The biliary system is divided into intrahepatic (the cystic duct that drains the liver) and extrahepatic structures (the gallbladder and the channels that guide bile to its main duodenal papilla at the second part of the duodenum). Cholangiocytes are the cells that make up the biliary system. These cholangiocytes become cancerous leading to biliary tract cancer that can either become intrahepatic or extrahepatic cholangiocarcinoma. Cholangiocarcinoma, yet another type of extrahepatic cholangiocarcinoma, includes two subtypes: distal cholangiocarcinoma which influences the pancreatic biliary ducts and gall bladder.
Even though each of these carcinomas possesses a similar epithelium their pathology can differ because of their anatomical location. The patients have a poor prognosis of cholangiocarcinoma which is an uncommon and aggressive cancer and it is usually detected at an advanced and uncurable stage. The late diagnosis usually results in the extensive involvement of blood vessels and regional lymph nodes by making the surgical removal very difficult.
Epidemiology
Between 0. 72 to 1. 62 cases per 100,000 people in the United States are diagnosed with cholangiocarcinoma yearly. Despite the fact that the phenomenon occurs in other parts of the world, the documented numbers rise even more in other countries around the globe. Northeastern part of Thailand (Asia) records the highest incidence rate over 80 per 100,000 most likely due to the common problems in these areas caused by the hepatobiliary fluke infection.
Many researches which has been carried out in the last decades have shown an increase in the prevalence of the disease called intrahepatic cholangiocarcinoma. This increase is a result of various factors which includes irritation and chronic inflammation of the bile ducts’ lining. Moreover, the prevalence is age-dependent phenomenon so it is more frequent among older people; it is more common among males than females. This might be because men are more likely to get primary sclerosing cholangitis, which is known as a risk factor and can appear in men as early as 40 years of age.
Anatomy
Pathophysiology
To ensure mutations in various genes like oncogene and tumor suppressor a chronic inflammation and irritation of the biliary system comes up that resembling other gastrointestinal malignancy occurs and starting with hyperplasia and ends up with metaplasia and dysplasia and ultimately leads to carcinoma.
IDH1 and IDH2 mutations in the Isocitrate dehydrogenase (IDH) gene have been observed in up to 20% of intrahepatic bile duct cancers. The statistic that although between 13% and 17% of IBC patients (intrahepatic bile duct cancer) exhibit FGFR (fibroblast growth factor receptor) gene fusion and translocation as well is also observed.
Fusion genes containing PRKACA and PRKACB that are the catalytic component of protein kinase A and whose expression is featured in pCCA and dCCA are involved. In addition, ROS1 gene fusions are found in 8 to 9% of cholangiocarcinomas.
Etiology
Prolonged inflammatory diseases may lead to stress-induced alterations in the bile duct epithelium, which may in turn be responsible for the changes that worsen biliary tract cancer. There is a well-known chronic inflammatory illness, which has been associated with biliary tract cancer and is called primary sclerosing cholangitis (PSC). It is usually associated with inflammatory bowel diseases and ulcerative colitis.
Common predisposition factors for gallbladder cancer include polyps of the gallbladder, congenital cysts of gallbladder and chronic gallbladder inflammation. Moreover, alcohol abuse and obesity can have an association with the development of cholangiocarcinoma.
Genetics
Prognostic Factors
Because of the late diagnosis and the limited treatment options, the biliary tract cancer has a very poor prognosis with the overall survival being lower than 10% and the mean survival time is less than two years.
The fact that still the median survival for patients with unresectable tumors by using a range of chemotherapeutic drugs is highly aggressive. For the treatment of early-stage cancer, surgery is the only method available. The prognosis after surgery depends on several factors such as the metastasis, involvement of the adjacent tissues, and the margin status.
Clinical History
Clinical Presentation by Stage:
Early Stage (Stage 0 and I):
Sometimes asymptomatic and unexpectedly found during imaging for other purposes.
Symptoms can be moderate in severity and present as abdominal pain, jaundice, or abnormal liver functional tests.
Locally Advanced (Stage II and III):
Symptoms become more clearly noticeable and may comprise jaundice, abdominal pain, unexplained weight loss, and pruritus (itching).
Jaundice is usually the first sign. Cholangitis may present along with some of the symptoms which are fever, chills and right upper quadrant pain.
Metastatic (Stage IV):
The show of symptoms is aggravated progressively with the spread of tumor to other organs such as the liver, lungs or peritoneum.
The signs may be obvious, like significant weight loss, extreme abdominal pain, ascites (accumulation of fluid in the abdomen), and other symptoms associated with organ malfunction.
Associated Comorbidities or Activities:
Chronic Liver Disease: As these patients could have a history of chronic liver diseases like hepatitis B or C, alcoholic liver disease or non-alcoholic fatty liver they face more chance for getting infection.
Gallstones: The presence of gallstones is a risk factor which indicates developing gallbladder cancer.
Primary Sclerosing Cholangitis (PSC): PSC is a risk factor for cholangiocarcinoma, which is the most common type of bile duct cancer and it is most commonly found in the intrahepatic bile ducts.
Biliary Inflammation: Persistent inflammation of bile ducts as seen in conditions like RPC can promote the risk of cholangiocarcinoma.
Heavy Alcohol Consumption: Gallbladder tumor is affiliated with uninterrupted heavy alcohol consumption, as one of the risk factors.
