer and liver fluke infection, and how they

are diagnosed. Health care providers use medical history, physical examination, blood tests,

medical imaging, and consultation with specialists to diagnose bile duct cancer (Veterans Health

Administration, 2017). Doctors can examine the body to look for indicators of sickness, such as

tumors or anything out of the ordinary (National Cancer Institute). Bilirubin is a substance in

human blood that can be a sign that something is wrong with the liver, bile ducts, or gallbladder

(National Cancer Institute). To detect cholangiocarcinoma, doctors can order lab tests of
Holly Stachler Stachler6

Professor Kretzer

English 1201

18 November 2021

someone's blood to check for bilirubin levels. They can also look for liver enzymes in someone’s

blood (National Cancer Institute). Ultrasounds, CT scans, MRI scans, and X-rays can be used to

examine the tumor and seek for evidence that it has spread (National Cancer Institute). To see if

a tumor is a cholangiocarcinoma, doctors can perform biopsies by using a needle to take a small

sample of the tumor out (National Cancer Institute).

An article written by Minji Koh titled “Radiation Therapy for Recurrent Extrahepatic

Bile Duct Cancer”, explains the different treatments for patients with cholangiocarcinoma.

Treatment for cholangiocarcinoma is based on a number of criteria, but there is no one-size-fits-

all solution (Koh, 2021). When diagnosed, most patients with cholangiocarcinoma have disease

that has advanced to a point where it is no longer treatable with surgery (Office of the

Commissioner, 2020). Resectable bile duct cancer is located in a specific area and hasn’t spread.

This form of bile duct cancer can be removed by surgery (National Cancer Institute). The sole

curative therapy option for extrahepatic bile duct cancer that has not spread is surgical resection,

however surgery candidates are limited (Koh, 2021). Even after curative surgical resection, more

than half of patients with bile duct carcinoma suffer recurrence. The surgical resection method

has a median survival duration of 19 months and a 3-year survival rate of 32 percent, which is

much greater than the survival rate of untreated patients (Koh, 2021).

Different surgeries can be used to treat patients with resectable bile duct cancer. When

the tumor is small and only affects the bile duct, surgery to remove it can be performed (National
Holly Stachler Stachler7

Professor Kretzer

English 1201

18 November 2021

Cancer Institute). A partial hepatectomy is a surgical treatment in which the cancerous portion of

the liver is removed (National Cancer Institute). The head of the pancreas, the gallbladder, a

portion of the stomach, a portion of the small intestine, and the bile duct are all removed during a

whipple surgery (National Cancer Institute). A biliary bypass, an endoscopic stent implantation,

and percutaneous transhepatic biliary drainage are all examples of palliative operations that can

be used to reduce symptoms and improve quality of life (National Cancer Institute). If cancer has

blocked the bile duct and bile has built up in the gallbladder, a biliary bypass is performed

(National Cancer Institute). To build a passage around the blocked location, the doctor will cut

the gallbladder or bile duct in the space before the blockage and stitch it past the blockage

(National Cancer Institute). If the tumor is blocking the bile duct, an endoscopic stent can be

implanted. The stent can be used to drain bile that has accumulated in a specific region. (National

Cancer Institute). A percutaneous transhepatic biliary drainage is a procedure used to x-ray the

liver and bile ducts. For this procedure, a thin needle is inserted into the skin below the ribs and

into the liver (National Cancer Institute). Even after a cholangiocarcinoma patient has had

surgery, the patient may be given chemotherapy or radiation therapy to destroy any remaining

cancer cells. It isn’t known whether or not these treatments after surgery will help keep the

cancer from coming back (National Cancer Institute).

Unresectable bile duct cancer is cancer that has spread from the primary tumor, and this

form cannot be removed by surgery (National Cancer Institute). Other therapies include radiation

therapy, chemotherapy, targeted therapy, and immunotherapy for people who are not candidates
Holly Stachler Stachler8

Professor Kretzer

English 1201

18 November 2021

for surgical resection (National Cancer Institute). Treatment for each patient is unique to their

condition. External radiation therapy aims a beam of energy directly at the tumor (National

Cancer Institute). Internal radiation therapy kills tumor cells by injecting small bits of radioactive

material into the tumor (National Cancer Institute). Chemotherapy is often used in conjunction

with radiation therapy when cancer has spread throughout the body (National Cancer Institute).

