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Pancreatic Carcinoma

Updated : May 14, 2024





Background

Pancreatic cancer is a term that refers to a type of carcinoma that develops in the pancreatic duct cells, called pancreatic ductal carcinoma. In the United States, it is the fourth-largest cause of cancer death. In the United States, the 5-year survival rate is between 5% and 15%. Overall, the survival rate is only 6%.

Surgical resection is now the sole curative therapy, but only 20% of pancreatic cancers are surgically resectable upon diagnosis. Close collaboration across multiple disciplines, including surgeons, oncologists, radiation oncologists, pathologists, and radiologists, is critical for patients with resectable cancer and borderline resectable disease to have a chance of survival.

Epidemiology

According to GLOBOCAN 2012 estimates, pancreatic cancer kills more than 331,000 people each year. It is the sixth leading cause of cancer death in both sexes. Pancreatic cancer has a 5-year survival rate of approximately 5% worldwide.

Pancreatic cancer incidence rates were highest in Northern America, Western Europe, Europe, and Australia/New Zealand for both sexes, in contrast, Middle Africa and South-Central Asia have the lowest incidence rates. Globally, there are some gender distinctions.

Men in Armenia, the Czech Republic, Slovakia, Hungary, Japan, and Lithuania face the highest chance of developing pancreatic cancer. Men from Pakistan and Guinea have the lowest risk for developing pancreatic cancer. Northern America, Western Europe, Northern Europe, and Australia/New Zealand have the highest incidences of female cancer.

Women have the lowest incidence rates in Middle Africa and Polynesia. For both genders, the incidence rates increase with age; the highest rates occur in those over the age of 70. Around 90% of all instances of pancreatic cancer occur in adults over the age of 55.

 

Anatomy

Pathophysiology

The pancreas is a glandular organ that functions as both an endocrine and an exocrine organ. Its overall function is to maintain metabolic homeostasis through the production of hormones that control blood glucose levels and enzymes that aid in digesting.

The pancreas is generated from the endodermal germ layer’s embryonic foregut. Two buds that eventually give rise to the dorsal and ventral pancreas emerge from the foregut during embryonic development. As these buds grow, they are gradually moved until they meet and join, becoming the adult pancreas.

Pancreatic progenitor cells differentiate into acinar, endocrine, or ductal cells in response to numerous developmental signals. Endocrine cells produce hormones such as insulin, glucagon, and somatostatin into the bloodstream to regulate blood glucose levels. This homeostatic function is responsible for fulfilling the metabolic requirements of numerous tissues and organs.

Acinar cells of the pancreatic duct release enzymes such as trypsinogen, chymotrypsinogen, lipase, and amylase. These enzymes then enter the small intestine, where they aid in the digestion of numerous macromolecules found in food, including proteins, carbohydrates, and lipids.

Pancreatic malfunction can result in a variety of commonly occurring disorders, including diabetes, pancreatitis, and cancer. The most prevalent of these disorders is diabetes. However, pancreatic cancer is by far the most lethal type, and its origin is frequently linked to other pancreatic illnesses, such as diabetes.

Pancreatic cancer is the fourth most common cause of death from cancer in the United States and it generally presents an unfavorable prognosis. Patients diagnosed with this disease have a median overall survival of less than six months and around an 8% five-year survival rate.

Pancreatic cancer has a poor prognosis in part due to ineffective early detection methods. Patients frequently exhibit no symptoms until the disease has spread throughout the body. Additionally, the medications utilized to treat pancreatic cancer are generally ineffective, failing to significantly improve patient life beyond a few months.

Overcoming these obstacles will be critical for the disease’s future treatment, as it is projected to overtake lung cancer as the second leading cause of cancer-related deaths in the United States by 2030.

Pancreatic malignancies can be endocrine or exocrine in origin. Thus, the histological appearance of endocrine and exocrine tumors can be observed to differentiate them. Endocrine tumors are infrequent, accounting for fewer than 5% of pancreatic malignancies.