Acuity of Presentation:
Gradual Onset: At first, the signs may appear slowly, frequently non-specific, thus resulting in the diagnosis being delayed.
Acute Onset: The progression to the complicated stages or conditions such as the biliary blockage can result in acute emergency presentations along with sudden nausea, unbearable abdominal pain, or cholangitis.
Staging:
Tumors of biliary tract commonly tend to progress according to the TNM staging system, which classifies the tumor on T (this is related to the extent of the primary tumor), N (changes in the regional lymph nodes), and M (the presence of distant metastasis). The stage decides the treatment and informs about future outcomes.
Stage 0: In-situ carcinomas.
Stage I: Limited to the bile duct or gallbladder wall; lymphatic structures in surrounding tissues and distant sites staying clear of infection.
Stage II: The tumors that invade the nearby tissues or organs, for example the liver, pancreas or the major blood vessels.
Stage III: Presence of cancer invading the adjacent lymph nodes but its absence in tissue and organs at a distance.
Stage IV: These cancers have the propensity to spread through the lymphatic system to the distant organs such as the liver, lungs, or peritoneum.
Physical Examination
Abdominal Examination: Palpation of abdomen (which includes identification of any possibilities of masses, tenderness, or the enlargement of organs).
Jaundice Assessment: Examination for jaundice, a yellowing of the skin and eyes which is usually a sign of biliary obstruction, is commonly used.
Lymph Node Examination: An examination of nodes in the neck, armpits, and groin areas should be done if they are enlarged, which is an indicator of cancer spreading to those areas.
Liver Function Tests: Though not necessarily a part of a physical exam, these tests may be ordered when there is clinical suspicion and signs of liver involvement.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Metastatic liver cancer
IgG4 related sclerosing cholangitis
Gallbladder adenomyomatosis
Hepatocellular carcinoma
Gallbladder adenomas
Gallbladder polyps
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Early Stage (Stage I and Stage II):
Surgery: Surgical excision is the fundamental treatment option for early biliary tract cancer whenever it can be implemented. This step can include the removal of the bile duct part or fully along with the gallbladder and surrounding tissues. Sometimes liver transplantation may be viewed as a possible option.
Adjuvant Therapy: Following surgical treatment may be an adjuvant chemotherapy or chemoradiotherapy in order to prevent tumor reoccurrence.
Advanced (Stage II, Stage III):
Surgery: In certain cases, surgical procedure may be a choice even for locally advanced disease and it may be more invasive than usual, possibly using removal of a vessel or an organ.
Neoadjuvant Therapy: The chemotherapeutic or chemo radiotherapeutic regimes can be used preoperatively to reduce the size of the tumor and to make it more operable.
Chemoradiotherapy: To medically inoperable tumors, chemoradiation therapy is a solution to such problems as help control the progress of the disease and also symptoms relief.
Advanced or Metastatic (Stage III and Stage IV):
Systemic Therapy: Chemotherapy is often the fundamental therapeutic approach for advanced or metastatic biliary tract cancer. Gemcitabine in combination with cisplatin is a typical chemotherapy regimen, however other regimens or targeted therapy may be taken into account depending on the particular characteristics of the tumor and the patient.
Palliative Care: Palliative therapies like stent placement to improve bile flow blockage, pain management, nutritional support, and supportive care to maintain a good quality of life are also an integral aspect of the treatment for advanced-stage illness.
Clinical Trials: Clinical trials might ensure the availability of the trial participants of investigational drugs, targeted therapies, immunotherapies, or even the novel approaches as methods of treatment for biliary tract cancer patients, those segregated in the advanced or refractory state.
Nutritional Support: Proper nutrition is of great importance for biliary tract cancer patients, particularly those who are undergoing the treatment. A registered dietitian will help with the measures like adequacy of nutrition amidst sickness, management of side effects like nausea and diminished appetite, and optimal calorie and nutrient intake at this moment.
Pain Management: Alternative pain management approaches like relaxation therapy, an imagery guide, acupuncture, and massage can help sufferers to feel less painful and injured.
Physical Activity: Physical activity and exercise can be a good way to improve the strength, endurance and overall wellness of the patients with biliary tract cancer. A well-designed exercise program, which will be created considering the user’s condition and preferences, may be helpful.
Psychosocial Support: It can be easy to have trouble emotionally when fighting against cancer. The counseling, support groups and other psychosocial interventions can be very helpful in providing emotional support, coping strategies and a sense of community for patients and their caregivers.
Role of Chemotherapy in the treatment of biliary tract cancer staging
Chemotherapeutic drugs are drugs aimed at killing or preventing the growth of the cancer cells. In the treatment of biliary tract cancer staging, various types of chemotherapeutic agents are used either alone or in combination to target cancer cells and to slow down the progression of the disease.
Cisplatin: Cisplatin is a platinum-based chemotherapeutic agent used in cancer treatment mechanisms by disrupting DNA of cancer cells and result in their death. It is usually combined with other chemotherapeutic agents, e.g., gemcitabine, for the treatment of the biliary tract cancer. Cisplatin-based regimens are the most popular adjuvant and palliative regimens.
Gemcitabine: Gemcitabine is a nucleoside analogue, chemotherapy drug, can hinder the reproduction of cancer cells by blocking DNA generation further. It has been found successful alongside cisplatin when treating advanced biliary tract cancer as a first treatment. Furthermore, the gemcitabine-based regimens are also used in adjuvant and neoadjuvant settings.