Many cholangiocarcinoma patients are too sick to undertake harsh chemotherapy or radiation,

and most cholangiocarcinomas do not react well to these treatments (Patel, 2011). Targeted

therapy is aimed directly at the mutations in cancer cells that help them to grow, divide, and

spread (National Cancer Institute). Immunotherapy strengthens the immune system to help the

body fight cancer cells. Immunotherapy is still being studied to see if it is a viable treatment for

cholangiocarcinoma (National Cancer Institute). Lastly, doctors can perform a liver transplant on

patients with hilar bile duct cancer (National Cancer Institute). All of these treatments can cause

side effects such as anemia, loss of appetite, bleeding and bruising, constipation, diarrhea,

swelling, fatigue, fertility issues, flu-like symptoms, hair loss, etc. (National Cancer Institute).

Patients with cholangiocarcinoma receive treatment that focuses on curing the cancer, alleviating

symptoms, and providing supportive care (Patel, 2011).

An article from the U.S. Food and Drug Administration titled, “FDA Approves First

Targeted Treatment for Patients with Cholangiocarcinoma, a Cancer of Bile Ducts,” explains

why Pemazyre was the first FDA approved treatment for patients with cholangiocarcinoma.

Adults with specific forms of advanced cholangiocarcinoma who have been previously treated
Holly Stachler Stachler9

Professor Kretzer

English 1201

18 November 2021

may be candidates for this treatment (Office of the Commissioner, 2020). Pemazyre has been

approved for the treatment of malignancies having a fusion of the fibroblast growth factor

receptor 2 gene (Office of the Commissioner, 2020). FGFR2 fusions have been reported in the

tumors of 9% to 14% of cholangiocarcinoma patients. Pemazyre is a pill that prevents tumor

cells from developing or spreading by blocking FGFR2 (Office of the Commissioner, 2020). The

results of a clinical trial including 107 patients with locally advanced or metastatic bile duct

carcinoma who had a FGFR2 fusion gene were used to approve this medication (Office of the

Commissioner, 2020). Pemazyre was given once a day for 14 days to each patient in this trial,

followed by 7 days without it (Office of the Commissioner, 2020). This treatment was repeated

every 21 days until the disease worsened or the patient's negative effects became unbearable

(Office of the Commissioner, 2020). During the trial, the patients were scanned every 8 weeks.

The overall response rate was calculated by counting how many patients had their tumors shrink

completely or partially after receiving Pemazyre (Office of the Commissioner, 2020). 24 patients

had a reaction that lasted 6 months or longer, and 7 patients had a response that lasted a year or

longer of the 38 patients who reacted to the medication (Office of the Commissioner, 2020).

People who had bad side effects most commonly experienced electrolyte disorders, alopecia,

diarrhea, nail toxicity, fatigue, taste distortion, nausea, constipation, dry eyes, dry mouth,

decreased appetite, vomiting, joint pain, abdominal pain, back pain, and dry skin (Office of the

Commissioner, 2020).
Holly Stachler Stachler10

Professor Kretzer

English 1201

18 November 2021

Recurrent bile duct cancer has a poor prognosis (Koh, 2021). Prognosis is the term used

to predict the expected development of a disease and expectations of survival. The prognosis is

determined by the location of the tumor, if the cancer has spread, and how much of the tumor

was removed during surgery (National Cancer Institute). Survival rates for people who develop

cholangiocarcinoma are estimated by how groups of people with this type of cancer have done in

the past (National Cancer Institute). The projected survival rates may not be accurate due to the

small number of patients who have suffered cholangiocarcinoma. Furthermore, these survival

statistics do not take into account newly discovered treatments (National Cancer Institute).After

5 years, 10% of individuals with extrahepatic cholangiocarcinoma are still alive. People with

early-stage intrahepatic cholangiocarcinoma had a survival rate of 24 percent five years

following diagnosis. If not found early, 8% are alive 5 years after diagnosis (National Cancer

Institute). The overall survival rate of 5 years or more is 20.3% (National Cancer Institute).

Around half of all untreated Cholangiocarcinoma patients die within 3-4 months of diagnosis due

to the indirect effects of tumor development, bile duct obstruction, or liver failure (Patel, 2011).

The earlier bile duct cancer is caught, the better the chance someone with this disease will

survive 5 years after being diagnosed (National Cancer Institute).

