Pancreatic cancer is an abnormal uncontrolled growth of tumor cells inside the pancreas.
The pancreas is a pear-shaped organ in the upper part of the abdomen involved in the digestion of food (exocrine pancreas) and regulation of hormones (Endocrine pancreas).
Pancreatic cancer histology differs based on the part from which it arises. Cancers most commonly arise from exocrine component and the most common type is Adenocarcinoma. Other tumors arising from the exocrine pancreas are IPMN (Intraductal papillary mucinous neoplasm), acinar cell carcinoma, adenosquamous carcinoma, mucinous cystic neoplasms, pancreatoblastoma, serous cystadenoma, signet ring cell carcinoma, solid and pseudopapillary tumors, squamous cell carcinoma, and undifferentiated carcinoma.
Cancers arising from the Endocrine pancreas are less common and known as pancreatic Neuroendocrine tumors (PNET) and they include Insulinoma, Gastrinoma, Glucogonomas, somatostatinomas, VIPomas, and nonfunctional PNETs. These tumors can be benign (non-cancerous) or malignant (cancerous) and are classified based on their hormone production and behavior.
In this article we will be discussing only about the adenocarcinoma histology which is the most common type of pancreatic cancer.
Pancreatic Cancer Causes
Pancreatic cancer occurs after a complex interplay of various risk factors contributing to its development. Various causes associated with its development are listed below
Smoking: Tobacco use is a significant risk factor for pancreatic cancer, with smokers being at least twice as likely to develop the disease compared to non-smokers. Chemicals in tobacco smoke can damage pancreatic cells over time, increasing cancer risk.
Age and Gender: Advancing age is a significant risk factor, with the majority of pancreatic cancer cases diagnosed in individuals over 65 years old. Men have a slightly higher risk of developing pancreatic cancer than women.
Family History and Genetics: Inherited genetic mutations, such as BRCA1, BRCA2, and PALB2 gene mutations, can increase the risk of pancreatic cancer. A family history of pancreatic cancer or certain hereditary cancer syndromes (e.g., Lynch syndrome, hereditary pancreatitis, Peutz-Jeghers Syndrome etc.) also raises the risk.
Chronic Pancreatitis: Long-term inflammation of the pancreas (chronic pancreatitis) due to alcohol abuse, gallstones, or other causes is linked to an increased risk of pancreatic cancer over time.
Diabetes: Chronic diabetes mellitus, especially with poorly controlled blood sugar levels, is associated with a higher risk of pancreatic cancer. The relationship between diabetes and pancreatic cancer is complex and requires further research.
Obesity and Diet: Obesity, a diet high in red and processed meats, and low intake of fruits, vegetables, and fiber may contribute to an increased risk of pancreatic cancer. Maintaining a healthy weight and balanced diet is essential for overall health and cancer prevention.
Occupational Exposures: Certain occupational exposures to chemicals such as pesticides, dyes, and metals may slightly elevate pancreatic cancer risk, although more research is needed to understand specific mechanisms.
A lot of research in continuously occuring in pathophysiology and contribution of each risk factor in the development of pancreatic cancer. Understanding about these factor can help in risk stratification of an individual about future development of cancer.
Pancreatic cancer Symptoms
Pancreas is located deep in the upper abdomen and is adjacent alot of important organs associated with digestive function. Many a times pancreatic cancer present in very late stages due to absence of symptoms or vague symptoms present in early disease. Below are listed symptoms associated with pancreatic cancer.
Abdominal Pain: Persistent, dull, or sharp pain in the upper abdomen or back is a common symptom of pancreatic cancer. The pain may worsen after eating or lying down and may not respond well to typical pain medications.
Jaundice: Yellowing of the skin and whites of the eyes (jaundice) occurs when pancreatic tumors block the bile duct, leading to bile buildup. Jaundice can cause itching, dark urine, pale stools, and yellowing of the skin and eyes.
Unexplained Weight Loss: Sudden and unexplained weight loss, despite normal eating habits, can be a sign of pancreatic cancer. This weight loss may result from a combination of factors, including cancer-related metabolic changes and decreased appetite.
Digestive Issues: Pancreatic cancer can affect digestion, leading to symptoms such as nausea, vomiting, indigestion, bloating, and changes in bowel habits (diarrhea or constipation).
Loss of Appetite: A decreased appetite or early satiety (feeling full quickly after eating small amounts) may occur due to pancreatic cancer affecting digestion and hormone regulation.
New-Onset Diabetes: In some cases, pancreatic cancer can cause new-onset diabetes or worsen existing diabetes. Sudden changes in blood sugar levels without obvious reasons should be evaluated by a healthcare professional.
Fatigue and Weakness: Generalized fatigue, weakness, and a sense of malaise can accompany pancreatic cancer, often due to the body’s response to the underlying disease.
Other symptoms include pain in the arm, legs, Unexplained fever, Chills etc.
These symptoms are very non specific and are often present in various other malignancies of digestive tract and in non malignant conditions also. Recognizing these symptoms along with medical examination by physician and relevant investigations can help in early diagnosis of disease.
Pancreatic cancer diagnosis
Screening tools for detection of early cancers in normal individuals are present in various other cancers but Unfortunately, no such screening investigation present for detection of early pancreatic cancer.
A thorough medical history along with physical examination is required following the doctor suggests a battery of different tests to diagnose and stage the disease. Not all tests are required in every individual. They are selected based on the findings on examination and report of initial investigations.