5-Fluorouracil (5-FU): 5-FU is a floropyrimidine that disrupts synthesis of DNA and RNA which results in the death of cancer cells. It may be applied alone or as a part of multimodal therapy for the biliary tract cancer treatment.
Capecitabine: Capecitabine is the oral version of 5-FU that is later converted into 5-FU in the human body. It could be the option for intravenous 5-FU and in the case of combination therapy with other chemotherapeutic agents it is used for treating biliary tract cancer.
Irinotecan: Irinotecan is a chemotherapy medicine working as topoisomerase I inhibitor which perturbs with DNA replication and transcription and thus cancer cells stop dividing and the organism dies. It can be applied as a first-line or salvage therapy for the later stages of biliary tract cancer either alone or in combination with other chemotherapy agents.
Role of Targeted therapy in the treatment of biliary tract cancer staging
Targeted therapy as well as pathologic staging of these tumors are critical components in medical care, especially for patients with distant disease that is unsuitable for conventional treatments. Targeted therapies use the principle of disease delineation to directly attack the nucleus sites that are damaged in cancer cell growth and progression.
Cetuximab: Cetuximab is a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR). It is indeed used together with the chemotherapy in patients who have biliary tract advanced cancer, especial those having a tumor that overexpresses the EGFR. Experimental studies have demonstrated favorable outcomes and cetuximab-based therapy seems promising for certain categories of patients.
Bevacizumab: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that promotes angiogenesis (the process of forming new blood vessels) within tumors. Bevacizumab may be employ as concurrent therapy with chemotherapy for metastatic biliary cancer to inhibit cancer growth and increase success rates.
Infigratinib: Infigratinib is a selective inhibitor of the Fitness growth factor receipt (FGFR) that sends positive results in the clinical trials for the bi-tractal organ cancer in the hypothesis stage with the patients having FGFR2 fusion or translocations. This technique is very effective as it works by blocking the aberrant FGFR signaling, which is a key driver of the growth and survival of cancer cells.
In ERCP, a flexible endoscope is passed through the mouth, the esophagus, and the stomach, and into the duodenum, thereby one can visualize the biliary and pancreatic ducts. Contrast dye is administered intravenously as these ducts are being visualized. X-ray images are taken after the imaging to screen for any tumor, stricture, or blockage.
In most cases, ERCP is often used for the identification of the biliary tract tumors’ locations, size, and extent of the disease, as well as for detecting complications like biliary obstruction or jaundice. This data is the key to right staging of the cancer, which will affect the choice of treatment and the prediction of the outcome.
In addition to staging, the experts might also opt for procedures that would involve the use of interventional radiology such as percutaneous transhepatic cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP) by way of which the tumor involvement would be further assessed and the treatment plan guided.
Before the treatment, the patient’s medical history, physical examination, and imaging studies are thoroughly evaluated. Imaging methods such as CT, MRI and PET scanning are employed to figure out tumour’s position, dimensions, and degree. Endoscopic and radiological procedures such as ultrasonography, CT scan, are performed for visualizing the biliary tract and tissue sampling for biopsy in order to correctly assess the cancer stage. Pathological staging is done on biopsy samples to find out the histological type, grade and the invasion into the adjacent tissues of the cancer.
The assessment of staging is usually carried out on x-ray, endoscopic, and pathological examinations with a view to predicting the prognosis and aiding the choice of treatment. Treatment group involves an interdisciplinary treatment plan team who sooner than later, crafts an individualized treatment plan that incorporates the cancer stage, the overall health status and treatment response.
The therapy can be either with the curative purpose of removing the tumor and preventing its recurrence or palliative with the intention of alleviating the symptoms and enhancing the quality of life. Patients are continuously checked for response to therapy and any side effects that may appear.
The biliary system is divided into intrahepatic (the cystic duct that drains the liver) and extrahepatic structures (the gallbladder and the channels that guide bile to its main duodenal papilla at the second part of the duodenum). Cholangiocytes are the cells that make up the biliary system. These cholangiocytes become cancerous leading to biliary tract cancer that can either become intrahepatic or extrahepatic cholangiocarcinoma. Cholangiocarcinoma, yet another type of extrahepatic cholangiocarcinoma, includes two subtypes: distal cholangiocarcinoma which influences the pancreatic biliary ducts and gall bladder.
Even though each of these carcinomas possesses a similar epithelium their pathology can differ because of their anatomical location. The patients have a poor prognosis of cholangiocarcinoma which is an uncommon and aggressive cancer and it is usually detected at an advanced and uncurable stage. The late diagnosis usually results in the extensive involvement of blood vessels and regional lymph nodes by making the surgical removal very difficult.
Between 0. 72 to 1. 62 cases per 100,000 people in the United States are diagnosed with cholangiocarcinoma yearly. Despite the fact that the phenomenon occurs in other parts of the world, the documented numbers rise even more in other countries around the globe. Northeastern part of Thailand (Asia) records the highest incidence rate over 80 per 100,000 most likely due to the common problems in these areas caused by the hepatobiliary fluke infection.
Many researches which has been carried out in the last decades have shown an increase in the prevalence of the disease called intrahepatic cholangiocarcinoma. This increase is a result of various factors which includes irritation and chronic inflammation of the bile ducts’ lining. Moreover, the prevalence is age-dependent phenomenon so it is more frequent among older people; it is more common among males than females. This might be because men are more likely to get primary sclerosing cholangitis, which is known as a risk factor and can appear in men as early as 40 years of age.
