Table of Contents

I. Introduction
II. Incidence and Mortality Rates of Pancreatic Cancer
III. Pancreatic Cancer and Risk Factors
IV. Types of Pancreatic Tumors
V. Diagnosis of Pancreatic Cancer
VI. Treatment of Pancreatic Cancer
VII. Challenges in the Treatment of Pancreatic Cancer
VIII. Diagnostic Tests and Markers for Pancreatic Cancer

Pancreatic cancer (pc) can be called as a highly lethal disease as the mortality due to the disease closely parallels incidence. Hence it is one of the deadliest cancer types. The disease is mostly asymptomatic until the disease reaches an advanced stage. Unfortunately, there is a lack of a standard process of screening patients at high risk (eg, those with a family history of pancreatic cancer and chronic pancreatitis). The highest incidence and mortality rates of pancreatic cancer are found in developed countries. According to World Cancer Research Fund (WCRF) & American Institute for Cancer Research (AICR), Pancreatic cancer is the 12th most commonly occurring cancer in men and the 11th most commonly occurring cancer in women.

There were 460,000 new cases in 2018. Hungary had the highest rate of pancreatic cancer out of top 20 countries followed by Uruguay. Latvia and Moldova topped in pancreatic cancer in men whereas United Arab Emirates (UAE) were highest in women, followed by Uruguay.

The pancreas is a gland located between the stomach and the spine. Pancreatic enzymes help in digestion and controlling blood-sugar levels. A regular process of cell division to form new cells in place of old occurs inside the body. However, sometimes this process breaks and cells may form a mass of tissue called a tumor. Some tumors are benign, they are abnormal but cannot invade other parts of the body. A malignant tumor is known by name cancer. The cells grow out of control and can spread to other tissues and organs. Even when cancer spreads to other areas of the body, it is still called pancreatic cancer if that is where it started. Pancreatic cancer often spreads to the liver, abdominal wall, lungs, bones and/or lymph nodes. Few of the known risk factors for the disease are cigarette smoking (relative risk increase of 2.5 times[1]), high body mass index and lack of physical activity[2], diabetes[3] and chronic pancreatitis[4]. The Continuous Update Project from WCRF & AICR mentioned that there is strong evidence that greater body fatness and greater adult attained height increase the risk of pancreatic cancer. There is some evidence that consuming red meat, processed meat, alcoholic drinks, foods containing saturated fatty acids and foods and drinks containing fructose might increase the risk of pancreatic cancer.

Pancreatic tumors are either exocrine or neuroendocrine (endocrine). About 94% of pancreatic cancers are exocrine whereas, 6% are neuroendocrine tumors (NETs), or islet cell tumors. NETs are less common but tend to have a better outlook (prognosis).

Adenocarcinoma is the most common type of pancreatic cancer. The diagnosis of the type of tumor is important as they respond differently to different treatments. It often goes undetected until it’s in an advanced stage. In the initial stages, it tends to be silent and painless. Few of the symptoms are Weight loss, Malaise, Loss of appetite, Elevated blood sugars, Jaundice, Abdominal pain, Back pain, Bloating, diabetes. However, there are many other causes for these types of symptoms so having any or all of these symptoms doesn’t mean a person has pancreatic cancer.

Imaging tests are performed along with physical examination for the disease diagnosis. If imaging studies detect a mass in the pancreas a pancreatic cancer diagnosis is likely, but not definite. A confirmation is done by biopsy and can be performed in several ways – Fine needle aspiration, Endoscopic retrograde cholangiopancreatography (ERCP) which collect images from the area, as well as take a small biopsy with a brush, Endoscopic ultrasound where an endoscope plucks some tissue from the mass and Laparoscopy.

PC treatment depends on its stage, which is often tricky. Imaging tests provide preliminary information, and to know the disease spread usually requires surgery. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status.

Surgery offers the best chance of controlling pancreatic cancer for a long time. But, most patients are diagnosed at later stages and are not eligible for surgery. Another challenge is that pancreatic tumors are surrounded by a dense tissue layer, called the stroma. This makes it difficult for treatment to reach the tumor. Researchers are studying ways to get treatment through the stroma to make it more effective

Diagnostic tests/markers to find pancreatic cancer in the earliest stages are the need of the hour. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. However, there is no reliable diagnostic biomarker for pancreatic cancer. Studies are ongoing for the potential tumor markers, carbohydrate antigen 19-9 (CA 19-9) is the most extensively studied. CA 19-9 does not necessarily indicate cancer or advanced disease[5] due to which, it performs poorly as a screening tool. Though, it has been reported to be used in the monitoring of recurrence after resection[6]. Many studies are investigating potential biomarkers like serum macrophage inhibitory cytokine 1 (MIC-1), CECAM-1, Span-1, DUPAN-2, Alpha4GnT, PAM4, and combined biomarkers with CEA, CA 19-9, and CA 242[7, 8].

A potential diagnostic tool comprising of a combined panel of protein and microRNAs serum exome with improved sensitivities and specificities for pancreatic cancer has emerged. However, they are yet to be tested within larger cohorts[9]. Inorganic nanomaterials such as gold and carbon nanotubes targeted towards specific pancreatic cancer cells have also been early research reviewing the use of, in early detection and diagnosis[10].

Also, some cancers have been successfully treated with targeted therapies which block specific mutations. But, these drugs have not been developed specifically for pancreatic cancer yet. As more studies are done, more targeted treatments will be developed and approved for pancreatic cancer patients whose tumors have specific molecular changes.

Pancreatic cancer screening is not feasible in the general population due to the low incidence of pancreatic cancer and the lack of a cheap, easy, accurate point of care screening test. With the technology getting better the continuing studies for early detection will make progress toward finding the disease earlier.

References

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