Health care professionals have been researching approaches for the prevention of

cholangiocarcinoma. Screening for and treating hepatolithiasis or liver flukes are two approaches

of preventing this disease, with the goal of reducing tumor formation associated with these

disorders (Patel, 2011). Another cholangiocarcinoma prevention strategy is to remove

Holly Stachler Stachler11

Professor Kretzer

English 1201

18 November 2021

choledochal cysts by surgery. People with these cysts typically have a higher risk of developing

cancer (Patel, 2011). Limiting smoking and alcohol use is something a person could do on their

own to prevent the development of cholangiocarcinoma.

After getting diagnosed with this disease, a person can feel hopeless and depressed. The

patients with cholangiocarcinoma have a small chance of survival. Even with treatment, it is

unlikely that the diagnosed person will live past the 5-year mark. Patients will develop side

effects from the treatments and often feel more discouraged than when the treatment began. It is

important for healthcare professionals to provide emotional support to their patients with

cholangiocarcinoma. It is also important for families of the diagnosed person to provide love and

support through the difficult times.

From researching cholangiocarcinoma, I have realized how devastating the disease is.

Even though bile duct cancer is rare, it is one of the most aggressive diseases a person could

develop. Cholangiocarcinoma is so aggressive because it attacks one of the most important parts

of the body, the liver and bile ducts. Most of the risk factors for developing this disease are non-

genetic and uncontrollable. The majority of people who develop cholangiocarcinoma don’t show

signs of the disease until the tumor blocks the bile ducts, and by this time it is too late. After

diagnosis, there is not much the doctors can do because the disease has progressed too much.

Individuals with this condition can live for months or years after being diagnosed, depending on

where the cancer is located and how far it has progressed (“Cholangiocarcinoma: Medlineplus
Holly Stachler Stachler12

Professor Kretzer

English 1201

18 November 2021

Genetics”, 2020). Options for the treatment of this disease are slim, and most patients with

cholangiocarcinoma aren’t able to undergo aggressive treatments. Bile duct cancer patients have

a poor prognosis, even with treatment. Surgical resection is the best treatment option, although

even after curative resection, the majority of patients who undergo a successful surgery

experience recurrence. Overall, my research led me to conclude that cholangiocarcinoma is an

extremely tragic disease with a small chance of patient survival.

Holly Stachler Stachler13

Professor Kretzer

English 1201

18 November 2021

Works Cited

“Cholangiocarcinoma: Medlineplus Genetics.” MedlinePlus, U.S. National Library of

Medicine, 18 Aug. 2020,

https://medlineplus.gov/genetics/condition/cholangiocarcinoma/. Accessed 07 Nov. 2021.

Commissioner, Office of the. “FDA Approves First Targeted Treatment for Patients with

Cholangiocarcinoma, a Cancer of Bile Ducts.” U.S. Food and Drug Administration,

FDA, 17 Apr. 2020, https://www.fda.gov/news-events/press-announcements/fda-

approves-first-targeted-treatment-patients-cholangiocarcinoma-cancer-bile-ducts.

Accessed 07 Nov. 2021.

“Comprehensive Cancer Information.” Edited by Patricia A. Ganz, National Cancer

Institute, Oxford University Press, https://www.cancer.gov/. Accessed 07 Nov. 2021.

Koh, Minji, et al. “Radiation Therapy for Recurrent Extrahepatic Bile Duct Cancer.”

PLoS ONE, vol. 16, no. 6, June 2021, pp. 1–12. EBSCOhost,

doi:10.1371/journal.pone.0253285. Accessed 07 Nov. 2021.

Patel, Tushar. “Cholangiocarcinoma--Controversies and Challenges.” Nature Reviews.

Gastroenterology & Hepatology, U.S. National Library of Medicine, Apr. 2011,

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888819/. Accessed 20 Nov. 2021

Holly Stachler Stachler14

Professor Kretzer

English 1201

18 November 2021

Veterans Health Administration. “Bile Duct Cancer (Cholangiocarcinoma) and Liver

Fluke Infection.” US Department of Veterans Affairs, 17 Mar. 2017,

https://www.publichealth.va.gov/exposures/infectious-diseases/cholangiocarcinoma.asp.

Accessed 07 Nov. 2021

Images:

“Comprehensive Cancer Information.” Edited by Patricia A. Ganz, National Cancer

Institute, Oxford University Press, https://www.cancer.gov/. Accessed 07 Nov. 2021.

“Jaundice Perth: Symptoms & Treatments - Liver Specialists & Surgeons.” The Surgeons

Collective Perth, 25 Oct. 2018,

https://www.thesurgeonscollective.com.au/conditions/jaundice-liver-failure-perth.