To ensure mutations in various genes like oncogene and tumor suppressor a chronic inflammation and irritation of the biliary system comes up that resembling other gastrointestinal malignancy occurs and starting with hyperplasia and ends up with metaplasia and dysplasia and ultimately leads to carcinoma.
IDH1 and IDH2 mutations in the Isocitrate dehydrogenase (IDH) gene have been observed in up to 20% of intrahepatic bile duct cancers. The statistic that although between 13% and 17% of IBC patients (intrahepatic bile duct cancer) exhibit FGFR (fibroblast growth factor receptor) gene fusion and translocation as well is also observed.
Fusion genes containing PRKACA and PRKACB that are the catalytic component of protein kinase A and whose expression is featured in pCCA and dCCA are involved. In addition, ROS1 gene fusions are found in 8 to 9% of cholangiocarcinomas.
Prolonged inflammatory diseases may lead to stress-induced alterations in the bile duct epithelium, which may in turn be responsible for the changes that worsen biliary tract cancer. There is a well-known chronic inflammatory illness, which has been associated with biliary tract cancer and is called primary sclerosing cholangitis (PSC). It is usually associated with inflammatory bowel diseases and ulcerative colitis.
Common predisposition factors for gallbladder cancer include polyps of the gallbladder, congenital cysts of gallbladder and chronic gallbladder inflammation. Moreover, alcohol abuse and obesity can have an association with the development of cholangiocarcinoma.
Because of the late diagnosis and the limited treatment options, the biliary tract cancer has a very poor prognosis with the overall survival being lower than 10% and the mean survival time is less than two years.
The fact that still the median survival for patients with unresectable tumors by using a range of chemotherapeutic drugs is highly aggressive. For the treatment of early-stage cancer, surgery is the only method available. The prognosis after surgery depends on several factors such as the metastasis, involvement of the adjacent tissues, and the margin status.
Clinical Presentation by Stage:
Early Stage (Stage 0 and I):
Sometimes asymptomatic and unexpectedly found during imaging for other purposes.
Symptoms can be moderate in severity and present as abdominal pain, jaundice, or abnormal liver functional tests.
Locally Advanced (Stage II and III):
Symptoms become more clearly noticeable and may comprise jaundice, abdominal pain, unexplained weight loss, and pruritus (itching).
Jaundice is usually the first sign. Cholangitis may present along with some of the symptoms which are fever, chills and right upper quadrant pain.
Metastatic (Stage IV):
The show of symptoms is aggravated progressively with the spread of tumor to other organs such as the liver, lungs or peritoneum.
The signs may be obvious, like significant weight loss, extreme abdominal pain, ascites (accumulation of fluid in the abdomen), and other symptoms associated with organ malfunction.
Associated Comorbidities or Activities:
Chronic Liver Disease: As these patients could have a history of chronic liver diseases like hepatitis B or C, alcoholic liver disease or non-alcoholic fatty liver they face more chance for getting infection.
Gallstones: The presence of gallstones is a risk factor which indicates developing gallbladder cancer.
Primary Sclerosing Cholangitis (PSC): PSC is a risk factor for cholangiocarcinoma, which is the most common type of bile duct cancer and it is most commonly found in the intrahepatic bile ducts.
Biliary Inflammation: Persistent inflammation of bile ducts as seen in conditions like RPC can promote the risk of cholangiocarcinoma.
Heavy Alcohol Consumption: Gallbladder tumor is affiliated with uninterrupted heavy alcohol consumption, as one of the risk factors.
Acuity of Presentation:
Gradual Onset: At first, the signs may appear slowly, frequently non-specific, thus resulting in the diagnosis being delayed.
Acute Onset: The progression to the complicated stages or conditions such as the biliary blockage can result in acute emergency presentations along with sudden nausea, unbearable abdominal pain, or cholangitis.
Staging:
Tumors of biliary tract commonly tend to progress according to the TNM staging system, which classifies the tumor on T (this is related to the extent of the primary tumor), N (changes in the regional lymph nodes), and M (the presence of distant metastasis). The stage decides the treatment and informs about future outcomes.
Stage 0: In-situ carcinomas.
Stage I: Limited to the bile duct or gallbladder wall; lymphatic structures in surrounding tissues and distant sites staying clear of infection.
Stage II: The tumors that invade the nearby tissues or organs, for example the liver, pancreas or the major blood vessels.
Stage III: Presence of cancer invading the adjacent lymph nodes but its absence in tissue and organs at a distance.
Stage IV: These cancers have the propensity to spread through the lymphatic system to the distant organs such as the liver, lungs, or peritoneum.
Abdominal Examination: Palpation of abdomen (which includes identification of any possibilities of masses, tenderness, or the enlargement of organs).
Jaundice Assessment: Examination for jaundice, a yellowing of the skin and eyes which is usually a sign of biliary obstruction, is commonly used.
Lymph Node Examination: An examination of nodes in the neck, armpits, and groin areas should be done if they are enlarged, which is an indicator of cancer spreading to those areas.
Liver Function Tests: Though not necessarily a part of a physical exam, these tests may be ordered when there is clinical suspicion and signs of liver involvement.