They have a median survival of 27 months and a 0.28 times lower risk of death when compared to the far more common pancreatic adenocarcinoma. Endocrine tumors are frequently produced from pancreatic islet cells and frequently release excessive amounts of pancreatic hormones on a constitutive basis.

They are further classified as insulinomas, glucagonomas, and gastrinomas based on their cell of origin and hormones secreted. Pancreatic endocrine tumors are easily identifiable because of their high hormone secretion, which results in severe symptoms such as hypoglycemia or rashes.

Pancreatic malignancies originating from exocrine cells are far more prevalent than endocrine tumors and are commonly categorized into two histological subgroups. Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor and accounts for more than 90% of pancreatic malignancies.

PDACs are generated from the epithelial cells that line the pancreatic duct and, as a result of their origin, resemble glands. Frequently, these tumors spread to the liver or lymph nodes. PDACs are frequently detected at a late stage, potentially after the cancer has metastasized, due to their lack of symptoms during the early stages of cancer growth.

As a result, anti-cancer therapies are typically ineffective, as malignancies have developed robust cytoprotective systems that facilitate drug resistance. Due to this aggressiveness and resistance to treatment, the projected median survival time for PDAC is as little as 4 months. PDACs are preceded by the development of precancerous lesions known as pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMNs).

IPMNs resemble protruding papillae (finger-like structures) in the pancreatic duct. Mucinous tumors, which account for fewer than 10% of pancreatic cancer cases, are the second most prevalent histological subtype. At the time of diagnosis, these tumors are often substantially less aggressive than adenocarcinomas and have a 0.88 times lower risk of mortality.

Mucinous tumors derive from the pancreatic ductal epithelium as well, but release mucin, which can be observed in and around the cells, giving them the appearance of ‘floating’. There are numerous more subtypes of pancreatic cancer, including those that start from undifferentiated acinar cells that mimic liver malignancies.

Etiology

Risk factors for pancreatic cancer include certain lifestyle-specific behaviors, gender, race, family history, age, and certain diseases and conditions.

Given below are some of these risk factors:

  • Around 20% of pancreatic cancers can be attributed to smoking
  • Individuals over the age of 55 have a higher rate of incidence
  • Obesity
  • Liver Cirrhosis
  • Chronic pancreatitis
  • Being of the male gender
  • Family history
  • African American race
  • Helicobacter pylori infection
  • Diabetes

Heavy coffee and alcohol consumption, lack of physical activity, drinking two or more aerated drinks per day, and eating excessive amounts of red meat could also possibly increase risk for pancreatic cancer.

Genetics

Inherited gene mutations, such as those associated with hereditary pancreatitis and inherited cancer syndromes such as hereditary breast and ovarian cancer syndrome, Peutz-Jeghers syndrome, Lynch syndrome, and familial atypical multiple mole melanoma, all contribute to the genetic basis of pancreatic cancers. However, such “hereditary pancreatic cancer” cases, in which pancreatic cancer is caused by a recognized genetic abnormality, account for a tiny proportion of pancreatic cancer cases.

The term “familial pancreatic cancer” (FPC) refers to families with at least two first-degree relatives (FDR) diagnosed with pancreatic cancer without a recognized genetic abnormality. Complex segregation analysis indicates that pancreatic cancer is aggregating in these families as a result of an undiagnosed autosomal dominantly inherited gene with decreased penetrance.   Although initial linkage studies revealed that the palladin gene (PALD) may be a pancreatic cancer susceptibility gene, these findings have not been verified.

According to studies of FPC kindreds, germline BRCA2 mutations may be detected in 17–19% of examined kindreds with incident pancreatic cancer. Klein et al. conducted a prospective study of 838 kindreds in the National Familial Pancreas Tumor Registry to determine the risk of pancreatic cancer in families with individuals suffering from pancreatic  cancer. The incidence ratios were calculated by comparing the number of incident pancreatic cancer cases to the projected number of cases based on numbers available in the SEER database.  Individuals with three or more affected FDRs with pancreatic cancer had a 32 times greater risk of getting pancreatic cancer.

