Pancreatic Ductal Carcinoma - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Cancer of the pancreas originates mainly from the exocrine glands. The exocrine glands are responsible for producing enzymes that help in digestion. Exocrine glands make up 85 to 90 % of pancreatic cells, and endocrine constitutes about 10 to 15 % of cells, including islets of Langerhans, which secretes insulin, glucagon, and other hormones.

What Causes Pancreatic Ductal Cancer?

Pancreatic ductal carcinoma is seen in 28,000 new individuals every year. Some of the factors responsible for aggregating pancreatic cancer are:

• The rate of pancreatic cancer is high in smokers than in non-smokers.

• People consuming alcohol and coffee have also been found to be at potential risk.

• Familial history of pancreatic cancer leads to 40 % more susceptibility in patients.

• It affects both the male and female populations equally.

• It is most commonly seen between 60 to 80 years of age.

• Mutations of multiple genes cause pancreatic ductal carcinoma. Some cancer-associated gene mutations are K-RAS and tumor suppressor gene CDKN2A, formerly p-16 genes that show a mutation in 90 % of cancers.

• However, the combined mutation of the K-RAS and CDKN2A gene is the unique mutation solely seen in pancreatic cancer.

• Mutation of the p53 gene into the TP 53 gene is seen in 50 % of pancreatic cancers.

• The tumor suppressor gene known as - deleted in pancreatic cancer 4 (DPC4) is absent in 50% of pancreatic cancer patients. This gene initiates growth factor events in cells.

• Specific DNA repair genes are also responsible for pancreatic cancer, such as BRCA2 and MLH1.

• The genes responsible for breast cancer ERBB2 (HER2/NEU) are also noted in 50 % of pancreatic cancer.

How Does a Pancreatic Ductal Cancer Appear?

Microscopically pancreatic ductal carcinoma appears in a glandular pattern. It can be both mucinous or non-mucin secreting. They appear small, irregularly shaped, and lined by anaplastic cuboidal or columnar epithelial cells. The tumor can invade surrounding tissues causing pain in the abdomen. In 20 % of tumor cases, it diffuses completely, involving the entire organ. Tumors arising from ductal epithelium are known as adenocarcinoma. They are the most prevalent forms of pancreatic cancer. Adenocarcinoma produces mucin and has a rich fibrous stroma supply. Increased fibrous lesions are also known as the desmoplastic lesion. These lesions appear as gritty, gray-white, hard masses.

Cancer of the exocrine pancreatic glands obstructs the bile flow. Obstruction of the bile can cause ulceration of the mucosa. Cancer of the endocrine gland of the pancreas involving the body and tail shows a non-invasive property. They are often detected once the disease has progressed extensively. These lesions are large and widely spread. Tumors of endocrine pancreatic glands rarely invade the surrounding organs like the spleen, adrenal glands, vertebral column, transverse column, and stomach. Lymph nodes are also involved during the invasion of adjacent cells like mesenteric, omental, gastric, peripancreatic, and portohepatic nodes are involved. During metastatic circulation, deposits are accumulated in the liver causing liver enlargement. Distant metastasis is observed in the lungs and bones of the body.

What Are the Clinical Features Seen in Pancreatic Ductal Cancer?

Pancreatic tumors are silent and metastasize to other organs. Due to its asymptomatic nature, early detection is hard to understand. Some of the clinical manifestations are:

• Pancreatic cancer spreads to the nearby nerve tissue and causes pain. This is considered to be the primary symptom experienced by patients. But diagnosis based on this symptom is made at a stage when the disease has progressed extensively.

• Obstructing the drainage system caused due to obstructive jaundice can be an initiating sign. This affects the external surface of the pancreas or the exocrine gland.

• The appearance of the Trousseau sign or phlebophlebitis is seen in pancreatic cancer.

• The pancreatic enzyme CA 19-9 (carcinoembryonic antigen) shows high values.

What Are the Symptoms of Pancreatic Ductal Carcinoma?

The pancreatic cancer symptoms start showcasing during the latter stages of the progression of the disease. Some of the symptoms noted are:

• Abdominal pain radiating to the back region.

• Loss of appetite and consequent weight loss.

• The pale color of the skin.

• Icterus or yellowish discoloration of the sclera of eyes (jaundice).

• Itchy skin.

• Dark urine.

• Pale-colored stool.

• Blood clots.

• Fatigue.

What Are the Factors Causing Risk in Pancreatic Ductal Cancer?

Factors that can prolong or severe the condition are:

• Smoking.

• Alcohol consumption.

• Diabetes.

• Pancreatitis.

• Obesity.

• Family history of cancer. For example, BRCA2 gene mutation and Lynch syndrome.

• Senile patients with comorbidities.

• Late diagnosis of disease.

How to Diagnose Pancreatic Ductal Cancer?

Early diagnosis is difficult in pancreatic cancer. However, specific diagnoses can be made depending on the pertaining symptoms. Such as:

• Abdominal Ultrasound: This helps to capture internal images. It shows dilated bile ducts in association with jaundice. Occasionally a mass is seen in the head of the pancreas. This can also be misinterpreted as a gas formation.

• Computed Tomography (CT): Underlining pancreatic malignancy is observed under contrast mass. CT scan has several values. If a tumor is detected, it is identified with the surrounding blood vessel. This helps to determine whether the cancerous lesion is operable or not.

• Screening for Metastasis: The spread of tumor cells to distant organs like the liver, abdominal cavity, and lungs is determined by additional interventional radiology and biopsy studies.

How to Treat Pancreatic Ductal Cancer?

Pancreatic ductal carcinoma is a deadly condition. Some of the treatment modalities practiced are:

• Surgical Management: Patients undergoing surgical therapy have a 20 % chance of resection. Tumors arising in the tail of the pancreas can be surgically removed by distal pancreatectomy. The tumors arising from the head of the pancreas are very complex and often treated using robotic surgery.

• Chemotherapy: Tumors are treated with adjuvant therapy using chemicals to kill cancer cells. All the treatments undertaken will not give a complete cure but will help in controlling further damage.

• Radiation: Radiation therapy damages cancer cells' genetic material, killing them or limiting their growth at high dosages. Cancer cells with DNA damage that cannot be repaired either cease proliferating or die. When the injured cells expire, the body degrades and eliminates them.

• Combination of All: Combined treatment of chemotherapy and radiotherapy are done.

Conclusion:

Pancreatic carcinoma is the fourth most cause of death due to cancer. The mortality rate of such cancer is less than five years. However, the late diagnosis due to its absent symptoms makes the treatment challenging. Hence, giving a poor prognosis.