Metastatic liver cancer
IgG4 related sclerosing cholangitis
Gallbladder adenomyomatosis
Hepatocellular carcinoma
Gallbladder adenomas
Gallbladder polyps
Early Stage (Stage I and Stage II):
Surgery: Surgical excision is the fundamental treatment option for early biliary tract cancer whenever it can be implemented. This step can include the removal of the bile duct part or fully along with the gallbladder and surrounding tissues. Sometimes liver transplantation may be viewed as a possible option.
Adjuvant Therapy: Following surgical treatment may be an adjuvant chemotherapy or chemoradiotherapy in order to prevent tumor reoccurrence.
Advanced (Stage II, Stage III):
Surgery: In certain cases, surgical procedure may be a choice even for locally advanced disease and it may be more invasive than usual, possibly using removal of a vessel or an organ.
Neoadjuvant Therapy: The chemotherapeutic or chemo radiotherapeutic regimes can be used preoperatively to reduce the size of the tumor and to make it more operable.
Chemoradiotherapy: To medically inoperable tumors, chemoradiation therapy is a solution to such problems as help control the progress of the disease and also symptoms relief.
Advanced or Metastatic (Stage III and Stage IV):
Systemic Therapy: Chemotherapy is often the fundamental therapeutic approach for advanced or metastatic biliary tract cancer. Gemcitabine in combination with cisplatin is a typical chemotherapy regimen, however other regimens or targeted therapy may be taken into account depending on the particular characteristics of the tumor and the patient.
Palliative Care: Palliative therapies like stent placement to improve bile flow blockage, pain management, nutritional support, and supportive care to maintain a good quality of life are also an integral aspect of the treatment for advanced-stage illness.
Clinical Trials: Clinical trials might ensure the availability of the trial participants of investigational drugs, targeted therapies, immunotherapies, or even the novel approaches as methods of treatment for biliary tract cancer patients, those segregated in the advanced or refractory state.
Oncology, Other
Nutritional Support: Proper nutrition is of great importance for biliary tract cancer patients, particularly those who are undergoing the treatment. A registered dietitian will help with the measures like adequacy of nutrition amidst sickness, management of side effects like nausea and diminished appetite, and optimal calorie and nutrient intake at this moment.
Pain Management: Alternative pain management approaches like relaxation therapy, an imagery guide, acupuncture, and massage can help sufferers to feel less painful and injured.
Physical Activity: Physical activity and exercise can be a good way to improve the strength, endurance and overall wellness of the patients with biliary tract cancer. A well-designed exercise program, which will be created considering the user’s condition and preferences, may be helpful.
Psychosocial Support: It can be easy to have trouble emotionally when fighting against cancer. The counseling, support groups and other psychosocial interventions can be very helpful in providing emotional support, coping strategies and a sense of community for patients and their caregivers.
Oncology, Other
Chemotherapeutic drugs are drugs aimed at killing or preventing the growth of the cancer cells. In the treatment of biliary tract cancer staging, various types of chemotherapeutic agents are used either alone or in combination to target cancer cells and to slow down the progression of the disease.
Cisplatin: Cisplatin is a platinum-based chemotherapeutic agent used in cancer treatment mechanisms by disrupting DNA of cancer cells and result in their death. It is usually combined with other chemotherapeutic agents, e.g., gemcitabine, for the treatment of the biliary tract cancer. Cisplatin-based regimens are the most popular adjuvant and palliative regimens.
Gemcitabine: Gemcitabine is a nucleoside analogue, chemotherapy drug, can hinder the reproduction of cancer cells by blocking DNA generation further. It has been found successful alongside cisplatin when treating advanced biliary tract cancer as a first treatment. Furthermore, the gemcitabine-based regimens are also used in adjuvant and neoadjuvant settings.
5-Fluorouracil (5-FU): 5-FU is a floropyrimidine that disrupts synthesis of DNA and RNA which results in the death of cancer cells. It may be applied alone or as a part of multimodal therapy for the biliary tract cancer treatment.
Capecitabine: Capecitabine is the oral version of 5-FU that is later converted into 5-FU in the human body. It could be the option for intravenous 5-FU and in the case of combination therapy with other chemotherapeutic agents it is used for treating biliary tract cancer.
Irinotecan: Irinotecan is a chemotherapy medicine working as topoisomerase I inhibitor which perturbs with DNA replication and transcription and thus cancer cells stop dividing and the organism dies. It can be applied as a first-line or salvage therapy for the later stages of biliary tract cancer either alone or in combination with other chemotherapy agents.
Oncology, Other
Targeted therapy as well as pathologic staging of these tumors are critical components in medical care, especially for patients with distant disease that is unsuitable for conventional treatments. Targeted therapies use the principle of disease delineation to directly attack the nucleus sites that are damaged in cancer cell growth and progression.
Cetuximab: Cetuximab is a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR). It is indeed used together with the chemotherapy in patients who have biliary tract advanced cancer, especial those having a tumor that overexpresses the EGFR. Experimental studies have demonstrated favorable outcomes and cetuximab-based therapy seems promising for certain categories of patients.
Bevacizumab: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that promotes angiogenesis (the process of forming new blood vessels) within tumors. Bevacizumab may be employ as concurrent therapy with chemotherapy for metastatic biliary cancer to inhibit cancer growth and increase success rates.
Infigratinib: Infigratinib is a selective inhibitor of the Fitness growth factor receipt (FGFR) that sends positive results in the clinical trials for the bi-tractal organ cancer in the hypothesis stage with the patients having FGFR2 fusion or translocations. This technique is very effective as it works by blocking the aberrant FGFR signaling, which is a key driver of the growth and survival of cancer cells.