Individuals with two affected FDRs had a 6.4 times greater risk, whereas those with one affected FDR had a 4.5 times higher risk (CI 0.54–16.3).  Due to the complexity of cancer risk assessment, a risk prediction model called PancPRO was developed to provide more specific risk estimates for individuals from FPC kindreds that consider factors such as age, family size, and family in relations while diagnosing pancreatic cancer.

Prognostic Factors

Patients who are diagnosed before their tumours have grown locally, or spread in another regions, generally have longer survival rates. These tumours can generally be surgically removed. 15-20% of all pancreatic tumours can be removed, including most stage I and II tumors.

Stage III tumors mostly don’t qualify for surgery but can be removed if an especially skilled and experienced specialist conducts the surgery. Pancreatic tumors often grow back in most patients. So, the 5-year survival rate for such patients is still a meagre 20-30%. On average, these patients live for 2.5 years.

 

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

everolimus

10

mg

orally

once a day

the total duration of therapy is continued until disease progression, or no toxicity occurs
Note:
Tablets need to be swallowed with a glass of water but do not chew, crush, or break the tablet
Do not combine the brands of Afinitor tablets and Afinitor Disperz to reach the desired dose
Only use any one of them



erlotinib

100

mg

Orally

once a day

; before 1 hour or 2 hours after meals
the duration of the therapy continues until disease progression, or unacceptable toxicity occurs
It is used for patients in combination with gemcitabine as a first-line treatment for patients with locally advanced, unresectable, or metastatic pancreatic cancer



Dose Adjustments

Renal Dose Adjustments:
for renal impairment, dosage adjustment requires, and caution is recommended.
Liver Dose Adjustments:
The treatment should be discontinued in patients with baseline hepatic impairment if the total serum bilirubin doubles or serum transaminases triple
The treatment should be discontinued in patients with normal pretreatment values if the total serum bilirubin >3 x ULN or serum transaminases >5 x ULN

olaparib 

300 mg orally twice daily. Continue for a year or until unacceptable toxicity, disease recurrence, or whichever occurs first



 
 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149791/

https://www.ncbi.nlm.nih.gov/books/NBK518996/

https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-prognosis

Pancreatic Carcinoma

Updated : May 14, 2024




Pancreatic cancer is a term that refers to a type of carcinoma that develops in the pancreatic duct cells, called pancreatic ductal carcinoma. In the United States, it is the fourth-largest cause of cancer death. In the United States, the 5-year survival rate is between 5% and 15%. Overall, the survival rate is only 6%.

Surgical resection is now the sole curative therapy, but only 20% of pancreatic cancers are surgically resectable upon diagnosis. Close collaboration across multiple disciplines, including surgeons, oncologists, radiation oncologists, pathologists, and radiologists, is critical for patients with resectable cancer and borderline resectable disease to have a chance of survival.

According to GLOBOCAN 2012 estimates, pancreatic cancer kills more than 331,000 people each year. It is the sixth leading cause of cancer death in both sexes. Pancreatic cancer has a 5-year survival rate of approximately 5% worldwide.

Pancreatic cancer incidence rates were highest in Northern America, Western Europe, Europe, and Australia/New Zealand for both sexes, in contrast, Middle Africa and South-Central Asia have the lowest incidence rates. Globally, there are some gender distinctions.

Men in Armenia, the Czech Republic, Slovakia, Hungary, Japan, and Lithuania face the highest chance of developing pancreatic cancer. Men from Pakistan and Guinea have the lowest risk for developing pancreatic cancer. Northern America, Western Europe, Northern Europe, and Australia/New Zealand have the highest incidences of female cancer.

Women have the lowest incidence rates in Middle Africa and Polynesia. For both genders, the incidence rates increase with age; the highest rates occur in those over the age of 70. Around 90% of all instances of pancreatic cancer occur in adults over the age of 55.

 

The pancreas is a glandular organ that functions as both an endocrine and an exocrine organ. Its overall function is to maintain metabolic homeostasis through the production of hormones that control blood glucose levels and enzymes that aid in digesting.