Imaging Tests: Imaging plays a crucial role in detecting pancreatic tumors and assessing their size, location, and involvement of surrounding structures. Common imaging techniques include CT scans, MRI scans, and endoscopic ultrasound (EUS). These tests provide detailed images of the pancreas and help doctors determine the extent of the disease.
A special method for CT scan is used called Pancreatic protocol CT. In this picture of pancreas are taken at different interval after injection of contrast material. It helps in better delineating the tumor spread and involvement of adjacent structures.
Blood Tests: Certain blood tests can aid in diagnosing pancreatic cancer by measuring levels of specific tumor markers and assessing overall health. Tumor markers are chemicals secreted by the tumor and are present in high levels in blood if a tumor is present in the body.
Elevated levels of CA 19-9, CEA, and CA 125 markers in the blood may indicate pancreatic cancer, although these markers can also be elevated in other conditions.
Biopsy and Tissue Sampling: A biopsy is often necessary to confirm pancreatic cancer diagnosis definitively. Tissue samples can be obtained through fine-needle aspiration (FNA) or core needle biopsy guided by imaging techniques such as EUS or CT scans. A pathologist analyzes the tissue samples under a microscope to identify cancerous cells and determine the cancer type and grade.
Endoscopic Retrograde Cholangiopancreatography (ERCP): ERCP combines endoscopy and X-ray imaging to visualize the pancreas, bile ducts, and pancreatic duct. It can help diagnose blockages, tumors, or other abnormalities in the pancreatic and bile ducts.
Positron Emission Tomography (PET) Scan: PET scans may be used to detect metastases or spread of pancreatic cancer to other parts of the body. It involves injecting a radioactive tracer that is taken up by cancer cells, allowing for detection with imaging.
Pancreatic cancer Treatment
Pancreatic cancer treatment is complex and as most cancers are detected in advanced stages, Treatment depends on the stage at which the disease is diagnosed and what is general condition of patient at the time of diagnosis.
A multidisciplinary team involving oncologists, Surgeons, radiologists and other allied medical branches make a tailor made plan for each individual patient.
Treatment in broad include surgery, Chemotherapy, radiation therapy, immuno and targeted therapy. Palliative therapy in patients who have advanced disease and not able to tolerate conventional therapy.
Surgery plays a crucial role in the treatment of pancreatic cancer, especially for localized tumors that are resectable (able to be removed surgically). Here are the main surgical procedures used for pancreatic cancer:
Whipple Procedure (Pancreaticoduodenectomy): This complex surgery is the most common procedure for tumors located in the head of the pancreas, where the bile duct and pancreatic duct meet. During the Whipple procedure, the surgeon removes the head of the pancreas, part of the small intestine (duodenum), gallbladder, common bile duct, and sometimes part of the stomach. The remaining organs are then reconstructed to restore digestive and bile flow.
Distal Pancreatectomy: In this surgery, the surgeon removes the body and tail of the pancreas when the tumor is located in these areas. The spleen may also be removed if the tumor involves the spleen or nearby blood vessels.
Total Pancreatectomy: In rare cases where the entire pancreas is affected by cancer, a total pancreatectomy may be performed. This surgery involves removing the entire pancreas. Patients undergoing total pancreatectomy require lifelong pancreatic enzyme replacement therapy and close monitoring of blood sugar levels due to the absence of pancreatic function.
Palliative Surgery: For advanced pancreatic cancer that is unresectable (cannot be completely removed), palliative surgery may be performed to alleviate symptoms and improve quality of life. This may involve bypass surgeries to relieve bile duct or intestinal blockages caused by the tumor.
Surgery for pancreatic cancer is a complex procedure that requires expertise in pancreatic and hepatobiliary surgery.
Chemotherapy: Chemotherapy uses drugs to kill cancer cells or stop them from growing. It may be used before surgery (neoadjuvant), after surgery (adjuvant), or as the primary treatment for advanced pancreatic cancer (unresectable tumors). Common chemotherapy drugs include gemcitabine, 5-fluorouracil (5-FU), nab-paclitaxel, and oxaliplatin.
Radiation Therapy: Radiation therapy uses high-energy rays to target and destroy cancer cells. It can be delivered externally (external beam radiation therapy) or internally (brachytherapy). Radiation therapy is often combined with chemotherapy (chemoradiation) for more effective treatment.
Targeted Therapy: Targeted therapy drugs target specific molecules or pathways involved in cancer growth. For pancreatic cancer, targeted therapies like erlotinib and cetuximab may be used in combination with chemotherapy for certain patients with advanced or metastatic disease.
Immunotherapy: Immunotherapy works by stimulating the immune system to recognize and attack cancer cells. While not yet a standard treatment for pancreatic cancer, ongoing research and clinical trials are exploring immunotherapy options such as checkpoint inhibitors (e.g., pembrolizumab) and vaccines for specific subsets of pancreatic cancer patients.
Palliative Care: Palliative care focuses on improving the quality of life for patients with advanced pancreatic cancer by managing symptoms such as pain, nausea, fatigue, and emotional distress. It is provided alongside curative treatments and is aimed at enhancing comfort and overall well-being.
Pancreatic cancer is a deadly disease with poor prognosis if the disease is detected at late stages. Thus having an understanding about the symptoms, risks factors and treatment modalities can help in detecting the cancer in early stages and thus can improve overall treatment outcomes.