In ERCP, a flexible endoscope is passed through the mouth, the esophagus, and the stomach, and into the duodenum, thereby one can visualize the biliary and pancreatic ducts. Contrast dye is administered intravenously as these ducts are being visualized. X-ray images are taken after the imaging to screen for any tumor, stricture, or blockage.
In most cases, ERCP is often used for the identification of the biliary tract tumors’ locations, size, and extent of the disease, as well as for detecting complications like biliary obstruction or jaundice. This data is the key to right staging of the cancer, which will affect the choice of treatment and the prediction of the outcome.
In addition to staging, the experts might also opt for procedures that would involve the use of interventional radiology such as percutaneous transhepatic cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP) by way of which the tumor involvement would be further assessed and the treatment plan guided.
Oncology, Other
Before the treatment, the patient’s medical history, physical examination, and imaging studies are thoroughly evaluated. Imaging methods such as CT, MRI and PET scanning are employed to figure out tumour’s position, dimensions, and degree. Endoscopic and radiological procedures such as ultrasonography, CT scan, are performed for visualizing the biliary tract and tissue sampling for biopsy in order to correctly assess the cancer stage. Pathological staging is done on biopsy samples to find out the histological type, grade and the invasion into the adjacent tissues of the cancer.
The assessment of staging is usually carried out on x-ray, endoscopic, and pathological examinations with a view to predicting the prognosis and aiding the choice of treatment. Treatment group involves an interdisciplinary treatment plan team who sooner than later, crafts an individualized treatment plan that incorporates the cancer stage, the overall health status and treatment response.
The therapy can be either with the curative purpose of removing the tumor and preventing its recurrence or palliative with the intention of alleviating the symptoms and enhancing the quality of life. Patients are continuously checked for response to therapy and any side effects that may appear.
The biliary system is divided into intrahepatic (the cystic duct that drains the liver) and extrahepatic structures (the gallbladder and the channels that guide bile to its main duodenal papilla at the second part of the duodenum). Cholangiocytes are the cells that make up the biliary system. These cholangiocytes become cancerous leading to biliary tract cancer that can either become intrahepatic or extrahepatic cholangiocarcinoma. Cholangiocarcinoma, yet another type of extrahepatic cholangiocarcinoma, includes two subtypes: distal cholangiocarcinoma which influences the pancreatic biliary ducts and gall bladder.
Even though each of these carcinomas possesses a similar epithelium their pathology can differ because of their anatomical location. The patients have a poor prognosis of cholangiocarcinoma which is an uncommon and aggressive cancer and it is usually detected at an advanced and uncurable stage. The late diagnosis usually results in the extensive involvement of blood vessels and regional lymph nodes by making the surgical removal very difficult.
Between 0. 72 to 1. 62 cases per 100,000 people in the United States are diagnosed with cholangiocarcinoma yearly. Despite the fact that the phenomenon occurs in other parts of the world, the documented numbers rise even more in other countries around the globe. Northeastern part of Thailand (Asia) records the highest incidence rate over 80 per 100,000 most likely due to the common problems in these areas caused by the hepatobiliary fluke infection.
Many researches which has been carried out in the last decades have shown an increase in the prevalence of the disease called intrahepatic cholangiocarcinoma. This increase is a result of various factors which includes irritation and chronic inflammation of the bile ducts’ lining. Moreover, the prevalence is age-dependent phenomenon so it is more frequent among older people; it is more common among males than females. This might be because men are more likely to get primary sclerosing cholangitis, which is known as a risk factor and can appear in men as early as 40 years of age.
To ensure mutations in various genes like oncogene and tumor suppressor a chronic inflammation and irritation of the biliary system comes up that resembling other gastrointestinal malignancy occurs and starting with hyperplasia and ends up with metaplasia and dysplasia and ultimately leads to carcinoma.
IDH1 and IDH2 mutations in the Isocitrate dehydrogenase (IDH) gene have been observed in up to 20% of intrahepatic bile duct cancers. The statistic that although between 13% and 17% of IBC patients (intrahepatic bile duct cancer) exhibit FGFR (fibroblast growth factor receptor) gene fusion and translocation as well is also observed.
Fusion genes containing PRKACA and PRKACB that are the catalytic component of protein kinase A and whose expression is featured in pCCA and dCCA are involved. In addition, ROS1 gene fusions are found in 8 to 9% of cholangiocarcinomas.
Prolonged inflammatory diseases may lead to stress-induced alterations in the bile duct epithelium, which may in turn be responsible for the changes that worsen biliary tract cancer. There is a well-known chronic inflammatory illness, which has been associated with biliary tract cancer and is called primary sclerosing cholangitis (PSC). It is usually associated with inflammatory bowel diseases and ulcerative colitis.
Common predisposition factors for gallbladder cancer include polyps of the gallbladder, congenital cysts of gallbladder and chronic gallbladder inflammation. Moreover, alcohol abuse and obesity can have an association with the development of cholangiocarcinoma.
Because of the late diagnosis and the limited treatment options, the biliary tract cancer has a very poor prognosis with the overall survival being lower than 10% and the mean survival time is less than two years.
The fact that still the median survival for patients with unresectable tumors by using a range of chemotherapeutic drugs is highly aggressive. For the treatment of early-stage cancer, surgery is the only method available. The prognosis after surgery depends on several factors such as the metastasis, involvement of the adjacent tissues, and the margin status.