The pancreas is generated from the endodermal germ layer’s embryonic foregut. Two buds that eventually give rise to the dorsal and ventral pancreas emerge from the foregut during embryonic development. As these buds grow, they are gradually moved until they meet and join, becoming the adult pancreas.

Pancreatic progenitor cells differentiate into acinar, endocrine, or ductal cells in response to numerous developmental signals. Endocrine cells produce hormones such as insulin, glucagon, and somatostatin into the bloodstream to regulate blood glucose levels. This homeostatic function is responsible for fulfilling the metabolic requirements of numerous tissues and organs.

Acinar cells of the pancreatic duct release enzymes such as trypsinogen, chymotrypsinogen, lipase, and amylase. These enzymes then enter the small intestine, where they aid in the digestion of numerous macromolecules found in food, including proteins, carbohydrates, and lipids.

Pancreatic malfunction can result in a variety of commonly occurring disorders, including diabetes, pancreatitis, and cancer. The most prevalent of these disorders is diabetes. However, pancreatic cancer is by far the most lethal type, and its origin is frequently linked to other pancreatic illnesses, such as diabetes.

Pancreatic cancer is the fourth most common cause of death from cancer in the United States and it generally presents an unfavorable prognosis. Patients diagnosed with this disease have a median overall survival of less than six months and around an 8% five-year survival rate.

Pancreatic cancer has a poor prognosis in part due to ineffective early detection methods. Patients frequently exhibit no symptoms until the disease has spread throughout the body. Additionally, the medications utilized to treat pancreatic cancer are generally ineffective, failing to significantly improve patient life beyond a few months.

Overcoming these obstacles will be critical for the disease’s future treatment, as it is projected to overtake lung cancer as the second leading cause of cancer-related deaths in the United States by 2030.

Pancreatic malignancies can be endocrine or exocrine in origin. Thus, the histological appearance of endocrine and exocrine tumors can be observed to differentiate them. Endocrine tumors are infrequent, accounting for fewer than 5% of pancreatic malignancies.

They have a median survival of 27 months and a 0.28 times lower risk of death when compared to the far more common pancreatic adenocarcinoma. Endocrine tumors are frequently produced from pancreatic islet cells and frequently release excessive amounts of pancreatic hormones on a constitutive basis.

They are further classified as insulinomas, glucagonomas, and gastrinomas based on their cell of origin and hormones secreted. Pancreatic endocrine tumors are easily identifiable because of their high hormone secretion, which results in severe symptoms such as hypoglycemia or rashes.

Pancreatic malignancies originating from exocrine cells are far more prevalent than endocrine tumors and are commonly categorized into two histological subgroups. Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor and accounts for more than 90% of pancreatic malignancies.

PDACs are generated from the epithelial cells that line the pancreatic duct and, as a result of their origin, resemble glands. Frequently, these tumors spread to the liver or lymph nodes. PDACs are frequently detected at a late stage, potentially after the cancer has metastasized, due to their lack of symptoms during the early stages of cancer growth.

As a result, anti-cancer therapies are typically ineffective, as malignancies have developed robust cytoprotective systems that facilitate drug resistance. Due to this aggressiveness and resistance to treatment, the projected median survival time for PDAC is as little as 4 months. PDACs are preceded by the development of precancerous lesions known as pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMNs).

IPMNs resemble protruding papillae (finger-like structures) in the pancreatic duct. Mucinous tumors, which account for fewer than 10% of pancreatic cancer cases, are the second most prevalent histological subtype. At the time of diagnosis, these tumors are often substantially less aggressive than adenocarcinomas and have a 0.88 times lower risk of mortality.

Mucinous tumors derive from the pancreatic ductal epithelium as well, but release mucin, which can be observed in and around the cells, giving them the appearance of ‘floating’. There are numerous more subtypes of pancreatic cancer, including those that start from undifferentiated acinar cells that mimic liver malignancies.

Risk factors for pancreatic cancer include certain lifestyle-specific behaviors, gender, race, family history, age, and certain diseases and conditions.