Clinical Presentation by Stage:
Early Stage (Stage 0 and I):
Sometimes asymptomatic and unexpectedly found during imaging for other purposes.
Symptoms can be moderate in severity and present as abdominal pain, jaundice, or abnormal liver functional tests.
Locally Advanced (Stage II and III):
Symptoms become more clearly noticeable and may comprise jaundice, abdominal pain, unexplained weight loss, and pruritus (itching).
Jaundice is usually the first sign. Cholangitis may present along with some of the symptoms which are fever, chills and right upper quadrant pain.
Metastatic (Stage IV):
The show of symptoms is aggravated progressively with the spread of tumor to other organs such as the liver, lungs or peritoneum.
The signs may be obvious, like significant weight loss, extreme abdominal pain, ascites (accumulation of fluid in the abdomen), and other symptoms associated with organ malfunction.
Associated Comorbidities or Activities:
Chronic Liver Disease: As these patients could have a history of chronic liver diseases like hepatitis B or C, alcoholic liver disease or non-alcoholic fatty liver they face more chance for getting infection.
Gallstones: The presence of gallstones is a risk factor which indicates developing gallbladder cancer.
Primary Sclerosing Cholangitis (PSC): PSC is a risk factor for cholangiocarcinoma, which is the most common type of bile duct cancer and it is most commonly found in the intrahepatic bile ducts.
Biliary Inflammation: Persistent inflammation of bile ducts as seen in conditions like RPC can promote the risk of cholangiocarcinoma.
Heavy Alcohol Consumption: Gallbladder tumor is affiliated with uninterrupted heavy alcohol consumption, as one of the risk factors.
Acuity of Presentation:
Gradual Onset: At first, the signs may appear slowly, frequently non-specific, thus resulting in the diagnosis being delayed.
Acute Onset: The progression to the complicated stages or conditions such as the biliary blockage can result in acute emergency presentations along with sudden nausea, unbearable abdominal pain, or cholangitis.
Staging:
Tumors of biliary tract commonly tend to progress according to the TNM staging system, which classifies the tumor on T (this is related to the extent of the primary tumor), N (changes in the regional lymph nodes), and M (the presence of distant metastasis). The stage decides the treatment and informs about future outcomes.
Stage 0: In-situ carcinomas.
Stage I: Limited to the bile duct or gallbladder wall; lymphatic structures in surrounding tissues and distant sites staying clear of infection.
Stage II: The tumors that invade the nearby tissues or organs, for example the liver, pancreas or the major blood vessels.
Stage III: Presence of cancer invading the adjacent lymph nodes but its absence in tissue and organs at a distance.
Stage IV: These cancers have the propensity to spread through the lymphatic system to the distant organs such as the liver, lungs, or peritoneum.
Abdominal Examination: Palpation of abdomen (which includes identification of any possibilities of masses, tenderness, or the enlargement of organs).
Jaundice Assessment: Examination for jaundice, a yellowing of the skin and eyes which is usually a sign of biliary obstruction, is commonly used.
Lymph Node Examination: An examination of nodes in the neck, armpits, and groin areas should be done if they are enlarged, which is an indicator of cancer spreading to those areas.
Liver Function Tests: Though not necessarily a part of a physical exam, these tests may be ordered when there is clinical suspicion and signs of liver involvement.
Metastatic liver cancer
IgG4 related sclerosing cholangitis
Gallbladder adenomyomatosis
Hepatocellular carcinoma
Gallbladder adenomas
Gallbladder polyps
Early Stage (Stage I and Stage II):
Surgery: Surgical excision is the fundamental treatment option for early biliary tract cancer whenever it can be implemented. This step can include the removal of the bile duct part or fully along with the gallbladder and surrounding tissues. Sometimes liver transplantation may be viewed as a possible option.
Adjuvant Therapy: Following surgical treatment may be an adjuvant chemotherapy or chemoradiotherapy in order to prevent tumor reoccurrence.
Advanced (Stage II, Stage III):
Surgery: In certain cases, surgical procedure may be a choice even for locally advanced disease and it may be more invasive than usual, possibly using removal of a vessel or an organ.
Neoadjuvant Therapy: The chemotherapeutic or chemo radiotherapeutic regimes can be used preoperatively to reduce the size of the tumor and to make it more operable.
Chemoradiotherapy: To medically inoperable tumors, chemoradiation therapy is a solution to such problems as help control the progress of the disease and also symptoms relief.
Advanced or Metastatic (Stage III and Stage IV):
Systemic Therapy: Chemotherapy is often the fundamental therapeutic approach for advanced or metastatic biliary tract cancer. Gemcitabine in combination with cisplatin is a typical chemotherapy regimen, however other regimens or targeted therapy may be taken into account depending on the particular characteristics of the tumor and the patient.
Palliative Care: Palliative therapies like stent placement to improve bile flow blockage, pain management, nutritional support, and supportive care to maintain a good quality of life are also an integral aspect of the treatment for advanced-stage illness.
Clinical Trials: Clinical trials might ensure the availability of the trial participants of investigational drugs, targeted therapies, immunotherapies, or even the novel approaches as methods of treatment for biliary tract cancer patients, those segregated in the advanced or refractory state.
Oncology, Other
Nutritional Support: Proper nutrition is of great importance for biliary tract cancer patients, particularly those who are undergoing the treatment. A registered dietitian will help with the measures like adequacy of nutrition amidst sickness, management of side effects like nausea and diminished appetite, and optimal calorie and nutrient intake at this moment.
Pain Management: Alternative pain management approaches like relaxation therapy, an imagery guide, acupuncture, and massage can help sufferers to feel less painful and injured.
Physical Activity: Physical activity and exercise can be a good way to improve the strength, endurance and overall wellness of the patients with biliary tract cancer. A well-designed exercise program, which will be created considering the user’s condition and preferences, may be helpful.
Psychosocial Support: It can be easy to have trouble emotionally when fighting against cancer. The counseling, support groups and other psychosocial interventions can be very helpful in providing emotional support, coping strategies and a sense of community for patients and their caregivers.
Oncology, Other
Chemotherapeutic drugs are drugs aimed at killing or preventing the growth of the cancer cells. In the treatment of biliary tract cancer staging, various types of chemotherapeutic agents are used either alone or in combination to target cancer cells and to slow down the progression of the disease.
Cisplatin: Cisplatin is a platinum-based chemotherapeutic agent used in cancer treatment mechanisms by disrupting DNA of cancer cells and result in their death. It is usually combined with other chemotherapeutic agents, e.g., gemcitabine, for the treatment of the biliary tract cancer. Cisplatin-based regimens are the most popular adjuvant and palliative regimens.
Gemcitabine: Gemcitabine is a nucleoside analogue, chemotherapy drug, can hinder the reproduction of cancer cells by blocking DNA generation further. It has been found successful alongside cisplatin when treating advanced biliary tract cancer as a first treatment. Furthermore, the gemcitabine-based regimens are also used in adjuvant and neoadjuvant settings.
5-Fluorouracil (5-FU): 5-FU is a floropyrimidine that disrupts synthesis of DNA and RNA which results in the death of cancer cells. It may be applied alone or as a part of multimodal therapy for the biliary tract cancer treatment.
Capecitabine: Capecitabine is the oral version of 5-FU that is later converted into 5-FU in the human body. It could be the option for intravenous 5-FU and in the case of combination therapy with other chemotherapeutic agents it is used for treating biliary tract cancer.
Irinotecan: Irinotecan is a chemotherapy medicine working as topoisomerase I inhibitor which perturbs with DNA replication and transcription and thus cancer cells stop dividing and the organism dies. It can be applied as a first-line or salvage therapy for the later stages of biliary tract cancer either alone or in combination with other chemotherapy agents.
Oncology, Other
Targeted therapy as well as pathologic staging of these tumors are critical components in medical care, especially for patients with distant disease that is unsuitable for conventional treatments. Targeted therapies use the principle of disease delineation to directly attack the nucleus sites that are damaged in cancer cell growth and progression.
Cetuximab: Cetuximab is a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR). It is indeed used together with the chemotherapy in patients who have biliary tract advanced cancer, especial those having a tumor that overexpresses the EGFR. Experimental studies have demonstrated favorable outcomes and cetuximab-based therapy seems promising for certain categories of patients.
Bevacizumab: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein that promotes angiogenesis (the process of forming new blood vessels) within tumors. Bevacizumab may be employ as concurrent therapy with chemotherapy for metastatic biliary cancer to inhibit cancer growth and increase success rates.
Infigratinib: Infigratinib is a selective inhibitor of the Fitness growth factor receipt (FGFR) that sends positive results in the clinical trials for the bi-tractal organ cancer in the hypothesis stage with the patients having FGFR2 fusion or translocations. This technique is very effective as it works by blocking the aberrant FGFR signaling, which is a key driver of the growth and survival of cancer cells.
In ERCP, a flexible endoscope is passed through the mouth, the esophagus, and the stomach, and into the duodenum, thereby one can visualize the biliary and pancreatic ducts. Contrast dye is administered intravenously as these ducts are being visualized. X-ray images are taken after the imaging to screen for any tumor, stricture, or blockage.
In most cases, ERCP is often used for the identification of the biliary tract tumors’ locations, size, and extent of the disease, as well as for detecting complications like biliary obstruction or jaundice. This data is the key to right staging of the cancer, which will affect the choice of treatment and the prediction of the outcome.
In addition to staging, the experts might also opt for procedures that would involve the use of interventional radiology such as percutaneous transhepatic cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP) by way of which the tumor involvement would be further assessed and the treatment plan guided.
Oncology, Other
Before the treatment, the patient’s medical history, physical examination, and imaging studies are thoroughly evaluated. Imaging methods such as CT, MRI and PET scanning are employed to figure out tumour’s position, dimensions, and degree. Endoscopic and radiological procedures such as ultrasonography, CT scan, are performed for visualizing the biliary tract and tissue sampling for biopsy in order to correctly assess the cancer stage. Pathological staging is done on biopsy samples to find out the histological type, grade and the invasion into the adjacent tissues of the cancer.
The assessment of staging is usually carried out on x-ray, endoscopic, and pathological examinations with a view to predicting the prognosis and aiding the choice of treatment. Treatment group involves an interdisciplinary treatment plan team who sooner than later, crafts an individualized treatment plan that incorporates the cancer stage, the overall health status and treatment response.
The therapy can be either with the curative purpose of removing the tumor and preventing its recurrence or palliative with the intention of alleviating the symptoms and enhancing the quality of life. Patients are continuously checked for response to therapy and any side effects that may appear.
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