Given below are some of these risk factors:

  • Around 20% of pancreatic cancers can be attributed to smoking
  • Individuals over the age of 55 have a higher rate of incidence
  • Obesity
  • Liver Cirrhosis
  • Chronic pancreatitis
  • Being of the male gender
  • Family history
  • African American race
  • Helicobacter pylori infection
  • Diabetes

Heavy coffee and alcohol consumption, lack of physical activity, drinking two or more aerated drinks per day, and eating excessive amounts of red meat could also possibly increase risk for pancreatic cancer.

Inherited gene mutations, such as those associated with hereditary pancreatitis and inherited cancer syndromes such as hereditary breast and ovarian cancer syndrome, Peutz-Jeghers syndrome, Lynch syndrome, and familial atypical multiple mole melanoma, all contribute to the genetic basis of pancreatic cancers. However, such “hereditary pancreatic cancer” cases, in which pancreatic cancer is caused by a recognized genetic abnormality, account for a tiny proportion of pancreatic cancer cases.

The term “familial pancreatic cancer” (FPC) refers to families with at least two first-degree relatives (FDR) diagnosed with pancreatic cancer without a recognized genetic abnormality. Complex segregation analysis indicates that pancreatic cancer is aggregating in these families as a result of an undiagnosed autosomal dominantly inherited gene with decreased penetrance.   Although initial linkage studies revealed that the palladin gene (PALD) may be a pancreatic cancer susceptibility gene, these findings have not been verified.

According to studies of FPC kindreds, germline BRCA2 mutations may be detected in 17–19% of examined kindreds with incident pancreatic cancer. Klein et al. conducted a prospective study of 838 kindreds in the National Familial Pancreas Tumor Registry to determine the risk of pancreatic cancer in families with individuals suffering from pancreatic  cancer. The incidence ratios were calculated by comparing the number of incident pancreatic cancer cases to the projected number of cases based on numbers available in the SEER database.  Individuals with three or more affected FDRs with pancreatic cancer had a 32 times greater risk of getting pancreatic cancer.

Individuals with two affected FDRs had a 6.4 times greater risk, whereas those with one affected FDR had a 4.5 times higher risk (CI 0.54–16.3).  Due to the complexity of cancer risk assessment, a risk prediction model called PancPRO was developed to provide more specific risk estimates for individuals from FPC kindreds that consider factors such as age, family size, and family in relations while diagnosing pancreatic cancer.

Patients who are diagnosed before their tumours have grown locally, or spread in another regions, generally have longer survival rates. These tumours can generally be surgically removed. 15-20% of all pancreatic tumours can be removed, including most stage I and II tumors.

Stage III tumors mostly don’t qualify for surgery but can be removed if an especially skilled and experienced specialist conducts the surgery. Pancreatic tumors often grow back in most patients. So, the 5-year survival rate for such patients is still a meagre 20-30%. On average, these patients live for 2.5 years.

 

everolimus

10

mg

orally

once a day

the total duration of therapy is continued until disease progression, or no toxicity occurs
Note:
Tablets need to be swallowed with a glass of water but do not chew, crush, or break the tablet
Do not combine the brands of Afinitor tablets and Afinitor Disperz to reach the desired dose
Only use any one of them



erlotinib

100

mg

Orally

once a day

; before 1 hour or 2 hours after meals
the duration of the therapy continues until disease progression, or unacceptable toxicity occurs
It is used for patients in combination with gemcitabine as a first-line treatment for patients with locally advanced, unresectable, or metastatic pancreatic cancer



Dose Adjustments

Renal Dose Adjustments:
for renal impairment, dosage adjustment requires, and caution is recommended.
Liver Dose Adjustments:
The treatment should be discontinued in patients with baseline hepatic impairment if the total serum bilirubin doubles or serum transaminases triple
The treatment should be discontinued in patients with normal pretreatment values if the total serum bilirubin >3 x ULN or serum transaminases >5 x ULN

olaparib 

300 mg orally twice daily. Continue for a year or until unacceptable toxicity, disease recurrence, or whichever occurs first



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149791/

https://www.ncbi.nlm.nih.gov/books/NBK518996/

https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-prognosis